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Sample records for experimental systemic sclerosis

  1. Systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Ahathya R

    2007-01-01

    Full Text Available Systemic sclerosis (scleroderma is a rare generalized disorder of connective tissue origin. This condition is predominantly a clinical diagnosis, based on the clinical signs and symptoms. Here is a case report of 26-year-old female patient with the classical features of this disease. This case is reported for its rarity and variable expressivity. This article also reviews the literature of this uncommon condition.

  2. Immune surveillance of the central nervous system in multiple sclerosis--relevance for therapy and experimental models.

    Science.gov (United States)

    Hussain, Rehana Z; Hayardeny, Liat; Cravens, Petra C; Yarovinsky, Felix; Eagar, Todd N; Arellano, Benjamine; Deason, Krystin; Castro-Rojas, Cyd; Stüve, Olaf

    2014-11-15

    Treatment of central nervous system (CNS) autoimmune disorders frequently involves the reduction, or depletion of immune-competent cells. Alternatively, immune cells are being sequestered away from the target organ by interfering with their movement from secondary lymphoid organs, or their migration into tissues. These therapeutic strategies have been successful in multiple sclerosis (MS), the most prevalent autoimmune inflammatory disorder of the CNS. However, many of the agents that are currently approved or in clinical development also have severe potential adverse effects that stem from the very mechanisms that mediate their beneficial effects by interfering with CNS immune surveillance. This review will outline the main cellular components of the innate and adaptive immune system that participate in host defense and maintain immune surveillance of the CNS. Their pathogenic role in MS and its animal model experimental autoimmune encephalomyelitis (EAE) is also discussed. Furthermore, an experimental model is introduced that may assist in evaluating the effect of therapeutic interventions on leukocyte homeostasis and function within the CNS. This model or similar models may become a useful tool in the repertoire of pre-clinical tests of pharmacological agents to better explore their potential for adverse events. Published by Elsevier B.V.

  3. [Systemic sclerosis: a multisystem disease

    NARCIS (Netherlands)

    Berrevoets, M.A.; Markhorst, J.; Meek, I.; Ede, A.E. van; Vonk, M.C.

    2014-01-01

    Systemic sclerosis is a rare, systemic autoimmune disease, characterized by inflammation, vasculopathy and fibrosis of the skin and internal organs. The disease is associated with a significantly increased morbidity and mortality, and can be rapidly progressive. Interstitial lung disease, renal

  4. Skin scoring in systemic sclerosis

    DEFF Research Database (Denmark)

    Zachariae, Hugh; Bjerring, Peter; Halkier-Sørensen, Lars

    1994-01-01

    Forty-one patients with systemic sclerosis were investigated with a new and simple skin score method measuring the degree of thickening and pliability in seven regions together with area involvement in each region. The highest values were, as expected, found in diffuse cutaneous systemic sclerosis...... (type III SS) and the lowest in limited cutaneous systemic sclerosis (type I SS) with no lesions extending above wrists and ancles. A positive correlation was found to the aminoterminal propeptide of type III procollagen, a serological marker for synthesis of type III collagen. The skin score...

  5. Vasculitis in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Lily Kao

    2010-01-01

    Full Text Available Systemic sclerosis (SSc is a multiorgan connective tissue disease characterized by autoantibody production and fibroproliferative stenosis of the microvasculature. The vascoluopathy associated with SSc is considered to be noninflammatory, yet frank vasculitis can complicate SSc, posing diagnostic and therapeutic challenges. Here, we have reviewed the literature for reports of small-, medium-, and large-vessel vasculitis occurring in SSc. Amongst 88 reported cases of vasculitis in SSc, patients with ANCA-associated vasculitis appear to present a unique subclass in that they combined typical features of SSc with the renal manifestation of ANCA-associated glomerulonephritis. Other vasculitic syndromes, including large-vessel vasculitis, Behcet's disease, cryoglobulinemia, and polyarteritis nodosa, are rarely encountered in SSc patients. ANCA-associated vasculitis needs to be considered as a differential diagnosis in SSc patients presenting with renal insufficiency, as renal manifestations may result from distinct disease processes and require appropriate diagnostic testing and treatment.

  6. Early-Life Antibiotic Exposure Causes Intestinal Dysbiosis and Exacerbates Skin and Lung Pathology in Experimental Systemic Sclerosis.

    Science.gov (United States)

    Mehta, Heena; Goulet, Philippe-Olivier; Mashiko, Shunya; Desjardins, Jade; Pérez, Gemma; Koenig, Martial; Senécal, Jean-Luc; Constante, Marco; Santos, Manuela M; Sarfati, Marika

    2017-11-01

    Patients with systemic sclerosis (SSc) display altered intestinal microbiota. However, the influence of intestinal dysbiosis on the development of experimental SSc remains unknown. Topoisomerase I peptide-loaded dendritic cell immunization induces SSc-like disease, with progressive skin and lung fibrosis. Breeders were given streptomycin and pups continued to receive antibiotic (ATB) until endpoint (lifelongATB). Alternately, ATB was withdrawn (earlyATB) or initiated (adultATB) during adulthood. Topoisomerase I peptide-loaded dendritic cell (no ATB) immunization induced pronounced skin fibrosis, with increased matrix (Col1a1), profibrotic (Il13, Tweakr), and vascular function (Serpine1) gene expression. Remarkably, earlyATB exposure was sufficient to augment skin Col5a1 and Il13 expression, and inflammatory cell infiltration, which included IL-13+ cells, mononuclear phagocytes, and mast cells. Moreover, skin pathology exacerbation was also observed in lifelongATB and adultATB groups. Oral streptomycin administration induced intestinal dysbiosis, with exposure limited to early life (earlyATB) being sufficient to cause long-term modification of the microbiota and a shift toward increased Bacteroidetes/Firmicutes ratio. Finally, aggravated lung fibrosis and dysregulated pulmonary T-cell responses were observed in earlyATB and lifelongATB but not adultATB-exposed mice. Collectively, intestinal microbiota manipulation with streptomycin exacerbated pathology in two distinct sites, skin and lungs, with early life being a critical window to affect the course of SSc-like disease. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Fructose Malabsorption in Systemic Sclerosis

    OpenAIRE

    Marie, Isabelle; Leroi, Anne-Marie; Gourcerol, Guillaume; Levesque, Herv?; M?nard, Jean-Fran?ois; Ducrotte, Philippe

    2015-01-01

    Abstract The deleterious effect of fructose, which is increasingly incorporated in many beverages, dairy products, and processed foods, has been described; fructose malabsorption has thus been reported in up to 2.4% of healthy subjects, leading to digestive clinical symptoms (eg, pain, distension, diarrhea). Because digestive involvement is frequent in patients with systemic sclerosis (SSc), we hypothesized that fructose malabsorption could be responsible for intestinal manifestations in thes...

  8. Lactose malabsorption in systemic sclerosis.

    Science.gov (United States)

    Marie, I; Leroi, A-M; Gourcerol, G; Levesque, H; Menard, J-F; Ducrotte, P

    2016-11-01

    There are no studies on systemic sclerosis (SSc) assessing the relationship between food intake, especially lactose, and gastrointestinal dysfunction. To determine the prevalence of lactose malabsorption, using lactose breath test, in patients with SSc. To evaluate the correlation between lactose malabsorption and gastrointestinal involvement. To predict which SSc patients exhibit lactose malabsorption. Seventy-seven consecutive Caucasian patients with SSc and 20 control subjects underwent lactose breath test. All patients also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. The prevalence of lactose malabsorption was higher in SSc patients than in controls (44.3% vs. 10%; P = 0.004). We observed a marked correlation between the presence of lactose malabsorption and: higher values of GSS (P lactose malabsorption, the median value of GSS of digestive symptoms was lower after initiation of lactose-free diet (P lactose malabsorption often occurs in patients with systemic sclerosis. Furthermore, our findings highlight the fact that lactose breath test is a helpful, noninvasive method, by identifying the group of patients with systemic sclerosis with symptomatic lactose malabsorption that may benefit from a reduction in lactose intake. © 2016 John Wiley & Sons Ltd.

  9. Progressive System Sclerosis - A Case Report

    Directory of Open Access Journals (Sweden)

    Jyothi S Kumar

    2003-01-01

    Full Text Available Progressive systemic sclerosis is a disease that involves connective tissues and.blood vessels leading to fibrosis. The skin as well as internal organs are involved. A case of progressive systemic sclerosis is presented and review of literature concerning oral manifestations of this condition is presented.

  10. Localized Scleroderma, Systemic Sclerosis and Cardiovascular Risk

    DEFF Research Database (Denmark)

    Hesselvig, Jeanette Halskou; Kofoed, Kristian; Wu, Jashin J

    2018-01-01

    Recent findings indicate that patients with systemic sclerosis have an increased risk of cardiovascular disease. To determine whether patients with systemic sclerosis or localized scleroderma are at increased risk of cardiovascular disease, a cohort study of the entire Danish population aged ≥ 18......,962 patients with systemic sclerosis were identified and compared with 5,428,380 people in the reference population. In systemic sclerosis, the adjusted HR was 2.22 (95% confidence interval 1.99-2.48). No association was seen between patients with localized scleroderma and cardiovascular disease. In conclusion......, systemic sclerosis is a significant cardiovascular disease risk factor, while patients with localized scleroderma are not at increased risk of cardiovascular disease....

  11. [Renal involvement in systemic sclerosis].

    Science.gov (United States)

    Jara, Luis J; Barrera, Antonio

    2006-11-01

    Renal crisis is one of the most severe complications of systemic sclerosis, and its frequency is 10%, and it is characterized by malignant hypertension, hyperreninemia, azotemia, microangiopathic hemolytic anemia, and renal failure. In the pathogenesis of renal affection, the main mechanism is the endothelial damage (thickness of arterial vessels), decrease of blood flow and hyperplasia of the yuxtaglomerular apparatus as well as release of renina. Pathological changes of scleroderma kidney are similar to those observed in other forms of malignant hypertension. Renal crisis was considered as fatal complications, however it is now successfully treated with angiotensin- converting enzyme inhibitors. Copyright © 2006 Elsevier España S.L. Barcelona. Published by Elsevier Espana. All rights reserved.

  12. Targeted Therapy in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Murray Baron

    2016-10-01

    Full Text Available Targeted therapies use an understanding of the pathophysiology of a disease in an individual patient. Although targeted therapy for systemic sclerosis (SSc, scleroderma has not yet reached the level of patient-specific treatments, recent developments in the understanding of the global pathophysiology of the disease have led to new treatments based on the cells and pathways that have been shown to be involved in the disease pathogenesis. The presence of a B cell signature in skin biopsies has led to the trial of rituximab, an anti-CD20 antibody, in SSc. The well-known properties of transforming growth factor (TGF-β in promoting collagen synthesis and secretion has led to a small trial of fresolimumab, a human IgG4 monoclonal antibody capable of neutralizing TGF-β. Evidence supporting important roles for interleukin-6 in the pathogenesis of SSc have led to a large trial of tocilizumab in SSc. Soluble guanylate cyclase (sGC is an enzyme that catalyzes the production of cyclic guanosine monophosphate (cGMP upon binding of nitric oxide (NO to the sGC molecule. Processes such as cell growth and proliferation are regulated by cGMP. Evidence that sGC may play a role in SSc has led to a trial of riociguat, a molecule that sensitizes sGC to endogenous NO. Tyrosine kinases (TKs are involved in a wide variety of physiologic and pathological processes including vascular remodeling and fibrogenesis such as occurs in SSc. This has led to a trial of nintedanib, a next-generation tyrosine-kinase (TK inhibitor which targets multiple TKs, in SSc.

  13. Evaluation of a radiolabelled peripheral benzodiazepine receptor ligand in the central nervous system inflammation of experimental autoimmune encephalomyelitis: a possible probe for imaging multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Mattner, F.; Katsifis, A.; Ballantyne, P. [ANSTO, Radiopharmaceuticals Division, Lucas Heights (Australia); Staykova, M.; Willenborg, D.O. [Australian National University Medical School, The Canberra Hospital, Neurosciences Research Unit, Woden, Canberra (Australia)

    2005-04-01

    Peripheral benzodiazepine receptors (PBRs) are upregulated on macrophages and activated microglia, and radioligands for the PBRs can be used to detect in vivo neuroinflammatory changes in a variety of neurological insults, including multiple sclerosis. Substituted 2-phenyl imidazopyridine-3-acetamides with high affinity and selectivity for PBRs have been prepared that are suitable for radiolabelling with a number of positron emission tomography and single-photon emission computed tomography (SPECT) isotopes. In this investigation, the newly developed high-affinity PBR ligand 6-chloro-2-(4'-iodophenyl)-3-(N,N-diethyl)imidazo[1,2-a]pyridine-3-acetamide, or CLINDE, was radiolabelled with{sup 123}I and its biodistribution in the central nervous system (CNS) of rats with experimental autoimmune encephalomyelitis (EAE) evaluated. EAE was induced in male Lewis rats by injection of an emulsion of myelin basic protein and incomplete Freund's adjuvant containing Mycobacterium butyricum. Biodistribution studies with{sup 123}I-CLINDE were undertaken on EAE rats exhibiting different clinical disease severity and compared with results in controls. Disease severity was confirmed by histopathology in the spinal cord of rats. The relationship between inflammatory lesions and PBR ligand binding was investigated using ex vivo autoradiography and immunohistochemistry on rats with various clinical scores. {sup 123}I-CLINDE uptake was enhanced in the CNS of all rats exhibiting EAE when compared to controls. Binding reflected the ascending nature of EAE inflammation, with lumbar/sacral cord > thoracic cord > cervical cord > medulla. The amount of ligand binding also reflected the clinical severity of disease. Ex vivo autoradiography and immunohistochemistry revealed a good spatial correspondence between radioligand signal and foci of inflammation and in particular ED-1{sup +} cells representing macrophages and microglia. These results demonstrate the ability of {sup 123}I

  14. Fructose Malabsorption in Systemic Sclerosis.

    Science.gov (United States)

    Marie, Isabelle; Leroi, Anne-Marie; Gourcerol, Guillaume; Levesque, Hervé; Ménard, Jean-François; Ducrotte, Philippe

    2015-09-01

    The deleterious effect of fructose, which is increasingly incorporated in many beverages, dairy products, and processed foods, has been described; fructose malabsorption has thus been reported in up to 2.4% of healthy subjects, leading to digestive clinical symptoms (eg, pain, distension, diarrhea). Because digestive involvement is frequent in patients with systemic sclerosis (SSc), we hypothesized that fructose malabsorption could be responsible for intestinal manifestations in these patients. The aims of this prospective study were to: determine the prevalence of fructose malabsorption, in SSc; predict which SSc patients are at risk of developing fructose malabsorption; and assess the outcome of digestive symptoms in SSc patients after initiation of standardized low-fructose diet. Eighty consecutive patients with SSc underwent fructose breath test. All SSc patients also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. The prevalence of fructose malabsorption was as high as 40% in SSc patients. We also observed a marked correlation between the presence of fructose malabsorption and: higher values of GSS score of digestive symptoms (P = 0.000004); and absence of delayed gastric emptying (P = 0.007). Furthermore, in SSc patients with fructose malabsorption, the median value of GSS score of digestive symptoms was lower after initiation of standardized low-fructose diet (4 before vs. 1 after; P = 0.0009). Our study underscores that fructose malabsorption often occurs in SSc patients. Our findings are thus relevant for clinical practice, highlighting that fructose breath test is a helpful, noninvasive method by: demonstrating fructose intolerance in patients with SSc; and identifying the group of SSc patients with fructose intolerance who may benefit from low-fructose diet. Interestingly, because the present series also shows that low-fructose diet resulted in a marked decrease of gastrointestinal clinical manifestations

  15. T cells in multiple sclerosis and experimental autoimmune encephalomyelitis.

    LENUS (Irish Health Repository)

    Fletcher, J M

    2012-02-01

    Multiple sclerosis (MS) is a demyelinating inflammatory disorder of the central nervous system (CNS), which involves autoimmune responses to myelin antigens. Studies in experimental autoimmune encephalomyelitis (EAE), an animal model for MS, have provided convincing evidence that T cells specific for self-antigens mediate pathology in these diseases. Until recently, T helper type 1 (Th1) cells were thought to be the main effector T cells responsible for the autoimmune inflammation. However more recent studies have highlighted an important pathogenic role for CD4(+) T cells that secrete interleukin (IL)-17, termed Th17, but also IL-17-secreting gammadelta T cells in EAE as well as other autoimmune and chronic inflammatory conditions. This has prompted intensive study of the induction, function and regulation of IL-17-producing T cells in MS and EAE. In this paper, we review the contribution of Th1, Th17, gammadelta, CD8(+) and regulatory T cells as well as the possible development of new therapeutic approaches for MS based on manipulating these T cell subtypes.

  16. Cardiac involvement in patients of systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Ahmad Qazi

    2008-01-01

    Full Text Available Background: Systemic sclerosis is a multi-systemic autoimmune disorder. Cardiac involvement by the disease, although not included in the diagnostic criteria, may be seen either clinically, histologically or may be revealed by various investigative modalities. Purpose: To see the profile of cardiac involvement in patients of systemic sclerosis. Materials and Methods: Forty-seven patients of systemic sclerosis were included in the study. After taking a complete history and doing a detailed physical examination, the patients were submitted to electrocardiogram ECG (all leads, echocardiography and x-ray chest. Furst′s organ indices scoring system for cardiac involvement was followed. Findings: Forty-seven patients of systemic sclerosis were included in the study. Five females gave a history of palpitations. A loud pulmonic heart sound was heard in 1. Arrhythmias were observed in 5 patients. Significantly, echocardiography revealed valvular involvement in 5 patients. Left ventricular hypertrophy was seen in 2 patients. Conclusions: In our patients, cardiac involvement was rare. In contrast to other studies, valvular involvement was a prominent feature. Limitations: Complete evaluation for arrhythmias with 24-h Holter monitor was not used

  17. Esophageal involvement in progressive systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Stephen A. Geller

    2013-10-01

    Full Text Available Progressive systemic sclerosis (PSSc is a chronic disease of unknown etiology characterized by progressive, abnormal accumulation of fibrous tissue in the skin and many organs. Characteristically, there is induration and thickening of the skin (scleroderma, abnormalities involving muscles, joints, and viscera. The first description was likely by William and Robert Watson in 1754.

  18. Mapping and predicting mortality from systemic sclerosis

    DEFF Research Database (Denmark)

    Elhai, Muriel; Meune, Christophe; Boubaya, Marouane

    2017-01-01

    OBJECTIVES: To determine the causes of death and risk factors in systemic sclerosis (SSc). METHODS: Between 2000 and 2011, we examined the death certificates of all French patients with SSc to determine causes of death. Then we examined causes of death and developed a score associated with all...

  19. Immune system alterations in amyotrophic lateral sclerosis

    DEFF Research Database (Denmark)

    Hovden, H; Frederiksen, J L; Pedersen, S W

    2013-01-01

    Amyotrophic lateral sclerosis is a disease of which the underlying cause and pathogenesis are unknown. Cumulatative data clearly indicates an active participation by the immune system in the disease. An increasingly recognized theory suggests a non-cell autonomous mechanism, meaning that multiple...

  20. Locus coeruleus damage and noradrenaline reductions in multiple sclerosis and experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Polak, Paul E; Kalinin, Sergey; Feinstein, Douglas L

    2011-03-01

    The endogenous neurotransmitter noradrenaline exerts anti-inflammatory and neuroprotective effects in vitro and in vivo. Several studies report that noradrenaline levels are altered in the central nervous system of patients with multiple sclerosis and rodents with experimental autoimmune encephalomyelitis, which could contribute to pathology. Since the major source of noradrenaline are neurons in the locus coeruleus, we hypothesized that alterations in noradrenaline levels are a consequence of stress or damage to locus coeruleus neurons. In C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein peptide 35-55 to develop chronic disease, cortical and spinal cord levels of noradrenaline were significantly reduced versus control mice. Immunohistochemical staining revealed increased astrocyte activation in the ventral portion of the locus coeruleus in immunized mice. The immunized mice showed neuronal damage in the locus coeruleus detected by a reduction of average cell size of tyrosine hydroxylase stained neurons. Analysis of the locus coeruleus of multiple sclerosis and control brains showed a significant increase in astrocyte activation, a reduction in noradrenaline levels, and neuronal stress indicated by hypertrophy of tyrosine hydroxylase stained cell bodies. However, the magnitude of these changes was not correlated with extent of demyelination or of cellular infiltrates. Together these findings demonstrate the presence of inflammation and neuronal stress in multiple sclerosis as well as in experimental autoimmune encephalomyelitis. Since reduced noradrenaline levels could be permissive for increased inflammation and neuronal damage, these results suggest that methods to raise noradrenaline levels or increase locus coeruleus function may be of benefit in treating multiple sclerosis.

  1. Esophageal transit scintigraphy in systemic sclerosis.

    Science.gov (United States)

    Chojnowski, Marek; Kobylecka, Małgorzata; Olesińska, Marzena

    2016-01-01

    Systemic sclerosis is a rare connective tissue disease, distinctive features of which are fibrosis and microangiopathy. The esophagus is one of the most commonly involved internal organs. Most patients experience dysphagia, difficulties in swallowing and gastro-esophageal reflux. However, in up to one third of cases, the initial onset of esophageal disease may be clinically silent. There are several diagnostic modalities available for assessing both morphological and functional abnormalities of the esophagus. If structural abnormalities are suspected, endoscopy is the method of choice. Functional evaluation is best achieved with manometry. Both endoscopy and manometry are invasive techniques, with low patient acceptance. Barium-contrast study is well tolerated, but qualitative assessment of functional abnormalities is imprecise. Esophageal scintigraphy is an easy, non-invasive, sensitive and specific diagnostic modality. It can detect esophageal dysfunction even in asymptomatic patients. In patients already diagnosed with systemic sclerosis, scintigraphy is useful in evaluating severity and progression of the disease.

  2. [Large vessels vasculopathy in systemic sclerosis].

    Science.gov (United States)

    Tejera Segura, Beatriz; Ferraz-Amaro, Iván

    2015-12-07

    Vasculopathy in systemic sclerosis is a severe, in many cases irreversible, manifestation that can lead to amputation. While the classical clinical manifestations of the disease have to do with the involvement of microcirculation, proximal vessels of upper and lower limbs can also be affected. This involvement of large vessels may be related to systemic sclerosis, vasculitis or atherosclerotic, and the differential diagnosis is not easy. To conduct a proper and early diagnosis, it is essential to start prompt appropriate treatment. In this review, we examine the involvement of large vessels in scleroderma, an understudied manifestation with important prognostic and therapeutic implications. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  3. Primary sclerosing cholangitis associated with systemic sclerosis.

    Science.gov (United States)

    Fraile, G; Rodríguez-García, J L; Moreno, A

    1991-02-01

    Primary sclerosing cholangitis is a chronic inflammatory fibrotic disorder strongly associated with inflammatory bowel disease. Although an association between some inflammatory fibrotic conditions, such as Riedel's thyroiditis and retroperitoneal fibrosis and primary sclerosing cholangitis has been described, to our knowledge there are no reports of primary sclerosing cholangitis in patients with systemic sclerosis. A patient with this combination of conditions is presented and the possible significance of the association discussed.

  4. Primary sclerosing cholangitis associated with systemic sclerosis.

    OpenAIRE

    Fraile, G.; Rodríguez-García, J. L.; Moreno, A.

    1991-01-01

    Primary sclerosing cholangitis is a chronic inflammatory fibrotic disorder strongly associated with inflammatory bowel disease. Although an association between some inflammatory fibrotic conditions, such as Riedel's thyroiditis and retroperitoneal fibrosis and primary sclerosing cholangitis has been described, to our knowledge there are no reports of primary sclerosing cholangitis in patients with systemic sclerosis. A patient with this combination of conditions is presented and the possible ...

  5. Capillaroscopy 2016: new perspectives in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Carmen Pizzorni

    2016-01-01

    Full Text Available Systemic sclerosis (SSc is an autoimmune disorder of unknown aetiology characterized by early impairment of the microvascular system. Nailfold microangiopathy and decreased peripheral blood perfusion are typical clinical aspects of SSc. The best method to evaluate vascular injury is nailfold videocapillaroscopy, which detects peripheral capillary morphology, and classifies and scores the abnormalities into different patterns of microangiopathy. Microangiopathy appears to be the best evaluable predictor of the disease development and has been observed to precede the other symptoms by many years. Peripheral blood perfusion is also impaired in SSc, and there are different methods to assess it: laser Doppler and laser speckle techniques, thermography and other emerging techniques.

  6. Immunomodulatory effects of helminths and protozoa in multiple sclerosis and experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Hasseldam, H; Hansen, C S; Johansen, F F

    2013-01-01

    Multiple sclerosis is a chronic inflammatory CNS disease, which affects about 1 in 1000 individuals in the western world. During the last couple of decades, epidemiological data have accumulated, pointing towards increases in incidence. This has been suggested to be linked to the relatively high hygiene standards that exist in the western world, with reduced exposure to various pathogens, including parasites, as a consequence. Parasites are known to employ various immunomodulatory and anti-inflammatory strategies, which enable them to evade destruction by the immune system. This is most likely one of the reasons for the disease-dampening effects, reported in numerous studies investigating parasite infections and autoimmunity. This review will focus on recent advances in the field of parasites as beneficial immunomodulators, in multiple sclerosis and the animal model experimental autoimmune encephalomyelitis. © 2012 Blackwell Publishing Ltd.

  7. Microwave and magnetic (M2) proteomics of the experimental autoimmune encephalomyelitis animal model of multiple sclerosis

    Science.gov (United States)

    Raphael, Itay; Mahesula, Swetha; Kalsaria, Karan; Kotagiri, Venkat; Purkar, Anjali B.; Anjanappa, Manjushree; Shah, Darshit; Pericherla, Vidya; Jadhav, Yeshwant Lal Avinash; Raghunathan, Rekha; Vaynberg, Michael; Noriega, David; Grimaldo, Nazul H.; Wenk, Carola; Gelfond, Jonathan A.L.; Forsthuber, Thomas G.; Haskins, William E.

    2013-01-01

    We hypothesized that quantitative MS/MS-based proteomics at multiple time points, incorporating rapid microwave and magnetic (M2) sample preparation, could enable relative protein expression to be correlated to disease progression in the experimental autoimmune encephalomyelitis (EAE) animal model of multiple sclerosis. To test our hypothesis, microwave-assisted reduction/alkylation/digestion of proteins from brain tissue lysates bound to C8 magnetic beads and microwave-assisted isobaric chemical labeling were performed of released peptides, in 90 s prior to unbiased proteomic analysis. Disease progression in EAE was assessed by scoring clinical EAE disease severity and confirmed by histopathologic evaluation for central nervous system inflammation. Decoding the expression of 283 top-ranked proteins (p proteomics is a rapid method to quantify putative prognostic/predictive protein biomarkers and therapeutic targets of disease progression in the EAE animal model of multiple sclerosis. PMID:23161666

  8. Microwave and magnetic (M(2) ) proteomics of the experimental autoimmune encephalomyelitis animal model of multiple sclerosis.

    Science.gov (United States)

    Raphael, Itay; Mahesula, Swetha; Kalsaria, Karan; Kotagiri, Venkat; Purkar, Anjali B; Anjanappa, Manjushree; Shah, Darshit; Pericherla, Vidya; Jadhav, Yeshwant Lal Avinash; Raghunathan, Rekha; Vaynberg, Michael; Noriega, David; Grimaldo, Nazul H; Wenk, Carola; Gelfond, Jonathan A L; Forsthuber, Thomas G; Haskins, William E

    2012-12-01

    We hypothesized that quantitative MS/MS-based proteomics at multiple time points, incorporating rapid microwave and magnetic (M(2) ) sample preparation, could enable relative protein expression to be correlated to disease progression in the experimental autoimmune encephalomyelitis (EAE) animal model of multiple sclerosis. To test our hypothesis, microwave-assisted reduction/alkylation/digestion of proteins from brain tissue lysates bound to C8 magnetic beads and microwave-assisted isobaric chemical labeling were performed of released peptides, in 90 s prior to unbiased proteomic analysis. Disease progression in EAE was assessed by scoring clinical EAE disease severity and confirmed by histopathologic evaluation for central nervous system inflammation. Decoding the expression of 283 top-ranked proteins (p proteomics is a rapid method to quantify putative prognostic/predictive protein biomarkers and therapeutic targets of disease progression in the EAE animal model of multiple sclerosis. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Work Disability in Early Systemic Sclerosis

    DEFF Research Database (Denmark)

    Sandqvist, Gunnel; Hesselstrand, Roger; Petersson, Ingemar F

    2015-01-01

    OBJECTIVE: To study work disability (WD) with reference to levels of sick leave and disability pension in early systemic sclerosis (SSc). METHODS: Patients with SSc living in the southern part of Sweden with onset of their first non-Raynaud symptom between 2003 and 2009 and with a followup of 36...... months were included in a longitudinal study. Thirty-two patients (26 women, 24 with limited SSc) with a median age of 47.5 years (interquartile range 43-53) were identified. WD was calculated in 30-day intervals from 12 months prior to disease onset until 36 months after, presented as the prevalence...

  10. Urticarial vasculitis appearing in the progression of systemic sclerosis.

    Science.gov (United States)

    Kato, Yoko; Aoki, Mikako; Kawana, Seiji

    2006-11-01

    We report a case of urticarial vasculitis that appeared during the course of limited cutaneous systemic sclerosis. The urticarial lesions responded to systemic administration of prednisolone. After the appearance of urticarial vasculitis, the progression of scleroderma in distal sites of her elbow and knee joint became apparent. We consider this case to be consistent with limited cutaneous systemic sclerosis. The patient started treatment with prednisolone and her edema as well as scleroderma softened gradually. We analyzed, by immunohistochemistry, the number of tryptase-positive mast cells of this case in the lesions of urticarial vasculitis as well as systemic sclerosis. The number of tryptase-positive mast cells in the lesions of urticarial vasculitis as well as systemic sclerosis was significantly increased compared to normal skin (P urticarial vasculitis and systemic sclerosis as a common factor.

  11. Congestive Cardiac Failure in a patient with Systemic Sclerosis ...

    African Journals Online (AJOL)

    TNHJOURNALPH

    BACKGROUND. Systemic sclerosis and other connective tissue diseases are thought to be rare in. Nigerians and are not common causes of heart failure compared to hypertensive heart disease. The presence of cardiac involvement in a patient with systemic sclerosis generally portends poor outcome. We therefore present ...

  12. Preliminary criteria for the very early diagnosis of systemic sclerosis

    DEFF Research Database (Denmark)

    Avouac, J; Fransen, Julie Munk; Walker, U A

    2011-01-01

    To identify a core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis (SSc).......To identify a core set of preliminary items considered as important for the very early diagnosis of systemic sclerosis (SSc)....

  13. Congestive cardiac failure in a patient with systemic sclerosis: Case ...

    African Journals Online (AJOL)

    Background: Systemic sclerosis and other connective tissue diseases are thought to be rare in Nigerians and are not common causes of heart failure compared to hypertensive heart disease. The presence of cardiac involvement in a patient with systemic sclerosis generally portends poor outcome. We therefore present a ...

  14. Quality of life in systemic sclerosis.

    Science.gov (United States)

    Almeida, Cristiana; Almeida, Isabel; Vasconcelos, Carlos

    2015-12-01

    Systemic sclerosis (SSc) is a chronic multi-system autoimmune disease associated with disability and reduced quality of life. There is no effective treatment or cure to SSc, so it is important improve global health of these patients and reduce morbidity and mortality associated with SSc. It was made a literature review about quality of life in patients with SSc, regarding the several factors that should be considered and evaluated when attending to SSc patients. It was also considered the validated scales and questionnaires used to measure outcomes in patients with SSc. We concluded that it is important to have an interdisciplinary approach to SSc patients considering the patient's cognitive representations of the disease and what they value most like mobility and hand function, pain, fatigue, sleep, depression and body image. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Inflammation subverts hippocampal synaptic plasticity in experimental multiple sclerosis.

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    Robert Nisticò

    Full Text Available Abnormal use-dependent synaptic plasticity is universally accepted as the main physiological correlate of memory deficits in neurodegenerative disorders. It is unclear whether synaptic plasticity deficits take place during neuroinflammatory diseases, such as multiple sclerosis (MS and its mouse model, experimental autoimmune encephalomyelitis (EAE. In EAE mice, we found significant alterations of synaptic plasticity rules in the hippocampus. When compared to control mice, in fact, hippocampal long-term potentiation (LTP induction was favored over long-term depression (LTD in EAE, as shown by a significant rightward shift in the frequency-synaptic response function. Notably, LTP induction was also enhanced in hippocampal slices from control mice following interleukin-1β (IL-1β perfusion, and both EAE and IL-1β inhibited GABAergic spontaneous inhibitory postsynaptic currents (sIPSC without affecting glutamatergic transmission and AMPA/NMDA ratio. EAE was also associated with selective loss of GABAergic interneurons and with reduced gamma-frequency oscillations in the CA1 region of the hippocampus. Finally, we provided evidence that microglial activation in the EAE hippocampus was associated with IL-1β expression, and hippocampal slices from control mice incubated with activated microglia displayed alterations of GABAergic transmission similar to those seen in EAE brains, through a mechanism dependent on enhanced IL-1β signaling. These data may yield novel insights into the basis of cognitive deficits in EAE and possibly of MS.

  16. Calcium Intervention Ameliorates Experimental Model of Multiple Sclerosis

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    Dariush Haghmorad

    2014-05-01

    Full Text Available Objective: Multiple sclerosis (MS is the most common inflammatory disease of the CNS. Experimental autoimmune encephalomyelitis (EAE is a widely used model for MS. In the present research, our aim was to test the therapeutic efficacy of Calcium (Ca in an experimental model of MS. Methods: In this study the experiment was done on C57BL/6 mice. EAE was induced using 200 μg of the MOG35-55 peptide emulsified in CFA and injected subcutaneously on day 0 over two flank areas. In addition, 250 ng of pertussis toxin was injected on days 0 and 2. In the treatment group, 30 mg/kg Ca was administered intraperitoneally four times at regular 48 hour intervals. The mice were sacrificed 21 days after EAE induction and blood samples were taken from their hearts. The brains of mice were removed for histological analysis and their isolated splenocytes were cultured. Results: Our results showed that treatment with Ca caused a significant reduction in the severity of the EAE. Histological analysis indicated that there was no plaque in brain sections of Ca treated group of mice whereas 4 ± 1 plaques were detected in brain sections of controls. The density of mononuclear infiltration in the CNS of Ca treated mice was lower than in controls. The serum level of Nitric Oxide in the treatment group was lower than in the control group but was not significant. Moreover, the levels of IFN-γ in cell culture supernatant of splenocytes in treated mice were significantly lower than in the control group. Conclusion: The data indicates that Ca intervention can effectively attenuate EAE progression.

  17. Stubborn rectal prolapse in systemic sclerosis.

    Science.gov (United States)

    Petersen, Sven; Tobisch, Alexander; Puhl, Gero; Kötter, Ina; Wollina, Uwe

    2017-01-01

    Systemic sclerosis (SSc) is an autoimmune connective tissue disorder. Anorectal involvement might typically cause fecal incontinence and rarely rectal prolapse. Here we report three female patients, who were admitted with a mean history of 10 years suffering from SSc. All patients presented with the initial symptom of anal incontinence, in all cases this was associated with rectal intussusception or rectal prolapse. The three women faced prolapse recurrence, independent of the initial procedure. After surgical removal of the prolapse, the incontinence remained. In SSc rectal prolapse syndrome might occur at an earlier age, and a primary prolapse of the ventral aspect of the rectal wall seems to be typical for this disease. If patients with prior diagnosis of SSc appear with third degree of fecal incontinence, it is suspected to be associated with rectal prolapse. The prolapse recurrence rate after surgery in SSc patients is high.

  18. Autoantibodies in systemic sclerosis: Unanswered questions

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    CRISTIANE eKAYSER

    2015-04-01

    Full Text Available Systemic sclerosis (SSc is an autoimmune disease characterized by vascular abnormalities, and cutaneous and visceral fibrosis. Serum autoantibodies directed to multiple intracellular antigens are present in more than 95% of patients and are considered a hallmark of SSc. They are helpful biomarkers for the early diagnosis of SSc and are associated with distinctive clinical manifestations. With the advent of more sensitive, multiplexed immunoassays, new and old questions about the relevance of autoantibodies in SSc are emerging. In this review we discuss the clinical relevance of autoantibodies in SSc emphasizing the more recently published data. Moreover, we will summarize recent advances regarding the stability of SSc autoantibodies over the course of disease, whether they are mutually exclusive and their potential roles in the disease pathogenesis.

  19. Progressive systemic sclerosis in childhood: A report of three cases

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    Belgaumkar Vasudha; Gokhale Neeta; Mahajan Pradeep; Tolat Sunil; Bhokare Anil; Kamble Shekhar

    2004-01-01

    Systemic sclerosis is unusual in childhood. We describe three children who presented with diffuse hidebound skin associated with gastrointestinal and pulmonary abnormalities. Cardiac and renal dysfunctions, which are often encountered in these patients, were notably absent in our cases.

  20. Plasma exchange in progressive systemic sclerosis

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    Mohammad Bagher Owlia

    2015-10-01

    Full Text Available Systemic sclerosis (SSc is an autoimmune systemic disease of unknown etiology. Present treatment modalities have limited impact on clinical/ laboratory outcomes. For the first time in our center, we used plasma exchange (PEx in a rather young woman with recent onset but progressive SSc. She is a 39-year-old woman with a recent history of skin stiffness, Raynaud’s phenomenon, nail fold capillary changes and newly diagnosis of SSc presented to us due to worsening her clinical symptoms even after initiation of routine remedies such as low dose oral prednisolone, Ca-channel blockers, azathioprine and pentoxyfylline. After obtaining written consent, interdisciplinary discussion with experts in this field and agreement we started a series of plasma exchange with FFP replacement for her. A dramatic clinical response was observed in respect to Raynaud’s phenomenon, skin stiffness, tendon rub after three sessions of PEx. Her modified Rodnan skin score (MRSS dropped from 36 (before commencement of therapy to 28 in day 4 and 18 in day 20 after 15 sessions of PEx. In conclusion PEx could significantly modify the course of SSc as observed in our case study. Elimination of culprit immune mediators/cytokines/autoantibodies could be the possible mechanism of action of PEx. 

  1. Coexistence of systemic sclerosis and sarcoidosis.

    Science.gov (United States)

    Godziszewska, Sabina; Widuchowska, Małgorzata; Kopeć-Mędrek, Magdalena; Kucharz, Eugeniusz Józef

    Coexistence of systemic sclerosis (SSc) and sarcoidosis (SA) is rarely reported; 21 cases only were reported in the English medical literature before 2011. It is suggested that low incidence of overlap syndrome of SSc with SA is resulted from different immune mechanisms involved in pathogenesis of the diseases. In SSc patients, a role of Th2 lymphocytes is suggested while in patients with SA such role is attributed to Th1 lymphocytes. The paper presents a 47-year-old woman suffering from SSc for over 6 years. CT scan of the lungs revealed the nodulus of the right lung and enlarged mediastinal lymphatic nodes. Pathologic evaluation of the nodulus provided basis for diagnosis of sarcoidosis. Diagnosis of SSc was based on clinical and capilaroscopic evaluation as well as detection of anti-topoisomerase I antibodies. In the course of the disease, fibrosis of the lung, pulmonary hypertension and cardiac abnormalities with rhythm disturbances were developed. Treatment included cyclophosphamide, mycophenolate mofetil, sildenafil, losartan. Stabilization of the general state of the patient was achieved.

  2. Systemic sclerosis, birth order and parity.

    Science.gov (United States)

    Russo, Paul A J; Lester, Susan; Roberts-Thomson, Peter J

    2014-06-01

    A recent study identified increasing birth order to be a risk factor for the development of systemic sclerosis (SSc). This finding supports the theory that transplacental microchimerism may be a key pathological event in the initiation of SSc. We investigated the relationship between birth order and parity and the age of onset of SSc in South Australia. A retrospective analysis of patient data in the South Australian Scleroderma Register was performed. Data were obtained from a mailed questionnaire. Control data was collected prospectively using a similar questionnaire. The relationship between birth order, family size or parity and risk of subsequent development of SSc was analyzed by mixed effects logistic regression analysis. Three hundred and eighty-seven index probands were identified and compared with 457 controls. Controls were well matched for gender, but not for age. No statistically significant relationship was identified between SSc and birth order, parity in females, family size, age at first pregnancy in females or gender of first child in parous females. Our data suggests that parity, age at first pregnancy and the gender of the first child are not relevant factors in our understanding of the epidemiology and pathogenesis of SSc. Birth order and family size in both genders also appears irrelevant. These results argue against microchimerism as being relevant in the pathogenesis of SSc and add further support to the theory that stochastic events may be important in the etiopathogenesis of SSc. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  3. Systemic sclerosis: patients' perceptions of their condition.

    Science.gov (United States)

    Richards, Helen L; Herrick, Ariane L; Griffin, Kerry; Gwilliam, Petra D H; Loukes, Jonathan; Fortune, Dónal G

    2003-10-15

    To examine patients' beliefs about systemic sclerosis (SSc) and to investigate the relationship between these beliefs, symptom report, and clinical and demographic variables. A total of 49 patients (7 male, 42 female) with SSc underwent clinical examination and completed the Revised Illness Perception Questionnaire. This measure assesses beliefs about symptoms, chronicity or recurrence of the condition, consequences, personal and treatment control, illness coherence, perceived causes of the condition, and patients' emotional response to their condition. The symptoms patients most frequently associated with their SSc were stiff joints (79%), pain (75%), and fatigue (75%). The most commonly reported causes of SSc were stress (53%), altered immunity (49%), and chance or bad luck (46%). More than 96% of patients believed that their condition would be chronic and 78% believed that the condition had serious consequences on their lives. Patients with diffuse cutaneous SSc reported more significant consequences of the condition and less personal control of their SSc compared with patients with limited cutaneous disease. There were no significant differences in illness beliefs between patients with nonsevere and severe ischemia. Multiple regression analyses indicated that illness beliefs, in particular perceived consequences associated with the condition, accounted for a significant proportion of the variance in emotional response to the condition. The beliefs held and symptoms experienced by patients with SSc are not ruled by disease subtype, skin score, functional ability, or severity of digital ischemia. This suggests patients' beliefs and emotional response are associated with the meaning they ascribe to their condition rather than its severity.

  4. Fatigue in systemic sclerosis: a systematic review.

    Science.gov (United States)

    Basta, Fabio; Afeltra, Antonella; Margiotta, Domenico Paolo Emanuele

    2017-12-15

    To systematically review fatigue in systemic sclerosis (SSc) in terms of prevalence, features, correlates, predictors and management. We performed a literature search in PubMed (Medline), EBSCO and COCHRANE databases up to June 2017 selecting articles regarding fatigue in SSc. The articles finally selected fulfilled the following eligibility criteria: written in English, referred to fatigue in SSc, reporting original data, including validated questionnaires measuring fatigue. A total of 43 records were included. Fatigue in SSc has a prevalence similar to that of other rheumatic diseases and is one of the most prevalent and debilitating symptom experienced by SSc patients. Fatigue leads to a significant impairment of quality of life, parenting, household and work ability. Fatigue is associated with psychosocial factors (depression, pain and sleep disorders), sociodemographic factors and clinical manifestations of the disease (pulmonary and gastrointestinal involvement). Indeed, the relationship with scores of disease activity is uncertain. Pharmacological therapeutic approaches were broadly ineffective in reducing fatigue. More encouraging results concern physical activity, complementary and alternative medicine. Adequate management of fatigue could lead to a marked improvement of the patient's quality of life, also contributing to reduction in SSc indirect costs.

  5. Genetic variants of CC chemokine genes in experimental autoimmune encephalomyelitis, multiple sclerosis and rheumatoid arthritis

    DEFF Research Database (Denmark)

    Ockinger, J; Stridh, P; Beyeen, A D

    2010-01-01

    Multiple sclerosis (MS) is a complex disorder of the central nervous system, causing inflammation, demyelination and axonal damage. A limited number of genetic risk factors for MS have been identified, but the etiology of the disease remains largely unknown. For the identification of genes...... regulating neuroinflammation we used a rat model of MS, myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), and carried out a linkage analysis in an advanced intercross line (AIL). We thereby redefine the Eae18b locus to a 0.88 Mb region, including a cluster...... of chemokine genes. Further, we show differential expression of Ccl2, Ccl11 and Ccl11 during EAE in rat strains with opposite susceptibility to EAE, regulated by genotype in Eae18b. The human homologous genes were tested for association to MS in 3841 cases and 4046 controls from four Nordic countries...

  6. Modulation of Multiple Sclerosis and Its Animal Model Experimental Autoimmune Encephalomyelitis by Food and Gut Microbiota

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    Ward J. van den Hoogen

    2017-09-01

    Full Text Available Multiple sclerosis (MS is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS, leading to demyelination, axonal damage, and symptoms such as fatigue and disability. Although the cause of MS is not known, the infiltration of peripherally activated immune cells into the CNS has a key pathogenic role. Accumulating evidence supports an important role of diet and gut microbiota in immune-mediated diseases. Preclinical as well as clinical studies suggest a role for gut microbiota and dietary components in MS. Here, we review these recent studies on gut microbiota and dietary interventions in MS and its animal model experimental autoimmune encephalomyelitis. We also propose directions for future research.

  7. Genetic variants of CC chemokine genes in experimental autoimmune encephalomyelitis, multiple sclerosis and rheumatoid arthritis

    DEFF Research Database (Denmark)

    Ockinger, J; Stridh, P; Beyeen, A D

    2010-01-01

    Multiple sclerosis (MS) is a complex disorder of the central nervous system, causing inflammation, demyelination and axonal damage. A limited number of genetic risk factors for MS have been identified, but the etiology of the disease remains largely unknown. For the identification of genes...... regulating neuroinflammation we used a rat model of MS, myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), and carried out a linkage analysis in an advanced intercross line (AIL). We thereby redefine the Eae18b locus to a 0.88 Mb region, including a cluster....... A haplotype in CCL2 and rs3136682 in CCL1 show a protective association to MS, whereas a haplotype in CCL13 is disease predisposing. In the HLA-DRB1* 15 positive subgroup, we also identified an association to a risk haplotype in CCL2, suggesting an influence from the human leukocyte antigen (HLA) locus. We...

  8. Tomography patterns of lung disease in systemic sclerosis

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    Bastos, Andrea de Lima; Correa, Ricardo de Amorim; Ferreira, Gilda Aparecida, E-mail: andrealb@ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina

    2016-09-15

    Currently, lung impairment is the leading factor responsible for the morbidity and mortality associated with systemic sclerosis. Therefore, the recognition of the various tomography patterns becomes decisive in the clinical management of these patients. In high-resolution computed tomography studies, the most common pattern is that of nonspecific interstitial pneumonia. However, there are other forms of lung involvement that must also be recognized. The aim of this study was to review the literature on the main changes resulting from pulmonary involvement in systemic sclerosis and the corresponding radiological findings, considering the current classification of interstitial diseases. We searched the Medline (PubMed), Lilacs, and SciELO databases in order to select articles related to pulmonary changes in systemic sclerosis and published in English between 2000 and 2015. The pulmonary changes seen on computed tomography in systemic sclerosis are varied and are divided into three main categories: interstitial, alveolar, and vascular. Interstitial changes constitute the most common type of pulmonary involvement in systemic sclerosis. However, alveolar and vascular manifestations must also be recognized and considered in the presence of atypical clinical presentations and inadequate treatment responses. (author)

  9. Tomography patterns of lung disease in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Andréa de Lima Bastos

    Full Text Available Abstract Currently, lung impairment is the leading factor responsible for the morbidity and mortality associated with systemic sclerosis. Therefore, the recognition of the various tomography patterns becomes decisive in the clinical management of these patients. In high-resolution computed tomography studies, the most common pattern is that of nonspecific interstitial pneumonia. However, there are other forms of lung involvement that must also be recognized. The aim of this study was to review the literature on the main changes resulting from pulmonary involvement in systemic sclerosis and the corresponding radiological findings, considering the current classification of interstitial diseases. We searched the Medline (PubMed, Lilacs, and SciELO databases in order to select articles related to pulmonary changes in systemic sclerosis and published in English between 2000 and 2015. The pulmonary changes seen on computed tomography in systemic sclerosis are varied and are divided into three main categories: interstitial, alveolar, and vascular. Interstitial changes constitute the most common type of pulmonary involvement in systemic sclerosis. However, alveolar and vascular manifestations must also be recognized and considered in the presence of atypical clinical presentations and inadequate treatment responses.

  10. Polyautoimmunity and familial autoimmunity in systemic sclerosis.

    Science.gov (United States)

    Hudson, Marie; Rojas-Villarraga, Adriana; Coral-Alvarado, Paola; López-Guzmán, Silvia; Mantilla, Ruben D; Chalem, Philippe; Baron, Murray; Anaya, Juan-Manuel

    2008-09-01

    Characterization of the extent to which particular combinations of autoimmune diseases occur in excess of that expected by chance may offer new insights into possible common pathophysiological mechanisms. The goal of this study was to investigate the spectrum of polyautoimmunity (i.e. autoimmune diseases co-occurring within patients) and familial autoimmunity (i.e. diverse autoimmune diseases co-occurring within families) in patients with systemic sclerosis (SSc). A cross-sectional study of two convenience samples of patients with SSc, one in Canada and the other in Colombia, was performed. History of other autoimmune diseases in the SSc patients as well as a family history of autoimmunity was obtained. Of 719 patients, 273 (38%) had at least one other autoimmune disease. A total of 366 autoimmune diseases were reported, of which the most frequent were autoimmune thyroid disease (AITD, 38%), rheumatoid arthritis (RA, 21%), Sjögren's syndrome (18%), and primary biliary cirrhosis (4%). There were 260 (36%) patients with first-degree relatives with at least one autoimmune disease, of which the most frequent were RA (18%) and AITD (9%). Having at least one first-degree relative with autoimmune disease was a significant predictor of polyautoimmunity in SSc patients. No significant differences in polyautoimmunity or familial autoimmunity were noted between diffuse and limited subsets of disease. Our results indicate that polyautoimmunity is frequent in patients with SSc and autoimmune diseases cluster within families of these patients. Clinically different autoimmune phenotypes might share common susceptibility variants, which acting in epistatic pleiotropy may represent risk factors for autoimmunity.

  11. Systemic sclerosis and prevalence of monoclonal immunoglobulin.

    Science.gov (United States)

    Trad, Salim; Nosbaum, Audrey; Musset, Lucile; Ghillani-Dalbin, Pascale; Launay, David; Costedoat-Chalumeau, Nathalie; Saadoun, David; Cabane, Jean; Hachulla, Eric; Hanslik, Thomas; Frances, Camille

    2014-12-01

    The purpose of this study was to estimate the prevalence of monoclonal immunoglobulin (MIg) among patients with systemic sclerosis (SSc) according to the capillary electrophoresis or immunofixation method of detection and to search for any related clinical correlations. Retrospective multicenter comparison of capillary electrophoresis and immunofixation results in SSc patients and of the characteristics of patients with and without MIg. The study included 244 SSc patients (216 women and 28 men, mean age: 55±14 years). Median time since SSc diagnosis was 51 months [0-320]; disease was diffuse in 48% of cases. Ten percent of patients had cancer, including Waldenström macroglobulinemia (n=1) and multiple myeloma (n=3). Capillary electrophoresis showed a γ-globulin anomaly in 41% of cases, and immunofixation in 18%: MIg (13.5%) and restriction of heterogeneity (4.5%). Capillary electrophoresis failed to detect 60% of the 33 MIg patients. Measurable MIg concentrations were obtained from 7 patients. MIg patients were significantly older at SSc diagnosis than those without MIg (p=0.002), had a lower diffusing capacity (p=0.002), a higher prevalence of pulmonary hypertension and cancer (p=0.002) and were more frequently positive for anti-mitochondrial and anti-beta2-glycoprotein-I antibodies (p=0.03 and p=0.02, respectively). Multivariate analyses showed that only age at test [hazard ratio 1.03 (95% CI, 1.00-1.07, p=0.04)] and presence of cancer [hazard ratio 4.46 (95% CI, 1.6-12.4, p=0.004)] were associated with MIg. Immunofixation detected a high prevalence of MIg among SSc patients especially in patients aged 50-years or older. MIg was not detected by the standard capillary electrophoresis in 60% of cases and was significantly associated with cancer. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Nutritional support in patients with systemic sclerosis.

    Science.gov (United States)

    Ortiz-Santamaria, Vera; Puig, Celia; Soldevillla, Cristina; Barata, Anna; Cuquet, Jordi; Recasens, Asunción

    2014-01-01

    Systemic sclerosis (SSc) is a chronic multisystem autoimmune disease which involves the gastrointestinal tract in about 90% of cases. It may contribute to nutritional deterioration. To assess whether the application of a nutritional support protocol to these patients could improve their nutritional status and quality of life. Single center prospective study, performed on an outpatient basis, in a county hospital. The Malnutrition Universal Screening Tool (MUST) was used to screen risk for malnutrition. Health questionnaire SF-36 and the Hospital Anxiety and Depression Scale were used to assess quality of life and psychopathology respectively. Weight, height, energy and protein requirements, macronutrient intake and nutritional biochemical parameters were evaluated. Nutritional intervention was performed in patients at risk for malnutrition. Of the 72 patients, 12.5% were at risk for malnutrition. Iron deficiency anemia (18.35%) and vitamin D deficiency (54%) were the most frequently observed nutritional deficits. The questionnaires on psychopathology and quality of life showed a high prevalence of anxiety and depression, and lower level poor quality of life in the physical and mental component. No significant improvements were observed in the weight, food intake, nutritional biochemical parameters, psychopathology and quality of life follow-up. Dietary intervention was able to maintain body weight and food intake. Iron deficiency anemia and vitamin D deficiency improved with iron and vitamine D supplements. No deterioration was observed in psychological assessment or quality of life. Studies with larger numbers of patients are needed to assess the efficacy of this intervention. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  13. Adie’s Tonic Pupil in Systemic Sclerosis: A Rare Association

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    Anusha Venkataraman

    2015-01-01

    Full Text Available We report a rare association of Adie’s tonic pupil in a patient with systemic sclerosis who was otherwise systemically stable. This paper is an effort to unravel whether the tonic pupil and systemic sclerosis are an association by chance (which may be the case or systemic sclerosis is the source of the tonic pupil.

  14. Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis.

    NARCIS (Netherlands)

    van Bon, L.; Affandi, A.J.; dr. Broen, J.C.A.; Christmann, R.B.; Marijnissen, R.J.; Stawski, L.; Farina, G.A.; Stifano, G.; Mathes, A.L.; Cossu, M.; York, M.; Collins, C.; Wenink, M.H.; Huijbens, R.; Hesselstrand, R.; Saxne, T.; Dimarzio, M; Wuttge, D.; Agarwal, S.K.; Reveille, J.D.; Assassi, S.; Mayes, M.D.; Deng, Y.; Drenth, J.P.; de Graaf, J.; den Heijer, M.; Kallenberg, C.G.; Bijl, M.; de Loof, A.; van der Berg, W.B.; Joosten, L.A.; Smith, V.; de Keyser, F.; Scorza, R.; Lunardi, C.; van Riel, P.L.C.M.; Vonk, M.; van Heerde, W.L.; Meller, S.; Homey, B.; Beretta, L.; Roest, M.; Trojanowska, M.; Lafyatis, R.; Radstake, T.R.D.J.; Soft Condensed Matter and Biophysics; Sub Soft Condensed Matter

    2014-01-01

    Background Plasmacytoid dendritic cells have been implicated in the pathogenesis of systemic sclerosis through mechanisms beyond the previously suggested production of type I interferon. Methods We isolated plasmacytoid dendritic cells from healthy persons and from patients with systemic sclerosis

  15. Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis

    NARCIS (Netherlands)

    Bon, L. van; Affandi, A.J.; Broen, J.C.A.; Christmann, R.B.; Marijnissen, R.J.; Stawski, L.; Farina, G.A.; Stifano, G.; Mathes, A.L.; Cossu, M.; York, M.; Collins, C.; Wenink, M.; Huijbens, R.; Hesselstrand, R.; Saxne, T.; DiMarzio, M.; Wuttge, D.; Agarwal, S.K.; Reveille, J.D.; Assassi, S.; Mayes, M.; Deng, Y.; Drenth, J.P.H.; Graaf, J. de; Heijer, M. den; Kallenberg, C.G.M.; Bijl, M. van der; Loof, A.; Berg, W.B. van den; Joosten, L.A.B.; Smith, V.; Keyser, F. de; Scorza, R.; Lunardi, C.; Riel, P.L.C.M. van; Vonk, M.C.; Heerde, W.L. van; Meller, S.; Homey, B.; Beretta, L.; Roest, M.; Trojanowska, M.; Lafyatis, R.; Radstake, T.R.D.J.

    2014-01-01

    BACKGROUND: Plasmacytoid dendritic cells have been implicated in the pathogenesis of systemic sclerosis through mechanisms beyond the previously suggested production of type I interferon. METHODS: We isolated plasmacytoid dendritic cells from healthy persons and from patients with systemic sclerosis

  16. Humoral and cellular immunity in progressive systemic sclerosis.

    Science.gov (United States)

    Sierakowski, S; Bernacka, K

    1987-01-01

    There is ever increasing evidence that immune disturbances can play an essential role in the pathogenesis of progressive systemic sclerosis. However, there are still a great many controversial opinions and complex studies in this domain are few. Tests of lymphocyte blastic transformation and of leukocyte migration inhibition as well as E and EAC rosette tests were performed and the serum level of A, G and M immunoglobulins and complement were estimated in 13 patients with progressive systemic sclerosis. The increase of serum IgA, IgG and IgM and the decrease of early and delayed E rosette formation was observed in the patients as compared with the control group. The patients also presented increase spontaneous and PHA induced lymphocyte blastic transformation. The results support the hypothesis of the role played by immune disturbances in the pathogenesis of progressive systemic sclerosis.

  17. Immunomodulatory effects of helminths and protozoa in multiple sclerosis and experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Hasseldam, Henrik; Hansen, C S; Johansen, F F

    2013-01-01

    one of the reasons for the disease-dampening effects, reported in numerous studies investigating parasite infections and autoimmunity. This review will focus on recent advances in the field of parasites as beneficial immunomodulators, in multiple sclerosis and the animal model experimental autoimmune...

  18. Experimental autoimmune encephalomyelitis in the common marmoset: a novel animal model for multiple sclerosis

    NARCIS (Netherlands)

    H.P.M. Brok (Herbert)

    2002-01-01

    textabstractMultiple sclerosis (MS) is a major cause of disability in young adults affecting approximately 15,000 people in The Netberlands. Critical aspects of the disease have been modeled by experimental autoimmune encephalomyelitis (EAE) in animals. The vast majority of investigators use rats

  19. Temporomandibular joint disorder in systemic sclerosis: a case report

    Science.gov (United States)

    Chebbi, Raja; Khalifa, Hanen Ben; Dhidah, Monia

    2016-01-01

    Systemic sclerosis have several effects on the orofacial region such as widening of the periodontal ligament space, xerostomia and bone resorption of the mandible. We report a case of systemic sclerosis with temporomandibular joint involvement in a 45-year-old female patient accompanied by severe limited mouth opening and pain in the right and left preauricular regions and tenderness in masseter muscles with a morning stiffness of jaws.Magnetic resonance imaging showed a resorption of mandibular condylar process, with disk and joint abnormalities. PMID:28292126

  20. INTERSTITIAL LUNG DISEASE ASSOCIATED WITH SYSTEMIC SCLEROSIS

    Directory of Open Access Journals (Sweden)

    L. P. Ananyeva

    2017-01-01

    Full Text Available The basis for the pathogenesis of systemic sclerosis (SS is immune disorders that initiate inflammation, as well as vasculopathy with obvious microcirculatory disturbances, and generalized fibrosis. In SS, lung injury is due to an arterial lesion and/or a fibrotic process in the lung parenchyma and occurs as two major syndromes that are rarely concurrent in one patient; these are pulmonary arterial hypertension and interstitial lung disease (ILD. In SS, lung injury negatively affects the prognosis and ranks first among the causes of death. The review focuses on ILD, the most common injury of the respiratory tract in SS, which is detectable in 80% of patients, as evidenced by multislice spiral computed tomography (MSCT of the chest. The histological manifestations are similar to those of idiopathic ILDs, but the histological type does not determine the prognosis. The course of ILD in SS is relatively benign, often subclinical. A severe progressive lesion develops only in 10–15% of cases. Clinically significant changes in the lung parenchyma develop early, within the first 3–5 years of the disease. Pulmonary functional tests show that relatively preserved and stable forced vital capacity is long recorded in the majority of patients, but the diffusing capacity of the lung is reduced in 70–80% of the patients. The values of pulmonary tests during the first examination are of prognostic value; the lower than normal they are, the worse the prognosis. Chest MSCT should be carried out in all patients with newly diagnosed SS, as the quantitative (prevalence and qualitative (frosted glass, honeycomb lung indicators affect the determination of therapy policy. ILD treatment is performed only in patients with obvious signs of progression, which are determined from the time course of changes in the decrease of values of pulmonary functional tests. Immunosuppressants, cyclophosphamide being the drug of choice, are used to treat ILD

  1. The Challenges of Dialysis in Systemic Sclerosis: Between the Devil and the Deep Blue Sea?

    Directory of Open Access Journals (Sweden)

    N. Brown

    2012-01-01

    Full Text Available We present the case of a patient with systemic sclerosis (SSc and end stage renal disease (ESRD who experienced complications of both peritoneal and haemodialysis. We review previously reported outcomes of patients with systemic sclerosis on dialysis and discuss potential shared mechanisms in both the disease pathogenesis and dialysis-related complications, particularly with regards to encapsulating peritoneal sclerosis (EPS.

  2. Systemic sclerosis in a patient with pityriasis rubra pilaris | Frikha ...

    African Journals Online (AJOL)

    Systemic sclerosis in a patient with pityriasis rubra pilaris. F Frikha, M Frigui, H Masmoudi, H Turki, Z Bahloul. Abstract. Pityriasis rubra pilaris (PRP) is a rare, chronic erythematous squamous disorder of unknown etiology. It has been found in association with several autoimmune diseases, including thyroiditis, myositis, ...

  3. Clinical prediction of 5-year survival in systemic sclerosis

    DEFF Research Database (Denmark)

    Fransen, Julie Munk; Popa-Diaconu, D; Hesselstrand, R

    2011-01-01

    Systemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but it has not been validated in other patients. The predictions of a prognostic model are usually less accura...

  4. Treatment outcome in early diffuse cutaneous systemic sclerosis

    DEFF Research Database (Denmark)

    Herrick, Ariane L; Pan, Xiaoyan; Peytrignet, Sébastien

    2017-01-01

    OBJECTIVES: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. METHODS: This was a prospective, observational cohort study of...

  5. Progressive systemic sclerosis in childhood: A report of three cases

    Directory of Open Access Journals (Sweden)

    Belgaumkar Vasudha

    2004-03-01

    Full Text Available Systemic sclerosis is unusual in childhood. We describe three children who presented with diffuse hidebound skin associated with gastrointestinal and pulmonary abnormalities. Cardiac and renal dysfunctions, which are often encountered in these patients, were notably absent in our cases.

  6. Clinical risk assessment of organ manifestations in systemic sclerosis

    DEFF Research Database (Denmark)

    Walker, U A; Tyndall, A; Czirják, L

    2007-01-01

    Systemic sclerosis (SSc) is a multisystem autoimmune disease, which is classified into a diffuse cutaneous (dcSSc) and a limited cutaneous (lcSSc) subset according to the skin involvement. In order to better understand the vascular, immunological and fibrotic processes of SSc and to guide its...

  7. Psychosocial issues and care for patients with systemic sclerosis

    NARCIS (Netherlands)

    Jewett, L.R.; Kwakkenbos, C.M.C.; Delisle, V.C.; Levis, B.; Thombs, B.D.; Varga, J.; Denton, C.P.; Wigley, F.M.; Allanore, Y.; Kuwana, M.

    2016-01-01

    People living with chronic medical conditions face challenges not only with respect to their physical health but also to their emotional and social well-being. Chronic conditions, such as systemic sclerosis (SSc or scleroderma), often result in significant disruptions to activities of daily living,

  8. Systemic sclerosis presenting as CREST syndrome: A case report ...

    African Journals Online (AJOL)

    creatinine (seen in 50% of patients), proteinuria, and microangiopathic hemolytic anemia (seen in 50% of patients). 4. Diagnosis. The diagnosis of systemic sclerosis is based on the identification of features that distinguish it from other disease, and thus a detailed history and careful physical examination are required. The.

  9. Systemic sclerosis in a patient with pityriasis rubra pilaris | Frikha ...

    African Journals Online (AJOL)

    Pityriasis rubra pilaris (PRP) is a rare, chronic erythematous squamous disorder of unknown etiology. It has been found in association with several autoimmune diseases, including thyroiditis, myositis, myasthenia gravis and vitiligo. Herein we report a case of systemic sclerosis in a patient with classic adult pityriasis rubra ...

  10. Characteristics of systemic sclerosis patients in Nairobi, Kenya : a ...

    African Journals Online (AJOL)

    Objectives: Systemic sclerosis is a rare rheumatologic disorder that has not been well characterized in African populations. No previous studies have been carried out in Kenya, or in the East African region. Design: A retrospective descriptive study. Methods: Records of patients at the Kenyatta National Hospital and Nairobi ...

  11. Recovery from severe dysphagia in systemic sclerosis - myositis ...

    African Journals Online (AJOL)

    Recovery from severe dysphagia in systemic sclerosis - myositis overlap: a case report. Keith J Chinniah, Girish M Mody. Department of Rheumatology, School of Clinical Medicine, College of Health Sciences,. University of KwaZulu-Natal and Inkosi Albert Luthuli Central Hospital, Durban, South Africa. Abstract.

  12. Recovery from severe dysphagia in systemic sclerosis - myositis ...

    African Journals Online (AJOL)

    Clinical case: A 56-year old African Black woman initially presented with systemic sclerosis (SSC) - myositis overlap and interstitial lung disease. She responded to high dose corticosteroids and cyclophosphamide followed by azathioprine, with improvement in her lung function and regression of the skin changes. Six years ...

  13. Systemic sclerosis presenting as CREST syndrome: A case report ...

    African Journals Online (AJOL)

    Systemic sclerosis (SSc) is a chronic multisystem disorder of unknown etiology, characterized by diffuse fibrosis; degenerative changes; and vascular abnormalities in the skin (scleroderma), articular structures, and internal organs especially the esophagus, GI tract, lung, heart, and kidney. We report the case of a 31 years ...

  14. Salt and Pepper Pigmentation - Skin Manifestation of Systemic Sclerosis.

    Science.gov (United States)

    Vijayaraju, D; Prakash, G; Yoganandh, T; Subramanian, S R; Ramkumar, S

    2015-09-01

    A 50 year old male presented with progressive difficulty in swallowing both liquid and solid food with no history of Raynaud's phenomenon. A general examination revealed skin changes in the form of thickening, hyperpigmentation and tightening of skin of fingers, hand, forearm and legs. The patient had painless skin induration over the legs, forearm and hand. Salt and pepper pigmentation was seen on the upper back (Figure 1a), over mastoid process (Figure 1b) and the concha of pinna (Figure 1c). Anti-Scl 70 was positive. Anti-centromere antibodies were negative. Pulmonary function testing (PFT) revealed very severe restrictive lung disease. Barium swallow study was normal. Despite being advised to undergo oesophageal manometry test in view of dysphagia, patient was not willing for the same. Diagnosis of systemic sclerosis was made. Systemic sclerosis is a disease in which extensive fibrosis, vascular alterations and autoantibodies against various cellular antigens being the principal features with a female to male ratio of 4:1. Skin pigmentation changes among other features of skin involvement include a salt-and-pepper appearance due to diffuse hyperpigmentation with sparing of the perifollicular areas. This may be due to the richer capillary network that may warm the perifollicular skin and preserve melanogenesis producing the perifollicular pigment retention in systemic sclerosis.1,2 Both cellular and humoral immune factors in combination with external factors such as trauma or inflammation may trigger the destruction of melanocytes.3 Moreover, various physical factors like temperature changes as well as genetic, hormonal factors may influence pigment formation. Such changes in pigmentation is also seen during repigmentation around hair follicles in vitiligo. Clinically, both vitiligo and depigmented lesions of systemic sclerosis present as chalk-white macules with well-defined borders. However, mucosal involvement is commonly seen in vitiligo while depigmented

  15. Mast Cells in the Pathogenesis of Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Rosetta Pedotti

    2012-11-01

    Full Text Available Mast cells (MCs are best known as key immune players in immunoglobulin E (IgE-dependent allergic reactions. In recent years, several lines of evidence have suggested that MCs might play an important role in several pathological conditions, including autoimmune disorders such as multiple sclerosis (MS and experimental autoimmune encephalomyelitis (EAE, an animal model for MS. Since their first description in MS plaques in the late 1800s, much effort has been put into elucidating the contribution of MCs to the development of central nervous system (CNS autoimmunity. Mouse models of MC-deficiency have provided a valuable experimental tool for dissecting MC involvement in MS and EAE. However, to date there is still major controversy concerning the function of MCs in these diseases. Indeed, although MCs have been classically proposed as having a detrimental and pro-inflammatory role, recent literature has questioned and resized the contribution of MCs to the pathology of MS and EAE. In this review, we will present the main evidence obtained in MS and EAE on this topic, and discuss the critical and controversial aspects of such evidence.

  16. Neuroprotection in Experimental Autoimmune Encephalomyelitis and Progressive Multiple Sclerosis by Cannabis-Based Cannabinoids.

    Science.gov (United States)

    Pryce, Gareth; Riddall, Dieter R; Selwood, David L; Giovannoni, Gavin; Baker, David

    2015-06-01

    Multiple sclerosis (MS) is the major immune-mediated, demyelinating, neurodegenerative disease of the central nervous system. Compounds within cannabis, notably Δ9-tetrahydrocannabinol (Δ9-THC) can limit the inappropriate neurotransmissions that cause MS-related problems and medicinal cannabis is now licenced for the treatment of MS symptoms. However, the biology indicates that the endocannabinoid system may offer the potential to control other aspects of disease. Although there is limited evidence that the cannabinoids from cannabis are having significant immunosuppressive activities that will influence relapsing autoimmunity, we and others can experimentally demonstrate that they may limit neurodegeneration that drives progressive disability. Here we show that synthetic cannabidiol can slow down the accumulation of disability from the inflammatory penumbra during relapsing experimental autoimmune encephalomyelitis (EAE) in ABH mice, possibly via blockade of voltage-gated sodium channels. In addition, whilst non-sedating doses of Δ9-THC do not inhibit relapsing autoimmunity, they dose-dependently inhibit the accumulation of disability during EAE. They also appear to slow down clinical progression during MS in humans. Although a 3 year, phase III clinical trial did not detect a beneficial effect of oral Δ9-THC in progressive MS, a planned subgroup analysis of people with less disability who progressed more rapidly, demonstrated a significant slowing of progression by oral Δ9-THC compared to placebo. Whilst this may support the experimental and biological evidence for a neuroprotective effect by the endocannabinoid system in MS, it remains to be established whether this will be formally demonstrated in further trials of Δ9-THC/cannabis in progressive MS.

  17. Transcriptomic meta-analysis of multiple sclerosis and its experimental models.

    Directory of Open Access Journals (Sweden)

    Barbara B R Raddatz

    Full Text Available BACKGROUND: Multiple microarray analyses of multiple sclerosis (MS and its experimental models have been published in the last years. OBJECTIVE: Meta-analyses integrate the information from multiple studies and are suggested to be a powerful approach in detecting highly relevant and commonly affected pathways. DATA SOURCES: ArrayExpress, Gene Expression Omnibus and PubMed databases were screened for microarray gene expression profiling studies of MS and its experimental animal models. STUDY ELIGIBILITY CRITERIA: Studies comparing central nervous system (CNS samples of diseased versus healthy individuals with n >1 per group and publically available raw data were selected. MATERIAL AND METHODS: Included conditions for re-analysis of differentially expressed genes (DEGs were MS, myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE in rats, proteolipid protein-induced EAE in mice, Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD, and a transgenic tumor necrosis factor-overexpressing mouse model (TNFtg. Since solely a single MS raw data set fulfilled the inclusion criteria, a merged list containing the DEGs from two MS-studies was additionally included. Cross-study analysis was performed employing list comparisons of DEGs and alternatively Gene Set Enrichment Analysis (GSEA. RESULTS: The intersection of DEGs in MS, EAE, TMEV-IDD, and TNFtg contained 12 genes related to macrophage functions. The intersection of EAE, TMEV-IDD and TNFtg comprised 40 DEGs, functionally related to positive regulation of immune response. Over and above, GSEA identified substantially more differentially regulated pathways including coagulation and JAK/STAT-signaling. CONCLUSION: A meta-analysis based on a simple comparison of DEGs is over-conservative. In contrast, the more experimental GSEA approach identified both, a priori anticipated as well as promising new candidate pathways.

  18. Modulation of Multiple Sclerosis and its Animal Model experimental Autoimmune encephalomyelitis by Food and Gut Microbiota

    NARCIS (Netherlands)

    van den Hoogen, Ward J.; Laman, Jon D.; 't Hart, Bert A.

    2017-01-01

    Multiple sclerosis (MS) is an autoimmune neurological disease characterized by chronic inflammation of the central nervous system (CNS), leading to demyelination, axonal damage, and symptoms such as fatigue and disability. Although the cause of MS is not known, the infiltration of peripherally

  19. Experimental in vivo and in vitro Models of Multiple Sclerosis: EAE and beyond

    NARCIS (Netherlands)

    Kipp, M.; van der Star, B.J.; Vogel, D.Y.S.; Puentes, F.; van der Valk, P.; Bakker, D.; Amor, S.

    2012-01-01

    Although the primary cause of multiple sclerosis (MS) is unknown, the widely accepted view is that aberrant (auto)immune responses possibly arising following infection(s) are responsible for the destructive inflammatory demyelination and neurodegeneration in the central nervous system (CNS). This

  20. Pathogenic CD8 T cells in Multiple Sclerosis and its experimental models

    Directory of Open Access Journals (Sweden)

    Eric S. Huseby

    2012-03-01

    Full Text Available A growing body of evidence suggests that autoreactive CD8 T cells contribute to the disease process in Multiple Sclerosis (MS. Lymphocytes in MS plaques are biased toward the CD8 lineage, and MS patients harbor CD8 T cells specific for multiple central nervous system (CNS antigens. Currently, there are relatively few experimental model systems available to study these pathogenic CD8 T cells in vivo. However, the few studies that have been done characterizing the mechanisms used by CD8 T cells to induce CNS autoimmunity indicate that several of the paradigms of how CD4 T cells mediate CNS autoimmunity do not hold true for CD8 T cells or for patients with MS. Thus, myelin-specific CD4 T cells are likely to be one of several important mechanisms that drive CNS disease in MS patients. The focus of this review is to highlight the current models of pathogenic CNS-reactive CD8 T cells and the molecular mechanisms these lymphocytes use when causing CNS inflammation and damage. Understanding how CNS-reactive CD8 T cells escape tolerance induction and induce CNS autoimmunity is critical to our ability to propose and test new therapies for MS.

  1. Multiple Sclerosis

    Science.gov (United States)

    Multiple sclerosis (MS) is a nervous system disease that affects your brain and spinal cord. It damages the myelin ... healthy cells in your body by mistake. Multiple sclerosis affects women more than men. It often begins ...

  2. Identification of gene expression patterns crucially involved in experimental autoimmune encephalomyelitis and multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Martin M. Herrmann

    2016-10-01

    Full Text Available After encounter with a central nervous system (CNS-derived autoantigen, lymphocytes leave the lymph nodes and enter the CNS. This event leads only rarely to subsequent tissue damage. Genes relevant to CNS pathology after cell infiltration are largely undefined. Myelin-oligodendrocyte-glycoprotein (MOG-induced experimental autoimmune encephalomyelitis (EAE is an animal model of multiple sclerosis (MS, a chronic autoimmune disease of the CNS that results in disability. To assess genes that are involved in encephalitogenicity and subsequent tissue damage mediated by CNS-infiltrating cells, we performed a DNA microarray analysis from cells derived from lymph nodes and eluted from CNS in LEW.1AV1 (RT1av1 rats immunized with MOG 91-108. The data was compared to immunizations with adjuvant alone or naive rats and to immunizations with the immunogenic but not encephalitogenic MOG 73-90 peptide. Here, we show involvement of Cd38, Cxcr4 and Akt and confirm these findings by the use of Cd38-knockout (B6.129P2-Cd38tm1Lnd/J mice, S1P-receptor modulation during EAE and quantitative expression analysis in individuals with MS. The hereby-defined underlying pathways indicate cellular activation and migration pathways mediated by G-protein-coupled receptors as crucial events in CNS tissue damage. These pathways can be further explored for novel therapeutic interventions.

  3. Live imaging of immune responses in experimental models of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Gabriela Constantin

    2016-11-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is the most common animal model of multiple sclerosis (MS, a chronic inflammatory autoimmune disease of the central nervous system (CNS characterized by multifocal perivascular infiltrates that predominantly comprise lymphocytes and macrophages. During EAE, autoreactive T cells first become active in the secondary lymphoid organs upon contact with antigen presenting cells (APCs, and then gain access to CNS parenchyma, through a compromised blood–brain barrier, subsequently inducing inflammation and demyelination. Two-photon laser scanning microscopy (TPLSM is an ideal tool for intravital imaging because of its low phototoxicity, deep tissue penetration and high resolution. In the last decade, TPLSM has been used to visualize the behavior of T cells and their contact with APCs in the lymph nodes and target tissues in several models of autoimmune diseases. The leptomeninges and cerebrospinal fluid represent particularly important points for T cell entry into the CNS and reactivation following contact with local APCs during the preclinical phase of EAE. In this review, we highlight recent findings concerning the pathogenesis of EAE and MS, emphasizing the use of TPLSM to characterize T cell activation in the lymph nodes and CNS, as well as the mechanisms of tolerance induction. Furthermore, we discuss how advanced imaging unveils disease mechanisms and helps to identify novel therapeutic strategies to treat CNS autoimmunity and inflammation.

  4. Live Imaging of Immune Responses in Experimental Models of Multiple Sclerosis.

    Science.gov (United States)

    Rossi, Barbara; Constantin, Gabriela

    2016-01-01

    Experimental autoimmune encephalomyelitis (EAE) is the most common animal model of multiple sclerosis (MS), a chronic inflammatory autoimmune disease of the central nervous system (CNS) characterized by multifocal perivascular infiltrates that predominantly comprise lymphocytes and macrophages. During EAE, autoreactive T cells first become active in the secondary lymphoid organs upon contact with antigen-presenting cells (APCs), and then gain access to CNS parenchyma, through a compromised blood-brain barrier, subsequently inducing inflammation and demyelination. Two-photon laser scanning microscopy (TPLSM) is an ideal tool for intravital imaging because of its low phototoxicity, deep tissue penetration, and high resolution. In the last decade, TPLSM has been used to visualize the behavior of T cells and their contact with APCs in the lymph nodes (LNs) and target tissues in several models of autoimmune diseases. The leptomeninges and cerebrospinal fluid represent particularly important points for T cell entry into the CNS and reactivation following contact with local APCs during the preclinical phase of EAE. In this review, we highlight recent findings concerning the pathogenesis of EAE and MS, emphasizing the use of TPLSM to characterize T cell activation in the LNs and CNS, as well as the mechanisms of tolerance induction. Furthermore, we discuss how advanced imaging unveils disease mechanisms and helps to identify novel therapeutic strategies to treat CNS autoimmunity and inflammation.

  5. Cellular and molecular mechanisms in the pathophysiology of systemic sclerosis.

    Science.gov (United States)

    Hua-Huy, T; Dinh-Xuan, A T

    2015-04-01

    Fibrosis is characterized by disproportionate accumulation of collagens and other extracellular matrix substances, resulting in organ dysfunction and failure. In systemic sclerosis, cellular and molecular mechanisms involved in the pathophysiology of fibrosis are highly complex and yet barely understood. Anatomopathological findings showed the coexistence of patchy inflammatory cell infiltration, microvascular injuries, and fibrotic foci. One of the most commonly accepted hypotheses considers endothelial activation as the triggering phenomenon inducing inflammatory and autoimmunity activation. The resulting cytokines and autoantibodies production accelerates the proliferating rate of normal fibroblasts and their transformation into myofibroblasts, leading to diffuse fibrosis. This review aims to focus on cellular and molecular mechanisms implicated in the fibrogenesis of systemic sclerosis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. Systemic Sclerosis Sine Scleroderma in Mexican Patients. Case Reports.

    Science.gov (United States)

    Vera-Lastra, Olga; Sauceda-Casas, Christian Alexis; Domínguez, María Del Pilar Cruz; Alvarez, Sergio Alberto Mendoza; Sepulceda-Delgado, Jesús

    2017-01-03

    Systemic sclerosis sine scleroderma (ssSSc) is a form of systemic sclerosis that is characterized by Raynaud's phenomenon (RP), visceral involvement without thickening of skin and anticentromere antibodies (ACA). We studied 10 ssSsc patients with a prevalence of 2%. The clinical signs were: RP 9/10, esophageal manifestations 8/10, pulmonary arterial hypertension 4/10, interstitial lung disease 4/10, cardiac signs 3/10 and ACA 8/10. In patients with RP, esophageal dysmotility, interstitial lung disease and pulmonary arterial hypertension should be tested for ACA in order to establish a prompt diagnosis and treatment of ssSSc. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  7. The Role of PPAR Gamma in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Andréa Tavares Dantas

    2015-01-01

    Full Text Available Fibrosis is recognized as an important feature of many chronic diseases, such as systemic sclerosis (SSc, an autoimmune disease of unknown etiology, characterized by immune dysregulation and vascular injury, followed by progressive fibrosis affecting the skin and multiple internal organs. SSc has a poor prognosis because no therapy has been shown to reverse or arrest the progression of fibrosis, representing a major unmet medical need. Recently, antifibrotic effects of PPARγ ligands have been studied in vitro and in vivo and some theories have emerged leading to new insights. Aberrant PPARγ function seems to be implicated in pathological fibrosis in the skin and lungs. This antifibrotic effect is mainly related to the inhibition of TGF-β/Smad signal transduction but other pathways can be involved. This review focused on recent studies that identified PPARγ as an important novel pathway with critical roles in regulating connective tissue homeostasis, with emphasis on skin and lung fibrosis and its role on systemic sclerosis.

  8. Motor System Plasticity and Compensation in Multiple Sclerosis

    OpenAIRE

    Daniel Zeller

    2015-01-01

    Multiple sclerosis (MS) affects the central nervous system (CNS) by inflammatory lesions, direct axonal injury, and by a rather diffuse and widespread neurodegeneration. For a long time, research has mainly focused on these destructive aspects of MS, while the compensatory effects of cellular repair and neural plasticity have received little consideration. However, as current effective immunomodulatory therapies may limit rather than preclude demyelination and axonal damage, additional therap...

  9. The Effect of Hydroalcoholic Extract of Truffle on Estrogen and Progesterone Levels in Experimental Model of Multiple Sclerosis (MS in Female Rats

    Directory of Open Access Journals (Sweden)

    Eslam Zabihi

    2017-06-01

    Full Text Available Abstract Background: The multiple sclerosis is a chronic disease of the central nervous system. Since the level of sex hormone and multiple sclerosis (MS disease affects one another, the aim of this study was to evaluate the impact of the hydroalcoholic extract of truffle on the hormone levels of estrogen and progesterone administered in experimental model of MS-induced rats. Materials and Methods: In this experimental study, 42 Wistar female rats, weighing 180±10 grams selected into 6 groups each consisting of 7 rats. Normal control didn’t receive any treatment and experimental group was given Cuprizone toxin (as a MS model inducer for 40 days. The experimental groups (2, 3, 4 and 5 in addition to Cuprizone received the normal saline, 110, 220 and 330 mg/kg/0.2ml (i.p. of Hydroalcoholic extract of truffle for 12 days too. Blood samples were taken at the end of the twelfth day from all groups involved and levels of sex hormones were measured. Results: Cuprizone decreases estrogen, progesterone levels and also causes weight loss, while injection of hydroalcoholic extract of truffle increased serum levels of estrogen (in experimental group 4 and progesterone (in experimental group 4 & 5 compared to MS-induced group. Conclusion: Results of the study revealed that the hydroalcoholic extract of truffle (at dosages of 220 and 330 mg/kg could increase estrogen and progesterone levels in rats experienced experimental multiple sclerosis.

  10. Spontaneous Compartment Syndrome of the Hand in Systemic Sclerosis.

    Science.gov (United States)

    Tanagho, Andy; Hatab, Sameh; Youssef, Sally; Ansara, Sameh

    2015-09-01

    Compartment syndrome refers to a condition of compromised circulation within a limited space due to increased pressure within that space. The reduced tissue perfusion results in reduced venous drainage, leading to increased interstitial tissue pressure and subsequent compromised arterial flow. Although not as common as compartment syndrome of the leg and forearm, compartment syndrome of the hand is not rare and can lead to devastating sequelae as a result of tissue necrosis. Compartment syndrome of the hand has several etiologies, including trauma, arterial injury, thermal injury, and constrictive bandaging. The cardinal clinical sign is pain that is aggravated by passive stretching of the muscles within the involved compartments. Extremity function is usually restored with expeditious fasciotomy of the involved myofascial compartments, and complications, such as intrinsic muscular dysfunction and Volkmann's ischemic contracture, can usually be prevented. There are no reported cases of compartment syndrome of the hand in patients with systemic sclerosis or Raynaud's phenomenon. Systemic sclerosis is a form of scleroderma that affects the skin and internal organs. The limited cutaneous subset affects the skin of the extremities but is associated with a set of characteristic features that includes calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly, and telangiectasia. This report describes an unusual case of a patient who had spontaneous compartment syndrome of the hand. The patient's concomitant limited cutaneous systemic sclerosis may have played a role in this unusual occurrence. The diagnosis was based on the clinical picture, and the symptoms resolved after surgical decompression. Copyright 2015, SLACK Incorporated.

  11. Gastric antral vascular ectasia--a cause of refractory anaemia in systemic sclerosis.

    LENUS (Irish Health Repository)

    Busteed, S

    2012-02-03

    Recurrent gastrointestinal haemorrhage is an uncommon manifestation of systemic sclerosis. We report a case of gastrointestinal bleeding due to gastric antral vascular ectasia (GAVE) in a patient with systemic sclerosis. Failure to recognise the condition as a cause of gastrointestinal bleeding may delay the instigation of appropriate treatment. GAVE should be considered in the differential diagnosis of anaemia in patients with autoimmune conditions such as systemic sclerosis and primary biliary cirrhosis.

  12. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS)

    Science.gov (United States)

    Constantinescu, Cris S; Farooqi, Nasr; O'Brien, Kate; Gran, Bruno

    2011-01-01

    Experimental autoimmune encephalomyelitis (EAE) is the most commonly used experimental model for the human inflammatory demyelinating disease, multiple sclerosis (MS). EAE is a complex condition in which the interaction between a variety of immunopathological and neuropathological mechanisms leads to an approximation of the key pathological features of MS: inflammation, demyelination, axonal loss and gliosis. The counter-regulatory mechanisms of resolution of inflammation and remyelination also occur in EAE, which, therefore can also serve as a model for these processes. Moreover, EAE is often used as a model of cell-mediated organ-specific autoimmune conditions in general. EAE has a complex neuropharmacology, and many of the drugs that are in current or imminent use in MS have been developed, tested or validated on the basis of EAE studies. There is great heterogeneity in the susceptibility to the induction, the method of induction and the response to various immunological or neuropharmacological interventions, many of which are reviewed here. This makes EAE a very versatile system to use in translational neuro- and immunopharmacology, but the model needs to be tailored to the scientific question being asked. While creating difficulties and underscoring the inherent weaknesses of this model of MS in straightforward translation from EAE to the human disease, this variability also creates an opportunity to explore multiple facets of the immune and neural mechanisms of immune-mediated neuroinflammation and demyelination as well as intrinsic protective mechanisms. This allows the eventual development and preclinical testing of a wide range of potential therapeutic interventions. LINKED ARTICLES This article is part of a themed issue on Translational Neuropharmacology. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.164.issue-4 PMID:21371012

  13. Acute oral tetrahydrobiopterin administration ameliorates endothelial dysfunction in systemic sclerosis.

    Science.gov (United States)

    Machin, Daniel R; Clifton, Heather L; Richardson, Russell S; Wray, D Walter; Donato, Anthony J; Frech, Tracy M

    2017-01-01

    Systemic sclerosis (SSc) is a rare, autoimmune disease characterised by endothelial dysfunction, which is associated with peripheral vasculopathy, such as digital ulcers (DU). We sought to determine if acute oral administration of tetrahydrobiopterin (BH4), an essential cofactor for endothelial nitric oxide synthase, would augment endothelial function in patients with SSc. Twelve SSc patients, of whom a majority had a history of DU, were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design. There were no differences in blood markers of oxidative stress and brachial artery blood pressure, diameter, blood velocity, shear rate, or blood flow at rest between placebo and BH4 (p>0.05). Whereas, after a 5 minute suprasystolic forearm cuff occlusion, brachial artery peak reactive hyperemia (placebo: 313±30 vs. BH4: 347±37 ml/min, pacute BH4 administration, indicating an improvement in endothelial function. To determine if the vasodilatory effects of BH4 were specific to the vascular endothelium, brachial artery blood flow and vasodilation in response to sublingual nitroglycerin were assessed, and were found to be unaffected by BH4 (p>0.05). These findings indicate that acute BH4 administration ameliorates endothelial dysfunction in patients with SSc. Given that endothelial dysfunction is known to be associated with DU in SSc patients, this study provides a proof-of-concept for the potential therapeutic benefits of BH4 in the prevention or treatment of DU in this population.

  14. Antiphospholipid Syndrome - A Case Report of Pulmonary Thromboembolism, Followed with Acute Myocardial Infarction in Patient with Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Marija Vavlukis

    2015-11-01

    CONCLUSION: The acquired antiphospholipid syndrome is common condition in patients with systemic autoimmune diseases, but relatively rare in patients with systemic sclerosis. Never the less, we have to be aware of it when treating the patients with systemic sclerosis.

  15. Role of innate immune system in systemic sclerosis.

    Science.gov (United States)

    Fullard, Nicola; O'Reilly, Steven

    2015-09-01

    Recognition of microbial or viral compounds is crucial to elicit an immune response and pattern recognition receptors (PRRs) form the first line of defence. An important family of PRRs are the Toll-like receptors (TLRs) with numerous evidences indicating their crucial role in identifying microbial or viral compounds. However, the danger theory, where the innate immune system responds to danger signals such as proteins released during damage or necrosis rather than only non-self is gaining ground. Indeed, TLRs are able to recognise endogenous molecules and have been implicated as key players in numerous autoimmune diseases including systemic sclerosis (SSc). TLR2 is known to be upregulated in SSc and has been shown to respond to the endogenous ligand amyloid A resulting in increased IL-6 secretion. TLR4 is now known to respond to a variety of endogenous ligands including fibronectin, containing alternatively spliced exons encoding type III repeat extra domain (EDA). EDA is only expressed upon tissue damage, and elevated levels can be found in SSc patients, idiopathic pulmonary fibrosis and cardiac allograft fibrosis, while deletion of EDA or TLR4 in mice reduces their fibrotic response. Further, stimulation of TLR8 with single-stranded RNA leads to increased expression of TIMP-1. This has been shown to require both IRAK4 and NF-κB with evidence suggesting autoantibodies bind to RNA to stimulate TIMP-1 production in monocytes. Therefore, TLR-mediated signalling provides numerous potential therapeutic targets for development of therapies for the treatment of multi-systemic autoimmune diseases.

  16. [Effect of dextran of 250.000 molecular weight on experimental cholesterin-sclerosis in rabbits].

    Science.gov (United States)

    Ferenc, S; Arpád, H; Gábor, L

    1976-07-01

    Effect of dextran of 250000 molecular weight on experimental cholesterin-sclerosis of rabbits was studied. Doses of 120 (mg/week) kg and 1200 (mg/week) kg administered during 12 weeks have resulted a protective effect. When doses of 1200 (mg/week) kg have been administered--in the aortic adventitia intensive cellular reaction, no hitherto described was revealed, which was considered to be a sing of the exhaustion of RES. This publication authors regard as a preliminary one. To clear whether the cellular reaction observed is a dextran-specific or macro-moleculespecific one further investigations are needed.

  17. The role of information system in multiple sclerosis management.

    Science.gov (United States)

    Ajami, Sima; Ahmadi, Golchehreh; Etemadifar, Masoud

    2014-12-01

    Multiple sclerosis (MS) is a chronic disease of central nervous system. The multiple sclerosis information system (MSIS), such as other information system (IS), depends on identification, collection and processing of data for producing useful information. Lack of the integrated IS for collecting standard data causes undesirable effects on exchanging, comparing, and managing. The aim of this study was to recognize the role of the IS in the MS management and determine the advantages and barriers in implementing of the MSIS. The present study was a nonsystematized review that was done in order to recognize the role of the IS in the MS management. In this study, electronic scientific resources such as scientific magazines and books and published topics at conferences were used. We used key words (IS, chronic disease management, and multiple sclerosis), their combination or their synonyms in title, key words, abstracts, and text of English articles and published reports from 1980 until 2013, and by using search engines such as Google, Google Scholar and scientific databases and electronic issues such as iPubMed, sufficiently important difference, Scopus, Medlib, and Magiran for gathering information. More than 200 articles and reports were collected and assessed and 139 of them. Findings showed that the MSIS can reduce of disease expenses through continuously collecting correct, accurate, sufficient, and timely patients and disease nature information; recoding; editing; processing; exchanging, and distributing among different health care centers. Although the MSIS has many advantages; but, we cannot ignore cultural, economic, technical, organizational, and managerial barriers. Therefore, it is necessary to do studies for preventing, reducing, and controlling them. One of the ways is to recognize the advantages of the MSIS and usage information technology in optimizing disease management.

  18. Profile of gastrointestinal involvement in patients with systemic sclerosis.

    Science.gov (United States)

    Schmeiser, T; Saar, P; Jin, D; Noethe, M; Müller, A; Soydan, N; Hardt, P D; Jaeger, C; Distler, O; Roeb, E; Bretzel, R G; Müller-Ladner, U

    2012-08-01

    Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disease. Of the numerous organ manifestations, involvement of the upper and lower gastrointestinal tract (GIT) appears to be the most frequent with regard to the clinical symptoms. However, as the frequency and clinical relevance of GI involvement in patients with SSc are not known in detail, the German network of the systemic sclerosis (DNSS) has developed a detailed questionnaire to evaluate the extent and profile of gastrointestinal involvement in SSc patients. The multi-symptom questionnaire was used at baseline and after 1 year in registered patients of the DNSS. In addition, the results were compared with gastrointestinal disorders in patients with SSc and other rheumatic diseases, as well as with the medical history of the patients. In total, 90 patients were included in the study. The results of the study show that in reality, a much higher (nearly all) percentage of (98,9%) patients than expected suffer from GI-symptoms, regardless of the stage of their disease. Of these, meteorism (87,8%) was the most common followed by coughing/sore voice (77,8%), heartburn (daytime 68,9%, nighttime 53,3%), diarrhea (67,8%), stomach ache (68,9%) and nausea (61,1%). Although SSc patients were treated according to the respective recommendations, only limited improvements with regard to GI-symptoms could be achieved after 1 year of follow-up. In addition, the study revealed that the multi-symptom questionnaire is a useful tool to contribute to identify the gastrointestinal sequelae in systemic sclerosis.

  19. Systemic sclerosis in a patient with pityriasis rubra pilaris

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    Hamida Turki

    2010-08-01

    Full Text Available Pityriasis rubra pilaris (PRP is a rare, chronic erythematous squamous disorder of unknown etiology. It has been found in association with several autoimmune diseases, including thyroiditis, myositis, myasthenia gravis and vitiligo. Herein we report a case of systemic sclerosis in a patient with classic adult pityriasis rubra pilaris. A 38 year old woman with classic adult type 1 pityriasis rubra pilaris (PRP developed progressive skin thickening of the trunk, face, upper and lower extremities after 2 years of PRP treatment with topical emollients and steroids. Clinical examination and immunological findings were consistent with SSc. Co-existence of these two rare conditions is documented for the first time

  20. Limited Mouth Opening Secondary to Diffuse Systemic Sclerosis

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    Tomoko Wada

    2013-01-01

    Full Text Available Systemic sclerosis (SSc is a relatively rare condition with an immunologically mediated pathogenesis. For reasons that are not clearly understood, dense collagen is deposited in the connective tissues of the body in extraordinary amounts. Although its dramatic effects are seen in association with the skin, the disease is often quite serious with visceral organ involvement. We describe a case of limited mouth opening secondary to diffuse SSc, improvement in mouth opening with passive jaw stretch exercises, and the challenges involved in performing dental procedures for such patients.

  1. A longitudinal study of pulmonary function in Danish patients with systemic sclerosis

    DEFF Research Database (Denmark)

    Jacobsen, Søren; Halberg, P; Ullman, S

    1997-01-01

    To determine the types, prevalence and development of respiratory abnormalities in patients with systemic sclerosis (SSc), and to correlate the results with clinical and serological findings.......To determine the types, prevalence and development of respiratory abnormalities in patients with systemic sclerosis (SSc), and to correlate the results with clinical and serological findings....

  2. Proteome-wide Analysis and CXCL4 as a Biomarker in Systemic Sclerosis

    NARCIS (Netherlands)

    van Bon, L.; Affandi, A. J.; Broen, J.; Christmann, R. B.; Marijnissen, R. J.; Stawski, L.; Farina, G. A.; Stifano, G.; Mathes, A. L.; Cossu, M.; York, M.; Collins, C.; Wenink, M.; Huijbens, R.; Hesselstrand, R.; Saxne, T.; DiMarzio, M.; Wuttge, D.; Agarwal, S. K.; Reveille, J. D.; Assassi, S.; Mayes, M.; Deng, Y.; Drenth, J. P. H.; de Graaf, J.; den Heijer, M.; Kallenberg, C. G. M.; Bijl, M.; Loof, A.; van den Berg, W. B.; Joosten, L. A. B.; Smith, V.; de Keyser, F.; Scorza, R.; Lunardi, C.; van Riel, P. L. C. M.; Vonk, M.; van Heerde, W.; Meller, S.; Homey, B.; Beretta, L.; Roest, M.; Trojanowska, M.; Lafyatis, R.; Radstake, T. R. D. J.

    2014-01-01

    BackgroundPlasmacytoid dendritic cells have been implicated in the pathogenesis of systemic sclerosis through mechanisms beyond the previously suggested production of type I interferon. MethodsWe isolated plasmacytoid dendritic cells from healthy persons and from patients with systemic sclerosis who

  3. Cardio-pulmonary involvement in systemic sclerosis: A study at a tertiary care center

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    Geetakiran Arakkal

    2017-01-01

    Conclusions: In our patients, pulmonary involvement was more common than cardiac involvement. Interstitial lung disease and cardiac involvement were more commonly seen in diffuse systemic sclerosis whereas pulmonary hypertension was more frequent in limited systemic sclerosis. Hence, it is important to screen the patients for cardiopulmonary involvement for early diagnosis and treatment and a better prognostic outcome.

  4. Docetaxel-Induced Systemic Sclerosis with Internal Organ Involvement Masquerading as Congestive Heart Failure

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    Bumsoo Park

    2017-01-01

    Full Text Available Systemic sclerosis, or scleroderma, is a complex medical disorder characterized by limited or diffuse skin thickening with frequent involvement of internal organs such as lungs, gastrointestinal tract, or kidneys. Docetaxel is a chemotherapeutic agent which has been associated with cutaneous side effects. An uncommon cutaneous side effect of docetaxel is scleroderma-like skin changes that extend from limited to diffuse cutaneous systemic sclerosis. Several case reports have been published regarding the association of docetaxel and systemic sclerosis. However, those reports demonstrated the association between docetaxel and scleroderma-like skin changes without internal organ involvement. Here, we report a case of systemic sclerosis with pulmonary arterial hypertension and a microangiopathic kidney involvement induced by docetaxel chemotherapy. After an exhaustive literature review, this could be the first case of docetaxel-induced systemic sclerosis involving internal organs.

  5. Helicobacter pylori infection reduces disease severity in an experimental model of multiple sclerosis

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    Katherine eCook

    2015-02-01

    Full Text Available Recent research has demonstrated that infection with the bacterial pathogen Helicobacter pylori is less common amongst patients with multiple sclerosis (MS, an inflammatory demyelinating disease of the central nervous system (CNS. We compared the prevalence of H. pylori amongst MS patients and healthy controls, and also investigated the impact of this infection on an animal model for MS, experimental autoimmune encephalomyelitis (EAE.The H. pylori status of 71 MS patients and 42 healthy controls was determined by serology. Groups of C57BL/6 mice were infected with H. pylori, or given a placebo, prior to inducing EAE. Clinical scores were assessed for all mice, and spleens and spinal cord tissue were harvested. CD4+ T cell subsets were quantified by flow cytometry, and T cell proliferation assays were performed.In MS patients the seroprevalence of H. pylori was half that of healthy controls (p=0.018. Over three independent experiments, prior H. pylori infection had a moderate effect in reducing the severity of EAE (p = 0.012. In line with this, the antigen-specific T cell proliferative responses of infected animals were significantly reduced (p=0.001, and there was a 4-fold reduction in the number of CD4+ cells in the CNS. CD4+ populations in both the CNS and the spleens of infected mice also contained greatly reduced proportions of IFNγ+, IL-17+, T-bet+, and RORγt+ cells, but the proportions of Foxp3+ cells were equivalent. There were no differences in the frequency of splenic CD4+cells expressing markers of apoptosis between infected and uninfected animals.H. pylori was less prevalent amongst MS patients. In mice, the infection exerted some protection against EAE, inhibiting both Th1 and Th17 responses. This could not be explained by the presence of increased numbers of Foxp3+ regulatory T cells, or T cell apoptosis. This is the first direct experimental evidence showing that H. pylori may provide protection against inflammatory demyelination

  6. Application of the 2012 revised diagnostic definitions for paediatric multiple sclerosis and immune-mediated central nervous system demyelination disorders

    NARCIS (Netherlands)

    van Pelt, E. Danielle; Neuteboom, Rinze F.; Ketelslegers, Immy A.; Boon, Maartje; Catsman-Berrevoets, Coriene E.; Hintzen, Rogier Q.

    Background Recently, the International Paediatric Multiple Sclerosis Study Group (IPMSSG) definitions for the diagnosis of immune-mediated acquired demyelinating syndromes (ADS) of the central nervous system, including paediatric multiple sclerosis (MS), have been revised. Objective To evaluate the

  7. Coexistence of diabetes mellitus type 1 with diffuse systemic sclerosis - case report and literature review.

    Science.gov (United States)

    Wielosz, Ewa; Kurowska, Maria; Suszek, Dorota; Majdan, Maria

    2017-01-01

    Diabetic sclerodactyly is a frequently recognized skin finding that may occur in patients with diabetes mellitus but coexistence of diabetes and systemic sclerosis is rare. We describe a case of coexistence of type 1 diabetes mellitus and systemic sclerosis in 42-year-old man with the history of Raynaud's phenomenon, progressive diffuse hardening of the skin and sclerodactyly, slowly worsening with time. The medical history included type 1 diabetes since childhood with microvascular complications. The patient presented a typical capillaroscopic scleroderma-like pattern, antinuclear antibodies and sclerotic lesions in gastrointestinal system. Summing up, our case represents the rare coexistence of autoimmune diseases like diabetes mellitus type 1 and systemic sclerosis.

  8. L-selectin and skin damage in systemic sclerosis.

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    James V Dunne

    Full Text Available L-selectin ligands are induced on the endothelium of inflammatory sites. L-selectin expression on neutrophils and monocytes may mediate the primary adhesion of these cells at sites of inflammation by mediating the leukocyte-leukocyte interactions that facilitate their recruitment. L-selectin retains functional activity in its soluble form. Levels of soluble L-selectin have been reported as both elevated and lowered in patients with systemic sclerosis (SSc. This preliminary study seeks to discern amongst these disparate results and to discover whether there is an association between L-selectin concentrations in plasma and skin damage in SSc patients.Nineteen cases with limited systemic sclerosis (lSSc and 11 cases with diffuse systemic sclerosis (dSSc were compared on a pairwise basis to age- and sex-matched controls. Criteria of the American College of Rheumatology were used to diagnose SSc. Skin involvement was assessed using the modified Rodnan skin score (mRSS. We find no association between mRSS and plasma L-selectin concentration in lSSc cases (p = 0.9944 but a statistically significant negative correlation in dSSc cases (R(2 = 73.11 per cent, p = 0.0008. The interpretation of the slope for dSSc cases is that for each increase of 100 ng/ml in soluble L-selectin concentration, the mRSS drops 4.22 (95 per cent CI: 2.29, 6.16. There was also a highly statistically significant negative correlation between sL-selectin and disease activity (p = 0.0007 and severity (p = 0.0007 in dSSc cases but not in lSSc cases (p = 0.2596, p = 0.7575, respectively.No effective treatments exist for skin damage in SSc patients. Nor is there a laboratory alternative to the modified Rodnan skin score as is the case for other organs within the body. Modulation of circulating L-selectin is a promising target for reducing skin damage in dSSc patients. Plasma levels of soluble L-selectin could serve as an outcome measure for dSSc patients in

  9. A review of experimental research on herbal compounds in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Zhang, Xue; Hong, Yan-Long; Xu, De-Sheng; Feng, Yi; Zhao, Li-Jie; Ruan, Ke-Feng; Yang, Xiu-Juan

    2014-01-01

    Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease worldwide, leading to progressive muscle atrophy and paralysis. The limited success of conventional treatment for ALS has prompted investigations into complementary and alternative therapies. Herbal remedies provide good prospects of ALS prevention and treatment, with advantages such as multiple targets, multiple links, and few side effects. Studies in vitro and in vivo have shown that herbs have a great potential for treatment of ALS, with therapeutic effects against oxidative stress, excitatory amino acid toxicity, neuroinflammation, and calcium cytotoxicity. Active monomers or ingredients extracted from herbs are considered promising candidates for ALS. Therefore, we review recent experimental research on monomers and compounds isolated from herbal remedies for preventing and treating ALS. Copyright © 2013 John Wiley & Sons, Ltd.

  10. An Update on the Treatment of the Cutaneous Manifestations of Systemic Sclerosis

    Science.gov (United States)

    Vitiello, Magalys; Abuchar, Adriana; Santana, Néstor; Dehesa, Luis

    2012-01-01

    Systemic sclerosis is a connective tissue disorder that affects multiple organs. Although the initial symptoms of the disease are vascular, skin involvement is almost universally present in patients with systemic sclerosis. The presence of Raynaud's phenomenon, progressive thickening of the skin, digital ulcers, and calcinosis all correlate proportionally with disease severity. Since no treatment is available to completely prevent the natural course of the disease, emphasis is often placed on managing symptoms and complications. In this review, the authors focus on the management of each one of the skin manifestations seen in systemic sclerosis, as the dermatologist may facilitate the early recognition and treatment of these complications. PMID:22798974

  11. Clinical Trial Design Issues in Systemic Sclerosis: an Update.

    Science.gov (United States)

    Gordon, Jessica K; Domsic, Robyn T

    2016-06-01

    Systemic sclerosis (scleroderma, SSc) is a multisystem disease characterized by vasculopathy, autoimmunity, and fibrosis. SSc has the highest disease-related mortality rate among the rheumatologic illnesses. In the USA, there remains no FDA-approved therapy. As our understanding of SSc pathogenesis improves, targeted therapies interrupting key pathways and mediators will be studied in clinical trials. However, clinical trials in SSc are fraught with challenges. Validated clinical outcome measures do not exist for all disease manifestations. It can be difficult to discern disease activity from damage. SSc is highly heterogeneous, with multiple different phenotypes, and predicting who will have progressive disease is not currently well understood. Biomarkers are in early stages of development and do not represent surrogate outcomes at this time. Given that SSc is uncommon, studies of similar disease aspects or populations can lead to competition for patients. This review will focus on current issues in SSc clinical trial design.

  12. Registry Evaluation of Digital Ulcers in Systemic Sclerosis

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    Felice Galluccio

    2010-01-01

    Full Text Available Digital ulcers are a very frequent complication of systemic sclerosis affecting about half of the SSc patients, and about 75% of the affected patients have their first DU episode within 5 years from their first non-Raynaud symptom. The lack of adequate classification criteria as well as the lack of knowledge of the development of DU have contributed to the opening of specific registries to better understand the natural history of these lesions. For these reason, specific disease registries play a fundamental role in this field of research. Thanks to the systematic collection of data and their subsequent analysis and comparison between different cohorts, it is possible to improve understanding of the underlying trigger mechanisms of DU development and to determine temporal trends. In the future, the development of recommendations for the management of DU remains of pivotal importance to prevent DU development and obtain rapid healing as well as reduction of pain and disability.

  13. Comprehensive approach to systemic sclerosis patients during pregnancy.

    Science.gov (United States)

    Rueda de León Aguirre, Alexandra; Ramírez Calvo, José Antonio; Rodríguez Reyna, Tatiana Sofía

    2015-01-01

    Systemic sclerosis (SSc) is a connective tissue disease that usually affects women, with a male:female ratio of 1:4-10. It was thought that there was a prohibitive risk of fatal complications in the pregnancies of patients with SSc. It is now known that the majority of these women undergo a normal progression of pregnancy if the right time is chosen and a close obstetric care is delivered. The obstetric risk will depend on the subtype and clinical stage of the disease, and the presence and severity of the internal organ involvement during the pregnancy. The management of these pregnancies should be provided in a specialized center, with a multidisciplinary team capable of identifying and promptly treating complications. Treatment should be limited to drugs with no teratogenic potential, except when renal crises or severe cardiovascular complications develop. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  14. Premature Ovarian Failure – An Unusual Manifestation of Systemic Sclerosis

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    Aruna Nigam

    2017-01-01

    Full Text Available A 31-year-old woman presented with secondary amenorrhoea and inability to conceive, which was of 3 years duration. She had Raynaud’s phenomenon for 16 years, primary hypothyroidism for 5 years, digital ulcers for 4 years and skin tightening for 2 years. She had an expressionless face, with loss of wrinkles and restriction of the mouth opening along with flexion contractures of the hands and the terminal digit resorptions. Investigations showed Antinuclear antibodies (ANA and anti-Scl 70 positivity confirming the presence of systemic sclerosis (SSc. The Follicle Stimulating Hormone (FSH level was elevated, the ovarian follicles were absent, and the endometrial thickness was reduced confirming premature ovarian failure (POF. POF causing infertility and secondary amenorrhoea in SSc is an unusual manifestation; moreover, POF occured without the involvement of other internal organs.

  15. Low-Dose Naltrexone for Pruritus in Systemic Sclerosis

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    Tracy Frech

    2011-01-01

    Full Text Available Pruritus is a common symptom in systemic sclerosis (SSc, an autoimmune disease which causes fibrosis and vasculopathy in skin, lung, and gastrointestinal tract (GIT. Unfortunately, pruritus has limited treatment options in this disease. Pilot trials of low-dose naltrexone hydrochloride (LDN for pruritus, pain, and quality of life (QOL in other GIT diseases have been successful. In this case series we report three patients that had significant improvement in pruritus and total GIT symptoms as measured by the 10-point faces scale and the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0 questionnaire. This small case series suggests LDN may be an effective, highly tolerable, and inexpensive treatment for pruritus and GIT symptoms in SSc.

  16. Vascular Alterations and Sexual Function in Systemic Sclerosis

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    Ann Julie Impens

    2010-01-01

    Full Text Available Sexual dysfunction is common in systemic sclerosis (SSc. Male erectile dysfunction (MED has been reported in around 80% of subjects and more than half of female patients fulfill criteria for diagnosis as female sexual arousal Disorder (FSAD. While some evidence supports a role for cavernosal fibrosis, abundant data suggest that MED is yet another clinical feature of SSc related to vasculopathy. The contribution of vasculopathy to the more complex issues of female sexual dysfunction is less clear. Inhibitors of Type V phosphodiesterase are effective in men with MED secondary to SSc. Limited study in women suggests inconsistent effects on behavior (frequency but not on measures related to perfusion. Sexual activity is an important component of quality of life and an important domain for the caregiver to address; it is not clear that it warrants primary consideration as a consistent measure of scleroderma-related vasculopathy.

  17. Cardiac tamponade preceding skin involvement in systemic sclerosis

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    L. Bozzola

    2011-09-01

    Full Text Available The frequency of pericardial involvement in Systemic Sclerosis (SSc is high on autoptic or echocardiographic studies, but the clinical recognition of pericarditis with or without effusion is rare. We describe a case of a 71-year-old female with no previous history of heart disease, who presented with a large pericardial effusion and tamponade that required pericardial drain. She had suffered from Raynaud’s phenomenon since 25 years. Six weeks after hospital discharge she complained of skin hardening on left leg. Pericardial tamponade is a very rare manifestation of SSc and occurs both early or late in the course of the disease, but in our case it preceded the recognition of scleroderma. We have only identified two other cases of pericardial effusion preceding cutaneous involvement in scleroderma.

  18. An update on an immune system that goes awry in systemic sclerosis

    NARCIS (Netherlands)

    Bon, L. van; Cossu, M.; Radstake, T.R.D.J.

    2011-01-01

    PURPOSE OF REVIEW: This review aims to provide an overview of the recent data that emerged, further substantiating the critical role of innate immunity in systemic sclerosis (SSc). RECENT FINDINGS: Driven by the evidence that newly identified SSc susceptibility genes are predominantly involved in

  19. Development and validation of a scale for mouth handicap in systemic sclerosis: the Mouth Handicap in Systemic Sclerosis scale

    Science.gov (United States)

    Mouthon, L; Rannou, F; Bérezné, A; Pagnoux, C; Arène, J‐P; Foïs, E; Cabane, J; Guillevin, L; Revel, M; Fermanian, J; Poiraudeau, S

    2007-01-01

    Objective To develop and assess the reliability and construct validity of a scale assessing disability involving the mouth in systemic sclerosis (SSc). Methods We generated a 34‐item provisional scale from mailed responses of patients (n = 74), expert consensus (n = 10) and literature analysis. A total of 71 other SSc patients were recruited. The test–retest reliability was assessed using the intraclass coefficient correlation and divergent validity using the Spearman correlation coefficient. Factor analysis followed by varimax rotation was performed to assess the factorial structure of the scale. Results The item reduction process retained 12 items with 5 levels of answers (total score range 0–48). The mean total score of the scale was 20.3 (SD 9.7). The test–retest reliability was 0.96. Divergent validity was confirmed for global disability (Health Assessment Questionnaire (HAQ), r = 0.33), hand function (Cochin Hand Function Scale, r = 0.37), inter‐incisor distance (r = −0.34), handicap (McMaster‐Toronto Arthritis questionnaire (MACTAR), r = 0.24), depression (Hospital Anxiety and Depression (HAD); HADd, r = 0.26) and anxiety (HADa, r = 0.17). Factor analysis extracted 3 factors with eigenvalues of 4.26, 1.76 and 1.47, explaining 63% of the variance. These 3 factors could be clinically characterised. The first factor (5 items) represents handicap induced by the reduction in mouth opening, the second (5 items) handicap induced by sicca syndrome and the third (2 items) aesthetic concerns. Conclusion We propose a new scale, the Mouth Handicap in Systemic Sclerosis (MHISS) scale, which has excellent reliability and good construct validity, and assesses specifically disability involving the mouth in patients with SSc. PMID:17502364

  20. The endocannabinoid system and its therapeutic exploitation in multiple sclerosis : Clues for other neuroinflammatory diseases.

    NARCIS (Netherlands)

    Chiurchiù, V.; Stelt, van der M.; Centonze, D.; Maccarrone, M.

    2017-01-01

    Multiple sclerosis is the most common inflammatory demyelinating disease of the central nervous system, caused by an autoimmune response against myelin that eventually leads to progressive neurodegeneration and disability. Although the knowledge on its underlying neurobiological mechanisms has

  1. Mortality and causes of death of 344 Danish patients with systemic sclerosis (scleroderma)

    DEFF Research Database (Denmark)

    Jacobsen, Søren; Halberg, P; Ullman, S

    1998-01-01

    To determine survival, mortality and causes of death in Danish patients with systemic sclerosis (scleroderma), and to analyse how these parameters are influenced by demographic variables and the extent of skin involvement....

  2. The use of serologic markers for collagen synthesis and degradation in systemic sclerosis

    DEFF Research Database (Denmark)

    Heickendorff, Lene; Zachariae, Hugh; Bjerring, Peter

    1995-01-01

    BACKGROUND: Systemic sclerosis is characterized by excessive accumulation of collagen in all involved organs. Serum markers of collagen synthesis and degradation, the aminoterminal propeptide of type III procollagen (PIIINP), the carboxyterminal propeptide of type I procollagen (PICP), and the cr...

  3. Recognizing systemic sclerosis: comparative analysis of various sets of classification criteria.

    Science.gov (United States)

    Romanowska-Próchnicka, Katarzyna; Walczyk, Marcela; Olesińska, Marzena

    2016-01-01

    Systemic sclerosis is a complex disease characterized by autoimmunity, vasculopathy and tissue fibrosis. Although most patients present with some degree of skin sclerosis, which is a distinguishing hallmark, the clinical presentation vary greatly complicating the diagnosis. In this regard, new classification criteria were jointly published in 2013 by American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR). A recent major development in the classification criteria is improved sensitivity, particularly for detecting early disease. The new criteria allow more cases to be classified as having systemic sclerosis (SSc), which leads to earlier treatment. Moreover it is clinically beneficial in preventing the disease progression with its irreversible fibrosis and organ damage. The aim of this review is to give insight into new classification criteria and current trends in the diagnosis of systemic sclerosis.

  4. Serum VEGF levels are related to the presence of pulmonary arterial hypertension in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Sakkas Lazaros

    2009-05-01

    Full Text Available Abstract Background The association between systemic sclerosis and pulmonary arterial hypertension (PAH is well recognized. Vascular endothelial growth factor (VEGF has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis. Methods Serum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography. Results Serum VEGF levels were higher in systemic sclerosis patients with sPAP ≥ 35 mmHg than in those with sPAP LCO were independent predictors of systolic pulmonary artery pressure. Conclusion Serum VEGF levels are increased in systemic sclerosis patients with sPAP ≥ 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis.

  5. Motor System Plasticity and Compensation in Multiple Sclerosis

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    Daniel Zeller

    2013-07-01

    Full Text Available Multiple sclerosis (MS affects the central nervous system (CNS by inflammatory lesions, direct axonal injury, and by a rather diffuse and widespread neurodegeneration. For a long time, research has mainly focused on these destructive aspects of MS, while the compensatory effects of cellular repair and neural plasticity have received little consideration. However, as current effective immunomodulatory therapies may limit rather than preclude demyelination and axonal damage, additional therapeutic strategies promoting compensation of CNS damage might be of great use for preventing persistent impairment in MS. As a precondition for the development of such strategies, which may encompass pharmacological and behavioural interventions, but also non-invasive stimulation techniques, it seems fundamental to get deeper insights into the mechanisms of plasticity and adaptation at the systemic level. This review will provide a brief overview of what is known about plasticity of the motor system in patients with MS at present, with the main focus relying on evidence from functional imaging, neurophysiology, and motor learning. Overall, rapid-onset motor plasticity seems to be preserved even in advanced stages of the disease. Reorganisation processes, which can be shown early in the course of MS, are functionally relevant for motor compensation. In advanced MS, however, the brain´s adaptive reserve might be exhausted due to exceeding CNS injury. Future studies should address the question of how the later stages of central motor plasticity can be promoted best to preserve the patient´s autonomy for as long as possible.

  6. The treatment of skin ulcers in patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    M. Matucci- Cerinic

    2011-09-01

    Full Text Available Systemic Sclerosis (Ssc is a complex disease of the connective tissue, characterized by progressive thickening and fibrosis of the skin and the internal organs and by diffused damage of the microvascular system. The fibrosis ones of the skin associated to the characteristic vascular alterations lead to the genesis of ulcers, more or less extended, often multiple, peripheral localization, chronic course, painful, able to influence patient’s quality of life. Indeed, immunity reactivity, the thinning and the loss of elasticity of the skin, the peripheral neurological damage and the eventual drug assumption that can reduce regenerative/reparative abilities, can easy chronicizzate an ulcer and become infected complicating still more the patient disease, rendering more difficult the cure often, ulcer evolves to gangrene, and in some cases, in amputation too. For all these reasons, we have begun to study ulcers therapy (local and systemic, considering this activity it leave integrating of the charitable distance of the sclerodermico patient, putting to point on strategy both diagnostic and therapeutic, but above all with the primary scope, if possible, is to prevent ulcers, in contrary case, to alleviate the pain and to render the quality of the life of the patient better.

  7. Effect of honey bee venom on lewis rats with experimental allergic encephalomyelitis, a model for multiple sclerosis.

    Science.gov (United States)

    Karimi, Akbar; Ahmadi, Farhad; Parivar, Kazem; Nabiuni, Mohammad; Haghighi, Saied; Imani, Sohrab; Afrouzi, Hossein

    2012-01-01

    Multiple sclerosis (MS) is a progressive and autoimmune neurodegenerative disease of the central nervous system (CNS). This disease is recognized through symptoms like inflammation, demyelination and the destruction of neurological actions. Experimental allergic encephalomyelitis (EAE) is a widely accepted animal model for MS. EAE is created in animals by injecting the tissue of myelin basic protein (MBP), CNS, or myelin oligodendrocyte glycoprotein (MOG) along with the adjuvant. EAE and MS are similar diseases. Honey Bee venom (Apis mellifera) contains a variety of low and high molecular weight peptides and proteins, including melittin, apamin, adolapin, mast cell degranulating peptide and phospholipase A2. Bee venom (BV) could exert anti-inflammatory and antinociceptive effects on the inflammatory reactions. The guinea pig spinal cord homogenate (GPSCH) is with the Complete Freund's Adjuvant (CFA), consisting of 1 mg/mL Mycobacterium tuberculosis. It was used for inducting EAE in Lewis rats for creating the MS model. The hematoxylin and eosin and luxol fast blue methods were used respectively in analyses of inflammation and detection of demyelination in the central nervous system. Furthermore, the ELISA and the high performance liquid chromatography (HPLC) were used for the assessment of tumor necrosis factor alpha (TNF-α) and nitrate in rats serum. In this study, we indicated that the treatment of EAE with Bee venom decreased the symptoms of clinical disorder, pathological changes, inflammatory cell infiltration, demyelination in the central nervous system, level of serum TNF-α, and the serum nitrates in rat EAE induced through GPSCH.

  8. Lesional-targeting of neuroprotection to the inflammatory penumbra in experimental multiple sclerosis

    NARCIS (Netherlands)

    Al-Izki, S.; Pryce, G.; Hankey, D.J.R.; Lidster, K.; von Kutzleben, S.M.; Browne, L.; Clutterbuck, L.; Posada, C.; Chan, A.W.E.; Amor, S.; Perkins, V.; Gerritsen, W.H.; Ummenthum, K.; Peferoen-Baert, R.; van der Valk, P.; Montoya, A.; Joel, S.P.; Garthwaite, J.; Giovannoni, G.; Selwood, D.L.; Baker, D.

    2014-01-01

    Progressive multiple sclerosis is associated with metabolic failure of the axon and excitotoxicity that leads to chronic neurodegeneration. Global sodium-channel blockade causes side effects that can limit its use for neuroprotection in multiple sclerosis. Through selective targeting of drugs to

  9. Persistent activation of microglia is associated with neuronal dysfunction of callosal projecting pathways and multiple sclerosis-like lesions in relapsing--remitting experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Rasmussen, Stine; Wang, Yue; Kivisäkk, Pia

    2007-01-01

    Cortical pathology, callosal atrophy and axonal loss are substrates of progression in multiple sclerosis (MS). Here we describe cortical, periventricular subcortical lesions and callosal demyelination in relapsing-remitting experimental autoimmune encephalomyelitis in SJL mice that are similar to...

  10. Micronutrients, their potential effect on patients with systemic sclerosis.

    Science.gov (United States)

    Wan, Ya-Nan; Yan, Jun-Wei; Peng, Wen-Jia; Zhang, Jun-Qing; Xiao, Chang-Chun; Wang, Bing-Xiang; Wang, Jing

    2014-09-01

    Over the past years, several evidences have supported an important role of specific micronutrients, including vitamin A, vitamin D and vitamin E in immune dysfunction, vascular involvement and fibrotic changes involved in systemic sclerosis (SSc) development. In PubMed, eight clinical trials about the therapy of micronutrients on SSc patients were searched out using medical subject headings terms (SSc: "scleroderma, localized", "scleroderma, systemic", "scleroderma, diffuse" and "scleroderma, limited"; vitamins "vitamin A", "thiamin", "riboflavin", "niacin", "pantothenic acid", "vitamin B 6", "biotin", "folic acid", "vitamin B 12", "inositol", "choline", "ascorbic acid", "vitamin D", "vitamin E", "tocopherols", "vitamin K" and "vitamin P"; and minerals: "calcium", "magnesium", "potassium", "sodium", "phosphorus", "sulfur", "chlorine", "iron", "copper", "iodine", "zinc", "selenium", "manganese", "molybdenum", "cobalt", "chromium", "tin", "vanadium", "silicon", "nickel" and "fluorine"). This brief review will summarize current understanding on that for the further prospect of future studies. Though the clinical trials for the treatment of SSc with micronutrients are still in their infancy, more researches are needed to substantiate the current results and accelerate the knowledge in this field.

  11. Eosinophilic Esophagitis in Two Patients with Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Tracy M. Frech

    2016-01-01

    Full Text Available The gastrointestinal tract (GIT is the most common extracutaneous organ system damaged in systemic sclerosis (SSc and is the presenting feature in 10% of patients. The esophagus as the portion of the GIT is the most commonly affected and there is an association of gastroesophageal reflux (GER with SSc interstitial lung disease (ILD. Thus, an aggressive treatment for GER is recommended in all SSc patients with ILD; however, it is recognized that a long-term benefit to this treatment is needed to understand its impact. In this case report we discuss the presence of eosinophilic esophagitis (EoE in two SSc patients and discuss the role for early EGD in SSc patients with moderate-severe GER symptoms for tissue study. Assessment of esophageal biopsy specimens for the presence of eosinophils and possibly ANA can help elucidate disease pathogenesis and direct therapy, as the presence of EoE in SSc has important management considerations, particularly with regards to dietary modification strategies.

  12. Mouse models of multiple sclerosis: experimental autoimmune encephalomyelitis and Theiler's virus-induced demyelinating disease.

    Science.gov (United States)

    McCarthy, Derrick P; Richards, Maureen H; Miller, Stephen D

    2012-01-01

    Experimental autoimmune encephalomyelitis (EAE) and Theiler's Murine Encephalitis Virus-Induced Demyelinating Disease (TMEV-IDD) are two clinically relevant murine models of multiple sclerosis (MS). Like MS, both are characterized by mononuclear cell infiltration into the CNS and demyelination. EAE is induced by either the administration of myelin protein or peptide in adjuvant or by the adoptive transfer of encephalitogenic T cell blasts into naïve recipients. The relative merits of each of these protocols are compared. Depending on the type of question being asked, different mouse strains and peptides are used. Different disease courses are observed with different strains and different peptides in active EAE. These variations are also addressed. Additionally, issues relevant to clinical grading of EAE in mice are discussed. In addition to EAE induction, useful references for other disease indicators such as DTH, in vitro proliferation, and immunohistochemistry are provided. TMEV-IDD is a useful model for understanding the possible viral etiology of MS. This section provides detailed information on the preparation of viral stocks and subsequent intracerebral infection of mice. Additionally, virus plaque assay and clinical disease assessment are discussed. Recently, recombinant TMEV strains have been created for the study of molecular mimicry which incorporate various 30 amino acid myelin epitopes within the leader region of TMEV.

  13. Interstitial lung disease in systemic sclerosis: where do we stand?

    Directory of Open Access Journals (Sweden)

    Susanna Cappelli

    2015-09-01

    Full Text Available Interstitial lung disease (ILD is common in systemic sclerosis (SSc patients and despite recent advances in the treatment is, at present, the major cause of death. Today, an early diagnosis of ILD is possible, and is mandatory to improve the prognosis of the disease. Pulmonary function tests and high-resolution computed tomography remain the mainstay for the diagnosis of SSc-ILD, but there is a growing interest in lung ultrasound. Recently, the correlation between severity of fibrosis and some peripheral blood biomarkers has been described. Nonselective immunosuppressors are still the main treatment for ILD, with cyclophosphamide (CYC most widely used to obtain remission. Novel therapies towards specific molecular and cellular targets have been suggested; in particular, rituximab (RTX has shown promising results, but further research is needed. It is of paramount importance to define the severity of the disease and the risk of progression in order to define the need for treatment and the treatment intensity. We propose the division of the treatment strategies at our disposal to induce remission into three categories: high intensity (haematopoietic stem cell transplantation, medium intensity (CYC and RTX and low intensity (azathioprine (AZA and mycophenolate mofetil (MMF. After obtaining remission, maintenance treatment with AZA or MMF should be started. In this review we explore new advances in the pathogenesis, diagnosis and treatment of SSc-ILD.

  14. Effects of the myofascial release in diffuse systemic sclerosis.

    Science.gov (United States)

    Martin, Marilene Marfin

    2009-10-01

    To improve breathing and functionality of the temporomandibular joint (TMJ) and hands, by increasing the range of motion (ROM), and to reduce the level of pain. Twenty myofascial release (MR) sessions in 2002 with assessments (chest expansion, mouth opening, ROM of wrist and fingers). Between the 19th and the 20th session there was a break of 110 days. Every winter, 1-3 sessions have been made. Chest: expansion increased by 3.5 cm and pain was eliminated at the scar from a biopsy; TMJ: an 8mm increase in mouth opening with pain eliminated; hands and fingers: increase of ROM in all joints of fingers and wrists, of up to 100%, reduction in ulcerations and recovery of nail growth. The connective tissue affected by diffuse systemic sclerosis (dSSc) is subject to remodeling through MR, receding when the work is interrupted. Resuming the treatment on a regular basis increased the ROM in joints, reduced the effects of the Raynaud Phenomenon and the pain.

  15. Unstabilized DNA breaks in lymphocytes of patients with systemic sclerosis.

    Science.gov (United States)

    Majone, Franca; Zamboni, Daniela; Cozzi, Franco; Montaldi, Anna; Grypiotis, Panagiotis; Luisetto, Roberto; Favaro, Maria; Tonello, Marta; Ruffatti, Amelia

    2006-01-01

    The clastogenic effects on DNA, proven by the presence of micronuclei (MN), and the protective cellular mechanisms normally used to stabilize DNA breaks were investigated in patients with systemic sclerosis (SSc). The frequency of micronucleated cells found in cultures of peripheral lymphocytes in patients was significantly higher than in the control group. The patient group with anti-centromere antibodies showed a significantly higher frequency of micronucleated cells than that observed in the patients with anti-topoisomerase I antibodies (4.22% versus 2.34%, p < 0.001). Moreover, we attempted to characterize MN for the presence or absence of DNA fragments with free 3'-OH ends by digoxigenin-dUTP (DIG-dUTP) using terminal deoxynucleotidil transferase. It was found that the frequency of MN containing DNA fragments with 3'-OH free ends (unstable fragments) increased in SSc patients compared to that observed in the control group. Moreover, this increase was significantly higher in lymphocytes of the patients with anti-centromere antibodies than in those with anti-topoisomerase I antibodies (35% versus 20.08%, p < 0.001). Our results indicate that in SSc patients there is an interference in the protective cellular mechanisms, normally stabilizing DNA breaks.

  16. Screening for pulmonary arterial hypertension in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    J-L. Vachiéry

    2009-09-01

    Full Text Available The onset and progression of pulmonary arterial hypertension (PAH in patients with systemic sclerosis (SSc can be particularly aggressive; however, effective treatments are available. Therefore, early identification of patients with suspected PAH, confirmation of diagnosis, and intervention is essential. PAH may be challenging to diagnose in its earliest stages, particularly in populations that have multiple causes of breathlessness, and, therefore, screening is required. The optimal screening tools and methodology are, as yet, unknown, and this is confounded by a lack of consensus over which patients to screen. Current practice favours annual screening of all SSc patients using Doppler echocardiography to detect elevated right heart pressures. This will typically identify most patients with the various forms of pulmonary hypertension found in SSc. The optimum thresholds for Doppler echocardiography are still subject to investigation, especially for patients with mild pulmonary hypertension, and this technique may, therefore, yield a significant number of false-positives and a currently unknown number of false-negatives. Confirmatory right heart catheterisation remains necessary in all suspected cases. Further research is needed to identify the optimal tools and the screening approach with greatest specificity and selectivity.

  17. Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Pier Andrea Nicolosi

    2016-01-01

    Full Text Available Fibrosis of the skin and of internal organs, autoimmunity, and vascular inflammation are hallmarks of Systemic Sclerosis (SSc. The injury and activation of endothelial cells, with hyperplasia of the intima and eventual obliteration of the vascular lumen, are early features of SSc. Reduced capillary blood flow coupled with deficient angiogenesis leads to chronic hypoxia and tissue ischemia, enforcing a positive feed-forward loop sustaining vascular remodelling, further exacerbated by extracellular matrix accumulation due to fibrosis. Despite numerous developments and a growing number of controlled clinical trials no treatment has been shown so far to alter SSc natural history, outlining the need of further investigation in the molecular pathways involved in the pathogenesis of the disease. We review some processes potentially involved in SSc vasculopathy, with attention to the possible effect of sustained vascular inflammation on the plasticity of vascular cells. Specifically we focus on mesenchymal transition, a key phenomenon in the cardiac and vascular development as well as in the remodelling of injured vessels. Recent work supports the role of transforming growth factor-beta, Wnt, and Notch signaling in these processes. Importantly, endothelial-mesenchymal transition may be reversible, possibly offering novel cues for treatment.

  18. Disease progression in systemic sclerosis-overlap syndrome is significantly different from limited and diffuse cutaneous systemic sclerosis.

    Science.gov (United States)

    Moinzadeh, Pia; Aberer, Elisabeth; Ahmadi-Simab, Keihan; Blank, Norbert; Distler, Joerg H W; Fierlbeck, Gerhard; Genth, Ekkehard; Guenther, Claudia; Hein, Ruediger; Henes, Joerg; Herich, Lena; Herrgott, Ilka; Koetter, Ina; Kreuter, Alexander; Krieg, Thomas; Kuhr, Kathrin; Lorenz, Hanns-Martin; Meier, Florian; Melchers, Inga; Mensing, Hartwig; Mueller-Ladner, Ulf; Pfeiffer, Christiane; Riemekasten, Gabriela; Sárdy, Miklós; Schmalzing, Marc; Sunderkoetter, Cord; Susok, Laura; Tarner, Ingo H; Vaith, Peter; Worm, Margitta; Wozel, Gottfried; Zeidler, Gabriele; Hunzelmann, Nicolas

    2015-04-01

    Systemic sclerosis (SSc)-overlap syndromes are a very heterogeneous and remarkable subgroup of SSc-patients, who present at least two connective tissue diseases (CTD) at the same time, usually with a specific autoantibody status. To determine whether patients, classified as overlap syndromes, show a disease course different from patients with limited SSc (lcSSc) or diffuse cutaneous SSc (dcSSc). The data of 3240 prospectively included patients, registered in the database of the German Network for Systemic Scleroderma and followed between 2003 and 2013, were analysed. Among 3240 registered patients, 10% were diagnosed as SSc-overlap syndrome. Of these, 82.5% were female. SSc-overlap patients had a mean age of 48±1.2 years and carried significantly more often 'other antibodies' (68.0%; poverlap patients was significantly earlier than in patients with lcSSc and occurred later than in patients with dcSSc. Oesophagus, kidney and PH progression was similar to lcSSc patients, whereas dcSSc patients had a significantly earlier onset. These data support the concept that SSc-overlap syndromes should be regarded as a separate SSc subset, distinct from lcSSc and dcSSc, due to a different progression of the disease, different proportional distribution of specific autoantibodies, and of different organ involvement. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  19. The interleukin 23 receptor gene does not confer risk to systemic sclerosis and is not associated with systemic sclerosis disease phenotype.

    NARCIS (Netherlands)

    Rueda, B.; Broen, J.; Torres, O.; Simeon, C.; Ortego-Centeno, N.; Schrijvenaars, M.M.; Vonk, M.C.; Fonollosa, V.; Hoogen, F.H.J. van den; Coenen, M.J.H.; Sanchez-Roman, J.; Aguirre-Zamorano, M.A.; Garcia-Portales, R.; Pros, A.; Camps, M.T.; Gonzalez-Gay, M.A.; Martin, J.; Radstake, T.R.D.J.

    2009-01-01

    OBJECTIVES: Multiple studies indicate the role of the interleukin (IL)-17/IL-23 axis in autoimmune diseases, including systemic sclerosis (SSc). The aim of the current study was to investigate the possible implication of the IL23R gene in SSc susceptibility and/or clinical phenotype. METHODS: An

  20. CpG Type A Induction of an Early Protective Environment in Experimental Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    James Crooks

    2017-01-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is an inflammatory, demyelinating disease of the CNS that mimics human multiple sclerosis (MS, and it is thought to be driven by Th1 and Th17 myelin-reactive cells. Although adaptive immunity is clearly pivotal in the pathogenesis of EAE, with an essential role of CD4+ T cells, little is known of early, innate responses in this experimental setting. CpG-rich oligodeoxynucleotides (ODNs, typically found in microbial genomes, are potent activators of TLR9 in plasmacytoid dendritic cells (pDCs. In this study, we compared the effects of two types of CpG, namely, type A and type B, on EAE. We found that treatment with CpG type A ODN (CpG-A, known to induce high amounts of IFN-α in pDCs, significantly reduced disease severity in EAE, relative to controls (12.63±1.86 versus 23.49±1.46, resp.; p=0.001. Treatment also delayed onset of neurological deficits and reduced spinal cord demyelination, while increasing the percentage of splenic regulatory (Foxp3+ CD4+ T cells. CpG-A likewise reduced the levels of IL-17 and IFN-γ in the CNS. Mechanistic insight into those events showed that CpG-A promoted a regulatory phenotype in pDCs. Moreover, adoptive transfer of pDCs isolated from CpG-A-treated mice inhibited CNS inflammation and induced disease remission in acute-phase EAE. Our data thus identify a link between TLR9 activation by specific ligands and the induction of tolerance via innate immunity mechanisms.

  1. Experimental Autonomous Vehicle Systems

    DEFF Research Database (Denmark)

    Ravn, Ole; Andersen, Nils Axel

    1998-01-01

    ANSI-C program extending the TCL system is used for plan execution and a combination of MATLAB and a custom made Java GUI as user interface on the remote operator console. The choice of these standard software components is explained and the individual components demonstrated. Examples of how specific...

  2. Purified Cannabidiol, the main non-psychotropic component of Cannabis sativa, alone, counteracts neuronal apoptosis in experimental multiple sclerosis.

    Science.gov (United States)

    Giacoppo, S; Soundara Rajan, T; Galuppo, M; Pollastro, F; Grassi, G; Bramanti, P; Mazzon, E

    2015-12-01

    Multiple Sclerosis (MS) is a global concern disease leading to a progressive, chronic and demyelinating condition, affecting the central nervous system (CNS). The pathology has an inflammatory/autoimmune origin; nevertheless, neuronal cell death mechanisms are not to be underestimated. The present study was designed to test the effects of intraperitoneal administration of cannabidiol (CBD), the main non-psychotropic cannabinoid of Cannabis sativa (CS), in an experimental model of MS. The aim is to evaluate the capability of CBD administration to thwart the cascade of mediators involved in MS-induced apoptosis. Experimental Autoimmune Encephalomyelitis (EAE) was induced by immunization with myelin oligodendroglial glycoprotein (MOG)35-55 peptide in mice. After immunization, mice were observed daily for signs of EAE and weight loss. Disease signs were evaluated using a standardized scoring system. Immunohistochemical and Western blot assessments of key apoptotic markers reveal that CBD treatment is able to avoid Fas pathway activation, phospho-ERK p42/44 and cleaved caspase-3 triggering as well as alterations in mitochondrial permeability due to Bax/Bcl-2 unbalance. Moreover, CBD interferes with p53-p21 axis activation. As results, the absence of tissue apobody formation in spinal cord tissues of EAE-mice treated with CBD was established. Most of therapeutic properties of CS are currently ascribed to the psychotropic effects of phenylterpenoid delta-9 tetrahydrocannabinol. We have demonstrated that, alone, purified CBD possesses an anti-apoptotic power against the neurodegenerative processes underlying MS development. This represents an interesting new profile of CBD that could lead to its introduction in the clinical management of MS.

  3. Gene therapy with mesenchymal stem cells expressing IFN‐ß ameliorates neuroinflammation in experimental models of multiple sclerosis

    Science.gov (United States)

    Marin‐Bañasco, C; Benabdellah, K; Melero‐Jerez, C; Oliver, B; Pinto‐Medel, M J; Hurtado‐Guerrero, I; de Castro, F; Clemente, D; Fernández, O; Martin, F; Leyva, L

    2017-01-01

    Background and Purpose Recombinant IFN‐ß is one of the first‐line treatments in multiple sclerosis (MS), despite its lack of efficacy in some patients. In this context, mesenchymal stem cells (MSCs) represent a promising therapeutic alternative due to their immunomodulatory properties and multipotency. Moreover, by taking advantage of their pathotropism, these cells can be genetically modified to be used as carriers for delivering or secreting therapeutic drugs into injured tissues. Here, we report the therapeutic effect of systemic delivery of adipose‐derived MSCs (AdMSCs), transduced with the IFN‐β gene, into mice with experimental autoimmune encephalomyelitis (EAE). Experimental Approach Relapsing–remitting and chronic progressive EAE were induced in mice. Cells were injected i.v. Disease severity, inflammation and tissue damage were assessed clinically, by flow cytometry of spleens and histopathological evaluation of the CNS respectively. Key Results Genetic engineering did not modify the biological characteristics of these AdMSCs (morphology, growth rate, immunophenotype and multipotency). Furthermore, the transduction of IFN‐ß to AdMSCs maintained and, in some cases, enhanced the functional properties of AdMSCs by ameliorating the symptoms of MS in EAE models and by decreasing indications of peripheral and central neuro‐inflammation. Conclusion and Implications Gene therapy was found to be more effective than cell therapy in ameliorating several clinical parameters in both EAE models, presumably due to the continuous expression of IFN‐β. Furthermore, it has significant advantages over AdMSC therapy, and also over systemic IFN‐ß treatment, by providing long‐term expression of the cytokine at therapeutic concentrations and reducing the frequency of injections, while minimizing dose‐limiting side effects. PMID:27882538

  4. TRAIL/TRAIL receptor system and susceptibility to multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Carlos López-Gómez

    Full Text Available The TNF-related apoptosis inducing ligand (TRAIL/TRAIL receptor system participates in crucial steps in immune cell activation or differentiation. It is able to inhibit proliferation and activation of T cells and to induce apoptosis of neurons and oligodendrocytes, and seems to be implicated in autoimmune diseases. Thus, TRAIL and TRAIL receptor genes are potential candidates for involvement in susceptibility to multiple sclerosis (MS. To test whether single-nucleotide polymorphisms (SNPs in the human genes encoding TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 are associated with MS susceptibility, we performed a candidate gene case-control study in the Spanish population. 59 SNPs in the TRAIL and TRAIL receptor genes were analysed in 628 MS patients and 660 controls, and validated in an additional cohort of 295 MS patients and 233 controls. Despite none of the SNPs withstood the highly conservative Bonferroni correction, three SNPs showing uncorrected p values<0.05 were successfully replicated: rs4894559 in TRAIL gene, p = 9.8×10(-4, OR = 1.34; rs4872077, in TRAILR-1 gene, p = 0.005, OR = 1.72; and rs1001793 in TRAILR-2 gene, p = 0.012, OR = 0.84. The combination of the alleles G/T/A in these SNPs appears to be associated with a reduced risk of developing MS (p = 2.12×10(-5, OR = 0.59. These results suggest that genes of the TRAIL/TRAIL receptor system exerts a genetic influence on MS.

  5. Detection of dermal systemic sclerosis using noncontact optical coherence elastography

    Science.gov (United States)

    Liu, Chih-Hao; Du, Yong; Singh, Manmohan; Li, Jiasong; Wu, Chen; Han, Zhaolong; Raghunathan, Raksha; Hsu, Thomas; Noorani, Shezaan; Hicks, M. John; Mohan, Chandra; Larin, Kirill V.

    2016-03-01

    Systemic sclerosis (SSc) is a connective tissue disease that results in excessive accumulation of collagen in the skin and internal organs. Overall, SSc is a rare disorder, but has a high mortality, particularly in last decade of life. To improve the survival rate, an accurate and early diagnosis is crucial. Currently, the modified Rodnan skin score (mRSS) is the gold standard for evaluating SSc progression based on clinical palpation at 17 sites on the body. However, this procedure can be time consuming, and the assessed score may be biased by the experience of the clinician, causing inter- and intraobserver variabilities. Moreover, the instrinsic elasticity of skin may further bias the mRSS assessment in the early stages of SSc, such as oedematous. To overcome these limitations, there is a need for a rapid, accurate, and objective assessment technique. Optical coherence elastography (OCE) is a novel, rapidly emerging technique, which can assess mechanical contrast in tissues with micrometer spatial resolution. In this work, we demonstrate the first use of OCE to assess the mechanical properties of control and SSc-like diseased skin non-invasively. A focused air-pulse induced an elastic wave in the skin, which was detected by a home-built OCE system. The elastic wave propagated significantly faster in SSc skin compared to healthy skin. The Young's modulus of the SSc skin was significantly higher than that of normal skin (P<0.05). Thus, OCE was able to objectively differentiate healthy and fibrotic skin completely noninvasively and is a promising and potentially useful new technology for quantifying skin involvement in SSc.

  6. Multiple Sclerosis

    Science.gov (United States)

    ... SEARCH Definition Treatment Prognosis Clinical Trials Organizations Publications Definition An unpredictable disease of the central nervous system, multiple sclerosis (MS) can range from relatively benign to somewhat disabling to devastating, as communication between the brain and other parts of the ...

  7. Elevated plasma homocysteine level is possibly associated with skin sclerosis in a series of Japanese patients with systemic sclerosis.

    Science.gov (United States)

    Motegi, Sei-Ichiro; Toki, Sayaka; Yamada, Kazuya; Uchiyama, Akihiko; Ishikawa, Osamu

    2014-11-01

    Homocysteine is a sulfhydryl-containing amino acid that is derived from dietary methionine, and there has been increasing evidence that elevated plasma homocysteine levels are associated with increased risk of cardiovascular diseases, including carotid, coronary and peripheral arterial disease (PAD). The association of plasma homocysteine levels with peripheral vascular involvements, such as Raynaud phenomenon (RP), digital ulcers (DU) in systemic sclerosis (SSc) patients has not been well studied. The objective of this study was to examine plasma homocysteine levels and their clinical associations in patients with SSc. Plasma homocysteine levels in 151 Japanese patients with SSc and 20 healthy controls were examined. No significant differences were observed in plasma homocysteine levels between SSc patients and healthy individuals. Demographic and clinical features of the SSc patients revealed that severe skin sclerosis, anti-topoisomerase I antibody positivity, complications of DU, acro-osteolysis (AO) and interstitial lung disease (ILD) were significantly more prevalent among the patients with elevated plasma homocysteine levels. The plasma homocysteine levels were positively correlated with modified Rodnan total skin score. The plasma homocysteine levels in the SSc patients with DU, AO and ILD were significantly higher than those in the SSc without DU, AO and ILD, respectively. Plasma homocysteine levels did not correlate with either the mean or max intima-media thickness (IMT) or plaque score, suggesting that plasma homocysteine levels might not be associated with carotid artery atherosclerosis in SSc patients. The measurement of plasma homocysteine levels in SSc patients might be useful for the risk stratifications of severe skin sclerosis, DU and AO. © 2014 Japanese Dermatological Association.

  8. Prevalence of fecal incontinence in a cohort of systemic sclerosis patients within a regional referral network.

    Science.gov (United States)

    Garros, A; Marjoux, S; Khouatra, C; Coppere, B; Grange, C; Hot, A; Roman, S; Damon, H; Mion, F

    2017-11-01

    The prevalence of gastrointestinal involvement in systemic sclerosis is higher than 75%. The estimated prevalence of fecal incontinence varies from 22% to 77%, but suffers from recruitment bias and patient reluctance. Our goal was to evaluate the prevalence of fecal incontinence in systemic sclerosis, and to identify associated risk factors. Patients were recruited in the referral systemic sclerosis network of the Lyon University Hospitals, using self-administered questionnaires including constipation, fecal incontinence and Bristol Stool scales, quality of life, anxiety and depression. The cohort was compared with the historical ORALIA cohort that established the prevalence of fecal incontinence in the general population of the Rhône-Alpes region (France). Seventy-seven patients were included (mean age: 60 years, range: 32-84), and 86% were female. These were compared to 153 ORALIA individuals matched for age and sex. Fecal incontinence was present in 38% of patients and 6% of the general population. A longer duration of systemic sclerosis was the only characteristic associated with fecal incontinence. Abnormal stool consistency was more frequent in patients with fecal incontinence. Fecal incontinence and abnormal stool consistency are common in systemic sclerosis and should be systematically addressed.

  9. Systemic Sclerosis and Perceptions of Quality in Primary Care.

    Science.gov (United States)

    Toci, Ashley L; Hyer, J Madison; Silver, Richard M; Nietert, Paul J; Hant, Faye N

    2016-05-01

    Among patients with systemic sclerosis (SSc), early recognition of potentially life-threatening organ involvement is critical. Because prompt recognition of early signs of organ involvement can dramatically alter a patient׳s outcome, it is crucial that patients and primary care providers (PCPs) recognize these symptoms. We conducted a survey of patients with SSc regarding their perceptions of the quality of their primary care, and whether or not they perceive the quality of their primary care to be impaired by their scleroderma diagnosis. A mail survey was sent to 525 patients with SSc seen at the Medical University of South Carolina. Questionnaire items addressed demographics and perceptions of their quality of their primary care. Of n = 140 respondents, most (74.5%) did not feel as though their diagnosis of SSc has resulted in barriers to appropriate or satisfactory care, and most (81.3%) answered that they had not ever felt as though their medical concerns were not being addressed because they had SSc. Perceptions of barriers were significantly (P < 0.05) associated with female sex and younger age, along with poorer overall quality of care and satisfaction with their primary care. Most patients with SSc value the quality of their primary care. However, some patients with SSc feel that their PCPs do not adequately monitor their blood pressure, reflux symptoms or shortness of breath. These results highlight the importance of PCPs in the overall care of patients with SSc and the need for continued education regarding close monitoring of signs and symptoms suggestive of possible life-threatening internal organ involvement. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  10. Abscisic acid ameliorates the systemic sclerosis fibroblast phenotype in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Bruzzone, Santina, E-mail: santina.bruzzone@unige.it [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Advanced Biotechnology Center, Largo Rosanna Benzi 10, 16132 Genova (Italy); Battaglia, Florinda [Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Mannino, Elena [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Parodi, Alessia [Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Fruscione, Floriana [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Advanced Biotechnology Center, Largo Rosanna Benzi 10, 16132 Genova (Italy); Basile, Giovanna [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Salis, Annalisa; Sturla, Laura [Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova (Italy); Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Negrini, Simone; Kalli, Francesca; Stringara, Silvia [Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Filaci, Gilberto [Centre of Excellence for Biomedical Research, University of Genova, Viale Benedetto XV 9, 16132 Genova (Italy); Department of Internal Medicine, Viale Benedetto XV 6, 16132 Genova (Italy); and others

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer ABA is an endogenous hormone in humans, regulating different cell responses. Black-Right-Pointing-Pointer ABA reverts some of the functions altered in SSc fibroblasts to a normal phenotype. Black-Right-Pointing-Pointer UV-B irradiation increases ABA content in SSc cultures. Black-Right-Pointing-Pointer SSc fibroblasts could benefit from exposure to ABA and/or to UV-B. -- Abstract: The phytohormone abscisic acid (ABA) has been recently identified as an endogenous hormone in humans, regulating different cell functions, including inflammatory processes, insulin release and glucose uptake. Systemic sclerosis (SSc) is a chronic inflammatory disease resulting in fibrosis of skin and internal organs. In this study, we investigated the effect of exogenous ABA on fibroblasts obtained from healthy subjects and from SSc patients. Migration of control fibroblasts induced by ABA was comparable to that induced by transforming growth factor-{beta} (TGF-{beta}). Conversely, migration toward ABA, but not toward TGF-{beta}, was impaired in SSc fibroblasts. In addition, ABA increased cell proliferation in fibroblasts from SSc patients, but not from healthy subjects. Most importantly, presence of ABA significantly decreased collagen deposition by SSc fibroblasts, at the same time increasing matrix metalloproteinase-1 activity and decreasing the expression level of tissue inhibitor of metalloproteinase (TIMP-1). Thus, exogenously added ABA appeared to revert some of the functions altered in SSc fibroblasts to a normal phenotype. Interestingly, ABA levels in plasma from SSc patients were found to be significantly lower than in healthy subjects. UV-B irradiation induced an almost 3-fold increase in ABA content in SSc cultures. Altogether, these results suggest that the fibrotic skin lesions in SSc patients could benefit from exposure to high(er) ABA levels.

  11. New insight on the Xq28 association with systemic sclerosis

    Science.gov (United States)

    Carmona, F David; Cénit, M Carmen; Diaz-Gallo, Lina-Marcela; Broen, Jasper C A; Simeón, Carmen P; Carreira, Patricia E; Callejas-Rubio, José-Luis; Fonollosa, Vicente; López-Longo, Francisco J; González-Gay, Miguel A; Hunzelmann, Nicolas; Riemekasten, Gabriela; Witte, Torsten; Kreuter, Alexander; Distler, Jörg H W; Madhok, Rajan; Shiels, Paul; van Laar, Jacob M; Schuerwegh, Annemie J; Vonk, Madelon C; Voskuyl, Alexandre E; Fonseca, Carmen; Denton, Christopher P; Herrick, Ariane; Worthington, Jane; Arnett, Frank C; Tan, Filemon K; Assassi, Shervin; Radstake, Timothy R D J; Mayes, Maureen D; Martín, Javier

    2013-01-01

    Objective To evaluate whether the systemic sclerosis (SSc)-associated IRAK1 non-synonymous single-nucleotide polymorphism rs1059702 is responsible for the Xq28 association with SSc or whether there are other independent signals in the nearby methyl-CpG-binding protein 2 gene (MECP2). Methods We analysed a total of 3065 women with SSc and 2630 unaffected controls from five independent Caucasian cohorts. Four tag single-nucleotide polymorphisms of MECP2 (rs3027935, rs17435, rs5987201 and rs5945175) and the IRAK1 variant rs1059702 were genotyped using TaqMan predesigned assays. A meta-analysis including all cohorts was performed to test the overall effect of these Xq28 polymorphisms on SSc. Results IRAK1 rs1059702 and MECP2 rs17435 were associated specifically with diffuse cutaneous SSc (PFDR=4.12×10−3, OR=1.27, 95% CI 1.09 to 1.47, and PFDR=5.26×10−4, OR=1.30, 95% CI 1.14 to 1.48, respectively), but conditional logistic regression analysis showed that the association of IRAK1 rs1059702 with this subtype was explained by that of MECP2 rs17435. On the other hand, IRAK1 rs1059702 was consistently associated with presence of pulmonary fibrosis (PF), because statistical significance was observed when comparing SSc patients PF+ versus controls (PFDR=0.039, OR=1.30, 95% CI 1.07 to 1.58) and SSc patients PF+ versus SSc patients PF− (p=0.025, OR=1.26, 95% CI 1.03 to 1.55). Conclusions Our data clearly suggest the existence of two independent signals within the Xq28 region, one located in IRAK1 related to PF and another in MECP2 related to diffuse cutaneous SSc, indicating that both genes may have an impact on the clinical outcome of the disease. PMID:23444193

  12. Disease-related nutritional risk and mortality in systemic sclerosis.

    Science.gov (United States)

    Cereda, Emanuele; Codullo, Veronica; Klersy, Catherine; Breda, Silvia; Crippa, Anna; Rava, Maria Luisa; Orlandi, Margherita; Bonardi, Chiara; Fiorentini, Maria Lina; Caporali, Roberto; Caccialanza, Riccardo

    2014-06-01

    To evaluate the relationship between mortality and nutritional risk associated with disease activity in Systemic Sclerosis (SSc). A single-centre prospective cohort study involving 160 SSc outpatients (median age, 62 years [25th-75th, 54-68]). Nutritional risk was assessed by the Malnutrition Universal Screening Tool (MUST), a screening tool that combines anthropometric parameters of nutritional status (body mass index [BMI] and percentage of unintentional weight loss [WL]) with the presence of an "acute disease" (as defined by a disease activity score ≥3 according to Valentini's criteria). Prevalence of high nutritional risk (MUST score ≥2) was 24.4% [95%CI, 17.4-31.3]. A low nutritional risk (MUST = 1) was detected in 30% of our study sample. In hazard analysis (median follow-up duration = 46 months [25th-75th percentile, 31-54]), high nutritional risk was significantly associated with mortality (HR = 8.3 [95%CI, 2.1-32.1]). The performance of the model based on nutritional risk including disease activity (Harrell's c = 0.74 [95%CI, 0.59-0.89]) was superior to that based on active disease alone (HR = 6.3 [95%CI, 1.8-21.7]; Harrell's c = 0.68 [95%CI, 0.53-0.84]). Risk scored only by anthropometric parameters (prevalence, 9.4% [95%CI, 4.6-14.2]) was not associated with mortality: HR = 2.8 [95%CI, 0.6-13.2]. In SSc outpatients MUST significantly predicts mortality. The combined assessment of nutritional parameters and disease activity significantly improves the evaluation of mortality risk. Disease-related nutritional risk screening should be systematically included in the clinical workup of every SSc patient. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  13. RARE CASE OF SYSTEMIC SCLEROSIS IN A CHILD AGED 4 MONTHS

    Directory of Open Access Journals (Sweden)

    S.S. Postnikov

    2007-01-01

    Full Text Available The article provides a clinical and morphologic description of a rare case of systemic sclerosis along with the beginning of the diseases during the infancy. In the clinical picture, the researchers identified occurrences of the systemic vasculitis: abundant cyanotic and red spotty rash with atrophy in the middle, thick edemas of legs and ankles, necrosis of the nail bone of the left little finger, banti's syndrome. In the histological picture, most characteristic peculiarities were: 3 stages of systemic sclerosis process development — inflammation, hardening and atrophy; disorganization of collagenous corium fibers; nidi of calcification along the borderline of corium and hypoderm; multiple ulcers of small and large intestines, perforation of one of which caused peritonitis and fatal outcome of the patient.Key words: infants, vasculitis, systemic sclerosis.

  14. Strongly correlated systems experimental techniques

    CERN Document Server

    Mancini, Ferdinando

    2015-01-01

    The continuous evolution and development of experimental techniques is at the basis of any fundamental achievement in modern physics. Strongly correlated systems (SCS), more than any other, need to be investigated through the greatest variety of experimental techniques in order to unveil and crosscheck the numerous and puzzling anomalous behaviors characterizing them. The study of SCS fostered the improvement of many old experimental techniques, but also the advent of many new ones just invented in order to analyze the complex behaviors of these systems. Many novel materials, with functional properties emerging from macroscopic quantum behaviors at the frontier of modern research in physics, chemistry and materials science, belong to this class of systems. The volume presents a representative collection of the modern experimental techniques specifically tailored for the analysis of strongly correlated systems. Any technique is presented in great detail by its own inventor or by one of the world-wide recognize...

  15. Insulin-like growth factor system in amyotrophic lateral sclerosis

    NARCIS (Netherlands)

    Wilczak, N; de Keyser, J; Cianfarani, S; Clemmons, DR; Savage, MO

    2005-01-01

    Insulin-like growth factor-I (IGF-I) is a neurotrophic factor with insulin-like metabolic activities, and possesses potential clinical applications, particularly in neurodegenerative disorders. Amyotrophic lateral sclerosis (ALS) is a chronic progressive devastating disorder of the central nervous

  16. Amyotrophic lateral sclerosis : moving towards a new classification system

    NARCIS (Netherlands)

    Al-Chalabi, Ammar; Hardiman, Orla; Kiernan, Matthew C; Chiò, Adriano; Rix-Brooks, Benjamin; van den Berg, Leonard H

    2016-01-01

    Amyotrophic lateral sclerosis is a progressive adult-onset neurodegenerative disease that primarily affects upper and lower motor neurons, but also frontotemporal and other regions of the brain. The extent to which each neuronal population is affected varies between individuals. The subsequent

  17. Remyelination of the Corpus Callosum by Olfactory Ensheathing Cell in an Experimental Model of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Mohammad Azimi Alamouti

    2015-10-01

    Full Text Available Multiple Sclerosis (MS causes loss of the myelin sheath, which leads to loss of neurons. Regeneration of myelin sheath stimulates axon regeneration and neurons’ survival. In this study, olfactory ensheathing cell (OEC transplantation is investigated to restore myelin sheath in an experimental model of MS in male mice.OECs were isolated from the olfactory mucosa of seven-day-old infant rats and cultured. Then, cells were evaluated and approved by flow cytometry by p75 and GFAP markers. A total of 32 mice (C57BL /6 were studied in four groups; 1 without any treatment (control, 2 Sham (receiving PBS, 3 MS model and 4 MS and OEC transplantation. MS was induced by adding Cuprizon in the diet of animals for six weeks. After the expiration of 20 days, histologic analysis was performed with approval of the presence of cells in the graft area and the removal of myelin and myelin regeneration with two types of luxal fast blue (LFB staining and immunohistochemistry. The purity of the cells ensheathing the olfactory was 90%.  There was a significant difference in Myelin percentage of PBS and OEC recipient groups (P≤0.05. MBP and PLP of the myelin sheath in the group receiving OECs were more than MS group.According to the findings, in MS model MBP and PLP of the myelin sheath is reduced. In the group receiving OECs, it was returned to a normal level significantly compared to the sham group received only PBS significant differences were observed. The OECs transplantation can improve myelin restoration.

  18. Identification of protein networks involved in the disease course of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Annelies Vanheel

    Full Text Available A more detailed insight into disease mechanisms of multiple sclerosis (MS is crucial for the development of new and more effective therapies. MS is a chronic inflammatory autoimmune disease of the central nervous system. The aim of this study is to identify novel disease associated proteins involved in the development of inflammatory brain lesions, to help unravel underlying disease processes. Brainstem proteins were obtained from rats with MBP induced acute experimental autoimmune encephalomyelitis (EAE, a well characterized disease model of MS. Samples were collected at different time points: just before onset of symptoms, at the top of the disease and following recovery. To analyze changes in the brainstem proteome during the disease course, a quantitative proteomics study was performed using two-dimensional difference in-gel electrophoresis (2D-DIGE followed by mass spectrometry. We identified 75 unique proteins in 92 spots with a significant abundance difference between the experimental groups. To find disease-related networks, these regulated proteins were mapped to existing biological networks by Ingenuity Pathway Analysis (IPA. The analysis revealed that 70% of these proteins have been described to take part in neurological disease. Furthermore, some focus networks were created by IPA. These networks suggest an integrated regulation of the identified proteins with the addition of some putative regulators. Post-synaptic density protein 95 (DLG4, a key player in neuronal signalling and calcium-activated potassium channel alpha 1 (KCNMA1, involved in neurotransmitter release, are 2 putative regulators connecting 64% of the identified proteins. Functional blocking of the KCNMA1 in macrophages was able to alter myelin phagocytosis, a disease mechanism highly involved in EAE and MS pathology. Quantitative analysis of differentially expressed brainstem proteins in an animal model of MS is a first step to identify disease-associated proteins and

  19. Insulin-like growth factor system in serum and cerebrospinal fluid in patients with multiple sclerosis

    NARCIS (Netherlands)

    Wilczak, N; Schaaf, M; Bredewold, R; Streefland, C; Teelken, A; De Keyser, J

    1998-01-01

    The insulin-like growth factor (IGF) system influences oligodendrocyte survival, myelination, and immune functions. We examined whether alterations in the circulating IGF system occur in multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system. We measured

  20. Citrullination of central nervous system proteins during the development of experimental autoimmune encephalomyelitis.

    NARCIS (Netherlands)

    Raijmakers, R.; Vogelzangs, J.H.P.; Croxford, J.L.; Wesseling, P.; Venrooij, W.J.W. van; Pruijn, G.J.M.

    2005-01-01

    Immunization of mammals with central nervous system (CNS)-derived proteins or peptides induces experimental autoimmune encephalomyelitis (EAE), a disease resembling the human autoimmune disease multiple sclerosis (MS). Both diseases are accompanied by destruction of a part of the of the myelin

  1. Safety and efficacy of subcutaneous tocilizumab in adults with systemic sclerosis (faSScinate) : a phase 2, randomised, controlled trial

    NARCIS (Netherlands)

    Khanna, Dinesh; Denton, Christopher P.; Jahreis, Angelika; van Laar, Jacob M.; Frech, Tracy M.; Anderson, Marina E.; Baron, Murray; Chung, Lorinda; Fierlbeck, Gerhard; Lakshminarayanan, Santhanam; Allanore, Yannick; Pope, Janet E.; Riemekasten, Gabriela; Steen, Virginia; Müller-Ladner, Ulf; Lafyatis, Robert; Stifano, Giuseppina; Spotswood, Helen; Chen-Harris, Haiyin; Dziadek, Sebastian; Morimoto, Alyssa; Sornasse, Thierry; Siegel, Jeffrey; Furst, Daniel E.

    2016-01-01

    Background Systemic sclerosis is a rare disabling autoimmune disease with few treatment options. The efficacy and safety of tocilizumab, an interleukin 6 receptor-α inhibitor, was assessed in the faSScinate phase 2 trial in patients with systemic sclerosis. Methods We did this double-blind,

  2. Gene therapy with mesenchymal stem cells expressing IFN-ß ameliorates neuroinflammation in experimental models of multiple sclerosis.

    Science.gov (United States)

    Marin-Bañasco, C; Benabdellah, K; Melero-Jerez, C; Oliver, B; Pinto-Medel, M J; Hurtado-Guerrero, I; de Castro, F; Clemente, D; Fernández, O; Martin, F; Leyva, L; Suardíaz, M

    2017-02-01

    Recombinant IFN-ß is one of the first-line treatments in multiple sclerosis (MS), despite its lack of efficacy in some patients. In this context, mesenchymal stem cells (MSCs) represent a promising therapeutic alternative due to their immunomodulatory properties and multipotency. Moreover, by taking advantage of their pathotropism, these cells can be genetically modified to be used as carriers for delivering or secreting therapeutic drugs into injured tissues. Here, we report the therapeutic effect of systemic delivery of adipose-derived MSCs (AdMSCs), transduced with the IFN-β gene, into mice with experimental autoimmune encephalomyelitis (EAE). Relapsing-remitting and chronic progressive EAE were induced in mice. Cells were injected i.v. Disease severity, inflammation and tissue damage were assessed clinically, by flow cytometry of spleens and histopathological evaluation of the CNS respectively. Genetic engineering did not modify the biological characteristics of these AdMSCs (morphology, growth rate, immunophenotype and multipotency). Furthermore, the transduction of IFN-ß to AdMSCs maintained and, in some cases, enhanced the functional properties of AdMSCs by ameliorating the symptoms of MS in EAE models and by decreasing indications of peripheral and central neuro-inflammation. Gene therapy was found to be more effective than cell therapy in ameliorating several clinical parameters in both EAE models, presumably due to the continuous expression of IFN-β. Furthermore, it has significant advantages over AdMSC therapy, and also over systemic IFN-ß treatment, by providing long-term expression of the cytokine at therapeutic concentrations and reducing the frequency of injections, while minimizing dose-limiting side effects. © 2016 The British Pharmacological Society.

  3. Systemic Sclerosis and Silicone Breast Implant: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Antonios Psarras

    2014-01-01

    Full Text Available Environmentally induced systemic sclerosis is a well-recognized condition, which is correlated with exposure to various chemical compounds or drugs. However, development of scleroderma-like disease after exposure to silicone has always been a controversial issue and, over time, it has triggered spirited debate whether there is a certain association or not. Herein, we report the case of a 35-year-old female who developed Raynaud’s phenomenon and, finally, systemic sclerosis shortly after silicone breast implantation surgery.

  4. A Case with Systemic Sclerosis Following Exposure To Silica and Vibration

    Directory of Open Access Journals (Sweden)

    Aslı Ürkmez

    2012-06-01

    Full Text Available Systemic sclerosis is an autoimmune disease characterized by inflammatory, vascular and sclerotic changes in the internal organs. Although the etiology is not known with certainty; silica dust, which is one of the environmental risk factors, can lead to scleroderma by some immunological changes. In this case, a mine worker, who worked in a mercury mine during a 15-year period, developed systemic sclerosis due to exposure to chronic silica and vibration, is presented. (Turk J Dermatol 2012; 6: 45-7

  5. Experimental Modeling of Dynamic Systems

    DEFF Research Database (Denmark)

    Knudsen, Morten Haack

    2006-01-01

    An engineering course, Simulation and Experimental Modeling, has been developed that is based on a method for direct estimation of physical parameters in dynamic systems. Compared with classical system identification, the method appears to be easier to understand, apply, and combine with physical...

  6. Systemic sclerosis: assessment and treatment : tight control in a tight disease

    NARCIS (Netherlands)

    Vonk, Madelon Clementina

    2008-01-01

    Systemic sclerosis(SSc) is a systemic auto immune disease, resulting in a decreased life expectancy in all, but especially in patients with diffuse cutaneous SSc. The major causes of death are pulmonary fibrosis and pulmonary hypertension. In this thesis the epidemiology of SSc and its pulmonary

  7. Digital ulcers predict a worse disease course in patients with systemic sclerosis

    DEFF Research Database (Denmark)

    Mihai, Carina; Landewé, Robert; van der Heijde, Désirée

    2016-01-01

    OBJECTIVE: Systemic sclerosis (SSc) is a systemic autoimmune disease with high morbidity and significant mortality. There is a great need of predictors that would allow risk stratification of patients with SSc and ultimately initiation of treatment early enough to ensure optimal clinical results....

  8. Aortic pulse wave velocity measurement in systemic sclerosis patients

    Directory of Open Access Journals (Sweden)

    M. Sebastiani

    2012-12-01

    Full Text Available Background. Systemic sclerosis (SSc is characterized by endothelial dysfunction and widespread microangiopathy. However, a macrovascular damage could be also associated. Aortic pulse wave velocity (aPWV is known to be a reliable indicator of arterial stiffness and a useful prognostic predictor of cardiovascular events. Moreover, aPWV may be easily measured by non-invasive, user-friendly tool. Aim of our study was to evaluate aPWV alterations in a series of SSc patients. Methods. The aPWV was evaluated in 35 consecutive female SSc patients and 26 sex- and age-matched healthy controls. aPWV alterations were correlated with cardiopulmonary involvement. Results. A significant increase of aPWV was observed in SSc patients compared to controls (9.4±3.2 m/s vs 7.3±1 m/s; P=0.002. In particular, 14/35 (40% SSc patients and only 1/26 (4% controls (P=0.0009 showed increased aPWV (>9 m/s cut-off value. Moreover, echocardiography evaluation showed an increased prevalence of right atrial and ventricular dilatation (atrial volume: 23.6±6.2 mL vs 20.3±4.3 mL, P=0.026; ventricular diameter 19.5±4.9 mm vs 15.9±1.6 mm; P=0.001 associated to higher values of pulmonary arterial systolic pressure (PAPs in SSc patients (31.5±10.4 mmHg vs 21.6±2.9 mmHg; P50 years old. Furthermore, altered aPWV was more frequently associated with limited cutaneous pattern, longer disease duration (≥5 years, and/or presence of anticentromere antibody (ACA. Conclusions. A significantly higher prevalence of abnormally increased aPWV was evidenced in SSc patients compared to healthy controls. The possibility of more pronounced and diffuse vascular damage in a particular SSc subset (ACA-positive subjects with limited cutaneous scleroderma and longer disease duration might be raised.

  9. Myelin debris regulates inflammatory responses in an experimental demyelination animal model and multiple sclerosis lesions

    NARCIS (Netherlands)

    Clarner, T.; Diederichs, F.; Berger, K.; Denecke, B.; Gan, L.; van der Valk, P.; Beyer, C.; Amor, S.; Kipp, M.

    2012-01-01

    In multiple sclerosis (MS), gray matter pathology is characterized by less pronounced inflammation when compared with white matter lesions. Although regional differences in the cytoarchitecture may account for these differences, the amount of myelin debris in the cortex during a demyelinating event

  10. Role of Anti-Osteopontin Antibodies in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

    Science.gov (United States)

    Clemente, Nausicaa; Comi, Cristoforo; Raineri, Davide; Cappellano, Giuseppe; Vecchio, Domizia; Orilieri, Elisabetta; Gigliotti, Casimiro L.; Boggio, Elena; Dianzani, Chiara; Sorosina, Melissa; Martinelli-Boneschi, Filippo; Caldano, Marzia; Bertolotto, Antonio; Ambrogio, Luca; Sblattero, Daniele; Cena, Tiziana; Leone, Maurizio; Dianzani, Umberto; Chiocchetti, Annalisa

    2017-01-01

    Osteopontin (OPN) is highly expressed in demyelinating lesions in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). OPN is cleaved by thrombin into N- (OPN-N) and C-terminal (OPN-C) fragments with different ligands and functions. In EAE, administering recombinant OPN induces relapses, whereas treatment with anti-OPN antibodies ameliorates the disease. Anti-OPN autoantibodies (autoAbs) are spontaneously produced during EAE but have never been detected in MS. The aim of the study was to evaluate anti-OPN autoAbs in the serum of MS patients, correlate them with disease course, and recapitulate the human findings in EAE. We performed ELISA in the serum of 122 patients collected cross-sectionally, and 50 patients with relapsing–remitting (RR) disease collected at diagnosis and followed longitudinally for 10 years. In the cross-sectional patients, the autoAb levels were higher in the RR patients than in the primary- and secondary-progressive MS and healthy control groups, and they were highest in the initial stages of the disease. In the longitudinal group, the levels at diagnosis directly correlated with the number of relapses during the following 10 years. Moreover, in patients with active disease, who underwent disease-modifying treatments, autoAbs were higher than in untreated patients and were associated with low MS severity score. The autoAb displayed neutralizing activity and mainly recognized OPN-C rather than OPN-N. To confirm the clinical effect of these autoAbs in vivo, EAE was induced using myelin oligodendrocyte glycoprotein MOG35–55 in C57BL/6 mice pre-vaccinated with ovalbumin (OVA)-linked OPN or OVA alone. We then evaluated the titer of antibodies to OPN, the clinical scores and in vitro cytokine secretion by spleen lymphocytes. Vaccination significantly induced antibodies against OPN during EAE, decreased disease severity, and the protective effect was correlated with decreased T cell secretion of interleukin 17 and

  11. Experimental models for the study of neurodegeneration in amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Tapia Ricardo

    2009-07-01

    Full Text Available Abstract Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease of unknown cause, characterized by the selective and progressive death of both upper and lower motoneurons, leading to a progressive paralysis. Experimental animal models of the disease may provide knowledge of the pathophysiological mechanisms and allow the design and testing of therapeutic strategies, provided that they mimic as close as possible the symptoms and temporal progression of the human disease. The principal hypotheses proposed to explain the mechanisms of motoneuron degeneration have been studied mostly in models in vitro, such as primary cultures of fetal motoneurons, organotypic cultures of spinal cord sections from postnatal rodents and the motoneuron-like hybridoma cell line NSC-34. However, these models are flawed in the sense that they do not allow a direct correlation between motoneuron death and its physical consequences like paralysis. In vivo, the most widely used model is the transgenic mouse that bears a human mutant superoxide dismutase 1, the only known cause of ALS. The major disadvantage of this model is that it represents about 2%–3% of human ALS. In addition, there is a growing concern on the accuracy of these transgenic models and the extrapolations of the findings made in these animals to the clinics. Models of spontaneous motoneuron disease, like the wobbler and pmn mice, have been used aiming to understand the basic cellular mechanisms of motoneuron diseases, but these abnormalities are probably different from those occurring in ALS. Therefore, the design and testing of in vivo models of sporadic ALS, which accounts for >90% of the disease, is necessary. The main models of this type are based on the excitotoxic death of spinal motoneurons and might be useful even when there is no definitive demonstration that excitotoxicity is a cause of human ALS. Despite their difficulties, these models offer the best possibility to establish

  12. Acutely damaged axons are remyelinated in multiple sclerosis and experimental models of demyelination.

    Science.gov (United States)

    Schultz, Verena; van der Meer, Franziska; Wrzos, Claudia; Scheidt, Uta; Bahn, Erik; Stadelmann, Christine; Brück, Wolfgang; Junker, Andreas

    2017-08-01

    Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally, the precise timing of acute axonal damage and remyelination has not been assessed so far. To shed light onto the interrelation between axons and the myelin sheath during de- and remyelination, we employed cuprizone- and focal lysolecithin-induced demyelination and performed time course experiments assessing the evolution of early and late stage remyelination and axonal damage. We observed damaged axons with signs of remyelination after cuprizone diet cessation and lysolecithin injection. Similar observations were made in early multiple sclerosis lesions. To assess the correlation of remyelination and axonal damage in multiple sclerosis lesions, we took advantage of a cohort of patients with early and late stage remyelinated lesions and assessed the number of APP- and SMI32- positive damaged axons and the density of SMI31-positive and silver impregnated preserved axons. Early de- and remyelinating lesions did not differ with respect to axonal density and axonal damage, but we observed a lower axonal density in late stage demyelinated multiple sclerosis lesions than in remyelinated multiple sclerosis lesions. Our findings suggest that remyelination may not only be protective over a long period of time, but may play an important role in the immediate axonal recuperation after a demyelinating insult. © 2017 The Authors GLIA Published by Wiley Periodicals, Inc.

  13. In vivo imaging of system xc- as a novel approach to monitor multiple sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Abraham; Szczupak, Boguslaw; Arrieta, Ander [CIC biomaGUNE, Molecular Imaging Unit, San Sebastian (Spain); Vazquez-Villoldo, Nuria; Soria, Federico N.; Domercq, Maria; Matute, Carlos [University of the Basque Country, Department of Neurosciences, Leioa (Spain); UPV/EHU, Achucarro Basque Center for Neuroscience, Zamudio (Spain); Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, Leioa (Spain); Gomez-Vallejo, Vanessa; Llop, Jordi [CIC biomaGUNE, Molecular Imaging Unit, San Sebastian (Spain); CIC biomaGUNE, Radiochemistry and Nuclear Imaging, San Sebastian (Spain); Padro, Daniel; Plaza-Garcia, Sandra; Reese, Torsten [CIC biomaGUNE, Molecular Imaging Unit, San Sebastian (Spain); CIC biomaGUNE, Magnetic Resonance Imaging, San Sebastian (Spain)

    2016-06-15

    Glutamate excitotoxicity contributes to oligodendroglial and axonal damage in multiple sclerosis pathology. Extracellular glutamate concentration in the brain is controlled by cystine/glutamate antiporter (system xc-), a membrane antiporter that imports cystine and releases glutamate. Despite this, the system xc{sup -} activity and its connection to the inflammatory reaction in multiple sclerosis (MS) is largely unknown. Longitudinal in vivo magnetic resonance (MRI) and positron emission tomography (PET) imaging studies with 2-[{sup 18}F]Fluoro-2-deoxy-D-glucose ([{sup 18}F]FDG), [{sup 11}C]-(R)-1-(2-chlorophenyl)-N-methyl-N-1(1-methylpropyl) -3-isoquinolinecarbox amide ([{sup 11}C]PK11195) and (4S)-4-(3-{sup 18}F-fluoropropyl)-L-glutamate ([{sup 18}F]FSPG) were carried out during the course of experimental autoimmune encephalomyelitis (EAE) induction in rats. [{sup 18}F]FSPG showed a significant increase of system xc{sup -} function in the lumbar section of the spinal cord at 14 days post immunization (dpi) that stands in agreement with the neurological symptoms and ventricle edema formation at this time point. Likewise, [{sup 18}F]FDG did not show significant changes in glucose metabolism throughout central nervous system and [{sup 11}C]PK11195 evidenced a significant increase of microglial/macrophage activation in spinal cord and cerebellum 2 weeks after EAE induction. Therefore, [{sup 18}F]FSPG showed a major capacity to discriminate regions of the central nervous system affected by the MS in comparison to [{sup 18}F]FDG and [{sup 11}C]PK11195. Additionally, clodronate-treated rats showed a depletion in microglial population and [{sup 18}F]FSPG PET signal in spinal cord confirming a link between neuroinflammatory reaction and cystine/glutamate antiporter activity in EAE rats. Altogether, these results suggest that in vivo PET imaging of system xc{sup -} could become a valuable tool for the diagnosis and treatment evaluation of MS. (orig.)

  14. Cortical pathology in multiple sclerosis.

    Science.gov (United States)

    Stadelmann, Christine; Albert, Monika; Wegner, Christiane; Brück, Wolfgang

    2008-06-01

    Multiple sclerosis is the most common chronic, disabling central nervous system disease in young adults, characterized by inflammatory demyelinating white matter lesions with glial scar formation and axonal loss. Lately, evidence has accumulated that large areas of grey matter are affected in multiple sclerosis patients. Findings in post-mortem brain tissue support the notion that cortical demyelination is frequent and extensive, especially in patients with chronic multiple sclerosis. Cortical lesions differ from white matter lesions with respect to inflammatory cell infiltration, gliosis, and remyelination. Thus, differences in cortical and white matter lesion pathogenesis have been proposed. Experimental models suggest a decisive role for antimyelin antibodies in cortical demyelination. Topical studies focus on damage to neurons, dendrites, and synapses in cortical multiple sclerosis lesions. Improved imaging techniques for the detection of cortical lesions are currently developed and will provide the basis for future clinicopathological correlative studies. In summary, recent years have opened our eyes to the extensive grey matter involvement in multiple sclerosis. Studies on the pathogenesis of cortical demyelination, cortical damage, and repair will elucidate basic principles of multiple sclerosis lesion formation. However, more sensitive imaging tools are required to study the impact of cortical lesions on clinical symptoms, disability, and disease progression.

  15. Tuberous sclerosis

    Science.gov (United States)

    ... However, tuberous sclerosis often appears as a new DNA mutation. These cases are not preventable. Alternative Names Bourneville disease Images Tuberous sclerosis, angiofibromas - face Tuberous sclerosis, hypopigmented ...

  16. Metallothionein expression in the central nervous system of multiple sclerosis patients

    DEFF Research Database (Denmark)

    Penkowa, M; Espejo, C; Ortega-Aznar, A

    2003-01-01

    Multiple sclerosis (MS) is a major chronic demyelinating and inflammatory disease of the central nervous system (CNS) in which oxidative stress likely plays a pathogenic role in the development of myelin and neuronal damage. Metallothioneins (MTs) are antioxidant proteins induced in the CNS by ti...

  17. Development of a five-year mortality model in systemic sclerosis patients by different analytical approaches.

    NARCIS (Netherlands)

    Beretta, L.; Santaniello, A.; Cappiello, F.; Chawla, N.V.; Vonk, M.C.; Carreira, P.E.; Allanore, Y.; Popa-Diaconu, D.A.; Cossu, M.; Bertolotti, F.; Ferraccioli, G.; Mazzone, A.; Scorza, R.

    2010-01-01

    OBJECTIVES: Systemic sclerosis (SSc) is a multiorgan disease with high mortality rates. Several clinical features have been associated with poor survival in different populations of SSc patients, but no clear and reproducible prognostic model to assess individual survival prediction in scleroderma

  18. Molecular and cellular profiling of systemic sclerosis and its preclinical stages

    NARCIS (Netherlands)

    Cossu, Marta

    2017-01-01

    The development of unrestrained fibrosis in the skin and internal organs is the hallmark of systemic sclerosis (SSc). Nevertheless, it is known that fibrosis is preceded by vascular and immune modifications. On the basis of SSc-specific autoantibodies and nailfold capillary lesions it is possible to

  19. Influence of TYK2 in systemic sclerosis susceptibility : a new locus in the IL-12 pathway

    NARCIS (Netherlands)

    López-Isac, Elena; Campillo-Davo, Diana; Bossini-Castillo, Lara; Guerra, Sandra G; Assassi, Shervin; Simeón, Carmen Pilar; Carreira, Patricia; Ortego-Centeno, Norberto; García de la Peña, Paloma; Beretta, Lorenzo; Santaniello, Alessandro; Bellocchi, Chiara; Lunardi, Claudio; Moroncini, Gianluca; Gabrielli, Armando; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jörg Hw; Voskuyl, Alexandre E; de Vries-Bouwstra, Jeska; Herrick, Ariane; Worthington, Jane; Denton, Christopher P; Fonseca, Carmen; Radstake, Timothy Rdj; Mayes, Maureen D; Martín, Javier

    OBJECTIVES: TYK2 is a common genetic risk factor for several autoimmune diseases. This gene encodes a protein kinase involved in interleukin 12 (IL-12) pathway, which is a well-known player in the pathogenesis of systemic sclerosis (SSc). Therefore, we aimed to assess the possible role of this locus

  20. Expression of specific chemokines and chemokine receptors in the central nervous system of multiple sclerosis patients

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Tani, M; Jensen, J

    1999-01-01

    Chemokines direct tissue invasion by specific leukocyte populations. Thus, chemokines may play a role in multiple sclerosis (MS), an idiopathic disorder in which the central nervous system (CNS) inflammatory reaction is largely restricted to mononuclear phagocytes and T cells. We asked whether...

  1. Analysis of the association between CD40 and CD40 ligand polymorphisms and systemic sclerosis

    NARCIS (Netherlands)

    Teruel, M.; Simeon, C.P.; Broen, J.C.A.; Vonk, M.C.; Carreira, P.; Camps, M.T.; Garcia-Portales, R.; Delgado-Frias, E.; Gallego, M.; Espinosa, G.; Spanish Scleroderma, G.; Beretta, L.; Airo, P.; Lunardi, C.; Riemekasten, G.; Witte, T.; Krieg, T.; Kreuter, A.; Distler, J.H.; Hunzelmann, N.; Koeleman, B.P.; Voskuyl, A.E.; Schuerwegh, A.J.; Gonzalez-Gay, M.A.; Radstake, T.R.D.J.; Martin, J.

    2012-01-01

    INTRODUCTION: The aim of the present study was to investigate the possible role of CD40 and CD40 ligand (CD40LG) genes in the susceptibility and phenotype expression of systemic sclerosis (SSc). METHODS: In total, 2,670 SSc patients and 3,245 healthy individuals from four European populations

  2. Influence of the IL6 Gene in Susceptibility to Systemic Sclerosis

    NARCIS (Netherlands)

    Cenit, M.C.; Simeon, C.P.; Vonk, M.C.; Callejas-Rubio, J.L.; Espinosa, G.; Carreira, P.; Blanco, F.J.; Narvaez, J.; Tolosa, C.; Roman-Ivorra, J.A.; Gomez-Garcia, I.; Garcia-Hernandez, F.J.; Gallego, M.; Garcia-Portales, R.; Egurbide, M.V.; Fonollosa, V.; Garcia de la Pena, P.; Lopez-Longo, F.J.; Gonzalez-Gay, M.A.; The Spanish Scleroderma, G.; Hesselstrand, R.; Riemekasten, G.; Witte, T.; Voskuyl, A.E.; Schuerwegh, A.J.; Madhok, R.; Fonseca, C.; Denton, C.; Nordin, A.; Palm, O.; Laar, J.M. van; Hunzelmann, N.; Distler, J.H.; Kreuter, A.; Herrick, A.; Worthington, J.; Koeleman, B.P.; Radstake, T.R.D.J.; Martin, J.

    2012-01-01

    OBJECTIVE: Systemic sclerosis (SSc) is a genetically complex autoimmune disease; the genetic component has not been fully defined. Interleukin 6 (IL-6) plays a crucial role in immunity and fibrosis, both key aspects of SSc. We investigated the influence of IL6 gene in the susceptibility and

  3. The STAT4 gene influences the genetic predisposition to systemic sclerosis phenotype.

    NARCIS (Netherlands)

    Rueda, B.; Broen, J.; Simeon, C.; Hesselstrand, R.; Diaz, B.; Suarez, H.; Ortego-Centeno, N.; Riemekasten, G.; Fonollosa, V.; Vonk, M.C.; Hoogen, F.H.J. van den; Sanchez-Roman, J.; Aguirre-Zamorano, M.A.; Garcia-Portales, R.; Pros, A.; Camps, M.T.; Gonzalez-Gay, M.A.; Coenen, M.J.H.; Airo, P.; Beretta, L.; Scorza, R.; Laar, J. van; Gonzalez-Escribano, M.F.; Nelson, J.L.; Radstake, T.R.D.J.; Martin, J.

    2009-01-01

    The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. A total of 1317 SSc patients [896 with limited cutaneous SSc (lcSSc) and 421 with diffuse cutaneous SSc (dcSSc)] and 3113 healthy

  4. Incidences and Risk Factors of Organ Manifestations in the Early Course of Systemic Sclerosis

    DEFF Research Database (Denmark)

    Jaeger, Veronika K; Wirz, Elina G; Allanore, Yannick

    2016-01-01

    OBJECTIVE: Systemic sclerosis (SSc) is a rare and clinically heterogeneous autoimmune disorder characterised by fibrosis and microvascular obliteration of the skin and internal organs. Organ involvement mostly manifests after a variable period of the onset of Raynaud's phenomenon (RP). We aimed t...

  5. Spontaneous pneumothorax from cryptococcal pneumonia in systemic sclerosis: a case report

    Directory of Open Access Journals (Sweden)

    Foocharoen Chingching

    2011-07-01

    Full Text Available Abstract Introduction Spontaneous pneumothorax is usually found in people with systemic sclerosis who have extensive pulmonary fibrosis with enlarged sub-pleural blebs. We report a case of spontaneous pneumothorax caused by cryptococcal pneumonia in a patient with systemic sclerosis with minimal sub-pleural emphysema. Case presentation A 49-year-old Thai man with underlying limited cutaneous systemic sclerosis presented with acute low-grade fever, progressive dyspnea and right pleuritic chest pain for five days. Our patient had pulmonary fibrosis with bronchiectasis of both lower lungs related to this underlying disease. He received only low-dose steroid therapy, without any immunosuppressant. A chest radiograph revealed right lung pneumothorax with cloudy yellow color pleural fluid. Cryptococcal pneumonia was diagnosed by positive identification of the cryptococcal antigen in the serum and pleural fluid. His symptoms improved after intercostal drainage and fluconazole therapy. Conclusion Infection can exacerbate symptoms in patients with systemic sclerosis with sub-pleural emphysema, thereby triggering a spontaneous pneumothorax. Pleural fluid--present but not initially seen because of the pneumothorax--could be a clue to a pre-existing pulmonary infection.

  6. A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis

    NARCIS (Netherlands)

    Bossini-Castillo, L.; Simeon, C.P.; Beretta, L.; Broen, J.C.A.; Vonk, M.C.; Rios-Fernandez, R.; Espinosa, G.; Carreira, P.; Camps, M.T.; Castillo, M.J.; Gonzalez-Gay, M.A.; Beltran, E.; Carmen Freire, M.; Narvaez, J.; Tolosa, C.; Witte, T.; Kreuter, A.; Schuerwegh, A.J.; Hoffmann-Vold, A.M.; Hesselstrand, R.; Lunardi, C.; Laar, J.M. van; Chee, M.M.; Herrick, A.; Koeleman, B.P.; Denton, C.P.; Fonseca, C.; Radstake, T.R.D.J.; Martin, J.; Spanish Scleroderma, G.

    2012-01-01

    INTRODUCTION: CD226 genetic variants have been associated with a number of autoimmune diseases and recently with systemic sclerosis (SSc). The aim of this study was to test the influence of CD226 loci in SSc susceptibility, clinical phenotypes and autoantibody status in a large multicenter European

  7. Systemic sclerosis and its pulmonary complications in The Netherlands: an epidemiological study.

    NARCIS (Netherlands)

    Vonk, M.C.; Broers, B.; Heijdra, Y.F.; Ton, E.; Snijder, R.; Dijk, A.P.J. van; Laar, J.M. van; Bootsma, H.J.; Hal, P.T. van; Hoogen, F.H.J. van den; Daele, P.L. van

    2009-01-01

    The prevalence and incidence of systemic sclerosis (SSc) in The Netherlands is unknown. The same holds true for its leading causes of death: pulmonary fibrosis and pulmonary arterial hypertension (PAH), for which effective treatment options have recently become available. OBJECTIVE: To establish the

  8. Systemic sclerosis and its pulmonary complications in The Netherlands : an epidemiological study

    NARCIS (Netherlands)

    Vonk, M. C.; Broers, B.; Heijdra, Y. F.; Ton, E.; Snijder, R.; van Dijk, A. P. J.; Bootsma, H.; van Hal, P. Th W.; van den Hoogen, F. H. J.; van Daele, P. L. A.; van Laar, J.M.

    The prevalence and incidence of systemic sclerosis (SSc) in The Netherlands is unknown. The same holds true for its leading causes of death: pulmonary fibrosis and pulmonary arterial hypertension (PAH), for which effective treatment options have recently become available. Objective: To establish the

  9. Long-term outcome of patients with systemic sclerosis requiring home parenteral nutrition.

    Science.gov (United States)

    Harrison, Elizabeth; Herrick, Ariane L; Dibb, Martyn; McLaughlin, John T; Lal, Simon

    2015-10-01

    Patients with systemic sclerosis may develop intestinal failure requiring home parenteral nutrition. However, few outcome data have been reported. This study aimed to review the outcome of patients with systemic sclerosis receiving home parenteral nutrition. Records of all patients with systemic sclerosis who commenced home parenteral nutrition, at a national intestinal failure unit were retrospectively reviewed. Disease characteristics, survival and outcome data were evaluated. Twenty five patients (20% male; median age: 55 years) were included over a 22-year period (37,200 central venous catheter days). All patients had small intestinal involvement. Prior to home parenteral nutrition, 16 failed enteral feeding. Nine patients were trained to self-administer their home parenteral nutrition; carers/relatives were trained for the remainder. Cumulative survivals on home parenteral nutrition at 2, 5 and 10 years were 75%, 37%, and 23%. Sixteen patients died from causes unrelated to home parenteral nutrition. Two patients were weaned off home parenteral nutrition. Seven patients survive on home parenteral nutrition (median: 41 months; range 9-178). Central venous catheter-related complications were low; these included occlusion (0.70 episodes per 1000 central venous catheter days), sepsis (0.19 episodes per 1000 central venous catheter days) and central venous thrombosis (0.11 episodes per 1000 central venous catheter days). This is the longest, largest reported series of patients with systemic sclerosis receiving home parenteral nutrition. It shows that home parenteral nutrition can be used safely and effectively in patients with very severe systemic sclerosis-related gastrointestinal involvement. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  10. Coping strategies for activities of daily living in women whose hands affected by systemic sclerosis.

    Science.gov (United States)

    Cinar, Fatma I; Unver, Vesile; Cinar, Muhammet; Yilmaz, Sedat; Simsek, Ismail; Tosun, Nuran; Erdem, Hakan; Yilmaz, Fatma; Pay, Salih; Dinc, Ayhan

    2014-06-01

    To determine the challenges experienced by women with systemic sclerosis, whose hands affected, while performing activities of daily living and their coping strategies. Many of the patients with systemic sclerosis experience difficulties in performing daily activities. One of the most important reasons for that is the impaired hand function due to their diseases. A descriptive cross-sectional design was conducted and questionnaire was used in this study. The study was performed in a Rheumatology Department at a tertiary-care hospital in Turkey between April 2010-December 2011. Nineteen patients with systemic sclerosis with hand involvement were enrolled in this study. The data were collected by using both a demographic data form and an Evaluation of Daily Activity Questionnaire. According to Evaluation of Daily Activity Questionnaire, the most scored dimension that patients can do with much difficulty was 'eating' and the dimension that patients unable to do was 'washing/clothes care'. In 'eating' dimension, the most difficult activities were 'opening glass jar', 'opening juice bottle' and 'opening bottle' that requiring the movement of rotation. Their coping strategies for these activities were as follows: try to open with a towel, try to remove the edge of the palm with a knife, use the hand palm and help from someone else (spouse, neighbour, etc.). In 'washing/clothes care' dimension, the most difficult activities were 'turning up hem of a skirt', 'washing up in bowl' and 'cutting out material'. For these activities, they use some coping strategies such as getting help from tailor, washing in the machine instead of hand washing. This study demonstrates that impaired hand function affects the daily life activities of patients with systemic sclerosis, and patients have developed some coping strategies to overcome these difficulties. The coping strategies used by patients can be helpful for the other patients with systemic sclerosis. © 2013 John Wiley & Sons Ltd.

  11. An Update on the Treatment of the Cutaneous Manifestations of Systemic Sclerosis: The Dermatologist's Point of View.

    Science.gov (United States)

    Vitiello, Magalys; Abuchar, Adriana; Santana, Néstor; Dehesa, Luis; Kerdel, Francisco A

    2012-07-01

    Systemic sclerosis is a connective tissue disorder that affects multiple organs. Although the initial symptoms of the disease are vascular, skin involvement is almost universally present in patients with systemic sclerosis. The presence of Raynaud's phenomenon, progressive thickening of the skin, digital ulcers, and calcinosis all correlate proportionally with disease severity. Since no treatment is available to completely prevent the natural course of the disease, emphasis is often placed on managing symptoms and complications. In this review, the authors focus on the management of each one of the skin manifestations seen in systemic sclerosis, as the dermatologist may facilitate the early recognition and treatment of these complications.

  12. Virtual rehabilitation for multiple sclerosis using a kinect-based system: randomized controlled trial.

    Science.gov (United States)

    Lozano-Quilis, Jose-Antonio; Gil-Gómez, Hermenegildo; Gil-Gómez, Jose-Antonio; Albiol-Pérez, Sergio; Palacios-Navarro, Guillermo; Fardoun, Habib M; Mashat, Abdulfattah S

    2014-11-12

    The methods used for the motor rehabilitation of patients with neurological disorders include a number of different rehabilitation exercises. For patients who have been diagnosed with multiple sclerosis (MS), the performance of motor rehabilitation exercises is essential. Nevertheless, this rehabilitation may be tedious, negatively influencing patients' motivation and adherence to treatment. We present RemoviEM, a system based on Kinect that uses virtual reality (VR) and natural user interfaces (NUI) to offer patients with MS an intuitive and motivating way to perform several motor rehabilitation exercises. It offers therapists a new motor rehabilitation tool for the rehabilitation process, providing feedback on the patient's progress. Moreover, it is a low-cost system, a feature that can facilitate its integration in clinical rehabilitation centers. A randomized and controlled single blinded study was carried out to assess the influence of a Kinect-based virtual rehabilitation system on the balance rehabilitation of patients with MS. This study describes RemoviEM and evaluates its effectiveness compared to standard rehabilitation. To achieve this objective, a clinical trial was carried out. Eleven patients from a MS association participated in the clinical trial. The mean age was 44.82 (SD 10.44) and the mean time from diagnosis (years) was 9.77 (SD 10.40). Clinical effectiveness was evaluated using clinical balance scales. Significant group-by-time interaction was detected in the scores of the Berg Balance Scale (P=.011) and the Anterior Reach Test in standing position (P=.011). Post-hoc analysis showed greater improvement in the experimental group for these variables than in the control group for these variables. The Suitability Evaluation Questionnaire (SEQ) showed good results in usability, acceptance, security, and safety for the evaluated system. The results obtained suggest that RemoviEM represents a motivational and effective alternative to traditional

  13. A CAD system for assessment of MRI findings to track the progression of multiple sclerosis

    Science.gov (United States)

    Wong, Alexis; Gertych, Arkadiusz; Zee, Chi-Shing; Guo, Bing; Liu, Brent J.

    2007-03-01

    Multiple sclerosis (MS) is a progressive neurological disease affecting myelin pathways. MRI has become the medical imaging study of choice both for the diagnosis and for the follow-up and monitoring of multiple sclerosis. The progression of the disease is variable, and requires routine follow-up to document disease exacerbation, improvement, or stability of the characteristic MS lesions or plaques. The difficulties with using MRI as a monitoring tool are the significant quantities of time needed by the radiologist to actually measure the size of the lesions, and the poor reproducibility of these manual measurements. A CAD system for automatic image analysis improves clinical efficiency and standardizes the lesion measurements. Multiple sclerosis is a disease well suited for automated analysis. The segmentation algorithm devised classifies normal and abnormal brain structures and measures the volume of multiple sclerosis lesions using fuzzy c-means clustering with incorporated spatial (sFCM) information. First, an intracranial structures mask in T1 image data is localized and then superimposed in FLAIR image data. Next, MS lesions are identified by sFCM and quantified within a predefined volume. The initial validation process confirms a satisfactory comparison of automatic segmentation to manual outline by a neuroradiologist and the results will be presented.

  14. RGMA and IL21R show association with experimental inflammation and multiple sclerosis

    DEFF Research Database (Denmark)

    Nohra, R; Beyeen, A D; Guo, J P

    2010-01-01

    31 showed linkage to EAE, PIA, anti-MOG antibodies and levels of tumor necrosis factor (TNF) and IL-6. Confidence intervals defined a limited set of potential candidate genes, with the most interesting being RGMA, IL21R and IL4R. We tested the association with multiple sclerosis (MS) in a Nordic case...... (EAE), anti-MOG antibodies and pristane-induced arthritis (PIA) in advanced intercross lines (AILs). Analysis in the tenth and twelfth generation of AILs resolved the region in two narrow QTL, Eae30 and Eae31. Eae30 showed linkage to MOG-EAE, anti-MOG antibodies and levels of interleukin-6 (IL-6). Eae...

  15. Cardiac transplant in young female patient diagnosed with diffuse systemic sclerosis.

    Science.gov (United States)

    Bennasar, Guillermo; Carlevaris, Leandro; Secco, Anastasia; Romanini, Felix; Mamani, Marta

    2016-01-01

    Systemic sclerosis (SS) in a multifactorial and systemic, chronic, autoimmune disease that affects the connective tissue. We present this clinical case given the low prevalence of diffuse SS with early and progressive cardiac compromise in a young patient, and treatment with cardiac transplantation. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  16. PK11195 binding to the peripheral benzodiazepine receptor as a marker of microglia activation in multiple sclerosis and experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Vowinckel, E; Reutens, D; Becher, B

    1997-01-01

    Activated glial cells are implicated in regulating and effecting the immune response that occurs within the CNS as part of multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). The peripheral benzodiazepine receptor (PBR) is expressed in glial cells. We...

  17. Circulating microparticles and plasma levels of soluble E- and P-selectins in patients with systemic sclerosis

    DEFF Research Database (Denmark)

    Iversen, Lars; Østergaard, O; Ullman, S

    2013-01-01

    Microparticles (MPs) may be involved in the pathogenesis of systemic sclerosis (SSc), which includes vasculopathy, endothelial cell activation, and coagulation activation. Circulating MPs from SSc patients were characterized and their relationship with soluble markers of vascular activation...

  18. A comparison of performance on the Keitel Functional Test by persons with systemic sclerosis and rheumatoid arthritis.

    Science.gov (United States)

    Poole, Janet L; New, Amy; Garcia, Christina

    2017-06-11

    The purpose of this study is to compare lower extremity impairments in persons with systemic sclerosis, rheumatoid arthritis, and healthy controls. The participants were a convenience sample of 64 persons with systemic sclerosis, 58 persons with rheumatoid arthritis, and 30 healthy controls. The Keitel Functional Test was used to assess lower extremity joint motion and strength. Demographic information on age, disease duration, employment, and perceived overall health was also collected. Significant differences were found between the healthy control group and both the systemic sclerosis and rheumatoid arthritis groups in rising from a chair, squatting, walking 30 m, walking up and downstairs, and the total score. For hip external rotation, there were significant differences between all three groups for the right hip; for the left hip, the systemic sclerosis group had significantly less motion than the other two groups. For standing on toes, there was only a significant difference between the systemic sclerosis and the healthy control groups. Persons with systemic sclerosis and rheumatoid arthritis have similar levels of lower extremity impairments but greater impairments compared to the healthy controls. These impairments may lead to decreased mobility paired with difficulties with activities of daily living such as lower extremity dressing, bathing, and feet care. Implications for Rehabilitation Persons with systemic sclerosis and rheumatoid arthritis have similar levels of lower extremity impairments but greater impairments compared to the healthy controls. Findings from this study indicate a need for rehabilitation for persons with systemic sclerosis and rheumatoid arthritis as the lower extremity impairments may lead to decreased mobility paired with difficulties with daily living activities such as lower extremity dressing, bathing, and feet care. The Keitel Functional Test could be used as a quick screening test for lower extremity impairments.

  19. Impaired quality of life in patients with systemic sclerosis compared to the general population and chronic dermatoses

    OpenAIRE

    Bretterklieber, Agnes; Painsi, Clemens; Avian, Alexander; Wutte, Nora; Aberer, Elisabeth

    2014-01-01

    Background Systemic sclerosis (SSc) is a rare and potentially life threatening autoimmune disorder. The burden of disease compared to other dermatoses is unknown. The purpose of this study was to assess both the quality of life in patients with SSc and the variables that are associated with poor quality of life. Forty-one patients with systemic sclerosis (29 limited, 2 diffuse, 10 undifferentiated forms) were assessed with respect to their health status and compared to published data for the ...

  20. A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis

    DEFF Research Database (Denmark)

    Ingegnoli, Francesca; Boracchi, Patrizia; Gualtierotti, Roberta

    2015-01-01

    OBJECTIVE: Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. METHODS: Data collected between June 2004 and April 2013 were examined with focus on capillar......OBJECTIVE: Qualitative capillaroscopy patterns in juvenile- and adult-onset systemic sclerosis (SSc) were studied in adulthood using data from the EULAR Scleroderma Trials and Research (EUSTAR) database. METHODS: Data collected between June 2004 and April 2013 were examined with focus...... in 61% of juvenile- and 55.5% of adult-onset SSc. The OR was 1.06 and 95% CI 0.34-3.56. CONCLUSION: This is the first exploratory study on the comparison of capillaroscopy between juvenile- and adult-onset SSc in adulthood. Juvenile-onset SSc had an increase prevalence of scleroderma pattern...

  1. Multiple sclerosis

    OpenAIRE

    Nicholas, Richard; Rashid, Waqar

    2012-01-01

    Multiple sclerosis is characterised by central nervous system lesions causing neurological dysfunction and other problems, such as fatigue, pain, depression, and anxiety. Early disease is usually relapsing and remitting, but most people develop secondary-progressive disease over time. No treatment has been shown to affect long-term outcome.Irreversible disability can occur, but life expectancy is generally not affected.

  2. Towards systemic sclerosis and away from primary biliary cirrhosis: the case of PTPN22

    OpenAIRE

    Daniel S. Smyk; Mytilinaiou, Maria G.; Milkiewicz, Piotr; Rigopoulou, Eirini I.; Invernizzi, Pietro; Bogdanos, Dimitrios P.

    2011-01-01

    Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by immune-mediated destruction of the small and medium size intrahepatic bile ducts. PBC patients often have concomitant autoimmune diseases, which are most often autoimmune thyroid disease, as well as Sicca syndrome. Occasionally, some PBC patients will also have systemic sclerosis of the limited cutaneous type (lcSSc). Conversely, up to one-fourth of SSc patients are positive for antimitochondrial antibody,...

  3. [Does garlic influence rheologic properties and blood flow in progressive systemic sclerosis?].

    Science.gov (United States)

    Rapp, Alexander; Grohmann, Gerald; Oelzner, Peter; Uehleke, Bernhard; Uhlemann, Christine

    2006-06-01

    According to traditional European naturopathy garlic is an agent that increases perfusion. In studies with healthy subjects and in-vitro research garlic has shown influences on erythrocyte and thrombocyte aggregation as well as on vasoregulation. However, data on its effects in clinical populations are still lacking. Garlic may be useful for systemic sclerosis which is characterised by impaired perfusion that often cannot sufficiently be influenced by standard treatment. We investigated if dried garlic powder can influence rheologic properties and vasomotor function in systemic sclerosis. During a randomised, double blind pilot study, 20 female inpatients with systemic sclerosis received a 7 day add-on therapy with either 900 mg dried garlic powder or placebo. Rheologic properties (erythrocyte aggregation, ADP-induced thromboycyte aggregation, plasma viscosity, fibrinogenous plasma level, blood sedimentation rate) were assessed initially as well as after 1 and 7 days of treatment. Vasomotor function was evaluated using near-infrared red photoplethysmography, a new diagnostic tool to assess microcirculation. Furthermore, acral skin temperature was measured. After 7 days, only the verum treatment had induced a significant reduction of ADP-induced thrombocyte aggregation and a decrease in erythrocyte aggregation. Results showed no significant effects on vasomotor function, but an immediate effect of garlic on acral skin temperature. According to the 'Qualitatenlehre' of traditional European naturopathy, garlic is classified as a 'heating agent'. Our results suggest that the improvement of rheologic properties could be a possible biological correlate for this. Although further research is required, we conclude garlic could be a rational add-on therapy in the 'Kaltekrankheit' ('cold disease') of systemic sclerosis.

  4. Cytokine concentrations in serum and bronchoalveolar lavage as marker for pathogenesis and prognosis in systemic sclerosis

    OpenAIRE

    Schmidt, Katrin

    2010-01-01

    Systemic sclerosis (SSc) is a rare connective tissue disease characterized by increased production of extracellular matrix, endothelial dysfunction and immunity abnormalities. SSc is considered as a devastating multiorgan disease of unknown etiology with an autoimmunological background. In the present work we have measured levels of cytokines and chemokines in bronchoalveolar lavage fluid (BALF) and serum in cohorts of Ssc-patients, patients with other lung diseases and healthy donors. We...

  5. Review of orofacial considerations of systemic sclerosis or scleroderma with report of analysis of 3 cases

    OpenAIRE

    Panchbhai, Arati; Pawar, Sangita; Barad, Anuradha; Kazi, Zamzam

    2016-01-01

    Scleroderma (skleros; hard, and derma; skin), is currently known as systemic sclerosis due to its progressive nature and widespread tissue involvement. It is a rare connective tissue disorder with a wide range of oral manifestations. Thickening of the skin is the hallmark of the disease. The patient education for self-care and multidisciplinary approach would be needed to manage the condition. The article presents the review of orofacial considerations in scleroderma with a report of analysis...

  6. Efficacy of Autologous Microfat Graft on Facial Handicap in Systemic Sclerosis Patients.

    Science.gov (United States)

    Sautereau, Nolwenn; Daumas, Aurélie; Truillet, Romain; Jouve, Elisabeth; Magalon, Jéremy; Veran, Julie; Casanova, Dominique; Frances, Yves; Magalon, Guy; Granel, Brigitte

    2016-03-01

    Autologous adipose tissue injection is used in plastic surgery for correction of localized tissue atrophy and has also been successfully offered for treatment of localized scleroderma. We aimed to evaluate whether patients with systemic sclerosis (SSc) and facial handicap could also benefit from this therapy. We included 14 patients (mean age of 53.8 ± 9.6 years) suffering from SSc with facial handicap defined by Mouth Handicap in Systemic Sclerosis Scale (MHISS) score more than or equal to 20, a Rodnan skin score on the face more than or equal to 1, and maximal mouth opening of less than 55 mm. Autologous adipose tissue injection was performed under local anesthesia using the technique of subcutaneous microinjection. The main objective of this study was an improvement of the MHISS score 6 months after the surgical treatment. The procedure was well tolerated. We observed a mean decrease in the MHISS score of 10.7 points (±5.1; P handicap, skin sclerosis, mouth opening limitation, sicca syndrome, and facial pain. Thus, this minimally invasive approach offers a new hope for face therapy for patients with SSc.

  7. Feasibility, acceptability and construct validity of EQ-5D in systemic sclerosis.

    Science.gov (United States)

    Gualtierotti, Roberta; Ingegnoli, Francesca; Scalone, Luciana; Cortesi, Paolo; Bruschi, Eleonora; Gerosa, Maria; Meroni, Pier Luigi

    2017-01-19

    Systemic sclerosis is a chronic disabling disease that is often associated with severe physical and psychological impairment. Nonetheless, health-related quality of life (HRQoL) in patients with systemic sclerosis is often left behind in clinical practice and research. One of the reasons for this lack of evaluation is the current use of tools, such as the short form-36 (SF-36) questionnaire, that are complete but complicated to use in everyday routine. Other self-reported outcome measures such as the health assessment questionnaire (HAQ) are simple, but specifically designed for physical disability. Our aim was to evaluate the feasibility, acceptability and construct validity of EQ-5D, a simple and quick self-assessment tool, and to compare its performance with SF-36 and HAQ. We investigated 119 consecutive patients with systemic sclerosis (94% female; age: median 63 years, interquartile range 53-70 years) at three different rheumatology centres. Acceptability was evaluated from comments made by the patients and feasibility on the basis of the number of patients needing assistance or not answering questions (missing data). Construct validity was based on both convergent and divergent validity between conceptually similar and dissimilar domains, respectively, of the compared instruments. EQ-5D was well accepted by patients. The percentage of patients missing data in at least one EQ-5D domain was 2.5%. Spearman's correlation coefficients between similar dimensions of EQ-5D vs SF-36 and vs HAQ were moderate (≥0.30) to strong (≥0.50); in contrast, correlation coefficients between less comparable dimensions were weak. As expected, the EQ-5D anxiety/depression domain did not correlate with any of the HAQ domains. The EQ-5D visual analogue scale (VAS) concordance with SF-36 general health domain and HAQ total score was strong (≥0.50 for both). Median value for the EQ-5D index (interquartile range) was 0.81 (0.75-0.86). The EQ-5D index had correlation coefficients >0

  8. A wireless body measurement system to study fatigue in multiple sclerosis

    DEFF Research Database (Denmark)

    Yu, Fei; Rabotti, Chiara; Bilberg, Arne

    2012-01-01

    Fatigue is reported as the most common symptom by patients with multiple sclerosis (MS). The physiological and functional parameters related to fatigue in MS patients are currently not well established. A new wearable wireless body measurement system, named Fatigue Monitoring System (FAMOS...... of the measurement system including the design of both hardware and dedicated signal processing algorithms. Twenty-six participants including 17 MS patients with fatigue and 9 sex- and age-matched healthy controls were included in the study for continuous 24 h monitoring. The preliminary results show significant...

  9. Relapsing and Progressive Tumefactive Demyelinating Form of Central Nervous System Involvement in a Patient with Progressive Systemic Sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ho Kyun [Dept. of Radiology, Catholic University of Daegu School of Medicine, Daegu (Korea, Republic of); Lee, Hui Joong [Dept. of Kyungpook National University Hospital, Daegu (Korea, Republic of)

    2013-03-15

    White matter hyper intensities (WMHI) on MRI are not rare in patients with progressive systemic sclerosis (PSS). In this presentation, WMHI were developed in both middle cerebellar peduncles and temporal white matter in a patient with PSS, and regressed after medication of high dose steroid. However, new lesions were developed in the subcortices of both precentral gyri, and progressed rapidly to tumefactive hyperintensity on MRI. We report an unusual relapsing and progressive tumefactive demyelinating form of central nervous system involvement in PSS.

  10. Metabolomics of cerebrospinal fluid reveals changes in the central nervous system metabolism in a rat model of multiple sclerosis

    NARCIS (Netherlands)

    Noga, M.J.; Dane, A.; Shi, S.; Attali, A.; Aken, H. van; Suidgeest, E.; Tuinstra, T.; Muilwijk, B.; Coulier, L.; Luider, T.; Reijmers, T.H.; Vreeken, R.J.; Hankemeier, T.

    2012-01-01

    Experimental Autoimmune Encephalomyelitis (EAE) is the most commonly used animal model for Multiple Sclerosis (MScl). CSF metabolomics in an acute EAE rat model was investigated using targetted LC-MS and GC-MS. Acute EAE in Lewis rats was induced by co-injection of Myelin Basic Protein with Complete

  11. Metabolomics of cerebrospinal fluid reveals changes in the central nervous system metabolism in a rat model of multiple sclerosis

    NARCIS (Netherlands)

    M. Noga (Marek); A. Dane (Adrie); S. Shi (Shanna); A. Attali (Amos); H. van Aken (Hans); E. Suidgeest (Ernst); T. Tuinstra (Tinka); B. Muilwijk (Bas); L. Coulier (Leon); T.M. Luider (Theo); R.M. Reijmers (Rogier); R. Vreeken (Rob); T. Hankemeier (Thomas)

    2012-01-01

    textabstractExperimental Autoimmune Encephalomyelitis (EAE) is the most commonly used animal model for Multiple Sclerosis (MScl). CSF metabolomics in an acute EAE rat model was investigated using targetted LC-MS and GC-MS. Acute EAE in Lewis rats was induced by co-injection of Myelin Basic Protein

  12. RGMA and IL21R show association with experimental inflammation and multiple sclerosis

    DEFF Research Database (Denmark)

    Nohra, R; Beyeen, A D; Guo, J P

    2010-01-01

    Rat chromosome 1 harbors overlapping quantitative trait loci (QTL) for cytokine production and experimental models of inflammatory diseases. We fine-dissected this region that regulated cytokine production, myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyeliti...... biomarkers and therapeutic targets....

  13. Cinnamon ameliorates experimental allergic encephalomyelitis in mice via regulatory T cells: implications for multiple sclerosis therapy.

    Science.gov (United States)

    Mondal, Susanta; Pahan, Kalipada

    2015-01-01

    Upregulation and/or maintenance of regulatory T cells (Tregs) during an autoimmune insult may have therapeutic efficacy in autoimmune diseases. Although several immunomodulatory drugs and molecules are available, most present significant side effects over long-term use. Cinnamon is a commonly used natural spice and flavoring material used for centuries throughout the world. Here, we have explored a novel use of cinnamon powder in protecting Tregs and treating the disease process of experimental allergic encephalomyelitis (EAE), an animal model of MS. Oral feeding of cinnamon (Cinnamonum verum) powder suppresses clinical symptoms of relapsing-remitting EAE in female PLP-TCR transgenic mice and adoptive transfer mouse model. Cinnamon also inhibited clinical symptoms of chronic EAE in male C57/BL6 mice. Dose-dependent study shows that cinnamon powder at a dose of 50 mg/kg body wt/d or higher significantly suppresses clinical symptoms of EAE in mice. Accordingly, oral administration of cinnamon also inhibited perivascular cuffing, maintained the integrity of blood-brain barrier and blood-spinal cord barrier, suppressed inflammation, normalized the expression of myelin genes, and blocked demyelination in the central nervous system of EAE mice. Interestingly, cinnamon treatment upregulated Tregs via reduction of nitric oxide production. Furthermore, we demonstrate that blocking of Tregs by neutralizing antibodies against CD25 abrogates cinnamon-mediated protection of EAE. Taken together, our results suggest that oral administration of cinnamon powder may be beneficial in MS patients and that no other existing anti-MS therapies could be so economical and trouble-free as this approach.

  14. Cinnamon ameliorates experimental allergic encephalomyelitis in mice via regulatory T cells: implications for multiple sclerosis therapy.

    Directory of Open Access Journals (Sweden)

    Susanta Mondal

    Full Text Available Upregulation and/or maintenance of regulatory T cells (Tregs during an autoimmune insult may have therapeutic efficacy in autoimmune diseases. Although several immunomodulatory drugs and molecules are available, most present significant side effects over long-term use. Cinnamon is a commonly used natural spice and flavoring material used for centuries throughout the world. Here, we have explored a novel use of cinnamon powder in protecting Tregs and treating the disease process of experimental allergic encephalomyelitis (EAE, an animal model of MS. Oral feeding of cinnamon (Cinnamonum verum powder suppresses clinical symptoms of relapsing-remitting EAE in female PLP-TCR transgenic mice and adoptive transfer mouse model. Cinnamon also inhibited clinical symptoms of chronic EAE in male C57/BL6 mice. Dose-dependent study shows that cinnamon powder at a dose of 50 mg/kg body wt/d or higher significantly suppresses clinical symptoms of EAE in mice. Accordingly, oral administration of cinnamon also inhibited perivascular cuffing, maintained the integrity of blood-brain barrier and blood-spinal cord barrier, suppressed inflammation, normalized the expression of myelin genes, and blocked demyelination in the central nervous system of EAE mice. Interestingly, cinnamon treatment upregulated Tregs via reduction of nitric oxide production. Furthermore, we demonstrate that blocking of Tregs by neutralizing antibodies against CD25 abrogates cinnamon-mediated protection of EAE. Taken together, our results suggest that oral administration of cinnamon powder may be beneficial in MS patients and that no other existing anti-MS therapies could be so economical and trouble-free as this approach.

  15. Genotype and haplotype analysis of ABCB1 at 1236, 2677 and 3435 among systemic sclerosis patients.

    Science.gov (United States)

    Barańska, Małgorzata; Rychlik-Sych, Mariola; Skrętkowicz, Jadwiga; Dudarewicz, Michał; Dziankowska-Bartkowiak, Bożena; Owczarek, Jacek; Waszczykowska, Elżbieta

    2017-08-01

    Systemic sclerosis (SSc) belongs to the group of systemic diseases of the connective tissue, which are characterized by a chronic autoimmune inflammatory process. P-glycoprotein, initially associated with the drug resistance in patients with cancer, becomes more and more often a subject of considerations in terms of its significance in the development of illnesses, including autoimmune diseases. The aim of the study was an attempt to answer the question whether there was a relationship between ABCB1 polymorphisms and morbidity of systemic sclerosis in a Polish population. The study was carried out in 61 patients with SSc and 100 healthy volunteers. Determination of polymorphisms C1236T and C3435T in ABCB1 was carried out with the PCR-RFLP (polymerase chain reaction - restriction fragment length polymorphism) method. The G2677T/A ABCB1 polymorphism was analysed with the allele-specific PCR method. No statistically significant differences were observed in the frequencies of ABCB1 genotypes and alleles between SSc patients and the control group. It was observed that haplotype 1236 C-2677 G-3435 T occurred in the group of patients with SSc statistically more frequently than in the group of healthy volunteers (25% vs. 15%; p = .032). Carriers of the haplotype demonstrated almost a twofold greater risk of SSc (OR = 1.85; p = .032). No statistically significant correlations for the other nine haplotypes were found. Presented results concerning the relationship of ABCB1 polymorphisms with susceptibility to systemic sclerosis are the first ones that were obtained in a Polish population. They imply that single nucleotide polymorphisms do not affect the risk for SSc, but the 1236 C-2677 G-3435 T haplotype might increase this risk.

  16. Mouse Models of Multiple Sclerosis: Experimental Autoimmune Encephalomyelitis and Theiler’s Virus-Induced Demyelinating Disease

    Science.gov (United States)

    McCarthy, Derrick P.; Richards, Maureen H.; Miller, Stephen D.

    2013-01-01

    Experimental autoimmune encephalomyelitis (EAE) and Theiler’s Murine Encephalitis Virus-Induced Demyelinating Disease (TMEV-IDD) are two clinically relevant murine models of multiple sclerosis (MS). Like MS, both are characterized by mononuclear cell infiltration into the CNS and demyelination. EAE is induced by either the administration of myelin protein or peptide in adjuvant or by the adoptive transfer of encephalitogenic T cell blasts into naïve recipients. The relative merits of each of these protocols are compared. Depending on the type of question being asked, different mouse strains and peptides are used. Different disease courses are observed with different strains and different peptides in active EAE. These variations are also addressed. Additionally, issues relevant to clinical grading of EAE in mice are discussed. In addition to EAE induction, useful references for other disease indicators such as DTH, in vitro proliferation, and immunohistochemistry are provided. TMEV-IDD is a useful model for understanding the possible viral etiology of MS. This section provides detailed information on the preparation of viral stocks and subsequent intracerebral infection of mice. Additionally, virus plaque assay and clinical disease assessment are discussed. Recently, recombinant TMEV strains have been created for the study of molecular mimicry which incorporate various 30 amino acid myelin epitopes within the leader region of TMEV. PMID:22933080

  17. Multiple Sclerosis

    OpenAIRE

    Gaby, Alan

    2013-01-01

    Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system. Common manifestations include paresthesias, diplopia, loss of vision, numbness or weakness of the limbs, bowel or bladder dysfunction, spasticity, ataxia, fatigue, and mental changes. Four main patterns of MS are recognized: relapsing remitting, primary progressive, secondary progressive, and progressive relapsing. The cause of MS is unknown, although it appears to be an autoimmune disease. M...

  18. Comparison of the expression levels of Fas and Apaf-1 genes in systemic sclerosis dermal fibroblasts

    Directory of Open Access Journals (Sweden)

    Majid Abed Khojasteh

    2016-07-01

    Full Text Available Background: Systemic sclerosis (SSc is an autoimmune rheumatic connective tissue disease. In normal wound healing process, fibroblasts are activated, proliferated and involved in tissue repair, and then removed by apoptosis. In systemic sclerosis, patient’s fibrosis occurs when fibroblasts become resistant to apoptosis and secrete a large amount of collagen and other extracellular matrixes. As the primary causes the disease are very complex and often unknown, it is necessary to consider or target the secondary causes of disease, such as the unresponsiveness of activated fibroblasts to apoptosis as the major factor in the creation and deployment of illness. In this study, we examined the expression levels of two key pro-apoptotic genes, Fas and Apaf-1, which are respectively involved in external and internal pathway of apoptosis. Methods: In a case-control study skin biopsy samples were obtained from 19 patients with diffuse SSc, and 16 healthy controls. Dermal fibroblasts were cultured and total RNA was isolated from cell populations using High Pure RNA Isolation Kit (Roche Applied Science, Mannheim, Germany, followed by cDNA synthesis using RevertAid First Strand cDNA Synthesis Kit (Thermo Fisher Scientific Inc., Massachusetts, USA. Real-time PCR was performed using SYBRGreen gene expression master mix (Takara Shuzo, Co., Ltd, Shiga, Japan and specific primers for Fas and Apaf-1. Real-time data were analyzed using the (2-ΔCT×1000 method. Statistical analysis was accomplished by using the SPSS software, v22 (IBM, Armonk, NY, USA. The P value less than 0.05 were recognized as a significant threshold. All data are represented as the mean ± SEM. Results: Our results showed no significant difference in Fas (P=0.8 and Apaf-1 (P=0.17 mRNA expression levels between skin fibroblasts of systemic sclerosis patients and healthy controls. Conclusion: In this study we observed no significant change in Apaf-1 and Fas mRNA levels in systemic sclerosis

  19. Systemic sclerosis presenting with severe digital ischemia: A rare case report

    Directory of Open Access Journals (Sweden)

    Sourya Acharya

    2015-01-01

    Full Text Available Digital ischemic loss is a cause of significant morbidity in patients with systemic sclerosis (SSc. Both small and large digital arteries are involved causing perfusion defects leading to ischemia. Microvascular disease causes intimal proliferation and luminal narrowing of small digital arteries, macrovascular disease causes narrowing or occlusion of larger digital arteries. Immediate clinical evaluation and treatment are mandatory at the onset of critical digital ischemia to prevent digital loss. We present a case of 38-year-old female suffering from SSc who presented with acute onset severe digital ischemia of all four limbs.

  20. Radiographic changes of the distal phalanx tuft of the hands in subjects with systemic sclerosis. Systematic review.

    Science.gov (United States)

    Izquierdo, Yojhan Edilberto; Calvo Páramo, Enrique; Castañeda, Luisa María; Gómez, Sandra Viviana; Zambrano, Fernán Santiago

    2016-10-13

    To determine abnormal plain radiograph findings of the distal phalanx tuft of the hand (DPTH) associated with systemic sclerosis in adults. A systematic review was developed following the parameters of the PRISMA guidelines in databases: MEDLINE, EMBASE, BIREME, Scielo, Google Scholar and others including as primary outcomes alterations of DPTH (erosions, resorption, sclerosis and proliferation) detected by simple radiography in subjects with systemic sclerosis. The prevalence of radiographic findings was synthesized using the fixed effects model. The statistical associations were expressed in terms of relative risk or odds ratio with their respective confidence intervals and p values. Twenty-two observational studies were included; the prevalence of DPTH resorption was 28.3% (95% CI: 0.256-0.312; p < .001); I(2)=80.4%, the prevalence of calcinosis was 15.6% (95% CI: 0.113-0.210; p < .001); I(2)=0%. No study reported proliferation or erosions and only one study described sclerosis of DPTH in 5 individuals. Resorption and calcinosis of DPTH are the characteristic radiographic findings in patients with systemic sclerosis. However, new studies with greater methodological strength are needed to establish associations between these phenomena and their presence in other connective tissue diseases. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  1. Effect of Macitentan on the Development of New Ischemic Digital Ulcers in Patients With Systemic Sclerosis: DUAL-1 and DUAL-2 Randomized Clinical Trials

    NARCIS (Netherlands)

    Khanna, D.; Denton, C.P.; Merkel, P.A.; Krieg, T.; Brun, F.O. Le; Marr, A.; Papadakis, K.; Pope, J.; Matucci-Cerinic, M.; Furst, D.E.; Vonk, M.C.

    2016-01-01

    IMPORTANCE: Digital ulcers in patients with systemic sclerosis are associated with pain and poor quality of life. Endothelin-1 promotes vasculopathy in systemic sclerosis after macitentan, an endothelin-1 blocker. OBJECTIVE: To evaluate the efficacy of macitentan in reducing the number of new

  2. System xC- is a mediator of microglial function and its deletion slows symptoms in amyotrophic lateral sclerosis mice.

    Science.gov (United States)

    Mesci, Pinar; Zaïdi, Sakina; Lobsiger, Christian S; Millecamps, Stéphanie; Escartin, Carole; Seilhean, Danielle; Sato, Hideyo; Mallat, Michel; Boillée, Séverine

    2015-01-01

    Amyotrophic lateral sclerosis is the most common adult-onset motor neuron disease and evidence from mice expressing amyotrophic lateral sclerosis-causing SOD1 mutations suggest that neurodegeneration is a non-cell autonomous process where microglial cells influence disease progression. However, microglial-derived neurotoxic factors still remain largely unidentified in amyotrophic lateral sclerosis. With excitotoxicity being a major mechanism proposed to cause motor neuron death in amyotrophic lateral sclerosis, our hypothesis was that excessive glutamate release by activated microglia through their system [Formula: see text] (a cystine/glutamate antiporter with the specific subunit xCT/Slc7a11) could contribute to neurodegeneration. Here we show that xCT expression is enriched in microglia compared to total mouse spinal cord and absent from motor neurons. Activated microglia induced xCT expression and during disease, xCT levels were increased in both spinal cord and isolated microglia from mutant SOD1 amyotrophic lateral sclerosis mice. Expression of xCT was also detectable in spinal cord post-mortem tissues of patients with amyotrophic lateral sclerosis and correlated with increased inflammation. Genetic deletion of xCT in mice demonstrated that activated microglia released glutamate mainly through system [Formula: see text]. Interestingly, xCT deletion also led to decreased production of specific microglial pro-inflammatory/neurotoxic factors including nitric oxide, TNFa and IL6, whereas expression of anti-inflammatory/neuroprotective markers such as Ym1/Chil3 were increased, indicating that xCT regulates microglial functions. In amyotrophic lateral sclerosis mice, xCT deletion surprisingly led to earlier symptom onset but, importantly, this was followed by a significantly slowed progressive disease phase, which resulted in more surviving motor neurons. These results are consistent with a deleterious contribution of microglial-derived glutamate during symptomatic

  3. Experimental coronary sclerosis induced by immobilization of rabbits: A new model of arteriosclerosis

    Science.gov (United States)

    Tyavokin, V. V.; Tjawokin, W. W.

    1980-01-01

    A new method for producing arteriosclerosis with coronary insufficiency in rabbits by means of immobilization is described and discussed. The experimentally induced atherosclerosis develops due to hypodynamics imposed by the reduced muscular activity without overloading with exogenous cholesterol. The atherosclerosis and coronary insufficiency are associated. With variations in the duration and extent of immobilization, coronary insufficiency alone or with atherosclerosis can be produced.

  4. Target regulation of PI3K/Akt/mTOR pathway by cannabidiol in treatment of experimental multiple sclerosis.

    Science.gov (United States)

    Giacoppo, Sabrina; Pollastro, Federica; Grassi, Gianpaolo; Bramanti, Placido; Mazzon, Emanuela

    2017-01-01

    This study was aimed to investigate whether treatment with purified cannabidiol (CBD) may counteract the development of experimental multiple sclerosis (MS), by targeting the PI3K/Akt/mTOR pathway. Although the PI3K/Akt/mTOR pathway was found to be activated by cannabinoids in several immune and non-immune cells, currently, there is no data about the effects of CBD in the PI3K/Akt/mTOR activity in MS. Experimental Autoimmune Encephalomyelitis (EAE), the most common model of MS, was induced in C57BL/6 mice by immunization with myelin oligodendroglial glycoprotein peptide (MOG) 35-55 . After EAE onset, which occurs approximately 14days after disease induction, mice were daily intraperitoneally treated with CBD (10mg/kg mouse) and observed for clinical signs of EAE. At 28days from EAE-induction, mice were euthanized and spinal cord tissues were sampled to perform immunohistochemical evaluations and western blot analysis. Our results showed a clear downregulation of the PI3K/Akt/mTOR pathway following EAE induction. CBD treatment was able to restore it, increasing significantly the phosphorylation of PI3K, Akt and mTOR. Also, an increased level of BNDF in CBD-treated mice seems to be involved in the activation of PI3K/Akt/mTOR pathway. In addition, our data demonstrated that therapeutic efficacy of CBD treatment is due to reduction of pro-inflammatory cytokines, like IFN-γ and IL-17 together with an up-regulation of PPARγ. Finally, CBD was found to promote neuronal survival by inhibiting JNK and p38 MAP kinases. These results provide an interesting discovery about the regulation of the PI3K/Akt/mTOR pathway by cannabidiol administration, that could be a new potential therapeutic target for MS management. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Intersticial pulmonary disease in patients with systemic sclerosis. Narrative review of the literature

    Directory of Open Access Journals (Sweden)

    Álvarez-Barreneche, María Fernanda

    2017-07-01

    Full Text Available Introduction: Systemic sclerosis is a chronic autoimmune disease, characterized by the triad of small vessel vasculopathy, immune system activation and increased deposits of extracellular matrix in the skin and internal organs. In the last few years, pulmonary involvement has gained relevance since the introduction of angiotensin enzyme converter inhibitors with the subsequent decline in scleroderma renal crisis mortality, transforming scleroderma lung disease in the leading cause of mortality. Pulmonary involvement can manifest as hypertension or interstitial lung disease, which usually occurs in patients with generalized scleroderma in the first three years of the disease. Its prognosis is poor without treatment which is aimed at stopping pulmonary function deterioration. Among treatment options, cyclophosphamide has the best evidence, and mycophenolate mofetil, rituximab, and stem cell and lung transplantation are currently under investigation with positive preliminary results. Objective: To describe, according to reports in the literature, epidemiology, pathophysiology, diagnostic methods, and treatment of interstitial lung disease in systemic sclerosis. Methods: Structured, non-systematic literature review, focused on the aforementioned aspects of interest. It included 52 articles.

  6. Arterial vasculopathy in systemic sclerosis: Computerized tomography (CT) angiographic features of macrovascular and microvascular upper limbs arteries

    NARCIS (Netherlands)

    Emad, Y.; Al-Sherbeni, H.; Ragab, Y.; Abo-El-Youn, I.; El-Shaarawy, N.; Nassar, D.Y.; Fathy, A.; Al-Hanafi, H.; Rasker, Johannes J.

    2014-01-01

    Objective To describe the CT angiographic findings of arterial vasculopathy in the major vessels as well as medium and micro vascular affection of the whole upper limbs arterial tree in patients with systemic sclerosis (SSc) with and without digital ulceration. Methods Twenty-two cases with systemic

  7. Systemic sclerosis: Current concepts in pathogenesis and therapeutic aspects of dermatological manifestations

    Directory of Open Access Journals (Sweden)

    Vishalakshi Viswanath

    2013-01-01

    Full Text Available Systemic sclerosis (SSc is a chronic, multisystem connective tissue disease with protean clinical manifestations. Recent advances in understanding the pathogenic mechanisms have led to development of target-oriented and vasomodulatory drugs which play a pivotal role in treating various dermatological manifestations. An exhaustive literature search was done using Medline, Embase, and Cochrane library to review the recent concepts regarding pathogenesis and evidence-based treatment of salient dermatological manifestations. The concept of shared genetic risk factors for the development of autoimmune diseases is seen in SSc. It is divided into fibroproliferative and inflammatory groups based on genome-wide molecular profiling. Genetic, infectious, and environmental factors play a key role; vascular injury, fibrosis, and immune activation are the chief pathogenic factors. Vitamin D deficiency has been documented in SSc and correlates with the severity of skin involvement. Skin sclerosis, Raynaud′s phenomenon (RP with digital vasculopathies, pigmentation, calcinosis, and leg ulcers affect the patient′s quality of life. Immunosuppressives, biologicals, and hematopoietic stem cell transplantation are efficacious in skin sclerosis. Endothelin A receptor antagonists, calcium-channel blockers, angiotensin receptor inhibitors, prostacyclin analogs, and phosphodiesterase type 5 (PDE-5 inhibitors are the mainstay in RP and digital vasculopathies. Pigmentation in SSc has been attributed to melanogenic potential of endothelin-1 (ET-1; the role of ET 1 antagonists and vitamin D analogs needs to be investigated. Sexual dysfunction in both male and female patients has been attributed to vasculopathy and fibrosis, wherein PDE-5 inhibitors are found to be useful. The future concepts of treating SSc may be based on the gene expression signature.

  8. Electrical storm in systemic sclerosis: Inside the electroanatomic substrate.

    Science.gov (United States)

    Casella, Michela; Carbucicchio, Corrado; Russo, Eleonora; Pizzamiglio, Francesca; Golia, Paolo; Conti, Sergio; Costa, Fabrizio; Dello Russo, Antonio; Tondo, Claudio

    2014-10-26

    We report the case of a 63-year-old woman affected by a severe form of systemic scleroderma with pulmonary involvement (interstitial fibrosis diagnosed by biopsy and moderate pulmonary hypertension) and cardiac involvement (paroxysmal atrial fibrillation, right atrial flutter treated by catheter ablation, ventricular tachyarrhythmias, previous dual chamber implantable cardioverter defibrillator implant). Because of recurrent electrical storms refractory to iv antiarrhythmic drugs the patient was referred to our institution to undergo catheter ablation. During electrophysiological procedure a 3D shell of cardiac anatomy was created with intracardiac echocardiography pointing out a significant right ventricular dilatation with a complex aneurysmal lesion characterized by thin walls and irregular multiple trabeculae. A substrate-guided strategy of catheter ablation was accomplished leading to a complete electrical isolation of the aneurism and to the abolishment of all abnormal electrical activities. The use of advanced strategies of imaging together with electroanatomical mapping added important information to the complex arrhythmogenic substrate and improved efficacy and safety.

  9. Thermography Improves Clinical Assessment in Patients with Systemic Sclerosis Treated with Ozone Therapy

    Directory of Open Access Journals (Sweden)

    Danuta Nowicka

    2017-01-01

    Full Text Available Objective. Treatment of scleroderma is challenging and limited. The aim of our study was to evaluate the usefulness of thermography in assessment of the clinical condition (joints movability and skin thickness in clinically advanced patients with systemic sclerosis before and after ozone therapy. Method. The study included 42 patients aged 32 to 73 years with advanced systemic sclerosis hospitalized in the university clinic between 2003 and 2006. Thermography and clinical examinations were conducted at baseline and after two series of bath in water with ozone. Results. The comparison of results showed significant increase in skin temperature by 2.5°C, significant increase in interphalangeal joints movability by 18 degrees, and significant decrease in skin score by 14.7 points. The skin temperature was correlated with skin score (r=-0.59 and joints movability (r=+0.8. Conclusions. Ozone therapy shows positive effect on clinical parameters and skin temperature as measured with thermography. The study indicated possibility of introducing ozonotherapy as an independent therapy in cases with low level of progression or during remission periods and as additional treatment in patients with advanced disease requiring immunosuppressive treatment. Thermography is useful in assessment of skin condition showing strong correlation between skin temperature and clinical parameters.

  10. A systematic review of overlapping microRNA patterns in systemic sclerosis and idiopathic pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Gianluca Bagnato

    2017-05-01

    Full Text Available Lung fibrosis can be observed in systemic sclerosis and in idiopathic pulmonary fibrosis, two disorders where lung involvement carries a poor prognosis. Although much has been learned about the pathogenesis of these conditions, interventions capable of reversing or, at the very least, halting disease progression are not available. Recent studies point to the potential role of micro messenger RNAs (microRNAs in cancer and tissue fibrogenesis. MicroRNAs are short non-coding RNA sequences (20–23 nucleotides that are endogenous, evolutionarily conserved and encoded in the genome. By acting on several genes, microRNAs control protein expression. Considering the above, we engaged in a systematic review of the literature in search of overlapping observations implicating microRNAs in the pathogenesis of both idiopathic pulmonary fibrosis (IPF and systemic sclerosis (SSc. Our objective was to uncover top microRNA candidates for further investigation based on their mechanisms of action and their potential for serving as targets for intervention against lung fibrosis. Our review points to microRNAs of the -29 family, -21-5p and -92a-3p, -26a-5p and let-7d-5p as having distinct and counter-balancing actions related to lung fibrosis. Based on this, we speculate that readjusting the disrupted balance between these microRNAs in lung fibrosis related to SSc and IPF may have therapeutic potential.

  11. Acro-osteolysis as an indicator of severity in systemic sclerosis.

    Science.gov (United States)

    Arana-Ruiz, Juan Carlos; Amezcua-Guerra, Luis Manuel

    2016-01-01

    Systemic sclerosis is a rare disease that predominantly affects women. The Medsger severity scale has been used to assess the severity, but it requires expensive and poorly accessible studies and it does not include complications such acrosteolysis, calcinosis, pericardial disease or hypothyroidism that occur on a relatively frequent basis in this disease. There is no study that considers if comorbidities, such as primary biliary cirrhosis, are related to gravity. To determine the correlation between severity and the presence of such complications. 40 patients with systemic sclerosis, dividing them into tertiles according to severity were studied. Dichotomous variables were described using percentages, while dimensional by averages+SD. Statistical inference was performed using chi square test or Kruskal-Wallis test with Dunn post-test, as appropriate. A significance at P<.05 was set. Of all the complications studied there were only differences in severity with acrosteolysis. Within comorbidities, primary biliary cirrhosis is not associated with gravity. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  12. Thermography Improves Clinical Assessment in Patients with Systemic Sclerosis Treated with Ozone Therapy.

    Science.gov (United States)

    Nowicka, Danuta

    2017-01-01

    Objective. Treatment of scleroderma is challenging and limited. The aim of our study was to evaluate the usefulness of thermography in assessment of the clinical condition (joints movability and skin thickness) in clinically advanced patients with systemic sclerosis before and after ozone therapy. Method. The study included 42 patients aged 32 to 73 years with advanced systemic sclerosis hospitalized in the university clinic between 2003 and 2006. Thermography and clinical examinations were conducted at baseline and after two series of bath in water with ozone. Results. The comparison of results showed significant increase in skin temperature by 2.5°C, significant increase in interphalangeal joints movability by 18 degrees, and significant decrease in skin score by 14.7 points. The skin temperature was correlated with skin score (r = -0.59) and joints movability (r = +0.8). Conclusions. Ozone therapy shows positive effect on clinical parameters and skin temperature as measured with thermography. The study indicated possibility of introducing ozonotherapy as an independent therapy in cases with low level of progression or during remission periods and as additional treatment in patients with advanced disease requiring immunosuppressive treatment. Thermography is useful in assessment of skin condition showing strong correlation between skin temperature and clinical parameters.

  13. Melatonin exacerbates acute experimental autoimmune encephalomyelitis by enhancing the serum levels of lactate: A potential biomarker of multiple sclerosis progression.

    Science.gov (United States)

    Ghareghani, Majid; Dokoohaki, Shima; Ghanbari, Amir; Farhadi, Naser; Zibara, Kazem; Khodadoust, Saeid; Parishani, Mohammad; Ghavamizadeh, Mehdi; Sadeghi, Heibatollah

    2017-01-01

    Melatonin has a beneficial role in adult rat models of multiple sclerosis (MS). In this study, melatonin treatment (10 mg/kg/d) was investigated in young age (5-6 weeks old) Lewis rat model of acute experimental autoimmune encephalomyelitis (EAE) followed by assessing serum levels of lactate and melatonin. Results showed that clinical outcomes were exacerbated in melatonin- (neurological score = 6) vs PBS-treated EAE rats (score = 5). Melatonin caused a significant increase in serum IFN-γ, in comparison to PBS-treated EAE rats whereas no considerable change in IL-4 levels were found, although they were significantly lower than those of controls. The ratio of IFN-γ/IL-4, an indicator of Th-1/Th-2, was significantly higher in PBS- and melatonin- treated EAE rats, in comparison to controls. Moreover, results showed increased lymphocyte infiltration, activated astrocytes (GFAP+ cells) but also higher demyelinated plaques (MBP-deficient areas) in the lumbar spinal cord of melatonin-treated EAE rats. Finally, serum levels of lactate, but not melatonin, significantly increased in the melatonin group, compared to untreated EAE and normal rats. In conclusion, our results indicated a relationship between age and the development of EAE since a negative impact was found for melatonin on EAE recovery of young rats by enhancing IFN-γ, the ratio of Th1/Th2 cells, and astrocyte activation, which seems to delay the remyelination process. While melatonin levels decline in MS patients, lactate might be a potential diagnostic biomarker for prediction of disease progression. Early administration of melatonin in the acute phase of MS might be harmful and needs further investigations. © 2016 John Wiley & Sons Australia, Ltd.

  14. Effectiveness of non-pharmacological interventions for fatigue in adults with multiple sclerosis, rheumatoid arthritis, or systemic lupus erythematosus: a systematic review.

    Science.gov (United States)

    Neill, Jane; Belan, Ingrid; Ried, Karin

    2006-12-01

    This paper reports a systematic review of non-pharmacological interventions for fatigue in adults with three common autoimmune conditions. A considerable proportion of people with multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus experience compromised quality of life due to fatigue. Recent reviews of pharmacotherapies for fatigue in these conditions remain inconclusive, and systematic evidence for effectiveness of non-pharmacological interventions was unavailable. Our paper addresses this gap. The literature search used the key words fatigue, energy, multiple sclerosis, rheumatoid arthritis and systemic lupus. It included 19 electronic databases and libraries, three evidence-based journals, two internet search engines, was dated 1987-2006, and limited to English. Non-pharmacological experimental studies about fatigue comprising more than five adults were included. Meta-analysis was not possible due to diverse interventions and outcome measures, therefore studies were analysed by types of interventions used to reduce fatigue. Of 653 hits, 162 papers were reviewed, and 36 met the inclusion criteria. Thirty-three primary studies reported 14 randomized controlled trials and 19 quasi-experimental designs. Most interventions were tested with people with multiple sclerosis. Exercise, behavioural, nutritional and physiological interventions were associated with statistically significant reductions in fatigue. Aerobic exercise was effective, appropriate and feasible for reducing fatigue among adults with chronic autoimmune conditions. Electromagnetic field devices showed promise. The diversity of interventions, designs, and using 24 different instruments to measure fatigue, limited comparisons. Low impact aerobic exercise gradually increasing in intensity, duration and frequency may be an effective strategy in reducing fatigue in some adults with chronic auto-immune conditions. However, fatigue is a variable and personal experience and a range of

  15. Systems-based medicine approaches to understand and treat complex diseases. The example of multiple sclerosis.

    Science.gov (United States)

    Baranzini, Sergio E

    2006-12-01

    Systems medicine is an emerging concept that acknowledges the complexity of a multitude of non-linear interactions among molecular and physiological variables. Under this new paradigm, rather than a collection of symptoms, diseases are seen as the product of deviations from a robust steady state compatible with life. This concept requires the incorporation of mathematics and physics to the more classical arsenal of physiology and molecular biology with which physicians are trained today. This review explores the diverse types of information that can be accumulated towards the understanding of multiple sclerosis (MS), a complex autoimmune disease that targets the central nervous system (CNS). The challenge of data integration and modeling of dynamical systems is discussed in the context of disease susceptibility and response to treatment. A theoretical framework that supports the use of combination therapy is also presented.

  16. Progressive systemic sclerosis with intraoral manifestations: A case report and review.

    Science.gov (United States)

    Srivastava, Rahul; Jyoti, Bhuvan; Bihari, Manorama; Pradhan, Shobhit

    2016-01-01

    The word scleroderma comes from two Greek words, "sclero" meaning hard and "derma" meaning skin. Scleroderma or progressive systemic sclerosis (PSS), a rare condition, was first characterized as a single condition in 1752 by Curzio of Naples. It generally affects woman between 30 and 50 years of age and has a low prevalence. Scleroderma is a disease of the immune system, blood vessels, and connective tissue. Dermal manifestations include stiff, tight, and shiny skin usually of the hands and feet due to swelling and thickening of the connective tissue as they become fibrotic or scarred. Other symptoms include difficulty in swallowing, bloating, abdominal pain, tiredness, lack of energy, weight loss, aching muscles, joints, and bones. The vital organs that may get involved are lungs, heart, and kidneys. We present a case report of PSS in a 45-year-old female patient with characteristic systemic and oral manifestations.

  17. Capparis spinosa protects against oxidative stress in systemic sclerosis dermal fibroblasts.

    Science.gov (United States)

    Cao, Yue-Lan; Li, Xin; Zheng, Min

    2010-07-01

    High reactive oxygen species (ROS), Ha-Ras, and active ERK1/2 in fibroblasts play an essential role in the pathogenesis of systemic sclerosis (SSc). The present study was carried out to evaluate the effects of the ethanol extract from fruits of Capparis Spinosa L. (ECS) on oxidative stress and ROS-ERK1/2-Ha-Ras signal loop in SSc dermal fibroblasts in vitro. Cultured dermal fibroblasts from three SSc patients and three normal controls were treated with ECS by different concentration (10, 50, 100 microg/ml). ECS significantly reduced the production of O2(-), H2O2, and ROS in SSc fibroblasts in a dose-dependent manner. ECS effectively minimized the loss of cell viability and apoptosis induced by H2O2 in normal and SSc fibroblasts. Furthermore, the protective effect of ECS on SSc fibroblasts was more significant than on normal ones. ECS decreased the expression of P-ERK1/2 and Ha-Ras in a dose-dependent manner. In conclusion, ECS exhibits a notable activity in protecting against oxidative stress and interrupting of ROS-ERK1/2-Ha-Ras signal loop in SSc, suggesting its potential protective effects against skin sclerosis.

  18. Coincidence of tuberous sclerosis and systemic lupus erythematosus-a case report.

    Science.gov (United States)

    Carrasco Cubero, Carmen; Bejarano Moguel, Verónica; Fernández Gil, M Ángeles; Álvarez Vega, Jose Luis

    2016-01-01

    Tuberous sclerosis, also called Bourneville Pringle disease, is a phakomatosis with potential dermal, nerve, kidney and lung damage. It is characterized by the development of benign proliferations in many organs, which result in different clinical manifestations. It is associated with the mutation of two genes: TSC1 (hamartin) and TSC2 (tuberin), with the change in the functionality of the complex target of rapamycin (mTOR). MTOR activation signal has been recently described in systemic lupus erythematosus (SLE) and its inhibition could be beneficial in patients with lupus nephritis. We report the case of a patient who began with clinical manifestations of tuberous sclerosis complex (TSC) 30 years after the onset of SLE with severe renal disease (tipe IV nephritis) who improved after treatment with iv pulses of cyclophosphamide. We found only two similar cases in the literature, and hence considered the coexistence of these two entities of great interest. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  19. Multiparametric MR investigation of the motor pyramidal system in patients with 'truly benign' multiple sclerosis.

    Science.gov (United States)

    Spanò, Barbara; Cercignani, Mara; Basile, Barbara; Romano, Silvia; Mannu, Rosalba; Centonze, Diego; Caltagirone, Carlo; Bramanti, Placido; Nocentini, Ugo; Bozzali, Marco

    2010-02-01

    One possible explanation for the mismatch between tissue damage and preservation of neurological functions in patients with benign multiple sclerosis (BMS) is that the pathophysiology differs from that occurring in other multiple sclerosis (MS) phenotypes. The objective of this study was to identify pathologically specific patterns of tissue integrity/damage characteristics of patients with BMS, and markers of potential prognostic value. The pyramidal system was investigated in 10 BMS patients and 20 controls using voxel-based morphometry to assess grey matter (GM) atrophy, and diffusion tractography and quantitative magnetization transfer to quantify the microstructural damage in the corticospinal tracts (CSTs). Widespread reductions in GM volume were found in patients compared with controls, including the primary motor cortex. A significant decrease was observed in the mean macromolecular pool ratio (F) of both CSTs, with no fractional anisotropy (FA) change. GM volume of the primary motor areas was associated with clinical scores but not with the CST parameters. The mismatch between F and FA suggests the presence of extensive demyelination in the CSTs of patients with BMS, in the absence of axonal damage. The lack of correlation with GM volume indicates a complex interaction between disruptive and reparative mechanisms in BMS.

  20. Improvement of Mouth Functional Disability in Systemic Sclerosis Patients over One Year in a Trial of Fat Transplantation versus Adipose-Derived Stromal Cells

    Directory of Open Access Journals (Sweden)

    Maria Giuseppina Onesti

    2016-01-01

    Full Text Available Background. Systemic sclerosis (SSc is a multisystem disease characterized by cutaneous and visceral fibrosis. Face and mouth changes include telangiectasia, sicca syndrome, and thinning and reduction of mouth width (microcheilia and opening (microstomia. We applied autologous fat transplantation compared with autologous adipose-derived stromal cells (ADSCs injection to evaluate the clinical improvement of mouth opening. Methods. From February to May 2013 ten consecutive SSc patients were enrolled from the outpatient clinic of Plastic Surgery Department of Sapienza University of Rome. Patients were divided into two groups as follows: 5 patients were treated with fat transplantation and 5 patients received infiltration of ADSCs produced by cell factory of our institution. To value mouth opening, we use the Italian version of Mouth Handicap in Systemic Sclerosis Scale (IvMHISS. Mouth opening was assessed in centimetres (Maximal Mouth Opening, MMO. In order to evaluate compliance and physician and patient satisfaction, we employed a Questionnaire of Satisfaction and the Visual Analogic Scale (VAS performed before starting study and 1 year after the last treatment. Results and Conclusion. We noticed that both procedures obtained significant results but neither one emerged as a first-choice technique. The present clinical experimentation should be regarded as a starting point for further experimental research and clinical trials.

  1. New model systems for experimental evolution.

    Science.gov (United States)

    Collins, Sinéad

    2013-07-01

    Microbial experimental evolution uses a few well-characterized model systems to answer fundamental questions about how evolution works. This special section highlights novel model systems for experimental evolution, with a focus on marine model systems that can be used to understand evolutionary responses to global change in the oceans. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  2. The magnitude of cytokine production by stimulated CD56+ cells is associated with early stages of systemic sclerosis

    NARCIS (Netherlands)

    Cossu, Marta; van Bon, L.; Nierkens, S; Bellocchi, Chiara; Santaniello, Alessandro; Dolstra, H.; Beretta, Lorenzo; Radstake, TRDJ

    2016-01-01

    Immune activation is a hallmark of systemic sclerosis (SSc). However, the immunological alterations that occur in preclinical and non-fibrotic SSc and that differentiate these subjects from those with primary Raynaud's phenomenon (PRP) or healthy controls (HC) are poorly defined. We isolated CD56+

  3. Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

    NARCIS (Netherlands)

    Denton, Christopher P.; Krieg, Thomas; Guillevin, Loic; Schwierin, Barbara; Rosenberg, Daniel; Silkey, Mariabeth; Zultak, Maurice; Matucci-Cerinic, Marco; Stetter, M.; Lackner, K.; Tomi, N.; Hafner, F.; Brodmann, M.; Kuen-Spiegel, M.; Kolle, H.; Raffier, B.; Hamberger, N.; Metz, S.; Siebel, C.; Trummer, M.; Thonhofer, R.; Illmer, X.; Trautinger, F.; Schmidt, P.; Rintelen, B.; Sautner, J.; Willfort-Ehringer, A.; Margeta, C.; Monshi, B.; Pirkhammer, D.; Richter, L.; Holzer, G.; Minmair, G.; Broll, H.; Takacs, M.; Hirschl, M.; Mesaric, P.; Feldmann, R.; Semmelweis, K.; Hundstorfer, M.; Reinhart, V.; Maurer, B.; Verner, D.; Distler, O.; Schmidt-Bosshard, R.; Bohmova, J.; Prochazkova, L.; Nemec, P.; Fojtik, Z.; Soukup, T.; Smrzova, A.; Suchy, D.; Zemanova, I.; Becvar, R.; Gawlik, A.; Koch, M.; Rauen, T.; Voss, B.; Kurthen, R.; Unholzer, A.; Starz, H.; Welzel, J.; Plaumann, K.; Merk, B.; Bloching, H. H.; Moosig, F.; Frey, P.; Kahl, S.; Schleenbecker, H.; Storck-Mueller, K.; Schwarting, A.; Hazenbiller, A.; Nichelmann, V.; Flaig, W.; Rumbaur, C.; Boesenberg, I.; Schmeiser, T.; Marx, J.; Mayer, L.; Stein, T.; Ochs, W.; Rasche, C.; Worm, M.; Riemekasten, G.; Deuschle, K.; Becker, M.; Kleiner, H. J.; Schulze, K.; Tiggers, C.; Peters, J.; Kirschke, J.; Schaefer, C.; Monshausen, M.; Mengden, T.; Sadeghlar, F.; Seidel, M.; Hillebrecht, C.; Andresen, J.; Reemtsen, R.; Stoeckl, F.; Sperling, S.; Podda, M.; Wagner, N.; Guenzel, J.; Wuerzburg, I.; Luethke, K.; Enderlein, M.; Kayser, M.; Gerber, A.; Haust, M.; Hoff, N. P.; Mota, R.; Akanay-Diesel, S.; Jahnke, K.; Mettler, S.; Toeller, S.; Zwenger, S.; Klein, E.; Hahn, K.; Beyer, C.; Distler, J.; Katzemich, A.; Erfurt-berge, C.; Sticherling, M.; Schuch, F.; Rapp, P.; Mitchell, A.; Freundlieb, C.; Rushentsova, U.; Himsel, A.; Henkemeier, U.; Eilbacher, P.; Ullrich-Guenther, C.; Neul, S.; Oelsner, M.; Hermanns, G.; Fiene, M.; Gause, A.; Mensing, C.; Klings, D.; Mensing, H.; Messall, J.; Zuper, R.; May, D.; Bruckner, L.; Sheikh, N.; Aries, P.; Kirchberg, S.; Funkert, A.; Blank, N.; Lupaschko, S.; Schwuerzer-Voit, M.; Meier, L.; Herr, U.; Meier, U.; Neek, G.; Wernitzsch, H.; Pfoehler, C.; Assmann, G.; Vosswinkel, J.; Krog, B.; Wollersdorfer, E.; Oltmann-Schroeder, J.; Zeuner, R.; Uhlig, S.; Barth, S.; Huegel, R.; Glaeser, R.; Rabe, B.; Schuster, J.; Scholz, J.; Kremer, K.; Robakidze-Torbahn, M.; Moinzadeh, P.; Mittag, M.; Dohse, A.; Muhlack, A.; Schultz, L.; Schult, S.; Frambach, Y.; Kettenbach, A.; Fell, I.; Schweda, K.; Steinbrink, K.; Podobinska, M.; Harmuth, W.; Nielen, C.; Kaczmarczyk, A.; Kellner, C.; von Oelhafen, J.; von Bildering, P. B.; Kunze, S.; Niedermeier, A.; Messer, G.; Sardy, M.; Bekou, V.; Belloni, B.; Huettig, B.; Ziai, M.; Hein, R.; Hallecker, A.; Gaubitz, M.; Hallermann, C.; Schmidt, K.; Herrgott, I.; Hildebrandt, B.; Eiden, E.; Guertler, I.; Gernot Scheibl, E.; Brand, H.; Kaeding, U.; Weiss, E.; Reischel, N.; Kern, S.; Baumann, C.; Hellmich, B.; Loeffler, C.; Pflugfelder, J.; Karaenke, P.; Ruchenburg, J.; Blume, J.; Zabel, M.; Deppermann, N.; Chromik, S.; Metzler, C.; Krupp, E.; Rumpel, H.; Krause Rostock, J.-O.; Kneitz, C.; Federow, I.; Schneider, K.; Semmler, M.; Hapke, S.; Barnd, A.; Linke, M.; Kampe-Juzak, E.; Knoebel, K.; Niefanger, K.; Wilhelm, H. U.; Lauterwein, B.; Fierlbeck, G.; Schanz, S.; Pfeiffer, C.; Hassel, R.; Wahn, H.; Schildt, K.; von Elling, A.; Boro, D.; Ebel, J.; Ahmadi, K.; Moritz, D.; Dietl, S.; Dyballa, J.; Alsheimer, B.; Schuetz, N.; Schuart, T.; Mueglich, C.; Tony, H. P.; Marina, P.; Deininger, F.; Hartmann, F.; Olsen, A. B.; Sondergaard, K. H.; Naderi, Y.; Iversen, L. V.; Karlsmark, T.; Knudsen, J. B.; Gil, J. G.; Lopez, J. C. F.; Tasende, J. A. P.; Gonzales, M. F.; Sandoval, A. A.; del Carmen Torres Martin, M.; Corteguera, M.; Barca, B. A.; Montes, I. C.; de la Torre, R. G.; Victoria Egurbide, M.; Pros, A.; Munoz, J.; Simeon, C. P.; Espinosa, G.; Espinposa, G.; Rodriguez, M. A. P.; Castellvi, I.; Mascaro, J. M.; Bellido, D.; Manzanedo, V. S.; Huertas, M. P.; Sanchez, M. D. M.; Trenado, M. S. S.; Garcia, P. V.; Gines Martinez, F.; Angeles Aquirre, M.; del Rio, A. H.; Vazquez, J. L. G.; Coleman, J. V.; Lopez, M. R.; Sanchez, P. S.; Aizpuru, E. M. F.; Mateo, F. J. N.; Callejas, J. L.; Ortego, N.; Santo, M. P.; Rubio, M.; Martin, I.; Cruz, A.; Crespo, M.; Ramos, P. C.; Fernandez, A. S.-A.; Filloy, J. A. M.; Rodriguez, T. R. V.; Marhuenda, A. R.; Blanco, J. J. R.; Hernan, M. G. B.; Mendoza, A. Z.; de la Puente, C.; Rabaneda, E. V.; de Vicuna, R. G.; del Mar Ripoll Macias, M.; del la Pena Lefebvre, P. G.; de Ramon, E.; Camps, M. T.; Fernandez, C.; Miguelez, R.; Uson, J.; Delgado, E. G.; Villaverde, V.; Maceiras, F.; Cruz, J.; Mosquera, J. A.; Mera, A.; Pampin, E. P.; Blanco, J. S.; Maneiro, J. R.; Diaz, J. J.; Losada, L.; Caamano, M.; Fernandez, S.; Insua, S. A.; Laurin, C. U.; Sanchez, J.; Fernandez, N. C.; Becerra, N. D.; Garcia, A.; Nicolas, G. M.; del Carmen Ortega de la O, M.; Rueda, A.; Calvo, J.; Roman Ivorra, J.; Sancho Alegre, J. J.; Barbado, J.; Montes, J.; Saez, L.; Kaarto, A.; Makinen, H.; Madaule, S.; Dadban, A.; Lok, C.; Ferrandiz, D.; Moiton, M. P.; Magy-Bertrand, N.; Taieb, A.; Droitcourt, C.; Belin, E.; Balquiere, S.; Prey, S.; Boulon, C.; Constans, J.; Richez, C.; Sassolas, B.; Misery, L.; Greco, M.; collet, E.; Berthier, S.; Leguy-Seguin, V.; Imbert, B.; Carpentier, P.; Blaise, S.; Maillard, H.; Beneton, N.; Launay, D.; Hachulla, E.; Woijtasik, G.; Charlanne, H.; Lambert, M.; Jourdain, N.; Hatron, P. Y.; Morell, S.; Spars, A.; Couraud, A.; Doeffel-hantz, V.; Fauchais, A. L.; Vidal, E.; Goudran, G.; Bezanahary, H.; Boussely, N.; Manea, P.; Dumonteil, S.; Loustaud-ratti, V.; Hot, A.; Coppere, B.; Desmurs-Clavel, H.; Ninet, J.; Girard-Madoux, M. H.; Granel, B.; Keynote, A.; Khau van Kien, A.; Rullier, P.; Le Quellec, A.; Riviere, S.; Bessis, D.; Cohen, J. D.; Farcas, C.; Granel-brocard, F.; Agard, C.; Durant, C.; Fuzibet, J. G.; Queyrel, V.; Berezne, A.; Guillevin, L.; Mouthon, L.; Frances, C.; Toledano, C.; Cabane, J.; Tiev, K.; Farge, D.; Keshtmand, H.; Lazareth, I.; Priollet, P.; Michon-Pasturel, U.; Wipff, J.; Assous, N.; Cartry, O.; Kostrzwewa, E.; Doutre, M. S.; Blum, L.; Reguiai, Z.; Letremy, A.; Perlat, A.; Cazalets-lacoste, C.; Decaux, O.; Jego, P.; Duval-modeste, A. B.; Deboves, O.; Sordet, C.; Chatelus, E.; Chiffot, H.; Sibillia, J.; Couret, B.; Moulis, G.; Sailler, L.; Adoue, D.; Gaches, F.; Diot, E.; Skowron, F.; Zenone, T.; Quemeneur, T.; Kyndt, X.; Wahl, D.; Zuily, S.; Moline, T.; Bravetti, V.; Galanopoulos, N.; Vasilopoulos, D.; Vlachoyannopoulos, P.; Kritikos, I.; Tsifetaki, N.; Koutroumbas, A.; Garyfallos, A.; Athanassiou, P.; Aslanidis, S.; Kamali, S.; Dimitroulas, T.; Galanopoulo, V.; Elezoglou, A.; Grier, A.; Murray, M.; O'Rourke, M.; Gabrielli, A.; Lapadula, G.; Serafino, L.; Terlizzi, N.; Bellissimo, S.; Stisi, S.; Malavolta, N.; Airo, P.; Vacca, A.; Battaglia, E.; Foti, R.; Mazzuca, S.; Bortoluzzi, A.; Trotta, F.; Galluccio, F.; Marucci, A.; Cantatore, F.; Bucci, R.; Puppo, F.; de Angeli, R.; Grassi, W.; Cipriani, P.; Mazzone, A.; Faggioli, P.; Severino, A.; Scorza, R.; Belloli, L.; Ughi, N.; Antivalle, M.; del Papa, N.; Maglione, W.; Zeni, S.; Ferri, C.; Colaci, M.; Varcasia, G.; Cuomo, G.; Cozzi, F.; Triolo, G.; Gatti, S.; Montecucco, C. M.; Doveri, M.; Nigro, A.; Olivieri, I.; Bajoochi, G.; Rosato, E.; Salsano, F.; Faustini, F.; Ferraccioli, G.; Colonna, L.; Pallotta, S.; Riccieri, V.; Mussi, A.; Bellisai, F.; Galeazzi, M.; Fusaro, E.; Saracco, M.; Pellerito, R.; Masolini, P.; de Vita, S.; Lombardi, S.; Lunardi, C.; Moolenburgh, J. D.; Heurkens, A. H. M.; Voskuyl, A.; Hak, A. E.; Stroes, E. S. K.; Remans, J.; Gerdes, V.; van Woerkom, J. M.; de Long, A. J. L.; Kaasjager, H. A. H.; Visser, H.; Janssen, M.; van Guldener, C.; van Neer, F.; Vos, P.; Peters, A. J.; Hulsmans, H.; Ronday, K.; Goekoop, R.; Ewals, J.; Valentijn, R.; de Bois, M.; Westedt, M. L.; Siewertsz van Reesema, D.; Knifjj-Dutmer, E.; Stolk, J. N.; Willems, H.; Kuiper-geertsma, D. G.; Baudaoin, P.; Fretter, P.; Westra, R.; Sonnaville, P. B. J.; Smit, A.; Bootsma, H.; Brouwer, L.; Bijl, M.; Molders, N.; Lebrun, C.; van der Veen, M. J.; Noordzij, M.; Houben, H.; Landewe, R. M. B.; Vercoutere, W.; Jahangier de Veen, Z. N.; Zijlstra, T. R.; Ubels, F.; Bruyn, G.; Jansen, P.; Schuerwegh, A.; Huizinga, T. W. J.; Paassen, P.; Hurkens, T.; Geurts, M.; van den Hoogen, F.; Vonk, M.; Jacobs, P. J. C.; Groenendael, J. H. L. M.; Seys, P.; van Zeben, D.; van Paassen, H.; Groenendael, J.; Han, K. H.; Wlarvens, M.; van Hagen, M.; van Daele, P.; Dolhain, R.; Gerards, A. H.; van der Lubbe, P.; Kanter, M. D. E.; Muller, W. H.; Ton, E.; van Krugten, M.; van Gameren, I.; Lanting, P.; den Hengst, C.; Gjessdal, C. G.; Hjertaker, S. L.; Madland, T. M.; Bendvold, A.; Bitter, H.; Hoffmann-Vold, A. M.; Midtvedt, O.; Bakland, G.; Aslkaksen, H. K.; Seip, M.; Kalstad, S.; Koldingsnes, W.; Grandauent, B.; Nordvag, B. Y.; Stran, E. K.; Skomsvoll, J.; Andersen, M.; Thomsen, R. S.; Pedersen, T.; Bakkeheim, V.; Cordeiro, A.; Alves, J.; Oliveira, S.; Coelho, P.; Resende, C.; Ponte, C.; Almeida, I.; Silva, I.; Santos, C.; Camara, I.; Costa, J.; Hellstrom, H.; Mohammad, A.; Lind, I.; Lind, K.; Bracin, T.; Liljequist, E.; Vingren, T.; Ostenson, A.; Hermansson, E.; Thorsson, C.; Soderlin, M.; Nordin, A.; Waldheim, E.; Vengemyr, K.; Albertsson, K.; Karlsson, M. L.; Rydvald, Y.; Rizk, M.; Dolnicar, A. S.; Lukac, J.; James, J.; McHugh, N.; Cole, S.; Brown, S.; Hamilton, A.; Faizal, A.; Hall, F.; Murphy, K.; Skingle, S.; Harris, H.; Madhok, F.; Hampson, R.; Baguley, E.; Ogunbambi G, O.; Lamb, J.; Anderson, M.; Moots, R.; White-Alao, B.; Morrison, C.; Dobson, J.; Gordon, P.; Salerno, R.; Denton, C.; Parker, L.; Ochiel, R.; Vincent, R.; Zimba, S.; Ngcozana, T.; Xu, Y.; D'Cruz, D.; Choong, L. M.; Herrick, A.; Wragg, E.; Manning, J.; Moore, T.; Kelsey, C.; Chakravarty, K.; Skyes, H.; Athiveer, P.

    2012-01-01

    The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). The DUO Registry is a European, prospective, multicentre, observational, registry of SSc

  4. Oral iloprost in Raynaud's phenomenon secondary to systemic sclerosis : A multicentre, placebo-controlled, dose-comparison study

    NARCIS (Netherlands)

    Black, CM; Halkier-Sorensen, L; Belch, JJF; Ullman, S; Madhok, R; Smit, AJ; Banga, JD; Watson, HR

    Objective. To identify the optimal dose of oral iloprost bn the basis of efficacy and tolerability in patients with Raynaud's phenomenon secondary to systemic sclerosis. Design. Multicentre, randomized, parallel-group comparison of two different doses of oral iloprost and placebo. Setting. European

  5. Clinical prediction of 5-year survival in systemic sclerosis: validation of a simple prognostic model in EUSTAR centres

    NARCIS (Netherlands)

    Fransen, J.; Popa-Diaconu, D.A.; Hesselstrand, R.; Carreira, P.; Valentini, G.; Beretta, L.; Airo, P.; Inanc, M.; Ullman, S.; Balbir-Gurman, A.; Sierakowski, S.; Allanore, Y.; Czirjak, L.; Riccieri, V.; Giacomelli, R.; Gabrielli, A.; Riemekasten, G.; Matucci-Cerinic, M.; Farge, D.; Hunzelmann, N.; Hoogen, F.H. Van den; Vonk, M.C.

    2011-01-01

    OBJECTIVE: Systemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but it has not been validated in other patients. The predictions of a prognostic model are usually

  6. Pneumatosis Intestinalis as the Initial Presentation of Systemic Sclerosis: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Farshid Ejtehadi

    2012-01-01

    Full Text Available Introduction. Pneumatosis intestinalis (PI is an uncommon pathology characterised by the presence of gas within the intestinal wall. It has been associated with various conditions, including connective tissue diseases. This is the first report of PI being the initial presentation of systemic sclerosis. Case Presentation. The patient, a 75-year-old female, presented with an 8-month history of worsening dysphagia and epigastric pain, as well as other nonspecific symptoms. Initial investigations with an oesophagogastroduodenoscopy diagnosed Candida oesophagitis and also identified an extrinsic compression of the gastric antrum. Subsequently a CT scan of the abdomen and pelvis showed moderately dilated small bowel loops and PI. Due to the patient’s stability, non-critical clinical condition, conservative management was instituted. More detailed investigations confirmed the diagnosis of systemic sclerosis with positive anticentromeric and antinuclear antibodies. The patient improved on methotrexate and was discharged with appropriate outpatient follow-up. Discussion. PI is a rare but well-documented pathology associated with connective tissue diseases, such as systemic sclerosis. In most cases, conservative management is preferable to surgical intervention, depending on the patient’s clinical presentation and progress. This is the first report of PI being the initial presentation of a patient with systemic sclerosis responsive to conservative management.

  7. CCR1+/CCR5+ mononuclear phagocytes accumulate in the central nervous system of patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Trebst, C; Sørensen, Torben Lykke; Kivisäkk, P

    2001-01-01

    Mononuclear phagocytes (monocytes, macrophages, and microglia) are considered central to multiple sclerosis (MS) pathogenesis. Molecular cues that mediate mononuclear phagocyte accumulation and activation in the central nervous system (CNS) of MS patients may include chemokines RANTES/CCL5 and ma...

  8. Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy

    NARCIS (Netherlands)

    Gorlova, Olga; Martin, Jose-Ezequiel; Rueda, Blanca; Koeleman, Bobby P. C.; Ying, Jun; Teruel, Maria; Diaz-Gallo, Lina-Marcela; Broen, Jasper C.; Vonk, Madelon C.; Simeon, Carmen P.; Alizadeh, Behrooz Z.; Coenen, Marieke J. H.; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; van Riel, Piet L. C. M.; Vanthuyne, Marie; van't Slot, Ruben; Italiaander, Annet; Ophoff, Roel A.; Hunzelmann, Nicolas; Fonollosa, Vicente; Ortego-Centeno, Norberto; Gonzalez-Gay, Miguel A.; Garcia-Hernandez, Francisco J.; Gonzalez-Escribano, Maria F.; Airo, Paolo; van Laar, Jacob; Worthington, Jane; Hesselstrand, Roger; Smith, Vanessa; de Keyser, Filip; Houssiau, Fredric; Chee, Meng May; Madhok, Rajan; Shiels, Paul G.; Westhovens, Rene; Kreuter, Alexander; de Baere, Elfride; Witte, Torsten; Padyukov, Leonid; Nordin, Annika; Scorza, Raffaella; Lunardi, Claudio; Lie, Benedicte A.; Hoffmann-Vold, Anna-Maria; Palm, Oyvind; Garcia de la Pena, Paloma; Carreira, Patricia; Varga, John; Hinchcliff, Monique; Lee, Annette T.; Gourh, Pravitt; Amos, Christopher I.; Wigley, Frederick M.; Hummers, Laura K.; Hummers, J.; Nelson, J. Lee; Riemekasten, Gabriella; Herrick, Ariane; Beretta, Lorenzo; Fonseca, Carmen; Denton, Christopher P.; Gregersen, Peter K.; Agarwal, Sandeep; Assassi, Shervin; Tan, Filemon K.; Arnett, Frank C.; Radstake, Timothy R. D. J.; Mayes, Maureen D.; Martin, Javier

    2011-01-01

    The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (IcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence

  9. Confirmation of CCR6 as a risk factor for anti-topoisomerase I antibodies in systemic sclerosis

    NARCIS (Netherlands)

    Ochoa, E.; Martin, J.E.; Assasi, S.; Beretta, L.; Carreira, P.; Guillen, A.; Simeon, C.P.; Koumakis, E.; Dieude, P.; Allanore, Y.; Garcia-Hernandez, F.J.; Espinosa, G.; Castellvi, I.; Trapiella, J.L.; Rodriguez, L.; Gonzalez-Gay, M.A.; Egurbide, M.V.; Saez, L.; Callejas-Rubio, J.L.; Vargas-Hitos, J.A.; Hunzelmann, N.; Riemekasten, G.; Witte, T. de; Distler, J.H.; Kreuter, A.; Lunardi, C.; Santaniello, A.; Tan, F.K.; Shiels, P.G.; Herrick, A.; Worthington, J.; Vonk, M.C.; Koeleman, B.P.C.; Radstake, T.R.; Mayes, M.D.; Martin, J.

    2015-01-01

    OBJECTIVES: The current knowledge of the influence of systemic sclerosis (SSc) risk loci in the clinical sub-phenotypes is still limited. The main limitation lies in the low frequency of some sub-phenotypes which could be solved by replication studies in independent cohorts and meta-analysis between

  10. Multiple sclerosis: a study of CXCL10 and CXCR3 co-localization in the inflamed central nervous system

    DEFF Research Database (Denmark)

    Sørensen, Torben Lykke; Trebst, Corinna; Kivisäkk, Pia

    2002-01-01

    T-cell accumulation in the central nervous system (CNS) is considered crucial to the pathogenesis of multiple sclerosis (MS). We found that the majority of T cells within the cerebrospinal fluid (CSF) compartment expressed the CXC chemokine receptor 3 (CXCR), independent of CNS inflammation. Quan...

  11. Assessment of English-French differential item functioning of the Satisfaction with Appearance Scale (SWAP) in systemic sclerosis

    NARCIS (Netherlands)

    Jewett, L.R.; Kwakkenbos, C.M.C.; Hudson, M.; Baron, M.; Thombs, B.D.

    2017-01-01

    The Satisfaction with Appearance Scale (SWAP) has been used to assess body image distress among people with the rare and disfiguring disease systemic sclerosis (SSc); however, it has not been validated across different languages groups. The objective was to examine differential item functioning of

  12. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial

    NARCIS (Netherlands)

    Laar, J.M. van; Farge, D.; Sont, J.K.; Naraghi, K.; Marjanovic, Z.; Larghero, J.; Schuerwegh, A.J.; Marijt, E.W.; Vonk, M.C.; Schattenberg, A.V.M.B.; Matucci-Cerinic, M.; Voskuyl, A.E.; Loosdrecht, A.A. van de; Daikeler, T.; Kotter, I.; Schmalzing, M.; Martin, T.; Lioure, B.; Weiner, S.M.; Kreuter, A.; Deligny, C.; Durand, J.M.; Emery, P.; Machold, K.P.; Sarrot-Reynauld, F.; Warnatz, K.; Adoue, D.F.; Constans, J.; Tony, H.P.; Papa, N. Del; Fassas, A.; Himsel, A.; Launay, D. de; Monaco, A. Lo; Philippe, P.; Quere, I.; Rich, E.; Westhovens, R.; Griffiths, B.; Saccardi, R.; Hoogen, F.H.J. van den; Fibbe, W.E.; Socie, G.; Gratwohl, A.; Tyndall, A.

    2014-01-01

    IMPORTANCE: High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. OBJECTIVE: To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of

  13. An MIF Promoter Polymorphism Is Associated with Susceptibility to Pulmonary Arterial Hypertension in Diffuse Cutaneous Systemic Sclerosis

    NARCIS (Netherlands)

    Bossini-Castillo, L.; Campillo-Davo, D.; Lopez-Isac, E.; Carmona, F.D.; Simeon, C.P.; Carreira, P.; Callejas-Rubio, J.L.; Castellvi, I.; Fernandez-Nebro, A.; Rodriguez-Rodriguez, L.; Rubio-Rivas, M.; Garcia-Hernandez, F.J.; Madronero, A.B.; Beretta, L.; Santaniello, A.; Lunardi, C.; Airo, P.; Hoffmann-Vold, A.M.; Kreuter, A.; Riemekasten, G.; Witte, T. de; Hunzelmann, N.; Vonk, M.C.; Voskuyl, A.E.; Vries-Bouwstra, J. de; Shiels, P.; Herrick, A.; Worthington, J.; Radstake, T.; Martin, J.

    2017-01-01

    OBJECTIVE: Systemic sclerosis (SSc) is a fibrotic immune-mediated disease of unknown etiology. Among its clinical manifestations, pulmonary involvement is the leading cause of mortality in patients with SSc. However, the genetic factors involved in lung complication are not well defined. We aimed to

  14. An MIF promoter polymorphism is associated with susceptibility to pulmonary arterial hypertension in diffuse cutaneous systemic sclerosis

    NARCIS (Netherlands)

    Bossini-Castillo, Lara; Campillo-Davo, Diana; Lopez-Isac, Elena; Carmona, Francisco David; Simeon, Carmen P.; Carreira, Patricia; Callejas-Rubio, Jose Luis; Castellvi, Ivan; Fernandez-Nebro, Antonio; Rodriguez-Rodriguez, Luis; Rubio-Rivas, Manel; Garcia-Hernandez, Francisco J.; Madronero, Ana Belen; Beretta, Lorenzo; Santaniello, Alessandro; Lunardi, Claudio; Airo, Paolo; Hoffmann-Vold, Anna-Maria; Kreuter, Alexander; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Vonk, Madelon C.; Voskuyl, Alexandre E.; de Vries-Bouwstra, Jeska; Shiels, Paul; Herrick, Ariane; Worthington, Jane; Radstake, Timothy R.D.J.; Martin, Javier

    2017-01-01

    Objective. Systemic sclerosis (SSc) is a fibrotic immune-mediated disease of unknown etiology. Among its clinical manifestations, pulmonary involvement is the leading cause of mortality in patients with SSc. However, the genetic factors involved in lung complication are not well defined. We aimed to

  15. Modulation of Fibrosis in Systemic Sclerosis by Nitric Oxide and Antioxidants

    Directory of Open Access Journals (Sweden)

    Audrey Dooley

    2012-01-01

    Full Text Available Systemic sclerosis (scleroderma: SSc is a multisystem, connective tissue disease of unknown aetiology characterized by vascular dysfunction, autoimmunity, and enhanced fibroblast activity resulting in fibrosis of the skin, heart, and lungs, and ultimately internal organ failure, and death. One of the most important and early modulators of disease activity is thought to be oxidative stress. Evidence suggests that the free radical nitric oxide (NO, a key mediator of oxidative stress, can profoundly influence the early microvasculopathy, and possibly the ensuing fibrogenic response. Animal models and human studies have also identified dietary antioxidants, such as epigallocatechin-3-gallate (EGCG, to function as a protective system against oxidative stress and fibrosis. Hence, targeting EGCG may prove a possible candidate for therapeutic treatment aimed at reducing both oxidant stress and the fibrotic effects associated with SSc.

  16. The Systemic Lupus Erythematosus IRF5 Risk Haplotype Is Associated with Systemic Sclerosis

    Science.gov (United States)

    Beretta, Lorenzo; Simeón, Carmen P.; Carreira, Patricia E.; Callejas, José Luis; Fernández-Castro, Mónica; Sáez-Comet, Luis; Beltrán, Emma; Camps, María Teresa; Egurbide, María Victoria; Airó, Paolo; Scorza, Raffaella; Lunardi, Claudio; Hunzelmann, Nicolas; Riemekasten, Gabriela; Witte, Torsten; Kreuter, Alexander; Distler, Jörg H. W.; Madhok, Rajan; Shiels, Paul; van Laar, Jacob M.; Fonseca, Carmen; Denton, Christopher; Herrick, Ariane; Worthington, Jane; Schuerwegh, Annemie J.; Vonk, Madelon C.; Voskuyl, Alexandre E.; Radstake, Timothy R. D. J.; Martín, Javier

    2013-01-01

    Systemic sclerosis (SSc) is a fibrotic autoimmune disease in which the genetic component plays an important role. One of the strongest SSc association signals outside the human leukocyte antigen (HLA) region corresponds to interferon (IFN) regulatory factor 5 (IRF5), a major regulator of the type I IFN pathway. In this study we aimed to evaluate whether three different haplotypic blocks within this locus, which have been shown to alter the protein function influencing systemic lupus erythematosus (SLE) susceptibility, are involved in SSc susceptibility and clinical phenotypes. For that purpose, we genotyped one representative single-nucleotide polymorphism (SNP) of each block (rs10488631, rs2004640, and rs4728142) in a total of 3,361 SSc patients and 4,012 unaffected controls of Caucasian origin from Spain, Germany, The Netherlands, Italy and United Kingdom. A meta-analysis of the allele frequencies was performed to analyse the overall effect of these IRF5 genetic variants on SSc. Allelic combination and dependency tests were also carried out. The three SNPs showed strong associations with the global disease (rs4728142: P  = 1.34×10−8, OR  = 1.22, CI 95%  = 1.14–1.30; rs2004640: P  = 4.60×10−7, OR  = 0.84, CI 95%  = 0.78–0.90; rs10488631: P  = 7.53×10−20, OR  = 1.63, CI 95%  = 1.47–1.81). However, the association of rs2004640 with SSc was not independent of rs4728142 (conditioned P  = 0.598). The haplotype containing the risk alleles (rs4728142*A-rs2004640*T-rs10488631*C: P  = 9.04×10−22, OR  = 1.75, CI 95%  = 1.56–1.97) better explained the observed association (likelihood P-value  = 1.48×10−4), suggesting an additive effect of the three haplotypic blocks. No statistical significance was observed in the comparisons amongst SSc patients with and without the main clinical characteristics. Our data clearly indicate that the SLE risk haplotype also influences SSc predisposition, and that

  17. Tuberous Sclerosis

    Science.gov (United States)

    ... StartEar InfectionBreastfeeding: How to Pump and Store Your Breast MilkAnemiaIrritable Bowel Syndrome (IBS) Home Diseases and Conditions Tuberous Sclerosis Condition Tuberous Sclerosis Share Print Table of ...

  18. Tuberous Sclerosis

    Science.gov (United States)

    Tuberous sclerosis is a rare genetic disease that causes benign tumors to grow in the brain and other organs. ... Kidney problems Some people have signs of tuberous sclerosis at birth. In others it can take time ...

  19. T Helper Cells in the Immunopathogenesis of Systemic Sclerosis – Current Trends

    Directory of Open Access Journals (Sweden)

    Krasimirova E.

    2017-05-01

    Full Text Available Systemic sclerosis (SSc is a chronic progressive autoimmune disease characterized by skin and multiorgan involvement with alterations in both the innate and adaptive immunities. The hallmark of the disease is widespread fibrosis engaging the skin and multiple internal organs, as well as the musculoskeletal system. There is mounting evidence that T cells are key players in the pathogenesis of scleroderma. The current review discusses the role of the different T helper (Th lymphocyte subsets in the processes of inflammation and fibrosis, characteristics for the pathogenesis of the disease. Cytokines produced by Th cell populations have a major effect on endothelial cells and fibroblasts in the context of favoring/inhibiting the vasculopathy and the fibrosis spread. The Th2 pro-fibrotic cytokines IL-4 and IL-13 have been shown to induce collagen synthesis by fibroblasts, whereas IFN-γ demonstrates an inhibitory effect. Increased Th17 cells are present in the scleroderma skin infiltrates. The combination of IL-17, IFN-γ and TGF-β levels in CD45RO and CD45RA cells from patients with SSc is useful to distinguish between the limited and the diffuse phenotype of the disease. There are accumulating data for functional and numerical alterations in the Tregs in SSc. High levels of TNF-α which might reduce the suppressive ability of Tregs have been described. According to some studies, the number of Tregs in scleroderma skin biopsies has been decreased against the normal absolute number of Tregs in peripheral blood of the same patients, which suggests suppressed immunomodulatory response. Other studies reported increased frequency of Tregs in peripheral blood of patients with systemic sclerosis and established a correlation with disease activity. The main immunological challenge remains the identification of the trigger of the autoimmune response in SSc, the causes for preferential Th2-type cell responses and the immunological differences between the

  20. Experimental Study of a Thermoelectric Generation System

    DEFF Research Database (Denmark)

    Zhu, Junpeng; Gao, Junling; Chen, Min

    2011-01-01

    A flat wall-like thermoelectric generation system is developed for applications in exhaust heat of kilns. The design of the whole experimental setup is presented. The essential performance of the thermoelectric generation system is tested, including open-circuit voltage, output power, and system ...

  1. Intranasal delivery of insulin and a nitric oxide synthase inhibitor in an experimental model of amyotrophic lateral sclerosis.

    Science.gov (United States)

    Martinez, J A; Francis, G J; Liu, W Q; Pradzinsky, N; Fine, J; Wilson, M; Hanson, L R; Frey, W H; Zochodne, D; Gordon, T; Toth, C

    2008-12-10

    Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disorder in which motor neurons may be targeted by oxidative and nitrergic stress without sufficient compensation by intrinsic support mechanisms. In this work, we addressed two key tenets of this hypothesis for the pathogenesis of ALS. Using superoxide dismutase (SOD) 1G93A mice, we studied the impact of reduction of nitrergic stress within the CNS with the use of a broad spectrum nitric oxide synthase (NOS) inhibitor, NG-nitro-l-arginine methyl ester. A separate cohort of SOD1G93A mice received direct insulin neurotrophic support, ligating receptors expressed upon motor neurons, to attempt protection against neuronal and functional motor dropout. For direct access, we used a novel form of intranasal delivery that provides peak concentration levels in the CNS within 1 h of delivery without systemic side effects at doses which previously rescued retrograde loss of motor axons after axotomy. To identify even minor impacts of these interventions on the outcome, we utilized an intensive program of serial behavioral and electrophysiological testing weekly, combined with endpoint quantitative morphometry and molecular analysis. This intensive evaluation enhanced our knowledge of the time course in SOD1G93A mice and impact of the SOD1G93A mutation upon motor neurons and their function. Neither intervention had even minimal impact upon slowing progression of disease in SOD1G93A mice. Our data argue against significant roles for nitrergic stress in promoting motor neuron loss and the importance of alternative neurotrophic support mechanisms that might support motor neurons and prevent disease progression in SOD1G93A mice.

  2. [Effect of Capparis spinosa on fibroblast proliferation and type I collagen production in progressive systemic sclerosis].

    Science.gov (United States)

    Cao, Yue-Lan; Li, Xin; Zheng, Min

    2008-03-01

    To investigate the effects of ethanolic extract from Capparis spinosa (ECS) on the fibroblast proliferation and type I collagen production in normal and progressive systemic sclerosis (PSS). Cellular activity was determined by the MTT method. Apoptosis was detected by flow cytometry analysis of Annexin V-stained cells. The expression levels of type I collagen messenger RNA and protein were analyzed by RT-PCR and western blot analysis. ECS could significantly inhibit the proliferation of fibroblast and reduced the expression of alpha2 (I) collagen mRNA and type I collagen protein in PSS in a dose-and time-dependent manner. ECS did not affect the proliferation of fibroblast and expression of type I collagen mRNA and protein in normal human. ECS could counteract the harmful effects on fibroblast by H2O2. ECS can effectively inhibit the fibroblast proliferation and type I collagen production in PSS.

  3. MicroRNAs Regulating Signaling Pathways: Potential Biomarkers in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Yisha Li

    2015-08-01

    Full Text Available Systemic sclerosis (SSc is a multisystem fibrotic and autoimmune disease. Both genetic and epigenetic elements mediate SSc pathophysiology. This review summarizes the role of one epigenetic element, known as microRNAs (miRNAs, involved in different signaling pathways of SSc pathogenesis. The expression of key components in transforming growth factor-β (TGF-β signaling pathway has been found to be regulated by miRNAs both upstream and downstream of TGF-β. We are specifically interested in the pathway components upstream of TGF-β, while miRNAs in other signaling pathways have not been extensively studied. The emerging role of miRNAs in vasculopathy of SSc suggests a promising new direction for future investigation. Elucidation of the regulatory role of miRNAs in the expression of signaling factors may facilitate the discovery of novel biomarkers in SSc and improve the understanding and treatment of this disease.

  4. Vitamin D in multiple sclerosis and central nervous system demyelinating disease--a review.

    Science.gov (United States)

    Burton, Jodie M; Costello, Fiona E

    2015-06-01

    The role of vitamin D as both a risk factor and a disease modifier in multiple sclerosis (MS) has a storied history with ongoing accumulation of supportive convergent evidence from animal data, clinical studies and trials, and biomarkers of disease. A detailed review of the published literature ranging from in vivo immune studies to human clinical studies of epidemiology, physiology, immunology, clinical, and radiological markers was undertaken. There is compelling evidence that vitamin D is not only a risk factor for central nervous system (CNS) demyelinating disease (namely MS) but also seems to modify both the inflammatory and neurodegenerative elements of the disease, with large-scale treatment trials underway. The authors also address questions of interest that remain unanswered. Vitamin D is an important contributor and modifiable risk factor in CNS demyelinating disease. Further work will determine whether it is also neuroprotective and if such benefits will apply to other inflammatory and degenerative neurological diseases.

  5. Previously undescribed pulpal and periodontal ligament calcifications in systemic sclerosis: a case report.

    Science.gov (United States)

    Jung, Sophie; Minoux, Maryline; Manière, Marie-Cécile; Martin, Thierry; Schmittbuhl, Matthieu

    2013-04-01

    Systemic sclerosis (SSc), a multisystem autoimmune disease characterized by widespread fibrosis, vascular alterations, autoimmunity, and inflammation, has effects on the hard and soft tissues of the orofacial region. The most common oral radiographic features correspond to widening of the periodontal ligament space and to mandibular resorption. In this report, cone-beam computerized tomography (CBCT) confirmed not only the well described periodontal features associated with SSc but also revealed previously undescribed calcifications within the periodontal ligament space of most maxillary teeth. Moreover, CBCT showed pulp calcifications in some incisors and premolars with these calcifications leading to root canal obliterations. Such manifestations (which could be linked to different major pathogenic features of SSc such as calcinosis, vasculopathy, and fibrosis) contribute to the phenotypic spectrum of the disease. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. High serum levels of YKL-40 in patients with systemic sclerosis are associated with pulmonary involvement

    DEFF Research Database (Denmark)

    Nordenbaek, C; Johansen, J S; Halberg, P

    2005-01-01

    with pulmonary SSc. RESULTS: Serum YKL-40 levels of the SSc patients were significantly higher than those of the controls (ppulmonary fibrosis by chest X-ray, obstructive ventilatory pattern, reduced diffusing capacity (DLco), and digital joint deformity due to skin retraction had......OBJECTIVES: YKL-40, a growth factor of connective tissue cells, is elevated in sera from patients with diseases characterized by inflammation, tissue remodelling, or fibrosis. The aim of the study was to determine serum YKL-40 levels in patients with systemic sclerosis (SSc) and to explore any...... significantly higher serum YKL-40 compared with patients without these findings. Patients with elevated serum YKL-40 had shorter survival times than patients with normal serum YKL-40 (p = 0.0005), although this was not independent of age and pulmonary function. YKL-40 protein expression was found...

  7. Lung structure and function relation in systemic sclerosis: Application of lung densitometry

    Energy Technology Data Exchange (ETDEWEB)

    Ninaber, Maarten K., E-mail: m.k.ninaber@lumc.nl [Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Stolk, Jan; Smit, Jasper; Le Roy, Ernest J. [Department of Pulmonology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Kroft, Lucia J.M. [Department of Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Els Bakker, M. [Division of Image Processing, Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Vries Bouwstra, Jeska K. de; Schouffoer, Anne A. [Department of Rheumatology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands); Staring, Marius; Stoel, Berend C. [Division of Image Processing, Radiology, Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden (Netherlands)

    2015-05-15

    Highlights: • A quantitative CT parameter of lung parenchyma in systemic sclerosis is presented. • We examine the optimal percentage threshold for the percentile density. • The 85th percentile density threshold correlated significantly with lung function. • A lung structure–function relation is confirmed. • We report applicability of Perc85 in progression mapping of interstitial lung disease. - Abstract: Introduction: Interstitial lung disease occurs frequently in patients with systemic sclerosis (SSc). Quantitative computed tomography (CT) densitometry using the percentile density method may provide a sensitive assessment of lung structure for monitoring parenchymal damage. Therefore, we aimed to evaluate the optimal percentile density score in SSc by quantitative CT densitometry, against pulmonary function. Material and methods: We investigated 41 SSc patients by chest CT scan, spirometry and gas transfer tests. Lung volumes and the nth percentile density (between 1 and 99%) of the entire lungs were calculated from CT histograms. The nth percentile density is defined as the threshold value of densities expressed in Hounsfield units. A prerequisite for an optimal percentage was its correlation with baseline DLCO %predicted. Two patients showed distinct changes in lung function 2 years after baseline. We obtained CT scans from these patients and performed progression analysis. Results: Regression analysis for the relation between DLCO %predicted and the nth percentile density was optimal at 85% (Perc85). There was significant agreement between Perc85 and DLCO %predicted (R = −0.49, P = 0.001) and FVC %predicted (R = −0.64, P < 0.001). Two patients showed a marked change in Perc85 over a 2 year period, but the localization of change differed clearly. Conclusions: We identified Perc85 as optimal lung density parameter, which correlated significantly with DLCO and FVC, confirming a lung parenchymal structure–function relation in SSc. This provides

  8. Translation, cultural adaptation and validation into portuguese (Brazil) in Systemic Sclerosis Questionnaire (SySQ).

    Science.gov (United States)

    Machado, Roberta Ismael Lacerda; Souto, Lais Medeiros; Freire, Eutilia Andrade Medeiros

    2014-01-01

    Systemic sclerosis (SSc) is a multisystem disease, autoimmune disorder characterized by a fibroblastic disfunction, with significant impact on quality of life (QoL), measured by instruments or questionnaires that usually were formulated in other languages and in different cultural contexts. Translate into Brazilian Portuguese, cross cultural adaptation and assess the reliability and validity of the Systemic Sclerosis Questionnaire (SySQ). Translation and adaptation: into Portuguese and cross-cultural adaptation was performed in accordance with studies on questionnaire translation methodology into other languages. Reliability: it was analyzed using three interviews with different interviewers, two on the same day (interobserver) and the third within 14 days of the first assessment (intraobserver).Validity was assessed by correlating clinical and quality of life parameters with the domain scores of Sysc. a descriptive analysis of the study sample. Reproducibility was assessed using an intraclass correlation coefficient (ICC). Internal consistency was assessed using Cronbach's alpha coefficient. To assess validity we used Spearman correlation coefficient. Five percent was the level of significance adopted for all statistical tests. In the evaluation of the questionnaires, the results were similar to the original questionnaire, the internal consistency ranging between 0.73 and 0.93 for each item. The interobserver reproducibility was very good for all domains (α = 0.786 to 0.983) and intraobserver agreement was considered very good for general symptoms domain (ICC = 0.916), good for musculoskeletal symptoms domain (ICC = 0.897) and cardiopulmonary domain (ICC = 0.842) and reasonable for gastrointestinal symptoms domain (ICC = 0.686). The Brazilian Portuguese version of SySQ proved to be reproducible and valid for our population, using a recognized methodology for translation and cultural adaptation of questionnaires, as well as to assess the reproducibility and

  9. Anti-citrullinated peptides antibodies in systemic sclerosis: Meta-analysis of frequency and meaning.

    Science.gov (United States)

    Laustriat, Guillaume; Ruyssen-Witrand, Adeline; Constantin, Arnaud; Barnetche, Thomas; Adoue, Daniel; Cantagrel, Alain; Degboé, Yannick

    2017-11-26

    Diagnosis of systemic sclerosis (SSc) is partially determined by the presence of specific autoantibodies often associated with specific clinical features. Recent studies report the presence of ACPA in SSc. We aimed to evaluate the prevalence of ACPA in SSc and to assess their influence on clinical presentation of SSc. A systematic literature search was performed using PubMed and Cochrane databases' publications between 1999 and March 2017. Search terms were: "systemic sclerosis [MeSH] AND (ACPA OR anti-CCP OR rheumatoid factor OR cohort OR value diagnostic)". In a first step, we selected cohorts with >50 SSc patients with ACPA identification, for ACPA frequency determination. In a second step, we included studies that analysed clinical profiles according to ACPA status. Meta-analyses were performed when at least two studies were available. First, we identified 13 observational studies with a total of 1231 SSc patients. The mean prevalence of ACPA in SSc was 9.2%. Secondly, we identified nine studies reporting clinical aspects according to ACPA status. Our meta-analyses showed a significant association between ACPA positivity and the presence of arthritis (odds ratio (OR)=22.48 [10.71-47.21]), joint erosions seen on X-rays (OR=14.79 [6.38-34.28]), pulmonary fibrosis (OR=2.75 [1.21-6.24]), oesophagus involvement (OR=2.72 [1.05-7.07]), and diffuse skin involvement (OR=2.21 [1.21-4.03]). The prevalence of ACPA in scleroderma is 9.2%. Our meta-analysis shows an increased risk for erosive arthritis, pulmonary fibrosis, oesophagus involvement and diffuse skin involvement, in patients with ACPA-positive SSc. ACPA should be systematically included in SSc assessment. Copyright © 2017 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  10. Unmet Needs in Systemic Sclerosis Understanding and Treatment: the Knowledge Gaps from a Scientist's, Clinician's, and Patient's Perspective.

    Science.gov (United States)

    Cossu, Marta; Beretta, Lorenzo; Mosterman, Petra; de Hair, Maria J H; Radstake, Timothy R D J

    2017-09-02

    Systemic sclerosis (SSc) is a highly heterogeneous disease caused by a complex molecular circuitry. For decades, clinical and molecular research focused on understanding the primary process of fibrosis. More recently, the inflammatory, immunological and vascular components that precede the actual onset of fibrosis, have become a matter of increasing scientific scrutiny. As a consequence, the field has started to realize that the early identification of this syndrome is crucial for optimal clinical care as well as for understanding its pathology. The cause of SSc cannot be appointed to a single molecular pathway but to a multitude of molecular aberrances in a spatial and temporal matter and on the backbone of the patient's genetic predisposition. These alterations underlie the plethora of signs and symptoms which patients experience and clinicians look for, ultimately culminating in fibrotic features. To solve this complexity, a close interaction among the patient throughout its "journey," the clinician through its clinical assessments and the researcher with its experimental design, seems to be required. In this review, we aimed to highlight the features of SSc through the eyes of these three professionals, all with their own expertise and opinions. With this unique setup, we underscore the importance of investigating the role of environmental factors in the onset and perpetuation of SSc, of focusing on the earliest signs and symptoms preceding fibrosis and on the application of holistic research approaches that include a multitude of potential molecular alterations in time in an unbiased fashion, in the search for a patient-tailored cure.

  11. Chlamydophila pneumoniae infection of the central nervous system in patients with multiple sclerosis.

    Science.gov (United States)

    Furrows, S J; Hartley, J C; Bell, J; Silver, N; Losseff, N; Stevenson, S; Chapman, M; Thompson, E J; Ridgway, G L; Giovannoni, G

    2004-01-01

    Chlamydophila pneumoniae has been postulated as an aetiological agent in the pathophysiology of multiple sclerosis. Previous studies show conflicting results. To investigate patients with multiple sclerosis and other neurological diseases for evidence of past or present infection with C pneumoniae. 19 patients with multiple sclerosis and 29 with other neurological diseases were studied. Evidence was sought for past or present infection with C pneumoniae using polymerase chain reaction (PCR) and cell culture of cerebrospinal fluid (CSF), and enzyme linked immunosorbent assay and microimmunofluorescence of serum. C pneumoniae was grown from the CSF of one patient with multiple sclerosis. PCR was negative in all cases. Anti-chlamydial antibodies were detected in the same proportion in each group. This study does not support the theory of an association between C pneumoniae and multiple sclerosis.

  12. Experimental functional realization of attribute grammar system

    Directory of Open Access Journals (Sweden)

    I. Attali

    2002-07-01

    Full Text Available In this paper we present an experimental functional realization of attribute grammar(AG system for personal computers. For AG system functioning only Turbo Prolog compiler is required. The system functioning is based on a specially elaborated metalanguage for AG description, universal syntactic and semantic constructors. The AG system provides automatic generation of target compiler (syntax--oriented software using Turbo Prolog as object language.

  13. Echocardiography may help detect pulmonary vasculopathy in the early stages of pulmonary artery hypertension associated with systemic sclerosis

    OpenAIRE

    Serra Walter; Chetta Alfredo; Santilli Daniele; Mozzani Flavio; Dall'Aglio Pier; Olivieri Dario; Cattabiani Maria; Ardissino Diego; Gherli Tiziano

    2010-01-01

    Abstract Background Pulmonary arterial hypertension (PAH) in patients with systemic sclerosis is associated with a poor prognosis, but this can be improved by early disease detection. Abnormal pulmonary and cardiac function can be detected early by means of echocardiography, whereas right heart catheterization is usually performed later. Objectives The purpose of this prospective study was to detect early the presence of pulmonary artery vasculopathy in patients with verified systemic scleros...

  14. Disease-related and psychosocial factors associated with depressive symptoms in patients with systemic sclerosis, including fear of progression and appearance self-esteem.

    NARCIS (Netherlands)

    Kwakkenbos, C.M.C.; Lankveld, W.G. van; Vonk, M.C.; Becker, E.S.; Hoogen, F.H.J. van den; Ende, C.H.M. van den

    2012-01-01

    OBJECTIVE: The prevalence of depressive symptoms is high in patients with systemic sclerosis (SSc, scleroderma). This study was conducted to determine which disease-related and psychosocial factors are associated with depressive symptoms, independent of sociodemographic factors. METHODS: In total,

  15. Disease-related and psychosocial factors associated with depressive symptoms in patients with systemic sclerosis, including fear of progression and appearance self-esteem

    NARCIS (Netherlands)

    Kwakkenbos, C.M.C.; Lankveld, W.G.J.M. van; Vonk, M.C.; Becker, E.S.; Hoogen, F.H.J. van den; Ende, C.H.M. van den

    2012-01-01

    Objective: The prevalence of depressive symptoms is high in patients with systemic sclerosis (SSc, scleroderma). This study was conducted to determine which disease-related and psychosocial factors are associated with depressive symptoms, independent of sociodemographic factors. Methods: In total,

  16. Toward a Cooperative Experimental System Development Approach

    DEFF Research Database (Denmark)

    1997-01-01

    This chapter represents a step towards the establishment of a new system development approach, called Cooperative Experimental System Development (CESD). CESD seeks to overcome a number of limitations in existing approaches: specification oriented methods usually assume that system design can...... be based solely on observation and detached reflection; prototyping methods often have a narrow focus on the technical construction of various kinds of prototypes; Participatory Design techniques—including the Scandinavian Cooperative Design (CD) approaches—seldom go beyond the early analysis...

  17. Comorbidity of Bipolar Disorder and Multiple Sclerosis: A Case Report

    OpenAIRE

    Necla Keskin; Soner Cakmak; Lut Tamam; Ahmet Turan Evlice

    2013-01-01

    Multiple sclerosis is a chronic demyelinating disease of a central nervous system. Neuropsychiatric symptoms are common in multiple sclerosis and bipolar disorder is one of the most common psychiatric disorders that coexist with multiple sclerosis. Manic episodes may be the first presenting symptom of multiple sclerosis as comorbid pathology or as an adverse effect of pharmacotherapies used in multiple sclerosis. The comorbidity of bipolar disorder and multiple sclerosis is well-proven but it...

  18. The "myth" of loss of angiogenesis in systemic sclerosis: a pivotal early pathogenetic process or just a late unavoidable event?

    Science.gov (United States)

    Matucci-Cerinic, Marco; Manetti, Mirko; Bruni, Cosimo; Chora, Ines; Bellando-Randone, Silvia; Lepri, Gemma; De Paulis, Amato; Guiducci, Serena

    2017-07-06

    Systemic sclerosis is considered a disease dominated by a "loss of angiogenesis", although in its early phases evidence indicates a disturbed angiogenic response only. In fact, microvascular changes are primarily due to endothelial cell injury, triggering downstream significant enlargement of the capillary in an inflammatory environment, followed by capillary rupture (microhemorrhages). Subsequent pro-angiogenic efforts lead to an aberrant angiogenesis and, eventually, to a total loss of vessel repair and regeneration (loss of angiogenesis). This clearly suggests that the pathogenetic process has a steady progression: from an early excessive pro-angiogenesis, to an aberrant microvascular regeneration, then ending with a late loss of angiogenesis. Herein, we suggest the loss of angiogenesis should not be considered as an overall "myth" characterizing systemic sclerosis but as a very late event of the vascular pathogenesis. Future research should be oriented essentially on the earlier phases dominated by excessive pro-angiogenesis and microvascular aberration.

  19. Overlap between systemic sclerosis and rheumatoid arthritis: a distinct clinical entity?

    Directory of Open Access Journals (Sweden)

    Alex Magno Coelho Horimoto

    Full Text Available ABSTRACT Introduction: Systemic sclerosis (SSc is an autoimmune disease of the connective tissue characterized by the triad of vascular injury, autoimmunity (cellular and humoral and tissue fibrosis. It is estimated that musculoskeletal pain is a common complaint of patients with SSc, ranging from 40 to 80%, and mainly in patients with early diffuse disease. Arthritis, clinically observed, may be a feature seen in the presentation of SSc, often leading to early diagnostic errors with rheumatoid arthritis (RA. In the course of the disease, arthritis is observed in 24–97% of patients with SSc. Objectives: To correlate the occurrence or nonoccurrence of arthritis in patients with SSc of the Midwest region of Brazil with possible distinct clinical and laboratory manifestations observed in three groups of patients. To report the frequency of true association between systemic sclerosis and rheumatoid arthritis in patients with clinically and radiologically observed synovitis. Methods: Sixty-one SSc patients were subsequently assessed every 3 months within 1 year, in order to clinically observe the occurrence of synovitis and its patterns of progression. Patients were divided into 3 groups: 41 patients with SSc without arthritis, 16 SSc patients with arthritis and 4 patients with overlap of SSc and RA. All patients underwent a radiological examination of the hands at the end of the study. Results: Among all patients evaluated, we found a female predominance (98.7%, mean age of 50.94 years, white color (49.2%, limited form of the disease (47.6%, time of diagnosis between 5 and 10 years (47.6% and duration of the disease of 8.30 years. Among all patients, 14 (22.9% had positive rheumatoid factor (RF, while among those with positive RF, only 10 patients had arthritis during one-year follow-up. The antibody anticitrulline (anti-CCP test was performed in 24 patients, being positive in 4 of them (16.7%, with positivity being observed only in patients with

  20. Improved pulmonary function following pirfenidone treatment in a patient with progressive interstitial lung disease associated with systemic sclerosis

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    Zarir F Udwadia

    2015-01-01

    Full Text Available Pirfenidone is an anti-fibrotic drug which has been approved for the management of patients with Idiopathic Pulmonary Fibrosis (IPF. However, its role in interstitial lung disease (ILD due to other causes such as systemic sclerosis (SSc is not clear. We present a case of a patient with SSc associated ILD who showed a subjective as well as objective improvement in lung function with pirfenidone.

  1. Ventilation distribution and small airway function in patients with systemic sclerosis

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    B.R.A. Silva

    2017-05-01

    Full Text Available Background: Despite the importance of traditional pulmonary function tests (PFTs in managing systemic sclerosis (SSc, many patients with pulmonary disease diagnosed by computed tomography (CT present with normal PFTs. Objective: To evaluate the efficacy of the nitrogen single-breath washout (N2SBW test in diagnosing SSc and to correlate N2SBW parameters with the PFT indexes used in the follow-up of these patients, clinical data, and CT findings. Methods: Cross-sectional study in which 52 consecutive SSc patients were subjected to spirometry, body plethysmography, analysis of the diffusing capacity for carbon monoxide (DLCO, analysis of respiratory muscle strength, N2SBW testing, and CT analysis. Results: Twenty-eight patients had a forced vital capacity (FVC that was 120% of the predicted value, while 15 patients had a closing volume/vital capacity (CV/VC that was >120% of the predicted value. A significant difference in Phase III slopeN2SBW was observed when the patients with predominant traction bronchiectasis and honeycombing were compared to the patients with other CT patterns (p < 0.0001. The Phase III slopeN2SBW was correlated with FVC (rs = −0.845, p < 0.0001 and DLCO (rs = −0.600, p < 0.0001, and the CV/VC was correlated with FVC (rs = −0.460, p = 0.0006 and residual volume/total lung capacity (rs = 0.328, p = 0.017. Conclusion: Ventilation heterogeneity is a frequent finding in SSc patients that is associated with restrictive damage, changes in pulmonary diffusion, and CT patterns. In addition, approximately one-third of the patients presented with findings that were compatible with small airway disease. Keywords: Systemic sclerosis, Respiratory function tests, Nitrogen single-breath washout test

  2. Distinctive Roles for α7*- and α9*-Nicotinic Acetylcholine Receptors in Inflammatory and Autoimmune Responses in the Murine Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis.

    Science.gov (United States)

    Liu, Qiang; Whiteaker, Paul; Morley, Barbara J; Shi, Fu-Dong; Lukas, Ronald J

    2017-01-01

    Previous studies have demonstrated immunosuppressive and anti-inflammatory effects of nicotine, including in the experimental autoimmune encephalomyelitis (EAE) model in mice of some forms of multiple sclerosis (MS). Other studies using knock-out (KO) mice have implicated nicotinic acetylcholine (ACh) receptors containing α7, α9, or β2 subunits (α7*-, α9*- or β2*-nAChR) in different, disease-exacerbating or disease-ameliorating processes. These outcomes are in harmony with gene expression analyses showing nAChR subunit mRNA in many classes of immune system cell types. Consistent with influences on disease status, predictable effects of nAChR subunit (and subtype) KO, or of nicotine exposure, are seen on immune cell numbers and distribution and on cytokine levels or other markers of immunity, inflammation, demyelination, and axonal degradation. Providing support for our hypotheses about distinctive roles for nAChR subtypes in EAE, here we have used direct and adoptive EAE induction and a nAChR subunit gene double knock-out (DKO) strategy. Immune cell expression of nAChR α9 subunits as protein is demonstrated by immunostaining of isolated CD4+, CD8+, CD11b+ and CD11c+ cells from wild-type (WT) mice, but not in cells from nAChR α9 subunit KO animals. Nicotine exposure is protective against directly-induced EAE in WT or α7/α9 DKO animals relative to effects seen in WT/vehicle-treated mice, but, remarkably, EAE is exacerbated in vehicle-treated α7/α9 DKO mice. Brain lesion volume and intra-cranial inflammatory activity similarly are higher in DKO/vehicle than in WT/vehicle-treated animals, although nicotine's protective effects are seen in each instance. By contrast, in adoptive transfer studies, disease severity is attenuated and disease onset is delayed in recipients of splenocytes from WT animals treated with nicotine rather than with vehicle. Moreover, protection as seen in nicotine-treated WT animals is the same in recipients of splenocytes from nAChR

  3. Distinctive Roles for α7*- and α9*-Nicotinic Acetylcholine Receptors in Inflammatory and Autoimmune Responses in the Murine Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Qiang Liu

    2017-09-01

    Full Text Available Previous studies have demonstrated immunosuppressive and anti-inflammatory effects of nicotine, including in the experimental autoimmune encephalomyelitis (EAE model in mice of some forms of multiple sclerosis (MS. Other studies using knock-out (KO mice have implicated nicotinic acetylcholine (ACh receptors containing α7, α9, or β2 subunits (α7*-, α9*- or β2*-nAChR in different, disease-exacerbating or disease-ameliorating processes. These outcomes are in harmony with gene expression analyses showing nAChR subunit mRNA in many classes of immune system cell types. Consistent with influences on disease status, predictable effects of nAChR subunit (and subtype KO, or of nicotine exposure, are seen on immune cell numbers and distribution and on cytokine levels or other markers of immunity, inflammation, demyelination, and axonal degradation. Providing support for our hypotheses about distinctive roles for nAChR subtypes in EAE, here we have used direct and adoptive EAE induction and a nAChR subunit gene double knock-out (DKO strategy. Immune cell expression of nAChR α9 subunits as protein is demonstrated by immunostaining of isolated CD4+, CD8+, CD11b+ and CD11c+ cells from wild-type (WT mice, but not in cells from nAChR α9 subunit KO animals. Nicotine exposure is protective against directly-induced EAE in WT or α7/α9 DKO animals relative to effects seen in WT/vehicle-treated mice, but, remarkably, EAE is exacerbated in vehicle-treated α7/α9 DKO mice. Brain lesion volume and intra-cranial inflammatory activity similarly are higher in DKO/vehicle than in WT/vehicle-treated animals, although nicotine’s protective effects are seen in each instance. By contrast, in adoptive transfer studies, disease severity is attenuated and disease onset is delayed in recipients of splenocytes from WT animals treated with nicotine rather than with vehicle. Moreover, protection as seen in nicotine-treated WT animals is the same in recipients of

  4. Dysregulation of the Autophagy-Endolysosomal System in Amyotrophic Lateral Sclerosis and Related Motor Neuron Diseases

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    Asako Otomo

    2012-01-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a heterogeneous group of incurable motor neuron diseases (MNDs characterized by a selective loss of upper and lower motor neurons in the brain and spinal cord. Most cases of ALS are sporadic, while approximately 5–10% cases are familial. More than 16 causative genes for ALS/MNDs have been identified and their underlying pathogenesis, including oxidative stress, endoplasmic reticulum stress, excitotoxicity, mitochondrial dysfunction, neural inflammation, protein misfolding and accumulation, dysfunctional intracellular trafficking, abnormal RNA processing, and noncell-autonomous damage, has begun to emerge. It is currently believed that a complex interplay of multiple toxicity pathways is implicated in disease onset and progression. Among such mechanisms, ones that are associated with disturbances of protein homeostasis, the ubiquitin-proteasome system and autophagy, have recently been highlighted. Although it remains to be determined whether disease-associated protein aggregates have a toxic or protective role in the pathogenesis, the formation of them results from the imbalance between generation and degradation of misfolded proteins within neuronal cells. In this paper, we focus on the autophagy-lysosomal and endocytic degradation systems and implication of their dysfunction to the pathogenesis of ALS/MNDs. The autophagy-endolysosomal pathway could be a major target for the development of therapeutic agents for ALS/MNDs.

  5. Progressive loss of lymphatic vessels in skin of patients with systemic sclerosis.

    Science.gov (United States)

    Manetti, Mirko; Milia, Anna Franca; Guiducci, Serena; Romano, Eloisa; Matucci-Cerinic, Marco; Ibba-Manneschi, Lidia

    2011-02-01

    Systemic sclerosis (SSc) is a connective tissue disorder characterized by microvascular and fibrotic changes in the skin and internal organs. The role of blood vessel dysfunction in the pathogenesis of SSc has been extensively investigated, but few studies have addressed the involvement of the lymphatic vascular system. Our aim was to evaluate dermal lymphatic vessels in patients with SSc according to different phases of skin involvement. Skin biopsies were obtained from the forearm of 25 SSc patients (10 early/15 late-stage disease) and 13 healthy controls. Skin sections were immunostained for podoplanin (D2-40), which is selectively expressed in lymphatic endothelial cells, and examined by confocal laser scanning microscopy. Lymphatic vessels were counted in the papillary and reticular dermis. Data were analyzed using Student's t test. The number of lymphatic vessels was significantly reduced in the papillary and reticular dermis of SSc patients compared with controls. In early SSc, lymphatic vessel counts were not different from controls in the papillary dermis, and showed a trend toward a reduction in the reticular dermis. In late SSc, a significant reduction in lymphatic vessels compared with controls was found in both the papillary and reticular dermis. The number of lymphatic vessels in the papillary dermis of late SSc was significantly lower than in early SSc. In SSc, lymphatic microangiopathy is linked to the progression of skin involvement. The progressive disappearance of lymphatic vessels may have a critical pathogenetic role in the progression of SSc from an early edematous phase to overt fibrosis.

  6. The enteric nervous system is a potential autoimmune target in multiple sclerosis.

    Science.gov (United States)

    Wunsch, Marie; Jabari, Samir; Voussen, Barbara; Enders, Michael; Srinivasan, Shanthi; Cossais, François; Wedel, Thilo; Boettner, Martina; Schwarz, Anna; Weyer, Linda; Göcer, Oktay; Schroeter, Michael; Maeurer, Mathias; Woenckhaus, Matthias; Pollok, Karolin; Radbruch, Helena; Klotz, Luisa; Scholz, Claus-Jürgen; Nickel, Joachim; Friebe, Andreas; Addicks, Klaus; Ergün, Süleyman; Lehmann, Paul V; Kuerten, Stefanie

    2017-08-01

    Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) in young adults that has serious negative socioeconomic effects. In addition to symptoms caused by CNS pathology, the majority of MS patients frequently exhibit gastrointestinal dysfunction, which was previously either explained by the presence of spinal cord lesions or not directly linked to the autoimmune etiology of the disease. Here, we studied the enteric nervous system (ENS) in a B cell- and antibody-dependent mouse model of MS by immunohistochemistry and electron microscopy at different stages of the disease. ENS degeneration was evident prior to the development of CNS lesions and the onset of neurological deficits in mice. The pathology was antibody mediated and caused a significant decrease in gastrointestinal motility, which was associated with ENS gliosis and neuronal loss. We identified autoantibodies against four potential target antigens derived from enteric glia and/or neurons by immunoprecipitation and mass spectrometry. Antibodies against three of the target antigens were also present in the plasma of MS patients as confirmed by ELISA. The analysis of human colon resectates provided evidence of gliosis and ENS degeneration in MS patients compared to non-MS controls. For the first time, this study establishes a pathomechanistic link between the well-established autoimmune attack on the CNS and ENS pathology in MS, which might provide a paradigm shift in our current understanding of the immunopathogenesis of the disease with broad diagnostic and therapeutic implications.

  7. Prevalence of Systemic Sclerosis in Primary Biliary Cholangitis Using the New ACR/EULAR Classification Criteria.

    Science.gov (United States)

    Zheng, Boyang; Vincent, Catherine; Fritzler, Marvin J; Senécal, Jean-Luc; Koenig, Martial; Joyal, France

    2017-01-01

    Systemic sclerosis (SSc) is a well-established disease associated with primary biliary cholangitis (PBC). However, the original 1980 American College of Rheumatology (ACR) criteria have poor sensitivity, especially for the detection of earlier SSc in previous studies. The objective was to evaluate the prevalence of SSc in patients with PBC using more sensitive 2001 LeRoy and Medsger criteria and the 2013 ACR/European League Against Rheumatism (EULAR) classification criteria. The secondary objective was to evaluate the frequency of individual clinical features. One hundred consecutive patients with PBC without previously diagnosed SSc were recruited between 2005 and 2007 from a tertiary care gastroenterology clinic. All patients underwent a complete clinical examination, determination of SSc-specific antibodies, and a nailfold capillary microscopy. Fulfillment of the 3 different criteria sets was analyzed, along with individual disease features. Of 100 patients with PBC, 1% met the ACR 1980 criteria, 22% met the 2001 LeRoy and Medsger criteria for early SSc, and 17% the 2013 ACR/EULAR criteria. Raynaud phenomenon, SSc-related antibodies, and SSc capillaroscopic patterns were the most prevalent findings, with the highest sensitivities to help guide future screening. Our data show a high prevalence of SSc in patients with PBC with probable underestimation by previous studies using the original ACR criteria. Comorbid SSc should be actively searched for based on newly described criteria to improve detection and increase benefits of earlier treatment.

  8. High Rhodotorula sequences in skin transcriptome of patients with diffuse systemic sclerosis.

    Science.gov (United States)

    Arron, Sarah T; Dimon, Michelle T; Li, Zhenghui; Johnson, Michael E; Wood, Tammara A; Feeney, Luzviminda; Angeles, Jorge G; Lafyatis, Robert; Whitfield, Michael L

    2014-08-01

    Previous studies have suggested a role for pathogens as a trigger of systemic sclerosis (SSc), although neither a pathogen nor a mechanism of pathogenesis is known. Here we show enrichment of Rhodotorula sequences in the skin of patients with early, diffuse SSc compared with that in normal controls. RNA-seq was performed on four SSc patients and four controls, to a depth of 200 million reads per patient. Data were analyzed to quantify the nonhuman sequence reads in each sample. We found little difference between bacterial microbiome and viral read counts, but found a significant difference between the read counts for a mycobiome component, R. glutinis. Normal samples contained almost no detected R. glutinis or other Rhodotorula sequence reads (mean score 0.021 for R. glutinis, 0.024 for all Rhodotorula). In contrast, SSc samples had a mean score of 5.039 for R. glutinis (5.232 for Rhodotorula). We were able to assemble the D1-D2 hypervariable region of the 28S ribosomal RNA (rRNA) of R. glutinis from each of the SSc samples. Taken together, these results suggest that R. glutinis may be present in the skin of early SSc patients at higher levels than in normal skin, raising the possibility that it may be triggering the inflammatory response found in SSc.

  9. Towards systemic sclerosis and away from primary biliary cirrhosis: the case of PTPN22.

    Science.gov (United States)

    Smyk, Daniel S; Mytilinaiou, Maria G; Milkiewicz, Piotr; Rigopoulou, Eirini I; Invernizzi, Pietro; Bogdanos, Dimitrios P

    2012-04-01

    Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by immune-mediated destruction of the small and medium size intrahepatic bile ducts. PBC patients often have concomitant autoimmune diseases, which are most often autoimmune thyroid disease, as well as Sicca syndrome. Occasionally, some PBC patients will also have systemic sclerosis of the limited cutaneous type (lcSSc). Conversely, up to one-fourth of SSc patients are positive for antimitochondrial antibody, the serologic hallmark of PBC. It is also common for SSc patients to have concomitant autoimmune disease, which may include PBC in rare cases. This has led to speculation of shared environmental and/or genetic factors, which lead to the development of PBC in SSc patients and vice versa. Recent genetic studies have revealed associations with several genes in both SSc and PBC. PTPN22 is one gene that has been associated with SSc, but not with PBC. It may be argued that some SSc patients with a particular genotype, which shares genes found in both conditions may develop PBC. Likewise, particular genes such as PTPN22 may infer susceptibility to SSc alone. The presence of PTPN22 may also contribute to the development of SSc in PBC patients. The lack of a large number of overlapping genes may, in part, explain the relative rarity of PBC with SSc and vice versa. This review will examine the literature surrounding the genetic associations of PBC and SSc, and the role of PTPN22 in particular.

  10. The Prevalence and Clinical Correlates of an Auscultatory Gap in Systemic Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Tracy M. Frech

    2012-01-01

    Full Text Available Introduction. Accurate blood pressure (BP measurement is essential to the diagnosis and management of hypertension in patients with systemic sclerosis (SSc to help prevent renal and cardiovascular complications. The presence of an auscultatory gap during manual BP measurement—the temporary disappearance of the Korotkoff sounds during cuff deflation—leads to a potentially important underestimate of systolic BP if undetected. Objectives. Since the presence of an auscultatory gap is frequently associated with increased vascular stiffness, we investigated its presence and correlates in 50 consecutive SSc patients. Methods. For each patient, BP was measured sequentially using three different approaches performed in the same order. Results. Sixteen of 50 patients (32% had an auscultatory gap which if undetected would have resulted in clinically important underestimates of systolic BP in 4 patients. The presence of an auscultatory gap was statistically associated with the presence of antibodies to RNA polymerase III (<0.0068 and SSc diagnosis type (<0.01. Conclusions. Our study demonstrates that auscultatory gaps are relatively common in SSc and correlate with markers for SSc vasculopathy. If undetected auscultatory gaps may result in clinically important underestimation of BP. Thus, electronic oscillometric BP may be preferred in SSc patients.

  11. Calcinosis preferentially affects the thumb compared to other fingers in patients with systemic sclerosis.

    Science.gov (United States)

    Gauhar, R; Wilkinson, J; Harris, J; Manning, J; Herrick, A L

    2016-07-01

    Although Raynaud's phenomenon often spares the thumb, clinical experience suggests conversely that, in patients with systemic sclerosis (SSc), the thumb is frequently affected by calcinosis (as is demonstrated on plain radiographs). Our aim was to investigate the hypothesis that, in patients with SSc, thumbs are more commonly affected by calcinosis than other digits. Sixty-eight hand radiographs with at least one area of calcinosis were identified. Each digit on both hands of each patient was assigned a severity score on a scale from 0 to 3 (0 = no calcinosis, 3 = most severe). The scoring was completed twice, including and excluding the metacarpals. Right hands were found to be associated with slightly higher scores than left hands [estimate 0.14, 95% confidence interval (CI) 0.03-0.26]. Scores were lower for other fingers compared to thumbs. There was strong evidence (p thumb to the little finger. There was no evidence that the pattern of severity across the fingers was different on left and right hands (p = 0.77). The results were similar whether or not metacarpals were included. The thumb is affected by calcinosis more than other digits, followed by the index finger. This observation provides insight into the pathogenesis of SSc-related calcinosis, which may relate more to repetitive trauma than to ischaemia.

  12. Multicriteria decision analysis methods with 1000Minds for developing systemic sclerosis classification criteria.

    Science.gov (United States)

    Johnson, Sindhu R; Naden, Raymond P; Fransen, Jaap; van den Hoogen, Frank; Pope, Janet E; Baron, Murray; Tyndall, Alan; Matucci-Cerinic, Marco; Denton, Christopher P; Distler, Oliver; Gabrielli, Armando; van Laar, Jacob M; Mayes, Maureen; Steen, Virginia; Seibold, James R; Clements, Phillip; Medsger, Thomas A; Carreira, Patricia E; Riemekasten, Gabriela; Chung, Lorinda; Fessler, Barri J; Merkel, Peter A; Silver, Richard; Varga, John; Allanore, Yannick; Mueller-Ladner, Ulf; Vonk, Madelon C; Walker, Ulrich A; Cappelli, Susanna; Khanna, Dinesh

    2014-06-01

    Classification criteria for systemic sclerosis (SSc) are being developed. The objectives were to develop an instrument for collating case data and evaluate its sensibility; use forced-choice methods to reduce and weight criteria; and explore agreement among experts on the probability that cases were classified as SSc. A standardized instrument was tested for sensibility. The instrument was applied to 20 cases covering a range of probabilities that each had SSc. Experts rank ordered cases from highest to lowest probability; reduced and weighted the criteria using forced-choice methods; and reranked the cases. Consistency in rankings was evaluated using intraclass correlation coefficients (ICCs). Experts endorsed clarity (83%), comprehensibility (100%), face and content validity (100%). Criteria were weighted (points): finger skin thickening (14-22), fingertip lesions (9-21), friction rubs (21), finger flexion contractures (16), pulmonary fibrosis (14), SSc-related antibodies (15), Raynaud phenomenon (13), calcinosis (12), pulmonary hypertension (11), renal crisis (11), telangiectasia (10), abnormal nailfold capillaries (10), esophageal dilation (7), and puffy fingers (5). The ICC across experts was 0.73 [95% confidence interval (CI): 0.58, 0.86] and improved to 0.80 (95% CI: 0.68, 0.90). Using a sensible instrument and forced-choice methods, the number of criteria were reduced by 39% (range, 23-14) and weighted. Our methods reflect the rigors of measurement science and serve as a template for developing classification criteria. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Increased IL-35 serum levels in systemic sclerosis and association with pulmonary interstitial involvement.

    Science.gov (United States)

    Dantas, Andréa Tavares; Gonçalves, Sayonara Maria Calado; Pereira, Michelly Cristiny; Gonçalves, Rafaela Silva Guimarães; Marques, Cláudia Diniz Lopes; Rego, Moacyr Jesus Barreto de Melo; Pitta, Ivan da Rocha; Duarte, Angela Luzia Branco Pinto; Pitta, Maira Galdino da Rocha

    2015-09-01

    The objective of this study is to assess the serum IL-35 level and its association with clinical manifestations in patients with systemic sclerosis (SSc). IL-35 serum levels were measured by ELISA from 56 patients with SSc and 53 healthy controls. Association of IL-35 serum levels were sought with clinical parameters. Serum IL-35 levels were significantly higher in SSc patients (5.08 ± 0.76 pg/ml) than in healthy individuals (1.89 ± 0.69 pg/ml; p 35 levels than those without fibrosis (7.75 ± 1.36 and 3.08 ± 0.70 pg/ml, respectively, p = 0.0022). IL-35 is elevated in the serum of patients with SSc and is associated with lung fibrosis. Our findings suggest that this cytokine can have a role in fibrotic diseases, but further studies are needed to address the role of IL-35 in the pathogenesis of SSc.

  14. Haematological Malignancies in Systemic Sclerosis Patients: Case Reports and Review of the World Literature.

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    Colaci, M; Giuggioli, D; Vacchi, C; Ferri, C

    2017-01-01

    Background. The association of systemic sclerosis (SSc) and haematological cancers was reported in a large number of case reports and cohort studies, describing SSc patients with highly heterogeneous clinical pictures. Objective. We reviewed the literature to better describe SSc patients with haematological malignancies. Methods. SSc cases complicated by haematological malignancies described in the world literature were collected; other 2 cases referred to our centre were reported. Results. One hundred-thirty SSc subjects were collected from 1954 up to date. The mean age of patients at cancer diagnosis was 56.1 ± 16.7 years; 72% of patients were females. In 60% of cases, the diagnosis of haematological malignancy was described within 5 years of SSc diagnosis. In 7.8% of cases, coexistence of Sjögren's syndrome or other autoimmune disorders was cited. Sixty-six cases with lymphoma (in the majority of cases B-cell neoplasms), 28 with leukaemia (chronic lymphocytic form in 9), 14 with multiple myeloma plus one solitary IgM plasmocytoma, and 16 with myeloproliferative disorders were found. No specific SSc subsets seem to be related to haematological malignancies. Conclusions. We remarked the importance of clinical work-up in SSc, in order to early diagnose and treat eventual occult haematological malignancies, especially during the first years of the disease.

  15. Systemic sclerosis and its pulmonary complications in The Netherlands: an epidemiological study.

    Science.gov (United States)

    Vonk, M C; Broers, B; Heijdra, Y F; Ton, E; Snijder, R; van Dijk, A P J; van Laar, J M; Bootsma, H; van Hal, P Th W; van den Hoogen, F H J; van Daele, P L A

    2009-06-01

    The prevalence and incidence of systemic sclerosis (SSc) in The Netherlands is unknown. The same holds true for its leading causes of death: pulmonary fibrosis and pulmonary arterial hypertension (PAH), for which effective treatment options have recently become available. To establish the prevalence and incidence of SSc and its pulmonary complications. Detailed information on patients in the POEMAS registry, "Pulmonary Hypertension Screening, a Multidisciplinary Approach in Scleroderma", consisting of 819 patients, was combined with a nationwide questionnaire. By combining the two sources the prevalence of SSc was found to be 8.9 per 100 000 adults. The incidence was 0.77 patients per 100 000 per year. PAH was diagnosed in 9.9% of SSc patients. The prevalence of interstitial lung disease in SSc varied from 19% to 47% depending on the definition used. This study clarifies the epidemiology of SSc in The Netherlands and confirms the frequent occurrence of pulmonary complications, based on 654 cases. This can and will be studied further in the ongoing POEMAS study.

  16. Patients with systemic sclerosis present increased DNA damage differentially associated with DNA repair gene polymorphisms.

    Science.gov (United States)

    Palomino, Gustavo Martelli; Bassi, Carmen L; Wastowski, Isabela J; Xavier, Danilo J; Lucisano-Valim, Yara M; Crispim, Janaina C O; Rassi, Diane M; Marques-Neto, Joao F; Sakamoto-Hojo, Elza T; Moreau, Philippe; Sampaio-Barros, Percival D; Donadi, Eduardo A

    2014-03-01

    Patients with systemic sclerosis (SSc) exhibit increased toxicity when exposed to genotoxic agents. In our study, we evaluated DNA damage and polymorphic sites in 2 DNA repair genes (XRCC1 Arg399Gln and XRCC4 Ile401Thr) in patients with SSc. A total of 177 patients were studied for DNA repair gene polymorphisms. Fifty-six of them were also evaluated for DNA damage in peripheral blood cells using the comet assay. Compared to controls, the patients as a whole or stratified into major clinical variants (limited or diffuse skin involvement), irrespective of the underlying treatment schedule, exhibited increased DNA damage. XRCC1 (rs: 25487) and XRCC4 (rs: 28360135) allele and genotype frequencies observed in patients with SSc were not significantly different from those observed in controls; however, the XRCC1 Arg399Gln allele was associated with increased DNA damage only in healthy controls and the XRCC4 Ile401Thr allele was associated with increased DNA damage in both patients and controls. Further, the XRCC1 Arg399Gln allele was associated with the presence of antinuclear antibody and anticentromere antibody. No association was observed between these DNA repair gene polymorphic sites and clinical features of patients with SSc. These results corroborate the presence of genomic instability in SSc peripheral blood cells, as evaluated by increased DNA damage, and show that polymorphic sites of the XRCC1 and XRCC4 DNA repair genes may differentially influence DNA damage and the development of autoantibodies.

  17. Primary Biliary Cirrhosis Associated with Systemic Sclerosis: Diagnostic and Clinical Challenges

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    Cristina Rigamonti

    2011-01-01

    Full Text Available Patients with primary biliary cirrhosis (PBC often have concurrent limited systemic sclerosis (SSc. Conversely, up to one-fourth of SSc patients are positive for PBC-specific antimitochondrial antibodies (AMA. The mechanisms responsible for the co-occurrence of these diseases are largely unknown. Genetic, epigenetic, environmental, and infectious factors appear to be important for the pathogenesis of the disease, but the hierarchy of events are not well defined. Patients with SSc and PBC have an increased morbidity and mortality compared with the general population, but whether the presence of both diseases in an affected individual worsens the prognosis and/or outcome of either disease is not clear. Some case reports suggested that the presence of SSc in PBC patents is associated with a more favorable prognosis of the liver disease, whereas others report an increased mortality in patients with PBC and SSc compared to patients with PBC alone. This paper discusses the features of patients with PBC-associated SSc. Our aims are to clarify some of the pathogenetic, diagnostic, and clinical challenges that are currently faced in the routine management of these patients. We also intend to provide some practical hints for practitioners that will assist in the early identification of patients with PBC-associated SSc.

  18. Mortality and survival in systemic sclerosis: systematic review and meta-analysis.

    Science.gov (United States)

    Rubio-Rivas, Manuel; Royo, Cristina; Simeón, Carmen Pilar; Corbella, Xavier; Fonollosa, Vicent

    2014-10-01

    To determine the mortality, survival, and causes of death in patients with systemic sclerosis (SSc) through a meta-analysis of the observational studies published up to 2013. We performed a systematic review and meta-analysis of the observational studies in patients with SSc and mortality data from entire cohorts published in MEDLINE and SCOPUS up to July 2013. A total of 17 studies were included in the mortality meta-analysis from 1964 to 2005 (mid-cohort years), with data from 9239 patients. The overall SMR was 2.72 (95% CI: 1.93-3.83). A total of 43 studies have been included in the survival meta-analysis, reporting data from 13,529 patients. Cumulative survival from onset (first Raynaud's symptom) has been estimated at 87.6% at 5 years and 74.2% at 10 years, from onset (non-Raynaud's first symptom) 84.1% at 5 years and 75.5% at 10 years, and from diagnosis 74.9% at 5 years and 62.5% at 10 years. Pulmonary involvement represented the main cause of death. SSc presents a larger mortality than general population (SMR = 2.72). Cumulative survival from diagnosis has been estimated at 74.9% at 5 years and 62.5% at 10 years. Pulmonary involvement represented the main cause of death. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. [Screening of pulmonary hypertension in a Spanish cohort of patients with systemic sclerosis].

    Science.gov (United States)

    García Hernández, Francisco José; Castillo Palma, María Jesús; Montero Mateos, Enrique; González León, Rocío; López Haldón, José Eduardo; Sánchez Román, Julio

    2016-01-01

    Pulmonary arterial hypertension (PAH) is an important cause of morbimortality in systemic sclerosis (SSc). Evolution is worse than that of subjects with idiopathic PAH, but prognosis improves when PAH is diagnosed early. The aim of this research is to describe results of a screening program for diagnosis of pulmonary hypertension (PH) carried out in a cohort of Spanish patients with SSc. PH screening was performed by transthoracic doppler echocardiography (TTDE) in 184 patients with SSc. Patients with systolic pulmonary arterial pressure estimated by TTDE>35 mmHg were evaluated per protocol to confirm diagnosis and type of PH. PAH was diagnosed in 25 patients (13.6%). Patients with diffuse and limited SSc developed PAH in a similar degree, 9/60 (15%) vs. 16/100 (16%), with no cases among patients with SSc "sine scleroderma" or "pre-scleroderma" (P<.001). The only clinical or epidemiological data characterizing patients with PAH were older age (mean age 67 years for patients with PAH vs. 56 years for those without PAH, P=.007), limited SSc, a trend toward shorter evolution of the underlying disease (median 8 years for patients with PAH vs. 10 years for those without PAH, P=.73), and a higher frequency of positive anticentromere antibodies (16 patients [64%] with PAH vs. 70 (48,3%) without PAH, P=.19). Prevalence of PAH in SSc was high and supports the implementation of a regular screening program. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  20. Hypogelsolinemia, a disorder of the extracellular actin scavenger system, in patients with multiple sclerosis

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    Janmey Paul A

    2010-11-01

    Full Text Available Abstract Background Extracellular gelsolin (GSN and GC-globulin/Vitamin D-binding protein (DBP appear to play an important role in clearing the actin from extracellular fluids and in modulating cellular responses to anionic bioactive lipids. In this study we hypothesized that cellular actin release and/or increase in bioactive lipids associated with multiple sclerosis (MS development will translate into alteration of the actin scavenger system protein concentrations in blood and cerebrospinal fluid (CSF of patients with MS. Methods We measured GSN and DBP concentrations in blood and CSF obtained from patients diagnosed with MS (n = 56 in comparison to a control group (n = 20 that includes patients diagnosed with conditions such as idiopathic cephalgia (n = 11, idiopathic (Bell's facial nerve palsy (n = 7 and ischialgia due to discopathy (n = 2. GSN and DBP levels were measured by Western blot and ELISA, respectively. Results We found that the GSN concentration in the blood of the MS group (115 ± 78 μg/ml was significantly lower (p Conclusions The decrease of GSN concentration in blood and CSF of MS subjects suggests that this protein may be involved in chronic inflammation associated with neurodegeneration. Additionally, the results presented here suggest the possible utility of GSN evaluation for diagnostic purposes. Reversing plasma GSN deficiency might represent a new strategy in MS treatment.

  1. Infection of the central nervous system, sepsis and amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Fang Fang

    Full Text Available Severe infections may lead to chronic inflammation in the central nervous system (CNS which may in turn play a role in the etiopathogenesis of amyotrophic lateral sclerosis (ALS. The relentless progression and invasive supportive treatments of ALS may on the other hand induce severe infections among ALS patients.The present study included 4,004 ALS patients identified from the Swedish Patient Register during 1991-2007 and 20,020 age and sex matched general population controls. Conditional logistic regression was used to estimate the odds ratios (ORs of ALS given a previous hospitalization for CNS infection or sepsis. Cox models were used to estimate the hazard ratios (HRs of hospitalization for CNS infection or sepsis after ALS diagnosis. Overall, previous CNS infection (OR: 1.3, 95% confidence interval [CI]: 0.8, 2.4 or sepsis (OR: 1.2, 95% CI: 0.9, 1.6 was not associated with ALS risk. However, compared to ALS free individuals, ALS cases were more likely to be hospitalized for sepsis after diagnosis (HR: 2.6, 95% CI: 1.9, 3.5. We did not observe a higher risk of CNS infection after ALS diagnosis.Our results suggest that acute and severe infections unlikely contribute to the development of ALS; however, ALS patients are at a higher risk of sepsis after diagnosis, compared to ALS free individuals.

  2. Rapid, noninvasive quantitation of skin disease in systemic sclerosis using optical coherence elastography

    Science.gov (United States)

    Du, Yong; Liu, Chih-Hao; Lei, Ling; Singh, Manmohan; Li, Jiasong; Hicks, M. John; Larin, Kirill V.; Mohan, Chandra

    2016-04-01

    Systemic sclerosis (SSc) is a connective tissue disease that results in excessive accumulation of collagen in the skin and internal organs. Overall, SSc has a rare morbidity (276 cases per million adults in the United States), but has a 10-year survival rate of 55%. Currently, the modified Rodnan skin score (mRSS) is assessed by palpation on 17 sites on the body. However, the mRSS assessed score is subjective and may be influenced by the experience of the rheumatologists. In addition, the inherent elasticity of skin may bias the mRSS assessment in the early stage of SSc, such as oedematous. Optical coherence elastography (OCE) is a rapidly emerging technique, which can assess mechanical contrast in tissues with micrometer spatial resolution. In this work, the OCE technique is applied to assess the mechanical properties of skin in both control and bleomycin (BLM) induced SSc-like disease noninvasively. Young's modulus of the BLM-SSc skin was found be significantly higher than that of normal skin, in both the in vivo and in vitro studies (p<0.05). Thus, OCE is able to differentiate healthy and fibrotic skin using mechanical contrast. It is a promising new technology for quantifying skin involvement in SSc in a rapid, unbiased, and noninvasive manner.

  3. Digital amputation in systemic sclerosis: prevalence and clinical associations. A retrospective longitudinal study.

    Science.gov (United States)

    Caramaschi, Paola; Biasi, Domenico; Caimmi, Cristian; Barausse, Giovanni; Sabbagh, Dania; Tinazzi, Ilaria; LA Verde, Valentina; Tonetta, Sara; Adami, Silvano

    2012-08-01

    To evaluate the prevalence of digital necrosis requiring surgical amputation in a single-center group of patients with systemic sclerosis (SSc) and to compare the characteristics of patients with and those without this severe complication. We reviewed the medical records of 188 patients with SSc [162 women, 26 men, mean age 59.2 yrs, mean disease duration 8.0 yrs, mean time from onset of Raynaud's phenomenon (RP) 11.7 yrs, median followup duration 92 mo] enrolled in the Rheumatology Unit since 2004. Demographic and clinical features were collected, as well as the presence of the typical risk factors for atherosclerosis. Nine patients (4.8%) underwent partial or total surgical digital amputation because of necrotic process; all these patients except 1 had a long history of multiple and persisting digital ulcers. All 9 patients had concomitant large-vessel involvement. Comparison of cases with and without digital amputation showed that this complication was associated with older age, long history of RP, long disease duration, presence of anticentromere antibody, and coexistence of peripheral artery disease and hypercholesterolemia. Discussion. We noted that 4.8% of patients with SSc underwent digital amputation. Our retrospective analysis suggests that peripheral artery disease is strongly associated with digital amputation. The preventive strategy for digital ulcers and amputation associated with SSc should include an extensive diagnostic and preventive investigation for peripheral atherosclerosis.

  4. Factors associated with oral hygiene practices among adults with systemic sclerosis

    Science.gov (United States)

    Yuen, Hon K.; Hant, Faye N.; Hatfield, Corey; Summerlin, Lisa M.; Smith, Edwin A.; Silver, Richard M.

    2013-01-01

    OBJECTIVE To identify factors associated with oral hygiene practices in adults with systemic sclerosis (SSc) METHODS In this cross-sectional study, 178 dentate adults with SSc received an oral examination which included measurement of oral aperture, assessment of manual dexterity to perform oral hygiene, as well as completion of the Center of Epidemiological Studies Depression (CES-D) Scale, and an oral health-related questionnaire. RESULTS Multivariable logistic regression modeling showed male, minority and high CES-D scores (i.e., clinically significant symptoms of depression) were associated with less likelihood of participants brushing teeth at least twice daily, but the presence of self-reported dry mouth symptoms increased the likelihood of toothbrushing. Having a dental visit in the past 12 months, and use of an adapted flossing or interdental cleaning device were significantly associated with daily dental flossing; however, having difficulty flossing teeth reduced the likelihood of daily flossing. CONCLUSIONS Overall, demographic variables were strongly associated with toothbrushing frequency, whereas, flossing self-efficacy and barriers were strongly associated with dental flossing frequency in adults with SSc. The results suggest that dental health professionals should take mental health into consideration when educating patients with SSc to improve their oral hygiene, and consider making referrals for patients exhibiting suspected clinically significant depressive symptoms to mental health professionals for further evaluation and treatment. In addition, an appropriate adapted flossing or interdental cleaning device should be recommended to increase dental flossing practices in this patient population. PMID:24128049

  5. Exercise-induced brachial artery blood flow and vascular function is impaired in systemic sclerosis.

    Science.gov (United States)

    Machin, Daniel R; Clifton, Heather L; Garten, Ryan S; Gifford, Jayson R; Richardson, Russell S; Wray, D Walter; Frech, Tracy M; Donato, Anthony J

    2016-12-01

    Systemic sclerosis (SSc) is a rare autoimmune disease characterized by debilitating fibrosis and vascular dysfunction; however, little is known about the circulatory response to exercise in this population. Therefore, we examined the peripheral hemodynamic and vasodilatory responses to handgrip exercise in 10 patients with SSc (61 ± 4 yr) and 15 age-matched healthy controls (56 ± 5 yr). Brachial artery diameter, blood flow, and mean arterial pressure (MAP) were determined at rest and during progressive static-intermittent handgrip exercise. Patients with SSc and controls were similar in body stature, handgrip strength, and MAP; however, brachial artery blood flow at rest was nearly twofold lower in patients with SSc compared with controls (22 ± 4 vs. 42 ± 5 ml/min, respectively; P exercise, there were no differences in MAP between the groups, exercise-induced hyperemia and therefore vascular conductance were ∼35% lower at all exercise workloads in patients with SSc (P exercise-induced brachial artery blood flow and conduit arterial vasodilatory dysfunction during handgrip exercise in SSc and suggest that elevated oxidative stress may play a role.

  6. The vascular perspective of systemic sclerosis: of chickens, mice and men.

    Science.gov (United States)

    Sgonc, R

    1999-11-01

    Systemic sclerosis (SSc), or scleroderma, is an autoimmune connective tissue disease characterized by structural and functional vascular abnormalities, perivascular mononuclear cell infiltration, and increased deposition of extracellular matrix in skin and internal organs. The initial stages of SSc are generally not accessible for analysis in man, therefore, the availability of appropriate animal models is of great importance for the elucidation of the pathogenesis of this disease. UCD-200 chickens show the entire clinical, histopathological and serological spectrum of SSc, whereas tight skin (Tsk)1/+ and Tsk2/+ mice, other animal models of scleroderma, lack the vascular injury. A parallel comparative study of skin biopsies of UCD-200 chickens and human SSc patients revealed that endothelial cell apoptosis, induced by anti-endothelial cell antibody (AECA)- dependent cellular cytotoxicity, is a primary event in the pathogenesis of SSc. This review focuses on recently established data on endothelial cell injury in animals with spontaneous disease and humans, AECA, adhesion molecules and cytokine profiles that support a vascular pathogenesis in scleroderma.

  7. Are There Clinical Differences in Limited Systemic Sclerosis according to Extension of Skin Involvement?

    Science.gov (United States)

    Scolnik, Marina; Catoggio, Luis J.; Lancioni, Eliana; Sabelli, Mirtha R.; Saucedo, Carla M.; Marin, Josefina; Soriano, Enrique R.

    2014-01-01

    Objectives. To examine the characteristics of our patients with limited systemic sclerosis (lSSc) for differences between Barnett Type 1 (sclerodactyly only) and Type 2 or intermediate (acrosclerosis-distal but may reach up to elbows and/or knees plus face) subsets. Methods. Records of patients between January 1, 2000, and December 31, 2011, with SSc or those with anti-Scl-70, anticentromere, or antinucleolar antibodies were reviewed. Only cases fulfilling ACR 1980 criteria were included and classified as diffuse or limited according to LeRoy's criteria. Limited SSc was separated into sclerodactyly and acrosclerosis (Barnett's Types 1 and 2). Results. 234 SSc patients (216 females) fulfilled criteria. Female/male ratio was 12 : 1; 24% had dSSc and 76% lSSC (64% Type 1 and 12% Type 2). Total follow-up was 688 patient-years. Within lSSC, the Type 2 group had significantly shorter duration of Raynaud's and more anti-Scl-70 and less anticentromere antibodies. In particular, interstitial lung disease (ILD) was significantly more prevalent in Type 2 group and similar to Type 3. Conclusions. These results appear to confirm that extension of skin involvement within limited SSc may identify two different subsets with clinical and serologic characteristics. PMID:25435879

  8. The Clinical Relevance of Antifibrillarin (anti-U3-RNP) Autoantibodies in Systemic Sclerosis.

    Science.gov (United States)

    Tall, F; Dechomet, M; Riviere, S; Cottin, V; Ballot, E; Tiev, K P; Montin, R; Morin, C; Chantran, Y; Grange, C; Jullien, D; Ninet, J; Chretien, P; Cabane, J; Fabien, N; Johanet, C

    2017-01-01

    Systemic sclerosis (SSc) is a heterogeneous autoimmune disease associated with several antinuclear autoantibodies useful to diagnosis and prognosis. The aim of the present multicentric study was to determine the clinical relevance of antifibrillarin autoantibodies (AFA) in patients with SSc. The clinical features of 37 patients with SSc positive for AFA (AFA+) and 139 SSc patients without AFA (AFA-) were collected retrospectively from medical records to enable a comparison between AFA- and AFA+ patients. Antifibrillarin autoantibodies were screened by an indirect immunofluorescence technique using HEp2 cells and identified by an in-house Western blot technique and/or an EliA test. Comparing AFA+ and AFA- patients, AFA+ patients were significantly younger at disease onset (36.9 versus 42.9; P = 0.02), more frequently male (P = 0.02) and of Afro-Caribbean descent (65% versus 7.7%; P Afro-Caribbean origin and can identify patients with SSc who are younger at disease onset and display a higher prevalence of myositis. © 2016 The Foundation for the Scandinavian Journal of Immunology.

  9. Nailfold capillaroscopy abnormalities as predictors of mortality in patients with systemic sclerosis.

    Science.gov (United States)

    Kayser, Cristiane; Sekiyama, Juliana Y; Próspero, Lucas C; Camargo, Cintia Z; Andrade, Luis E C

    2013-01-01

    Peripheral microangiopathy is a hallmark of systemic sclerosis (SSc) and can be early detected by nailfold capillaroscopy (NFC). This study aimed to examine whether more severe peripheral microangiopathy at NFC are predictive factor for death in SSc patients. 135 SSc patients who performed NFC between June 2001 and July 2009 were included. The following NFC parameters were evaluated: number of capillary loops/mm, avascular score (scored from 0 to 3), and number of enlarged and giant capillary loops. Univariate and multivariate regression models were used to analyse the association of mortality with NFC and clinical parameters. At the time of the analysis (August 2010), 123 patients were alive, and 12 were dead. By univariate analysis, male gender, forced vital capacity 1.5 on NFC were associated with a significantly increase risk of death. By multivariate analysis, an avascular score >1.5 was the only independent predictor of death (hazard ratio 2.265). Survival rates from diagnosis at 1, 5 and 10 years were lower in patients with avascular score >1.5 (97%, 86%, and 59%, respectively) compared with those with avascular score ≤1.5 (97%, 97%, and 91% respectively) (p=0.009 by log rank test). Avascular scores higher than 1.5 at NFC was an independent predictor of death in SSc, suggesting that NFC can be useful for predicting SSc outcome.

  10. Assessment of autonomic nervous system dysfunction in multiple sclerosis and association with clinical disability

    Science.gov (United States)

    Kale, Nilufer; Magana, Setty; Agaoglu, Jale; Tanik, Osman

    2009-01-01

    Recent studies have reported autonomic dysfunction (AD) in multiple sclerosis (MS), and bladder and/or bowel dysfunction, orthostatic hypotension, and cardiac adaptation disorders have been observed in a wide range of patients (15–80%). The primary aim of this study is to investigate the frequency and association of AD in MS patients, assessed by sympathetic skin response (SSR) and a symptoms questionnaire. The secondary aims are to study the association of AD and disease disability assessed by expanded disability status scale (EDSS), as well as disease duration. One hundred clinically definite MS (CDMS) patients were evaluated for autonomic nervous system (ANS) dysfunction by use of an autonomic symptoms questionnaire and SSR testing. The relationship between these methods, AD and disease-related parameters, such as the expanded disability status scale (EDSS) and disease duration were all evaluated. Sixty-five per cent of the patients presented with AD and 29% of these patients had abnormal SSR results. MS patients with high EDSS values (EDSS>4) and longer disease duration were more likely to have ANS dysfunction (p<0.0001). ANS dysfunction is not uncommon in CDMS patients and thus non-invasive investigations of AD are warranted to optimize AD evaluation and disease management. PMID:21577363

  11. Biopsychosocial typologies of pain in a cohort of patients with systemic sclerosis.

    Science.gov (United States)

    Merz, Erin L; Malcarne, Vanessa L; Assassi, Shervin; Nair, Deepthi K; Graham, Tiffany A; Yellman, Brayden P; Estrada-Y-Martin, Rosa M; Mayes, Maureen D

    2014-04-01

    Despite being a common problem in systemic sclerosis (SSc; scleroderma), the extant literature on pain has primarily focused on biomedical correlates, or bivariate relationships with a few psychological characteristics. There is a need to investigate the more heuristic biopsychosocial model, which incorporates the simultaneous contributions of medical, psychological, and social variables in understanding pain. Patients with SSc (n = 333) received clinical examinations and completed self-report surveys at enrollment in the Genetics versus Environment in Scleroderma Outcome Study. Latent profile analysis was used to derive biopsychosocial profiles of patients using skin thickening, percent predicted forced vital lung capacity, perceived physical health, health worry, mental health, and social support. The profiles were examined in relation to pain and pain medication usage. A 3-profile solution provided the best fit to the data. Based on the biopsychosocial indicators, the profiles were characterized as managing (n = 217), resilient (n = 86), and distressed (n = 30). Between-group differences for pain emerged, with the distressed group, whose disease was less severe than the resilient group, reporting the highest pain and the greatest utilization of pain medication. Clinicians should consider biopsychosocial characteristics as contributing factors to the experience of pain in patients with SSc. Patients who are similar to those in the distressed profile may be at an increased risk for pain and would likely benefit from a referral to a behavioral health or other ancillary service provider for pain management, rather than relying solely on pharmacologic therapies. Copyright © 2014 by the American College of Rheumatology.

  12. Interferon-¿ regulates oxidative stress during experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Espejo, C.; Penkowa, Milena; Saez-Torres, I.

    2002-01-01

    Neurobiology, experimental autoimmune encephalomyelitis IFN-d, multiple sclerosis, neurodegeneration, oxidative stress......Neurobiology, experimental autoimmune encephalomyelitis IFN-d, multiple sclerosis, neurodegeneration, oxidative stress...

  13. Genetic background can result in a marked or minimal effect of gene knockout (GPR55 and CB2 receptor in experimental autoimmune encephalomyelitis models of multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Sofia Sisay

    Full Text Available Endocannabinoids and some phytocannabinoids bind to CB1 and CB2 cannabinoid receptors, transient receptor potential vanilloid one (TRPV1 receptor and the orphan G protein receptor fifty-five (GPR55. Studies using C57BL/10 and C57BL/6 (Cnr2 (tm1Zim CB2 cannabinoid receptor knockout mice have demonstrated an immune-augmenting effect in experimental autoimmune encephalomyelitis (EAE models of multiple sclerosis. However, other EAE studies in Biozzi ABH mice often failed to show any treatment effect of either CB2 receptor agonism or antagonism on inhibition of T cell autoimmunity. The influence of genetic background on the induction of EAE in endocannabinoid system-related gene knockout mice was examined. It was found that C57BL/6.GPR55 knockout mice developed less severe disease, notably in female mice, following active induction with myelin oligodendrocyte glycoprotein 35-55 peptide. In contrast C57BL/6.CB2 (Cnr2 (Dgen receptor knockout mice developed augmented severity of disease consistent with the genetically and pharmacologically-distinct, Cnr2 (tm1Zim mice. However, when the knockout gene was bred into the ABH mouse background and EAE induced with spinal cord autoantigens the immune-enhancing effect of CB2 receptor deletion was lost. Likewise CB1 receptor and transient receptor potential vanilloid one knockout mice on the ABH background demonstrated no alteration in immune-susceptibility, in terms of disease incidence and severity of EAE, in contrast to that reported in some C57BL/6 mouse studies. Furthermore the immune-modulating influence of GPR55 was marginal on the ABH mouse background. Whilst sedative doses of tetrahydrocannabinol could induce immunosuppression, this was associated with a CB1 receptor rather than a CB2 receptor-mediated effect. These data support the fact that non-psychoactive doses of medicinal cannabis have a marginal influence on the immune response in MS. Importantly, it adds a note of caution for the translational

  14. Spotlight on tocilizumab and its potential in the treatment of systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Sakkas LI

    2016-08-01

    Full Text Available Lazaros I Sakkas Department of Rheumatology and Clinical Immunology, Medical School, University of Thessaly, Larissa, Greece Abstract: Systemic sclerosis (SSc is a multisystem disease characterized by extensive collagen deposition in skin and internal organs, fibrointimal microvasculopathy, and activation of the immune system. T cells and B cells can promote fibrosis in SSc. Interleukin (IL-6 is implicated in the pathogenesis of SSc. IL-6 is increased in the peripheral blood and lesional skin from patients with SSc, and induces fibroblast collagen production directly and indirectly by inducing profibrotic M2 macrophages. IL-6 also induces Th17 differentiation and promotes B cell differentiation toward Ig-producing plasma cells. IL-6 is also implicated in the pathogenesis of SSc in animal models as it is increased in mice with bleomycin-induced fibrosis, whereas neutralization of IL-6 in these mice prevents skin fibrosis. IL-6 acts on cells by binding to IL-6 receptor (IL-6R which is transmembrane or soluble, and then recruits the signal-transducing glycoprotein 130 which is ubiquitously expressed. Tocilizumab is an anti-IL-6R humanized monoclonal antibody that blocks IL-6-mediated signaling. Tocilizumab has been approved for the treatment of moderate-to-severe rheumatoid arthritis, for polyarticular and systemic juvenile idiopathic arthritis, and for Castleman’s disease, and is well tolerated. Case reports and a Phase II, randomized trial in SSc have shown some improvement of skin tightness and delayed deterioration of lung function. A Phase III randomized trial in SSc is anticipated. Keywords: biologics, B cells, fibrosis, IL-6, IL-6 receptor

  15. On the respiratory mechanics measured by forced oscillation technique in patients with systemic sclerosis.

    Directory of Open Access Journals (Sweden)

    Ingrid Almeida Miranda

    Full Text Available BACKGROUND: Pulmonary complications are the most common cause of death and morbidity in systemic sclerosis (SSc. The forced oscillation technique (FOT offers a simple and detailed approach to investigate the mechanical properties of the respiratory system. We hypothesized that SSc may introduce changes in the resistive and reactive properties of the respiratory system, and that FOT may help the diagnosis of these abnormalities. METHODOLOGY/PRINCIPAL FINDINGS: We tested these hypotheses in controls (n = 30 and patients with abnormalities classified using spirometry (n = 52 and pulmonary volumes (n = 29. Resistive data were interpreted with the zero-intercept resistance (Ri and the slope of the resistance (S as a function of frequency. Reactance changes were evaluated by the mean reactance between 4 and 32 Hz (Xm and the dynamic compliance (Crs,dyn. The mechanical load was evaluated using the absolute value of the impedance in 4 Hz (Z4Hz. A compartmental model was used to obtain central (R and peripheral (Rp resistances, and alveolar compliance (C. The clinical usefulness was evaluated by investigating the area under the receiver operating characteristic curve (AUC. The presence of expiratory flow limitation (EFL was also evaluated. For the groups classified using spirometry, SSc resulted in increased values in Ri, R, Rp and Z4Hz (p0.90. In groups classified by pulmonary volume, SSc resulted in reductions in S, Xm, C and Crs,dyn (p0.80. It was also observed that EFL is not common in patients with SSc. CONCLUSIONS/SIGNIFICANCE: This study provides evidence that the respiratory resistance and reactance are changed in SSc. This analysis provides a useful description that is of particular significance for understanding respiratory pathophysiology and to ease the diagnosis of respiratory abnormalities in these patients.

  16. The effect of core stability exercises on functional capacity and fatigue in patients with multiple sclerosis

    OpenAIRE

    Hosein Shahrokhi; Amir Letafatkar; Amir Barati; Hasan Daneshmandi; Ali Ashraf Jamshidi

    2017-01-01

    Background : Multiple sclerosis (MS) is a chronic progressive disease on the central nervous system with signs and symptoms such as fatigue and reduced functional capacity. The purpose of this study was to assess the effect of core stability exercises on functional capacity and fatigue in patients with multiple sclerosis. Materials and Methods: The present quasi-experimental study used a pretest-posttest design. The subjects with the age of 20-40, expanded disability status scale (EDSS) 1...

  17. Alterations in the hypothalamic melanocortin pathway in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Vercruysse, Pauline; Sinniger, Jérôme; El Oussini, Hajer; Scekic-Zahirovic, Jelena; Dieterlé, Stéphane; Dengler, Reinhard; Meyer, Thomas; Zierz, Stephan; Kassubek, Jan; Fischer, Wilhelm; Dreyhaupt, Jens; Grehl, Torsten; Hermann, Andreas; Grosskreutz, Julian; Witting, Anke; Van Den Bosch, Ludo; Spreux-Varoquaux, Odile; Ludolph, Albert C; Dupuis, Luc

    2016-04-01

    Amyotrophic lateral sclerosis, the most common adult-onset motor neuron disease, leads to death within 3 to 5 years after onset. Beyond progressive motor impairment, patients with amyotrophic lateral sclerosis suffer from major defects in energy metabolism, such as weight loss, which are well correlated with survival. Indeed, nutritional intervention targeting weight loss might improve survival of patients. However, the neural mechanisms underlying metabolic impairment in patients with amyotrophic lateral sclerosis remain elusive, in particular due to the lack of longitudinal studies. Here we took advantage of samples collected during the clinical trial of pioglitazone (GERP-ALS), and characterized longitudinally energy metabolism of patients with amyotrophic lateral sclerosis in response to pioglitazone, a drug with well-characterized metabolic effects. As expected, pioglitazone decreased glycaemia, decreased liver enzymes and increased circulating adiponectin in patients with amyotrophic lateral sclerosis, showing its efficacy in the periphery. However, pioglitazone did not increase body weight of patients with amyotrophic lateral sclerosis independently of bulbar involvement. As pioglitazone increases body weight through a direct inhibition of the hypothalamic melanocortin system, we studied hypothalamic neurons producing proopiomelanocortin (POMC) and the endogenous melanocortin inhibitor agouti-related peptide (AGRP), in mice expressing amyotrophic lateral sclerosis-linked mutant SOD1(G86R). We observed lower Pomc but higher Agrp mRNA levels in the hypothalamus of presymptomatic SOD1(G86R) mice. Consistently, numbers of POMC-positive neurons were decreased, whereas AGRP fibre density was elevated in the hypothalamic arcuate nucleus of SOD1(G86R) mice. Consistent with a defect in the hypothalamic melanocortin system, food intake after short term fasting was increased in SOD1(G86R) mice. Importantly, these findings were replicated in two other amyotrophic

  18. The economic burden and health-related quality of life associated with systemic sclerosis in France.

    Science.gov (United States)

    Chevreul, K; Brigham, K Berg; Gandré, C; Mouthon, L

    2015-05-01

    To provide data on the economic burden and health-related quality of life (HRQoL) associated with systemic sclerosis (SSc) in France and to raise awareness of the repercussions of this disease for patients and caregivers and on the health and social care system. A cross-sectional study was carried out on 147 patients recruited through the Association des Sclérodermiques de France (ASF), the French association for SSc patients. Data on the patients' use of resources were obtained retrospectively from an online questionnaire and costs were estimated by a bottom-up approach. The HRQoL patients and caregivers was assessed with the five-level EURQol-5 Dimension (EQ-5D-5L) health questionnaire. The average annual cost of SSc was estimated at EUR 22,459 per patient. Direct healthcare costs amounted to EUR 8452, direct non-healthcare formal costs to EUR 1606, direct non-healthcare informal costs to EUR 1875, and indirect costs resulting from patients' absence from the labour market to EUR 10,526. The main contributors to SSc costs were hospitalizations and early retirement. Mean EQ-5D utility scores were 0.49 for patients and 0.66 for caregivers. Although SSc is a rare disease, its economic burden from a societal perspective is substantial and the consequences for HRQoL are significant for both patients and caregivers in France, underscoring the need to develop tailored policies targeted at improving patients' care and reducing the long-term impact of SSc.

  19. Increase in platelet non-integrin type I collagen receptor in patients with systemic sclerosis.

    Science.gov (United States)

    Chiang, Thomas M; Takayama, Hiroshi; Postlethwaite, Arnold E

    2006-01-01

    Microvascular injury is one of the major pathogenetic processes involved in systemic sclerosis (SSc). Interaction of the platelet types I and III collagen receptors with their respective ligand in the exposed subendothelial stroma as a result of ongoing microvascular injury in SSc patients results in platelet activation and aggregation with the release of mediators, which contribute to vascular damage and inflammation. We have found that there is a twofold increase in radiolabeled type I collagen binding to washed platelets from patients with SSc compared to platelets obtained from normal volunteers. Western blot analyses showed that the non-integrin platelet type I collagen receptor protein (65 kDa) is increased dramatically in lysates of platelet from patients with SSc. However, the integrin (alpha(2)beta(1)) and other non-integrin receptors such as glycoprotein VI, glycoprotein IV, and the platelet receptor for type III collagen remain unchanged. In addition, platelet lysates from rheumatic disease controls (rheumatoid arthritis, osteoarthritis, gout, and systemic lupus erythematosus) do not show any significant increases. There is no nitrotyrosylation on 65 kDa in patients with SSc compared to controls, suggesting this might also contribute to binding of CI to the 65-kDa CIR. These results suggest that there is a specific increase in the number of platelet type I collagen receptors in SSc patient's platelets. In addition, the activity of nitric oxide synthase is decreased in patients' platelet lysates compared to controls. The increase in platelet expression of the 65-kDa non-integrin platelet type I collagen receptor may explain the enhanced aggregation of platelets from patients with SSc to CI in vitro and microvascular thrombosis in the disease in vivo.

  20. Vitamin D supplementation and systemic inflammation in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Røsjø, Egil; Steffensen, Linn H; Jørgensen, Lone; Lindstrøm, Jonas C; Šaltytė Benth, Jūratė; Michelsen, Annika E; Aukrust, Pål; Ueland, Thor; Kampman, Margitta T; Torkildsen, Øivind; Holmøy, Trygve

    2015-12-01

    Observational studies have suggested that vitamin D may reduce inflammation in relapsing-remitting multiple sclerosis (RRMS), but this has not been clearly confirmed in randomized controlled trials. To further explore the possible anti-inflammatory effects of vitamin D in RRMS, we examined the effect of high-dose oral vitamin D3 on eleven markers of systemic inflammation in 68 RRMS patients enrolled in a double-blinded randomized placebo-controlled trial of vitamin D3 supplementation (20,000 IU/week) (NCT00785473). Serum inflammation markers and 25-hydroxyvitamin D (25(OH)D) were measured at baseline and week 96, and no restrictions were set on additional standard immunomodulatory treatment for RRMS. The mean 25(OH)D level rose from 56 ± 29 to 123 ± 34 nmol/L among patients receiving vitamin D3 supplementation, whereas only a minor increase from 57 ± 22 to 63 ± 24 nmol/L was seen in the placebo group. However, no significant differences appeared between the vitamin D group and the placebo group for any of the inflammation markers. Patients on immunomodulatory therapy had significantly higher levels of interleukin-1 receptor antagonist and chemokine (C-X-C motif) ligand 16 than patients without immunomodulatory treatment, but there were no clear synergistic effects between immunomodulatory therapy and vitamin D3 supplementation on any of the inflammation markers. The rise in 25(OH)D levels after vitamin D3 supplementation was unaffected by immunomodulatory treatment. We conclude that in this study of RRMS patients, high-dose oral vitamin D3 supplementation prominently increased serum 25(OH)D levels without affecting markers of systemic inflammation, while a more anti-inflammatory phenotype was found among patients on immunomodulatory treatment.

  1. Novel identification of the IRF7 region as an anticentromere autoantibody propensity locus in systemic sclerosis

    Science.gov (United States)

    Carmona, F David; Gutala, Ramana; Simeón, Carmen P; Carreira, Patricia; Ortego-Centeno, Norberto; Vicente-Rabaneda, Esther; García-Hernández, Francisco J; de la Peña, Paloma García; Fernández-Castro, Mónica; Martínez-Estupiñán, Lina; Egurbide, María Victoria; Tsao, Betty P; Gourh, Pravitt; Agarwal, Sandeep K; Assassi, Shervin; Mayes, Maureen D; Arnett, Frank C; Tan, Filemon K; Martín, Javier

    2012-01-01

    Objective Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are related chronic autoimmune diseases of complex aetiology in which the interferon (IFN) pathway plays a key role. Recent studies have reported an association between IRF7 and SLE which confers a risk to autoantibody production. A study was undertaken to investigate whether the IRF7 genomic region is also involved in susceptibility to SSc and the main clinical features. Methods Two case-control sets of Caucasian origin from the USA and Spain, comprising a total of 2316 cases of SSc and 2347 healthy controls, were included in the study. Five single nucleotide polymorphisms (SNPs) in the PHRF1-IRF7-CDHR5 locus were genotyped using TaqMan allelic discrimination technology. A meta-analysis was performed to test the overall effect of these genetic variants on SSc. Results Four out of five analysed SNPs were Significantly associated with the presence of anticentromere autoantibodies (ACA) in the patients with SSc in the combined analysis (rs1131665: pFDR=6.14 × 10−4, OR=0.78; rs4963128: pFDR=6.14 × 10−4, OR=0.79; rs702966: pFDR=3.83 × 10−3, OR=0.82; and rs2246614: pFDR=3.83 × 10−3, OR=0.83). Significant p values were also obtained when the disease was tested globally; however, the statistical significance was lost when the ACA-positive patients were excluded from the study, suggesting that these associations rely on ACA positivity. Conditional logistic regression and allelic combination analyses suggested that the functional IRF7 SNP rs1131665 is the most likely causal variant. Conclusions The results show that variation in the IRF7 genomic region is associated with the presence of ACA in patients with SSc, supporting other evidence that this locus represents a common risk factor for autoantibody production in autoimmune diseases. PMID:21926187

  2. Tuberous Sclerosis Syndrome

    Science.gov (United States)

    ... of Cancer > Tuberous Sclerosis Complex Request Permissions Tuberous Sclerosis Complex Approved by the Cancer.Net Editorial Board , 11/2016 What is tuberous sclerosis complex? Tuberous sclerosis complex (TSC) is a hereditary ...

  3. ALS (Amyotrophic Lateral Sclerosis)

    Science.gov (United States)

    ... Disorders » Patient & Caregiver Education » Fact Sheets Amyotrophic Lateral Sclerosis (ALS) Fact Sheet What is amyotrophic lateral sclerosis? ... I get more information? What is amyotrophic lateral sclerosis? Amyotrophic lateral sclerosis (ALS) is a group of ...

  4. Effects of sarpogrelate hydrochloride on skin ulcers and quality of life in patients with systemic sclerosis.

    Science.gov (United States)

    Yoshimasu, Takashi; Ikeda, Takaharu; Uede, Koji; Kanazawa, Nobuo; Furukawa, Fukumi

    2012-06-01

    5-Hydroxytryptamine 2A serotonin receptor (5-HT(2A) ) is associated with the contraction of vascular smooth muscle, platelet aggregation and thrombus formation and coronary artery spasms. Sarpogrelate hydrochloride (sarpogrelate) is a selective 5-HT(2A) antagonist and was supposed to be effective for Raynaud's phenomenon with collagen disease. Sarpogrelate has not been investigated regarding the effects, safety and quality of life (QOL) in patient with skin ulcers of collagen disease. Eleven patients with skin ulcers and systemic sclerosis (SSc) were administrated sarpogrelate p.o. three times a day for 3-6 months. The area (mean ± standard error) of skin ulcer at the pretreatment, and after 3 and 6 months of sarpogrelate intake was 2.1 ± 0.8, 0.2 ± 0.1 and 0.1 ± 0.1 mm(2), respectively. The reduction of skin ulcer area was significant after 3 months of sarpogrelate intake. In assessment of QOL, scores of symptoms and emotions but not of functioning were significantly improved after sarpogrelate intake. The global score (mean ± SE) of Skindex-16 at pretreatment, and after 3 and 6 months of sarpogrelate intake was 31.8 ± 8.7, 23.7 ± 8.3 and 10.9 ± 4.6, respectively. The score was significantly improved after 6 months of sarpogrelate intake. There were no obvious side-effects during this study. Sarpogrelate was considered to be a useful drug to improve skin ulcers and QOL in patients with SSc. © 2011 Japanese Dermatological Association.

  5. Detection of anti-mitochondrial antibodies by immunoprecipitation in patients with systemic sclerosis.

    Science.gov (United States)

    Ceribelli, Angela; Isailovic, Natasa; De Santis, Maria; Generali, Elena; Satoh, Minoru; Selmi, Carlo

    2018-01-01

    To describe a new immunoprecipitation pattern identified in Italian patients affected by systemic sclerosis (SSc), corresponding to the pyruvate dehydrogenase antigen complex recognized by anti-mitochondrial antibodies (AMA) in primary biliary cholangitis (PBC). Autoantibodies in sera from 85 patients with SSc were tested by protein- and RNA-immunoprecipitation. Immunoprecipitation-Western blot was used to determine the identified proteins, and medical records re-evaluated for liver function tests and PBC. In 13/85 (15%) SSc sera, a unique set of 75-50-40-34kD proteins that had not been previously reported, was noted. The four proteins were identified as the proteins X/E3BP, E1α, E1β, and E2/E3 of the pyruvate dehydrogenase antigen complex by immunoprecipitation-Western blot. From clinical record evaluation, 9/13 (69%) SSc patients with this new pattern were positive for AMA by routine indirect immunofluorescence, and 7/13 (54%) had a diagnosis of PBC, while 4/13 (31%) manifested no biochemical signs of cholestasis. Twelve of 13 patients with SSc and AMA by immunoprecipitation have a limited cutaneous form of SSc and anti-centromere antibodies. We describe a pattern of 4 proteins in 15% of SSc patients, identified for the first time by protein-immunoprecipitation. This pattern corresponds to serum AMA against the pyruvate dehydrogenase antigen complex and it must be considered in the interpretation of protein-immunoprecipitation results. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Nintedanib inhibits fibroblast activation and ameliorates fibrosis in preclinical models of systemic sclerosis.

    Science.gov (United States)

    Huang, Jingang; Beyer, Christian; Palumbo-Zerr, Katrin; Zhang, Yun; Ramming, Andreas; Distler, Alfiya; Gelse, Kolja; Distler, Oliver; Schett, Georg; Wollin, Lutz; Distler, Jörg H W

    2016-05-01

    Nintedanib is a tyrosine kinase inhibitor that has recently been shown to slow disease progression in idiopathic pulmonary fibrosis in two replicate phase III clinical trials. The aim of this study was to analyse the antifibrotic effects of nintedanib in preclinical models of systemic sclerosis (SSc) and to provide a scientific background for clinical trials in SSc. The effects of nintedanib on migration, proliferation, myofibroblast differentiation and release of extracellular matrix of dermal fibroblasts were analysed by microtitre tetrazolium and scratch assays, stress fibre staining, qPCR and SirCol assays. The antifibrotic effects of nintedanib were evaluated in bleomycin-induced skin fibrosis, in a murine sclerodermatous chronic graft-versus-host disease model and in tight-skin-1 mice. Nintedanib dose-dependently reduced platelet-derived growth factor-induced and transforming growth factor-β-induced proliferation and migration as well as myofibroblast differentiation and collagen release of dermal fibroblasts from patients with and healthy individuals. Nintedanib also inhibited the endogenous activation of SSc fibroblasts. Nintedanib prevented bleomycin-induced skin fibrosis in a dose-dependent manner and was also effective in the treatment of established fibrosis. Moreover, treatment with nintedanib ameliorated fibrosis in the chronic graft-versus-host disease model and in tight-skin-1 mice in well-tolerated doses. We demonstrate that nintedanib effectively inhibits the endogenous as well as cytokine-induced activation of SSc fibroblasts and exerts potent antifibrotic effects in different complementary mouse models of SSc. These data have direct translational implications for clinical trials with nintedanib in SSc. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  7. Small, medium but not large arteries are involved in digital ulcers associated with systemic sclerosis.

    Science.gov (United States)

    Aïssou, Linda; Meune, Christophe; Avouac, Jérôme; Meunier, Marine; Elhaï, Muriel; Sorbets, Emmanuel; Kahan, André; Allanore, Yannick

    2016-07-01

    Digital ulcers (DU) are a burden in systemic sclerosis (SSc). Microangiopathy is a cardinal feature of SSc that plays a critical role in the development of DU. However, whether injury of medium or large vessels also contributes to DU in SSc remains controversial. To measure concomitantly in SSc patients with and without active DU: (i) the Augmentation Index of the reflected wave (Aix_75) by radial applanation tonometry, an index of small and medium arterial function; (II) the aortic pulse wave velocity (PWV), a marker of large vessel injury (aortic stiffness). Sixty-three consecutive SSc patients were included (49 females, aged 60 [49-65] years, disease duration of 8.5 [5-13] years), including 10 (15.9%) with active DU. Patients with active DU versus those without had increased Aix_75 (35% [28-38] versus 28% [20-34], P=0.041) whereas no difference existed in PWV (7.0m/s [6.7-10.1] versus 7.6m/s [6.8-8.7], P=0.887), in systolic, diastolic, as well as aortic pulse pressure (P=0.126, 0.592, and 0.161, respectively). When compared to patients in the low tertile, patients having Aix_75 in the highest tertile had 10-fold more DU (OR=10.23; 95% CI 1.12 to 93.34, P=0.039). The presence of DU is associated with increased Aix_75 whereas there is no relation with PWV. These data suggest that small and medium arteries are involved in the occurrence of DU whether large vessel stiffness does not contribute. Whether Aix_75 is predictive of further DU remained to be studied. Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  8. Sjögren's syndrome in rheumatoid arthritis and progressive systemic sclerosis. A comparative study.

    Science.gov (United States)

    Andonopoulos, A P; Drosos, A A; Skopouli, F N; Moutsopoulos, H M

    1989-01-01

    One hundred and eleven patients with rheumatoid arthritis (RA) and 44 with progressive systemic sclerosis (PSS) were prospectively evaluated for evidence of Sjögren's syndrome (Ss). The diagnosis was established when a patient with a lip biopsy focal lymphocytic infiltration score of greater than or equal to 2+ in Tarpley's scale had keratoconjunctivitis sicca (KCS) and/or xerostomia. Out of 44 RA and 10 PSS patients with positive lip biopsy, 34 and 9 had criteria for Ss respectively, suggesting a 31% prevalence of Ss in RA and a 20.5% in PSS. Six per cent of the RA patients spontaneously offered complaints of subjective xerophthalmia whereas 11.1% and 22.2% of those with PSS did so for subjective xerophthalmia and xerostomia respectively. However, specific questionnaire elicited subjective xerophthalmia in 38.2% and subjective xerostomia in 5.9% of the RA patients, whereas in 55.5% and 66.7% of the PSS ones respectively. Parotid gland enlargement was detected in 20.6% of the RA and in 44.4% of the PSS patients with Ss. Anti-Ro (SSA) antibodies were present in the sera of 23.5% and 33.3% of them respectively. Severe extraglandular manifestations were unusual in both groups. Our results suggest that, although both Ss in RA and that in PSS lack prominent exocrine gland symptomatology, certain differences between the two and similarities of the latter to primary Ss, would not justify the term 'secondary Ss' for the syndrome accompanying scleroderma, as it has been applied to that accompanying RA.

  9. Stretching Reduces Skin Thickness and Improves Subcutaneous Tissue Mobility in a Murine Model of Systemic Sclerosis.

    Science.gov (United States)

    Xiong, Ying; Berrueta, Lisbeth; Urso, Katia; Olenich, Sara; Muskaj, Igla; Badger, Gary J; Aliprantis, Antonios; Lafyatis, Robert; Langevin, Helene M

    2017-01-01

    Although physical therapy can help preserve mobility in patients with systemic sclerosis (SSc), stretching has not been used systematically as a treatment to prevent or reverse the disease process. We previously showed in rodent models that stretching promotes the resolution of connective tissue inflammation and reduces new collagen formation after injury. Here, we tested the hypothesis that stretching would impact scleroderma development using a mouse sclerodermatous graft-versus-host disease (sclGvHD) model. The model consists in the adoptive transfer (allogeneic) of splenocytes from B10.D2 mice (graft) into Rag2(-/-) BALB/c hosts (sclGvHD), resulting in skin inflammation followed by fibrosis over 4 weeks. SclGvHD mice and controls were randomized to stretching in vivo for 10 min daily versus no stretching. Weekly ultrasound measurements of skin thickness and subcutaneous tissue mobility in the back (relative tissue displacement during passive trunk motion) successfully captured the different phases of the sclGvHD model. Stretching reduced skin thickness and increased subcutaneous tissue mobility compared to no stretching at week 3. Stretching also reduced the expression of CCL2 and ADAM8 in the skin at week 4, which are two genes known to be upregulated in both murine sclGvHD and the inflammatory subset of human SSc. However, there was no evidence that stretching attenuated inflammation at week 2. Daily stretching for 10 min can improve skin thickness and mobility in the absence of any other treatment in the sclGvHD murine model. These pre-clinical results suggest that a systematic investigation of stretching as a therapeutic modality is warranted in patients with SSc.

  10. Newer insights into the management of interstitial lung disease in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Robert L Mango

    2017-01-01

    Full Text Available Interstitial lung disease (ILD is a debilitating complication of systemic sclerosis (SSc and now the leading cause of death in SSc patients, largely from progressive respiratory failure or advanced pulmonary hypertension. Despite significant advances in our understanding of the epidemiology and pathogenesis of SSc-ILD, there are significant uncertainties in the approach to managing these patients given the heterogeneity of presentation, substantial variability in progression, and presence of comorbid cardiopulmonary conditions, particularly pulmonary hypertension and esophageal dilation with recurrent aspiration pneumonitis that portend poor prognosis. Early detection of progressive lung involvement based on worsening pulmonary physiology and quantification of fibrosing alveolitis severity on high-resolution computed tomography is critical as response to immunomodulatory agents is usually best when initiated earlier in the disease course. A selected group of patients may benefit from early referral for hematopoietic stem cell transplantation or lung/heart–lung transplant. The last decade has seen a significant advance in evidence-based approaches to treatment of SSc-ILD with immune suppressants, and there are several ongoing treatment trials with recent advances in understanding of the role of pro-inflammatory and profibrotic cytokines in SSc-ILD. The efficacy of antifibrotic agents in idiopathic pulmonary fibrosis has also provided another promising avenue for utilization in these patients. In this review, we will provide an up-to-date review of the treatment options for SSc-ILD, the ongoing studies moving this field forward, emerging treatments for SSc-ILD, and propose a management algorithm for SSc-ILD, based on the available evidence in the literature and our experience.

  11. Sociodemographic and disease correlates of body image distress among patients with systemic sclerosis.

    Directory of Open Access Journals (Sweden)

    Lisa R Jewett

    Full Text Available Body image concerns are infrequently studied in systemic sclerosis (SSc, even though significant visible disfigurement is common. The objective of this study was to identify sociodemographic and disease-related correlates of dissatisfaction with appearance and social discomfort among people with SSc.SSc patients came from the 15-center Canadian Scleroderma Research Group Registry. Sociodemographic information was based on patient self-report. Disease characteristics were obtained via physician examinations. The Brief-SWAP was used to assess dissatisfaction with appearance and social discomfort. Structural equation models were conducted with MPlus to determine the relationship of dissatisfaction with appearance and social discomfort with age, sex, education, marital status, race/ethnicity, disease duration, skin involvement, telangiectasias, skin pigmentation changes, and hand contractures.A total of 489 SSc patients (432 female, 57 male were included. Extent of skin involvement was significantly associated with both dissatisfaction with appearance and social discomfort (standardized regression coefficients = 0.02, p = 0.001; 0.02, p = 0.020, respectively, as was skin involvement in the face (0.18, p = 0.016; 0.23, p = 0.006, respectively. Greater social discomfort was robustly associated with younger age (-0.017, p<0.001 and upper-body telangiectasias (0.32, p = 0.021. Dissatisfaction with appearance was associated with hand contractures (0.07, p = 0.036.This study found that dissatisfaction with appearance and social discomfort were associated with numerous disfiguring characteristics of SSc, in addition to age. These results underline that there are multiple factors contributing to body image distress in SSc, as well as the need to attend to both disease and social contexts in understanding the impact of disfigurement among patients.

  12. Capillary loss on nailfold capillary microscopy is associated with mortality in systemic sclerosis.

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    Pavan, Thais Rohde; Bredemeier, Markus; Hax, Vanessa; Capobianco, Karina Gatz; da Silva Mendonça Chakr, Rafael; Xavier, Ricardo Machado

    2018-02-01

    The objective of this study is to test the association of the severity of nailfold capillaroscopy (NFC) abnormalities with mortality in systemic sclerosis (SSc). One hundred and seventy SSc patients underwent an extensive evaluation (including high-resolution computed tomography, pulmonary function tests, and Doppler echocardiography) at baseline following a standard protocol. Capillary loss on NFC was evaluated using the avascular score (AS, ranging from 0 to 3), and the mean number of ectasias, megacapillaries, and hemorrhages per finger was also recorded. After a mean period of 10.1 ± 4.9 years, the life status of the patients was ascertained. Univariate and multivariate Cox proportional hazards models were used for statistical analysis. Overall, 73 patients died. By univariate Cox analysis, the AS was significantly associated with mortality (hazard ratio [HR] = 1.64, 95% CI 1.22 to 2.19, p = 0.001). In our study, this association was stronger than that of race, gender, anticentromere antibodies, anti-topoisomerase I antibodies, and form of disease and had similar strength to that of skin score in univariate analyses. However, after controlling for a combination of variables (age, skin score, gender, race, signs of peripheral ischemia, and extent of interstitial lung disease, all independently associated with mortality), the association of AS with mortality was blunted (HR = 1.15, 95% CI 0.80 to 1.65, p = 0.445). Other NFC variables were not related to mortality. AS was associated with higher risk of death and, despite not having an independent association with mortality after controlling for a set of demographic and clinical variables, may be a useful tool in prognostic evaluation of SSc.

  13. Medical signs and symptoms associated with disability, pain, and psychosocial adjustment in systemic sclerosis.

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    Malcarne, Vanessa L; Hansdottir, Ingunn; McKinney, Ann; Upchurch, Renn; Greenbergs, Helen L; Henstorf, Gretchen H; Furst, Daniel E; Clements, Philip J; Weisman, Michael H

    2007-02-01

    To examine physician-assessed medical signs and patient-reported medical symptoms as correlates of 3 quality of life (QOL) outcomes in patients with systemic sclerosis (SSc): disability, pain, and psychosocial adjustment. One hundred fourteen patients with SSc underwent a comprehensive clinical examination including determination of skin thickening [Modified Rodnan Skin Score (MRSS)]. Patients reported current symptoms and completed standardized questionnaires assessing disability and pain (Health Assessment Questionnaire) and psychosocial adjustment (Psychosocial Adjustment to Illness Scale). Regression analysis was used to examine physician-determined and patient-reported correlates of the 3 outcomes. MRSS was a significant correlate of all outcomes, although it explained only a small amount of the variance in psychosocial adjustment. Patient-reported postprandial bloating was the strongest correlate of psychosocial adjustment, explaining more than twice as much variance as MRSS. After accounting for MRSS, patient-reported dependent edema significantly correlated with all outcomes. For disability, significant correlates were physician-determined joint tenderness and number of tender points, and patient-reported joint pain on motion, joint contracture, extremity ulcers other than digital, and dyspnea. Patient-reported joint tenderness was significantly associated with pain. Regression analysis supported a model in which disability and pain mediated the relationship between MRSS and psychosocial adjustment. Skin score is strongly associated with disability and pain, but only weakly associated with psychosocial adjustment. Dependent edema has negative implications across quality-of-life outcomes. Disability and pain mediate the relationship between disease severity and psychosocial adjustment to disease. Assessment (including self-report of patient symptoms) of specific medical signs and symptoms may indicate SSc patients experiencing diminished QOL.

  14. Ultrasound lung comets: new echographic sign of lung interstitial fibrosis in systemic sclerosis

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    C. Giacomelli

    2011-09-01

    Full Text Available Objective: Interstitial lung disease (ILD and pulmonary arterial hypertension (PAH are common complications of systemic sclerosis (SSc. Echocardiography evaluates PAH, and chest sonography detects even mild ILC as ultrasound lung comets (ULC, i.e. multiple comet-tails fanning out from the lung surface and originating from subpleural interlobular septa thickened by fibrosis. Aim: to assess ILaD and PAH by integrated cardiac and chest ultrasound in SSc. Methods: We enrolled 30 consecutive SSc patients (age= 54±13 years, 23 females in the Rheumatology Clinic of Pisa University. In all, we assessed systolic pulmonary arterial pressure (SPAP, from maximal velocity of tricuspid regurgitation flow, and ULC score with chest sonography (summing the number of ULC from each scanning space of anterior and posterior right and left chest, from second to fifth intercostal space. All patients underwent plasma assay for anti-topoisomerase antibodies (anti-Scl70, and antiicentromere associated with development of pulmonary involvement. Twenty-eight patients also underwent high resolution computed tomography, HRCT (from 0= no fibrosis to 3= honey combing. Results: ULC number - but not SPAP - was correlated to HRCT fibrosis and presence Scl-70 antibodies. ULC number was similar in localized or diffuse forms (16±20 vs 21±19, p=ns and was unrelated to SPAP (r=0.216, p=ns. Conclusions: Chest sonography assessment and ULC allow a complete, simple, radiation-free characterization of interstitial lung involvement in SSc - all in one setting and with the same instrument, same transducer and the same sonographer. In particular, ULC number is associated with HRCT evidence of lung fibrosis and presence of Scl-70 antibodies.

  15. Caveolin-1 deficiency may predispose African Americans to systemic sclerosis-related interstitial lung disease.

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    Reese, Charles; Perry, Beth; Heywood, Jonathan; Bonner, Michael; Visconti, Richard P; Lee, Rebecca; Hatfield, Corey M; Silver, Richard M; Hoffman, Stanley; Tourkina, Elena

    2014-07-01

    Interstitial lung disease (ILD) is the leading cause of death in patients with systemic sclerosis (SSc; scleroderma). Although SSc-related ILD is more common and severe in African Americans than in Caucasians, little is known about factors underlying this significant health disparity. The aim of this study was to examine the role that low expression of caveolin-1 might play in susceptibility to ILD among African Americans. Assays of monocyte migration toward stromal cell-derived factor 1 (SDF-1) were performed using monocytes from Caucasian and African American healthy donors and patients with SSc. For fibrocyte differentiation studies, total peripheral blood mononuclear cells were incubated on fibronectin-coated plates. Protein expression was evaluated by immunohistochemistry and Western blotting. Monocytes from healthy African American donors and those from patients with SSc had low caveolin-1 levels, enhanced migration toward the CXCR4 ligand SDF-1, and enhanced differentiation to fibrocytes. Enhanced migration and differentiation of monocytes from African Americans and patients with SSc appeared to be attributable to the lack of caveolin-1, because restoring caveolin-1 function using a caveolin-1 scaffolding domain peptide inhibited these processes. Although they differed from monocytes from Caucasians, monocytes from both African Americans and patients with SSc were not identical, because SSc monocytes showed major increases from baseline in ERK, JNK, p38, and Smad2/3 activation, while monocytes from African Americans showed only limited ERK activation and no activation of JNK, p38, or Smad2/3. In contrast, SDF-1 exposure caused no additional ERK activation in SSc monocytes but did cause significant additional activation in monocytes from African Americans. African Americans may be predisposed to SSc-related ILD due to low baseline caveolin-1 levels in their monocytes, potentially affecting signaling, migration, and fibrocyte differentiation. The monocytes of

  16. Presence of organ‑specific antibodies in patients with systemic sclerosis.

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    Wielosz, Ewa; Majdan, Maria; Koszarny, Arkadiusz; Dryglewska, Magdalena; Tabarkiewicz, Jacek

    2016-10-05

    INTRODUCTION According to the literature, organ‑specific antibodies may be present in the course of systemic sclerosis (SSc). OBJECTIVES The aim of this study was to assess the prevalence of antithyroid antibodies (antithyroid peroxidase antibodies [anti‑TPO] and antithyroglobulin antibodies) and of antimitochondrial antibodies (AMAs), as well as to evaluate their clinical significance in patients with SSc. PATIENTS AND METHODS The study involved 86 consecutive in‑hospital patients with SSc (32 patients with diffuse cutaneous SSc [dcSSc] and 54 with limited cutaneous SSc [lcSSc]). Patients were observed for autoimmune thyroid diseases (ATDs) and primary biliary cirrhosis (PBC). Serum samples were obtained from each patient. RESULTS Positive antithyroid antibody titers were observed in 27 patients (31%) and positive AMA titers-in 11 patients (13%). ATD was diagnosed in 26 patients (30%) and PBC-in 10 patients (12%) with SSc. No significant differences in the prevalence of antithyroid antibodies were found between patients with dcSSc and those with lcSSc, but the prevalence of AMAs was significantly higher in patients with lcSSc compared with those with dcSSc. The prevalence of anti‑Ro‑52 antibodies was significantly higher in the SSc group with positive anti‑TPO antibody titers compared with the SSc group with negative anti‑TPO antibody titers. The prevalence of anticentromere antibodies (ACAs) was significantly higher in the SSc group with positive AMA titers compared with the SSc group with negative AMA titers. CONCLUSIONS The prevalence of organ‑specific antibodies in SSc patients is relatively high. The prevalence of AMAs is higher in patients with lcSSc than in those with dcSSc and is strongly associated with the presence of ACAs. Patients with SSc should be evaluated for coexisting ATDs and PBC.

  17. Familial autoimmunity and polyautoimmunity in 60 Brazilian Midwest patients with systemic sclerosis

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    Alex Magno Coelho Horimoto

    Full Text Available ABSTRACT Introduction: Systemic sclerosis (SSc is a connective tissue disease of unknown etiology, characterized by a triad of vascular injury, autoimmunity and tissue fibrosis. It is known that a positive family history is the greatest risk factor already identified for the development of SSc in a given individual. Preliminary observation of a high prevalence of polyautoimmunity and of familial autoimmunity in SSc patients support the idea that different autoimmune phenotypes may share common susceptibility variants. Objectives: To describe the frequency of familial autoimmunity and polyautoimmunity in 60 SSc patients in the Midwest region of Brazil, as well as to report the main autoimmune diseases observed in this association of comorbidities. Methods: A cross-sectional study with recruitment of 60 consecutive patients selected at the Rheumatology Department, University Hospital, Medicine School, Federal University of Mato Grosso do Sul (FMUFMS, as well as interviews of their relatives during the period from February 2013 to March 2014. Results: A frequency of 43.3% of polyautoimmunity and of 51.7% of familial autoimmunity in SSc patients was found. Patients with the presence of polyautoimmunity and familial autoimmunity presented primarily the diffuse form of SSc, but this indicator did not reach statistical significance. The autoimmune diseases most frequently observed in polyautoimmunity patients were: Hashimoto's thyroiditis (53.8%, Sjögren's syndrome (38.5%, and inflammatory myopathy (11.5%. The main autoimmune diseases observed in SSc patients' relatives were: Hashimoto's thyroiditis (32.3%, rheumatoid arthritis (22.6%, and SLE (22.6%. The presence of more than one autoimmune disease in SSc patients did not correlate with disease severity or activity. Conclusions: From the high prevalence of coexisting autoimmune diseases found in SSc patients, we stress the importance of the concept of shared autoimmunity, in order to promote a

  18. Nailfold digital capillaroscopic findings in patients with diffuse and limited cutaneous systemic sclerosis.

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    Shenavandeh, Saeedeh; Haghighi, Mahyar Yousefipour; Nazarinia, Mohammad Ali

    2017-01-01

    Systemic sclerosis (SSc) is a chronic disease with microvascular damage. Nailfold capillaroscopy is a non-invasive method used for evaluating capillaries in SSc. Its findings could be related to the internal organ involvement and SSc course. In this study, we aimed to determine the association of the capillaroscopic patterns of nailfold capillaries with the disease subtypes of SSc, disease duration, and clinical manifestations. Seventy patients with SSc (15 cases with diffuse cutaneous SSc [DcSSc] and 55 patients with limited SSc [LcSSc]) were studied. The patients were classified into early and intermediate/late DcSSc and LcSSc regarding their disease duration. The capillaroscopy findings were classified into normal, 'early', 'active' and 'late' scleroderma patterns, and 'non-specific' changes. The association of the nailfold capillaroscopy changes and their components with clinical manifestations was also studied. We studied 15 DcSSc and 55 LcSSc patients. No association was found between the patterns of capillaroscopic changes and these subtypes. There were 8 early DcSSc, 7 intermediate/late DcSSc, 34 early LcSSc, and 21 intermediate/late LcSSc patients. In patients with LcSSc, the 'early' scleroderma pattern of capillaroscopy was associated with early disease based on duration. We found a direct association between some capillary components and some clinical findings. Also, some capillaroscopic components had an inverse association with some clinical manifestations. We found no association between the patterns of capillaroscopy and SSc subtypes; early scleroderma pattern of capillaroscopy was significantly associated with early LcSSc, compatible with the slower course of the disease in LcSSc. Subtle changes, capillary elongation, and capillary tortuosity had an inverse association with clinical manifestations and might be considered as good prognostic factors.

  19. The arthropathy of systemic sclerosis: a 12 month prospective clinical and imaging study

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    Montagna, Giovanni La; Malesci, Domenico; Valentini, Gabriele [Seconda Universita di Napoli, Dipartimento Medico-Chirurgico di Internistica, Clinica e Sperimentale ' ' F Magrassi e A Lanzara' ' , Unita Operativa di Reumatologia, Naples (Italy); Sodano, Antonio; Capurro, Vittorio [Universita ' ' Federico II' ' , Dipartimento di Diagnostica per Immagini e Radioterapia, Naples (Italy)

    2005-01-01

    To assess the clinical and radiological features of systemic sclerosis (SSc) joint involvement in a prospective cross-sectional study. Seventy-six consecutive patients with SSc divided into clinical and serological subsets were investigated. Clinical and radiological assessments of the hands and feet were carried out. Three radiological patterns of inflammatory, degenerative and fibrotic changes were predefined. The Health Assessment Questionnaire (HAQ) disability index (DI) and individual components of the HAQ-DI were also evaluated. The highest impairments on the HAQ-DI (median 0.44; range 0-2.87) were detected in subdimensions such as hygiene, grip and activity components. Clinically articular involvement, arthralgia and finger contractures were seen more frequently than arthritis, and a significantly higher prevalence of finger flexion was found in patients with diffuse cutaneous SSc (P=0.03) compared with the other SSc subtypes. Radiologically, distal interphalangeal joint space narrowing and flexion deformity indicating periarticular fibrosis were frequently detected. Juxta-articular osteoporosis, joint space narrowing and flexion contractures of the fingers were seen significantly more frequently in the hands. A significantly higher frequency of fibrotic pattern were found in the hands whereas a degenerative pattern was more frequent in the feet (P<0.05). Finally, significant correlations were detected between flexion contractures and a radiological fibrotic pattern (P<0.001), and the severity scores of peripheral vascular impairment (P=0.026) and skin (P=0.007). This cross-sectional prospective study confirms that an arthropathy is common in SSc patients and shows that it is a major determinant of disability. A classification of radiological alterations into three specific patterns is proposed. (orig.)

  20. Severity and features of frailty in systemic sclerosis-associated interstitial lung disease.

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    Guler, Sabina A; Kwan, Joanne M; Winstone, Tiffany A; Milne, Kathryn M; Dunne, James V; Wilcox, Pearce G; Ryerson, Christopher J

    2017-08-01

    Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is characterized by multiple symptoms and comorbidities. The cumulative impact of these deficits can be summarized using the concept of frailty; however, frailty has not been characterized in patients with SSc-ILD. Patients with SSc-ILD and non-CTD fibrotic ILD were recruited from specialized clinics. Frailty was assessed using a 42-item patient-reported Frailty Index, calculated as the proportion of reported deficits divided by the total number of surveyed items. Frailty was defined as a Frailty Index >0.21. Unadjusted and multivariate analyses were used to identify correlates of frailty. The study cohort included 86 patients with SSc-ILD and 167 patients with non-CTD fibrotic ILD. The mean age in SSc-ILD was 60.5 years, 80% were women, and on average patients had mild to moderate restrictive lung function impairment (mean FVC 78%-predicted, DLCO 51%-predicted). The mean Frailty Index was 0.23 ± 0.15, with 55% of the SSc-ILD population meeting criteria for frailty. Dyspnea had the strongest association with the Frailty Index (r = 0.62, p frailty on multivariate analysis. Frailty severity was similar in SSc-ILD and non-CTD fibrotic ILD, including with adjustment for differences in baseline cohort characteristics. Frailty is highly prevalent in patients with SSc-ILD, indicating that chronological age significantly underestimates biological age in this population. Dyspnea is the variable with the strongest association with frailty in SSc-ILD; however, future studies are needed to identify additional modifiable determinants of frailty and the ability of frailty to predict outcomes in SSc-ILD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Systemic sclerosis interstitial lung disease evaluation: comparison between semiquantitative and quantitative computed tomography assessments.

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    Ariani, A; Lumetti, F; Silva, M; Santilli, D; Mozzani, F; Lucchini, G; Delsante, G; Sverzellati, N

    2014-01-01

    The pulmonary fibrosis extent in systemic sclerosis (SSc) has a prognostic value. Chest Computed Tomography (CT) is the gold standard to detect an interstitial lung disease (ILD). Semi-quantitative scores and quantitative methods can estimate the ILD. The first ones have a considerable inter-intraobserver variability, while quantitative scores, based on distribution of lung attenuation parameters (also called CT indexes), can be obtained through expensive and not so user-friendly software. The aim of this work is to investigate whether a DICOM-viewer open-source software (OsiriX) can obtain CT indexes correlating with semi-quantitative scores. Sixty-three chest CTs of ILD-SSc patients were assessed with two semi-quantitative methods (visual extent and limited/extensive ILD grading) and then blindly processed with OsiriX to obtain the distribution parameters of lung attenuation (kurtosis, skewness and mean). Semiquantitative assessment and CT indexes were compared through the Spearman rank test and Mann-Whitney test. All CT indexes showed a statistically significant correlation of moderate degree with the visual extent semi-quantitative assessment (p-value less than 0.05). Skewness was the lung attenuation distribution parameter with the strongest correlation (r =-0.378, p-value = 0.0023). Moreover, CT indexes of patients with an extensive and limited disease were statistically different (p less than 0.01). CT indexes correlating with a radiological semi-quantitative ILD assessment can be obtained through OsiriX. CT indexes can be considered very helpful to discriminate patients with extensive and limited ILD.

  2. Prevalence, incidence, survival, and disease characteristics of systemic sclerosis in a large US population.

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    Mayes, Maureen D; Lacey, James V; Beebe-Dimmer, Jennifer; Gillespie, Brenda W; Cooper, Brenda; Laing, Timothy J; Schottenfeld, David

    2003-08-01

    To estimate the prevalence, incidence, survival, and disease characteristics of systemic sclerosis (SSc) in the Detroit tricounty area. A census of SSc cases for the period 1989-1991 was conducted in the Detroit area, using multiple sources for case identification. Diagnoses were verified by medical record review. Capture-recapture analysis was used to estimate the total SSc population. Cases of localized scleroderma (morphea and linear disease) were excluded. Based on 706 verified cases of SSc, prevalence was initially estimated to be 242.0 cases per million adults (95% confidence interval [95% CI] 213-274), with an annual incidence of 19.3 new cases per million adults per year (95% CI 12.4-30.2). Capture-recapture analysis, based on the degree of overlap of verified cases among multiple sources, resulted in a revised prevalence estimate of 276 cases per million adults (95% CI 245-310). Sex- and race-specific prevalence estimates were significantly higher for women than for men, and for blacks than for whites. The average age at diagnosis was significantly younger for blacks than for whites. Compared with white patients, black patients were almost twice as likely to have diffuse disease (prevalence proportion ratio 1.86, 95% CI 1.48-2.35). Median survival was approximately 11 years. Factors negatively affecting survival included male sex (hazard ratio 1.81, 95% CI 1.29-2.55) and older age at diagnosis (hazard ratio 1.04, 95% CI 1.03-1.05). This study establishes baseline estimates of SSc occurrence and characteristics in a large US cohort consisting primarily of black adults and white adults. These data should facilitate research regarding the role of geographic, ethnic, racial, and environmental factors for this disease in comparison populations.

  3. CURRENT VIEWS ON THE HETEROGENEITY OF RENAL INVOLVEMENTS IN PATIENTS WITH SYSTEMIC SCLEROSIS

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    A. V. Gordeev

    2015-01-01

    Full Text Available Systemic sclerosis (SS, is an autoimmune connective tissue disease, the main clinical signs of which are due to disseminated microcirculatory disorders and fibrosis of the skin and viscera. Morphological examinations showed that 80% of patients with SS had renal changes, including those unassociated with rheumatic diseases. Whereas the prevalence of scleroderma renal crisis is now estimated to be 2–5%, there is considerably often an asymptomatic reduction in renal function (silent uremia, which is caused by multimorbidity and comorbidity. Its incidence in patients with SS may be as high as 55%. The presence of autoimmune connective tissue disease may be itself regarded as a risk factor of renal involvement. Fifteen-year survival is 72% in SS patients with no renal involvement and not more than 13% in those having renal involvement. In patients with SS, proteinuria is one of the most important independent risk factors for fatal outcomes (relative risk, 3.34, leaving far behind canonical risk factors, such as pulmonary hypertension, restrictive lung disease (a forced expiratory volume in one second to forced vital capacity ratio of <80%, respiratory failure (NYHA Class III and IV, as well as decreased lung diffuse capacity and high skin scores. The authors first propose a concept of the existence and pathogenesis of chronic scleroderma nephropathy, the basis for which is the vascular endothelial dysfunction phenomenon developing in different structural components of the nephron and kidney as a whole.

  4. Validation of the ACR/EULAR classification criteria for systemic sclerosis in patients with early scleroderma.

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    Araújo, Farley Carvalho; Camargo, Cíntia Zumstein; Kayser, Cristiane

    2017-11-01

    The aim of this study was to validate the 2013 ACR/EULAR classification criteria for systemic sclerosis (SSc) in patients with SSc, including patients with early SSc. Fifty-six consecutive patients with early SSc (2001 LeRoy and Medsger criteria), 122 patients with established SSc (1980 ACR classification criteria), and 141 patients with SSc-like disorders were included in this cross-sectional study. The diagnostic performance of the 2013 ACR/EULAR criteria was compared with the 1980 ACR criteria in several subsets of patients. The performance of individual variables was also obtained. Receiver operating characteristic (ROC) curves and optimal cut-off values were computed. The sensitivity and specificity in the whole cohort of 178 SSc patients were 77.6 and 98.5%, respectively, using the 2013 ACR/EULAR criteria and 68.5 and 100%, respectively, using the 1980 ACR criteria. Twenty-eight percent of the patients with early SSc met the 2013 ACR/EULAR criteria. Among the patients with early SSc, 53% of those who had Raynaud's phenomenon, abnormal capillaroscopy and positive SSc-related antibodies met the 2013 ACR/EULAR criteria. The area under the ROC curve was 0.975 (95% confidence interval 0.962-0.987). The best cut-off value for the total score was ≥8 (sensitivity 82%; specificity 97.9%). The individual variables with the highest specificity values were proximal skin thickening, sclerodactyly (specificity 100%), telangiectasia and SSc-related antibodies (specificity 98.6%). Raynaud's phenomenon had the best sensitivity (99.4%) but had low specificity (4.2%). In conclusion, the 2013 ACR/EULAR classification criteria showed high accuracy and increased sensitivity in the classification of patients with early SSc.

  5. Geographic variation as a risk factor for digital ulcers in systemic sclerosis patients: a multicentre registry.

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    Souza, Ejr; Muller, C S; Horimoto, Amc; Rezende, R A; Guimarães, I; Mariz, H A; Dantas, A T; Da Costa, I P; Del-Rio, Apt; Sekiyama, J; Kahwage, C B; Kayser, C

    2017-07-01

    To evaluate the influence of geographic variation on the risk of digital ulcer (DU) development in systemic sclerosis (SSc) patients. This cross-sectional, multicentre study evaluated patients with SSc from centres located in different geographic regions of Brazil (subtropical and tropical climate zones). Demographic and clinical data were collected. The study included 141 patients with SSc (26 from the subtropical and 115 from the tropical zone). In total, 43 DUs were observed in 23 (16%) of the patients. By a simple logistic regression model, the presence of DUs was associated with a higher modified Rodnan skin score, previous necrosis or amputation of the extremities, flexion contracture of the fingers, active smoking, higher avascular score on capillaroscopy, higher severity of Raynaud's phenomenon, a higher Health Assessment Questionnaire Disability Index (HAQ-DI) score, a higher visual analogue scale score for Raynaud's phenomenon and overall disease, and the subtropical climate zone. Using multiple logistic regression, the presence of DUs was significantly associated with patients living in the subtropical climate zone [odds ratio (OR) = 5.4, p = 0.002], necrosis or amputation (OR = 5.2, p = 0.011), and a higher HAQ-DI score (OR = 2.6, p = 0.021). In this multicentre study in a continental country with different climates, patients with SSc living in a subtropical climate region had a 5.4 times higher risk of developing DUs than patients living in a warmer region (tropical climate), suggesting a more severe course of peripheral vasculopathy among patients living in geographic regions with relatively cold weather.

  6. Clinical and autoantibody profile in systemic sclerosis: baseline characteristics from a West Malaysian cohort.

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    Sujau, Ibrahim; Ng, Chin Teck; Sthaneshwar, Pavai; Sockalingam, Sargunan; Cheah, Tien Eang; Yahya, Fariz; Jasmin, Raja

    2015-05-01

    To evaluate the clinical and antibody profile of systemic sclerosis (SSc) in a Malaysian cohort. Consecutive patients with SSc in University Malaya Medical Centre from March to November 2012 were included in this study. In addition to clinical characterization, all subjects underwent autoantibody testing using Euroline immunoblot assay. The association between clinical features and autoantibody profile was evaluated. There were 31, predominantly Chinese (45.2%), subjects. Limited cutaneous disease was the most common subtype (71%). Raynaud's phenomenon was the most commonly observed feature (83.9%). Nine (29%) had esophageal dysmotility symptoms and 23 (74.2%), including all patients with diffuse SSc, had symptoms of gastro-esophageal reflux disease (GERD). Restrictive pattern on pulmonary function test and evidence of lung fibrosis were seen in more than 70% of patients. Echocardiographic evidence of pulmonary arterial hypertension was seen in 58.1%. Telangiectasia, calcinosis, digital ulcers, digital pulp loss or pitting were seen more commonly in the diffuse subtype. The two most prevalent autoantibodies were anti-Scl-70 and anti-Ro-52. The presence of anti-Scl-70 was significantly associated with restrictive lung disease (P = 0.05). Anti-Ro-52 was associated with control subjects with other autoimmune diseases (P = 0.043). The presence of anti-PM-Scl-75 was associated with overlap syndrome (P = 0.032). Patients with anticentromere antibodies were more likely to have vasculitic rash (P = 0.012). In Malaysia, SSc most commonly affects the Chinese. Limited cutaneous is more common than diffuse subtype. Features of CREST (calcinosis, Reynaud disease, esophageal dysmotility, sclerodactyly, telangiectasia) are more commonly observed in the diffuse cutaneous subgroup. Anti-Scl-70 and anti-Ro-52 antibodies are promising biomarkers for pulmonary involvement in SSc. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  7. Unstabilized DNA breaks in lymphocytes of patients with different subsets of systemic sclerosis.

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    Majone, Franca; Cozzi, Franco; Tonello, Marta; Olivieri, Silvia; Montaldi, Anna; Favaro, Maria; Visentin, Serena; Luisetto, Roberto; Ruffatti, Amelia

    2007-06-01

    The clastogenic effects on DNA, proven by the presence of micronuclei (MN) and the protective cellular mechanisms normally used to stabilize DNA breaks were investigated in three subsets of patients with systemic sclerosis (SSc). The frequency of MN found in cultures of peripheral lymphocytes in patients with anticentromere and antitopoisomerase I antibodies was significantly higher than that in the control group. The group with anticentromere antibody showed a significantly higher frequency of MN than did the subjects with antitopoisomerase antibody (4.22% versus 2.34%, P < 0.001). Patients with anti-RNA polymerase III, instead, had a low prevalence of typical micronucleated cells (0.98%), not significantly different from that of the healthy controls (0.82%). Moreover, when MN was characterized for the presence or absence of DNA fragments with free 3'-OH ends by digoxigenin-dUTP (DIG-dUTP) using terminal deoxynucleotidil transferase, its frequency was found to be increased in the groups with anticentromere and antitopoisomerase I antibodies with respect to that in the controls. The increase was significantly higher in the lymphocytes of the patients with anticentromere than in those with antitopoisomerase I antibody (35% versus 20.08%, P < 0.001). Nonetheless, the prevalence of unstable DNA fragments in patients with anti-RNA polymerase III antibody was low (2.05%) and not significantly different from that of the control group (1.18%). Our results indicate that there is a clastogenic effect on DNA and an interference in the protective cellular mechanisms normally stabilizing DNA breaks only in some subsets of SSc patients.

  8. Incidence of cancer among patients with systemic sclerosis in Korea: results from a single centre.

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    Kang, K Y; Yim, H W; Kim, I-J; Yoon, J U; Ju, J H; Kim, H-Y; Park, S-H

    2009-01-01

    The aim of this study was to determine whether the incidence of cancer has increased among patients with systemic sclerosis (SSc) in Korea. The study subjects consisted of 112 patients who had been consecutively evaluated for at least 6 months between 1990 and 2007. We retrospectively reviewed their medical records, investigated the incidence rate of cancer and compared it with that of the Korea National Cancer Centre database. Nine out of 112 patients developed cancer (four males and five females). The average age at diagnosis of cancer was 56.4 years and the mean disease duration was 8.9 years. The standardized incidence ratio (SIR) for SSc patients was 4.2 [95% confidence interval (CI) 2.3-6.1], 3.7 for women (95% CI 1.2-6.2) and 6.4 for men (95% CI 1.6-11.2). Lung cancer was the most common cancer (n = 4), followed by oesophagus (n = 1), stomach (n = 1), liver (n = 1), pancreas (n = 1), and squamous cell carcinoma of unknown origin (n = 1). All patients who developed lung cancer were female and non-small cell carcinoma in origin. The SIR of lung cancer in female patients was 23.0 (95% CI 6.0-40.0). Two out of four lung cancer patients had concomitant interstitial lung disease (ILD); all were non-smokers. Treatment agents, autoantibodies, smoking, and lung involvement were not significantly different between SSc patients with or without cancer. The SIR of cancer was significantly higher in SSc patients, and especially in those who were male, than in the general population. Lung cancer was the most common cancer. Active surveillance for the detection of cancer should be performed in all SSc patients.

  9. Long-term cyclic intravenous iloprost in systemic sclerosis: clinical experience from a single center

    Directory of Open Access Journals (Sweden)

    A. Di Vita

    2012-07-01

    Full Text Available The aim of the present study was to retrospectively evaluate response to therapy in 73 patients affected by systemic sclerosis (SSc who underwent long-term cyclic treatment with intravenous iloprost for peripheral vascular involvement (average duration of treatment 54.12±41.04 months. Seventy-three SSc patients were enrolled. Data were collected by reviewing clinical records and by phone or direct interview. Patients underwent a thorough physical examination at the end of follow up. The incidence of severe vascular manifestations was also assessed. Statistical analysis was performed by Wilcoxon’s signed rank test and descriptive statistics using Statview software. In this study cohort, 55 of 73 (75.2% patients had a history of ischemic digital ulcers (DUs; 28 patients (38.4% had active DUs at the beginning of treatment. Skin ulcers healed completely in 25 of 28 patients (89.3% at the end of the first treatment. However, 40 of 55 patients (72.6% relapsed after an average of 24 months. There was a significant correlation between relapse rate and/or number of ulcers and clinical factors (diffuse subset, changes in results of Allen’s test, NT-pro BNP levels. The annual incidence of pulmonary arterial hypertension (PAH was 2.34 (95%CI: 0.94-4.83 per 100 person years, the rate of gangrene was 2.7%, and no cases of scleroderma renal crisis were recorded. The incidence of PAH and of digital gangrene was higher than that observed in unselected SSc case series. These data suggest that our patients treated with iloprost have a higher vascular involvement than large case series of unselected SSc patients. A number of clinical factors are correlated to the severity of vascular involvement and could have an impact on the response to therapy. The clinical significance of these findings requires clarification and further investigation is needed.

  10. Probiotics for the treatment of systemic sclerosis-associated gastrointestinal bloating/ distention.

    Science.gov (United States)

    Frech, Tracy M; Khanna, Dinesh; Maranian, Paul; Frech, Edward J; Sawitzke, Allen D; Murtaugh, Maureen A

    2011-01-01

    Treatment for gastrointestinal tract (GIT) disease in systemic sclerosis (SSc) is challenging as no immunosuppressive or anti-fibrotic therapy is available with clearly proven efficacy. Probiotics are viable, non-pathogenic microorganisms that are hypothesized to improve the composition of the intestinal microbiota from a potentially harmful composition to a composition that is beneficial to the host. Our hypothesis is that GIT symptoms in SSc patients with moderate bloating would improve with probiotic implementation. Ten patients with a moderate-to-severe distention/bloating score (1.25-3.00) on the University of California Los Angeles Scleroderma Clinical Trials Consortium Gastrointestinal Tract 2.0 (UCLA SCTC GIT 2.0), but otherwise stable organ disease not requiring any medication adjustment were recruited from the University of Utah Scleroderma Center. We compared the GIT 2.0 scores at baseline and after 2 months of use of Align (bifidobacterium infantis; 109 CFU per capsule) or Culturelle (lactobacillus GG; 109 CFU per capsule) using paired t-test and calculated effect size (ES). Significant improvement in total GIT 2.0 score (ES = 0.82), reflux (ES = 0.33), bloating/distention (ES = 1.76), and emotional scales (ES = 0.18) were reported after two months of daily probiotic use. This pilot study suggests probiotics significantly improve the reflux, distention/ bloating, and total GIT scales in SSc patients. As hypothesized, the largest effect was seen in distention/bloating scale. Probiotics may be useful for treatment of SSc-associated distention/ bloating.

  11. Autologus peripheral stem cell transplantation in a patient with diffuse systemic sclerosis: our experience

    Directory of Open Access Journals (Sweden)

    A. Olivieri

    2011-09-01

    Full Text Available The diffuse form of systemic sclerosis (SSc can often lead to a rapidly progressive course with the involvement of the visceral organs which causes a severe prognosis. The 5-years cumulative mortality is between 30 and 60%, depending on the clinic form at the onset. Until now, no drug treatment has been proved to be efficacious against the progression of the disease or the regression of the fibrosis. Recently autologous peripheral blood stem cell (PBSC transplantation has been found to be promising. We introduce the case of a patient, male, 56 years old, who came under our observation on February 2001, suffering from a SSc with a severe multisystem involvement of lungs, skin, heart and gastrointestinal tract, and a positive antibodies anti-Scl-70. The 8 months therapy, at first with iloprost and cyclophosphamide, then with bolus of cyclophosphamide, was ineffective, with a rapid worsening of the cutaneous and pulmonary involvement. Under the patient agreement we decided to carry out an autologous PBSC transplantation. On December 2001, we obtained the PBSC mobilization after the administration of cyclophsphamide and lenograstim and the PBSC recovery with two leucoaferesis procedures. On February 2002, we gave the conditioning therapy with: thiotepa, cyclophosphamide, fludarabine, rabbit antilymphocytic globulin; then we made the infusion of PBSC. The bone marrow recovery (GN >500 and PLT >20.000 arrived at the day + 10. For three months after the transplantion we made an antibacterial, antiviral and antifungin prophylaxis with valacocyclovir, co-trimoxazole and fluconazole. The one-year follow-up has shown an essentially good response with the improving of the skin involvement and of the subjective indicators of the disease, while the pulmonary involvement don’t seen modified from the high dose therapy.

  12. Autoantibody to Th ribonucleoprotein (nucleolar 7-2 RNA protein particle) in patients with systemic sclerosis

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    Okano, Y.; Medsger, T.A. Jr. (Univ. of Pittsburgh School of Medicine, PA (USA))

    1990-12-01

    We studied sera of 371 consecutive new patients with systemic sclerosis (SSc; scleroderma) who were first evaluated during 1984-1988. All sera were tested for antinuclear antibodies by immunofluorescence staining using HEp-2 cells as substrate. We excluded 219 sera showing dark nucleoli and screened for antibodies to Th in the remaining 152 sera by immunoprecipitation of a 32P-labeled HeLa cell extract. Fifteen (4.0%) of 371 sera were anti-Th+. Anti-Th antibodies were present in 14 (8.4%) of 167 SSc patients with limited cutaneous involvement, in 1 of 167 with diffuse cutaneous involvement, and in 0 of 37 with SSc overlap syndrome. Among 244 controls with other connective tissue diseases, anti-Th was detected in only 3 patients, all having primary Raynaud's phenomenon of less than 2 years duration. In the subgroup with SSc with limited cutaneous involvement, the 14 anti-Th+ patients had a significantly greater frequency of puffy fingers, small bowel involvement, and hypothyroidism, and a significantly lower frequency of arthralgia and/or arthritis. Their cumulative survival rate from the time of onset of symptoms was lower than that for anti-Th- patients (78% versus 91% at 10 years), primarily due to 3 deaths from pulmonary arterial hypertension (2 from primary pulmonary hypertension and 1 from pulmonary hypertension secondary to pulmonary interstitial fibrosis). Serum anti-Th antibodies are present almost exclusively in patients with SSc with limited cutaneous involvement or in those with primary Raynaud's phenomenon whose disease may evolve to SSc with limited cutaneous involvement, and these antibodies may identify those patients who are at greater risk for reduced survival.

  13. Determinants of impairment in lung diffusing capacity in patients with systemic sclerosis.

    Science.gov (United States)

    Guarnieri, Gabriella; Zanatta, Elisabetta; Mason, Paola; Scarpa, Maria Cristina; Pigatto, Erika; Maestrelli, Piero; Cozzi, Franco

    2015-01-01

    Lung diffusing capacity for carbon monoxide (DLCO) is impaired in interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) associated to systemic sclerosis (SSc), but the mechanism of DLCO reduction remains controversial. We hypothesised that the determinants of DLCO impairment differ in interstitial or vascular involvement of the lung of SSc patients. DLCO was partitioned into alveolar-capillary membrane conductance (Dm) and pulmonary capillary blood volume (Vc) using combined single-breath DLNO and DLCO measurements. Seventeen SSc patients without pulmonary involvement (SSc), 20 SSc patients with ILD (SSc-ILD), with and without PAH, and 21 healthy controls were included. DLNO and Dm were reduced in SSc patients as compared with controls, whereas Vc was not significantly different. SSc-ILD patients showed a highly significant decrease in Dm and Vc as compared with SSc patients and controls. Vc tended to be more reduced than Dm in SSc-ILD patients with PAH. Dm and Vc were negatively correlated with PAPs and HCRT scores, but the relationship with the HRCT score was stronger. DLNO is more sensitive than DLCO in detecting functional impairment in SSc without radiologic or haemodynamic alterations. A disproportional reduction of Dm relative to Vc suggests a thickening of the blood-gas diffusion barrier in these patients. In SSc patients with detectable ILD, the gas exchange impairment is due to both components of lung diffusing capacity, and partitioning of DLCO in Dm and Vc is of little use in distinguishing the patients with only ILD from those with ILD complicated by PAH.

  14. Increased Epicardial Fat Volume Is Independently Associated with the Presence and Severity of Systemic Sclerosis.

    Science.gov (United States)

    Long, Benjamin D; Stojanovska, Jadranka; Brown, Richard K J; Attili, Anil K; Jackson, Eizabeth A; Ognenovski, Vladimir

    2017-12-01

    The study aimed to determine if intrathoracic fat volumes are associated with the presence and severity of systemic sclerosis (SSc), defined by the presence of pulmonary arterial hypertension (PAH). A total of 265 patients were included in the study, 202 of whom had SSc (134 had SSc with no PAH and 68 had SSc-associated PAH) and who underwent high-resolution computed tomography, and 63 controls who underwent coronary computed tomography angiography with calcium scoring. Intrathoracic and epicardial (EFV) fat volumes were quantified by manual tracing of the mediastinum and the pericardium, the difference of which represents the extrapericardial fat volume. Associations between these three fat volumes and the presence and severity of SSc, adjusted for cardiovascular risk factors and interstitial lung disease, were evaluated by logistic regression analysis. Of the 202 patients with SSc, the mean age was 55 years (ranged from 20 to 86), and 79% (159 of 202) were women. Adjusted EFV (odds ratio [OR]: 1.065; 95% confidence interval [CI]: 1.046-1.084, P = fat volume (OR: 1.028, 95% CI: 1.017-1.038, P = fat volume (OR: 1.033, 95% CI: 1.023-1.043, P = 0.001) were associated with the presence of SSc. Only EFV was associated with SSc severity (adjusted OR: 1.010, 95% CI: 1.003-1.018, P = 0.007). Increased epicardial fat volume is associated with the presence and severity of SSc, independent of cardiovascular risk factors and interstitial lung disease. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  15. Outcomes in Systemic Sclerosis-related Lung Disease following Lung Transplantation

    Science.gov (United States)

    Sottile, Peter D; Iturbe, David; Katsumoto, Tamiko R; Connolly, M Kari; Collard, Harold R; Leard, Lorriana A; Hays, Steven; Golden, Jeffrey A; Hoopes, Charles; Kukreja, Jasleen; Singer, Jonathan P

    2013-01-01

    Background Lung disease (LD) is the leading cause of death in systemic sclerosis (SSc). The diagnosis of SSc-related LD (SSc-LD) is often a contraindication to lung transplantation (LT) due to concerns that extra-pulmonary involvement will yield worse outcomes. We sought to evaluate post-transplant outcomes in persons with SSc-LD with esophageal involvement compared to persons with non-connective tissue disease related interstitial lung disease (nCTD-ILD). Methods From 1998-2012, persons undergoing LT for SSc-LD were age and gender matched in a 2:1 fashion to controls undergoing LT for nCTD-ILD. Esophageal function was assessed by pH testing and manometry. We defined esophageal dysfunction as the presence of a DeMeester score >14 or dysmotility more severe than “mild non-specific disorder”. The primary outcome was post-transplant survival. Secondary outcomes included freedom from bronchiolitis obliterans syndrome (fBOS) and rates of acute rejection. Survival and fBOS were estimated with Kaplan-Meier methods. Acute rejection was compared with Students t-test. Results Survival was similar in 23 persons with SSc-LD and 46 controls who underwent LT (p=0.47). For the SSc-LD group, 1- and 5-year survival was 83% and 76% compared to 91% and 64% in the nCTD-ILD group. There were no differences in fBOS (p=0.83). Rates of acute rejection were less in SSc-ILD (p=0.05). Esophageal dysfunction was not associated with worse outcomes (p>0.55). Conclusions Persons with SSc-LD appear to have similar survival and fBOS as persons transplanted for nCTD-ILD. The risk of acute rejection after transplant may be reduced in persons with SSc-LD. Esophageal involvement does not appear to impact outcomes. PMID:23545509

  16. An Oriental Medicine, Hyungbangpaedok-San Attenuates Motor Paralysis in an Experimental Model of Multiple Sclerosis by Regulating the T Cell Response.

    Science.gov (United States)

    Choi, Jong Hee; Lee, Min Jung; Jang, Minhee; Kim, Eun-Jeong; Shim, Insop; Kim, Hak-Jae; Lee, Sanghyun; Lee, Sang Won; Kim, Young Ock; Cho, Ik-Hyun

    2015-01-01

    The preventive and therapeutic mechanisms in multiple sclerosis are not clearly understood. We investigated whether Hyungbangpaedok-san (HBPDS), a traditional herbal medicine, has a beneficial effect in experimental autoimmune encephalomyelitis (EAE) mice immunized with myelin oligodendrocyte glycoprotein peptide (MOG 35-55). Onset-treatment with 4 types of HBPDS (extracted using distilled water and 30%/70%/100% ethanol as the solvent) alleviated neurological signs, and HBPDS extracted within 30% ethanol (henceforth called HBPDS) was more effective. Onset-treatment with HBPDS reduced demyelination and the recruitment/infiltration and activation of microglia/macrophages in the spinal cord of EAE mice, which corresponded to the reduced mRNA expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), iNOS, and chemokines (MCP-1, MIP-1α, and RANTES) in the spinal cord. Onset-treatment with HBPDS inhibited changes in the components of the blood-brain barrier such as astrocytes, adhesion molecules (ICAM-1 and VCAM-1), and junctional molecules (claudin-3, claudin-5, and zona occludens-1) in the spinal cord of EAE mice. Onset-treatment with HBPDS reduced the elevated population of CD4+, CD4+/IFN-γ+, and CD4+/IL-17+ T cells in the spinal cord of EAE mice but it further increased the elevated population of CD4+/CD25+/Foxp3+ and CD4+/Foxp3+/Helios+ T cells. Pre-, onset-, post-, but not peak-treatment, with HBPDS had a beneficial effect on behavioral impairment in EAE mice. Taken together, HBPDS could alleviate the development/progression of EAE by regulating the recruitment/infiltration and activation of microglia and peripheral immune cells (macrophages, Th1, Th17, and Treg cells) in the spinal cord. These findings could help to develop protective strategies using HBPDS in the treatment of autoimmune disorders including multiple sclerosis.

  17. Pain in Parkinson's disease and multiple sclerosis: its relation to the medial and lateral pain systems

    NARCIS (Netherlands)

    Scherder, E.J.A.; Wolters, E.C.M.J.; Polman, C.H.; Sergeant, J.A.; Swaab, D.F.

    2005-01-01

    Although pain is one of the major clinical symptoms of Parkinson's disease (PD) and multiple sclerosis (MS), it is often neglected and therefore undertreated. The question why the perception of pain in stages without cognitive impairment is not affected by the neuropathology has not been addressed

  18. Pain in Parkinson's disease and multiple sclerosis : Its relation to the medial and lateral pain systems

    NARCIS (Netherlands)

    Scherder, E; Wolters, E; Polman, C; Sergeant, J; Swaab, D

    2005-01-01

    Although pain is one of the major clinical symptoms of Parkinson's disease (PD) and multiple sclerosis (MS), it is often neglected and therefore undertreated. The question why the perception of pain in stages without cognitive impairment is not affected by the neuropathology has not been addressed

  19. A system mathematical model of a cell-cell communication network in amyotrophic lateral sclerosis.

    Science.gov (United States)

    Shao, Hongwei; He, Ying; Li, King C P; Zhou, Xiaobo

    2013-03-01

    Amyotrophic lateral sclerosis (ALS) is a devastating and chronic neurodegenerative disease without any known cure. In the brain and spinal cord of both patients and animal models with ALS, neuroinflammation is a prominent pathological hallmark which is characterized by infiltrating T cells at sites of motor neuron injury. Their presence in mutant Cu(2+)/Zn(2+) superoxide dismutase (mSOD1) induced ALS plays an important role in shifting the response of microglia from neuroprotective to neurotoxic. In order to better understand how these cells and their communication network collectively modulate the disease progression, we have established a mathematical model integrating diverse cells and cytokines. According to the experimental data sets, we first refined this model by identifying a link between TGFβ and M1 microglia which can produce an optimized model to fit data sets better. Then based on this model, parameters were estimated using genetic algorithm. Sensitivity analysis of these parameters identified several factors such as the release rate of IFNγ by T helper 1 (Th1) cells, which may be related to the heterogeneity between the patients with different survival times. Furthermore, the tests on T cell based therapeutic strategies indicated that elimination of Th1 cells is the most effective approach extending survival time. This confirmed the dominant role of Th1 cells in leading the rapid disorder in the later stage of ALS. For the therapies targeting cytokines, injection of IL6 can essentially augment the neuroprotective response and extend the life effectively by elevating the level of IL4, a neuroprotective cytokine, while directly injected IL4 will decay rapidly in the ALS microenvironment and cannot provide a persistent protective effect. On the other hand, in spite of the attractive effect of direct elimination of mSOD1 or self-antigen, it is difficult to implement in CNS. As an alternative, elimination of IFNγ can be chosen as another effective

  20. Doppler ultrasound study of penis in men with systemic sclerosis: a correlation with Doppler indices of renal and digital arteries.

    Science.gov (United States)

    Rosato, E; Barbano, B; Gigante, A; Cianci, R; Molinaro, I; Quarta, S; Digiulio, M A; Messineo, D; Pisarri, S; Salsano, F

    2013-01-01

    Erectile dysfunction (ED) prevalence in male systemic sclerosis (SSc) is high and its pathogenesis is unclear. The aim of the study is to assess correlation between Doppler ultrasound indices of penis and kidneys or digital arteries in male systemic sclerosis. Fourteen men with systemic sclerosis were enrolled in this study. Erectile function was investigated by the International Index of Erectile Function-5. Peak systolic velocity, end diastolic velocity, resistive index, pulsative index, and systolic/diastolic ratio were measured on the cavernous arteries at the peno-scrotal junction in the flaccid state, on the interlobar artery of both kidneys and all ten proper palmar digital arteries. Ten (71 percent) patients have an International Index of Erectile Function-5 less than 21. Reduction of penis peak systolic velocity was observed in all SSc subjects. Doppler indices of cavernous arteries correlate with the International Index of Erectile Function-5. The renal and digital arteries resistive index demonstrated a good correlation (p less than 0.0001) with International Index of Erectile Function-5. A positive correlation exists between penis and kidney arteries Doppler indices: end diastolic velocity (p less than 0.05, r=0.54), resistive index (p less than 0.0001, r=0.90), systolic/diastolic ratio (p less than 0.01, r=0.69). A positive correlation was observed between penis and digital arteries Doppler indices: peak systolic velocity (p less than 0.01, r=0.68), end diastolic velocity (p less than 0.01, r=0.75), resistive index (p less than 0.001, r=0.79), systolic/diastolic ratio (p less than 0.05, r=0.59). A correlation exists between arterial impairment of penis and renal or digital arteries.

  1. Overlap syndrome with Sjögren's syndrome and systemic sclerosis in a steel rolling mill worker: a case report.

    Science.gov (United States)

    Yi, Min-Kee; Choi, Won-Jun; Han, Sung-Woo; Song, Seng-Ho; Lee, Dong-Hoon; Kyung, Sun Young; Han, Sang-Hwan

    2016-01-01

    There are few reports about work-related factors associated with Sjögren's syndrome. We report a case of overlap syndrome with Sjögren's syndrome and systemic sclerosis. A 54-year-old man was admitted due to dyspnea on exertion. The results of physical examination and laboratory findings were compatible with Sjögren's syndrome with systemic sclerosis. The patient had no pre-existing autoimmune disease, and denied family history of autoimmune disease. The patient worked in the large-scale rolling department of a steel manufacturing company for 25 years. Hot rolling is a rolling process performed at between 1100 °C and 1200 °C, generating a high temperature and a large amount of fumes, involving jet-spraying of water throughout the process to remove the instantaneously generated oxide film and prevent the high generation of fumes. In this process, workers could be exposed to silica produced by thermal oxidation. Other potential toxic substances including nickel and manganese seemed to be less likely associated with the patient's clinical manifestations. Occupational exposure to silica seemed to be associated with the patient's clinical manifestations of overlap syndrome with Sjögren's syndrome and systemic sclerosis. Although the underlying mechanism is still unclear, autoimmune disease including Sjögren's syndrome affects women more often than men and there was no family history of autoimmune disease. These suggested that there was an association between occupational silica exposure and the disease of the patient. Future research about the association between long-term low dose exposure to silica and the development of autoimmune diseases should be encouraged.

  2. Is SOD1 loss of function involved in amyotrophic lateral sclerosis?

    Science.gov (United States)

    Saccon, Rachele A; Bunton-Stasyshyn, Rosie K A; Fisher, Elizabeth M C; Fratta, Pietro

    2013-08-01

    Mutations in the gene superoxide dismutase 1 (SOD1) are causative for familial forms of the neurodegenerative disease amyotrophic lateral sclerosis. When the first SOD1 mutations were identified they were postulated to give rise to amyotrophic lateral sclerosis through a loss of function mechanism, but experimental data soon showed that the disease arises from a--still unknown--toxic gain of function, and the possibility that loss of function plays a role in amyotrophic lateral sclerosis pathogenesis was abandoned. Although loss of function is not causative for amyotrophic lateral sclerosis, here we re-examine two decades of evidence regarding whether loss of function may play a modifying role in SOD1-amyotrophic lateral sclerosis. From analysing published data from patients with SOD1-amyotrophic lateral sclerosis, we find a marked loss of SOD1 enzyme activity arising from almost all mutations. We continue to examine functional data from all Sod1 knockout mice and we find obvious detrimental effects within the nervous system with, interestingly, some specificity for the motor system. Here, we bring together historical and recent experimental findings to conclude that there is a possibility that SOD1 loss of function may play a modifying role in amyotrophic lateral sclerosis. This likelihood has implications for some current therapies aimed at knocking down the level of mutant protein in patients with SOD1-amyotrophic lateral sclerosis. Finally, the wide-ranging phenotypes that result from loss of function indicate that SOD1 gene sequences should be screened in diseases other than amyotrophic lateral sclerosis.

  3. Set membership experimental design for biological systems

    Directory of Open Access Journals (Sweden)

    Marvel Skylar W

    2012-03-01

    Full Text Available Abstract Background Experimental design approaches for biological systems are needed to help conserve the limited resources that are allocated for performing experiments. The assumptions used when assigning probability density functions to characterize uncertainty in biological systems are unwarranted when only a small number of measurements can be obtained. In these situations, the uncertainty in biological systems is more appropriately characterized in a bounded-error context. Additionally, effort must be made to improve the connection between modelers and experimentalists by relating design metrics to biologically relevant information. Bounded-error experimental design approaches that can assess the impact of additional measurements on model uncertainty are needed to identify the most appropriate balance between the collection of data and the availability of resources. Results In this work we develop a bounded-error experimental design framework for nonlinear continuous-time systems when few data measurements are available. This approach leverages many of the recent advances in bounded-error parameter and state estimation methods that use interval analysis to generate parameter sets and state bounds consistent with uncertain data measurements. We devise a novel approach using set-based uncertainty propagation to estimate measurement ranges at candidate time points. We then use these estimated measurements at the candidate time points to evaluate which candidate measurements furthest reduce model uncertainty. A method for quickly combining multiple candidate time points is presented and allows for determining the effect of adding multiple measurements. Biologically relevant metrics are developed and used to predict when new data measurements should be acquired, which system components should be measured and how many additional measurements should be obtained. Conclusions The practicability of our approach is illustrated with a case study. This

  4. Tuberous Sclerosis

    Science.gov (United States)

    ... Division of Neuroscience Director, NIH BRAIN Initiative® Health Scientist Administrator Channels Synapses Circuits Cluster Scientific Director, Division of Intramural Research Featured Director's Message menu search Enter Search Term Submit Search Tuberous Sclerosis Information ...

  5. EBV-positive primary central nervous system lymphomas in monozygote twins with common variable immunodeficiency and suspected multiple sclerosis.

    Science.gov (United States)

    Jensen, M K; Koch-Henriksen, N; Johansen, P; Varming, K; Christiansen, C B; Knudsen, F

    1997-12-01

    Common variable immunodeficiency represents the most frequently occurring primary immunodeficiency disorder and is usually detected sporadically in patients with no family history of immunodeficiency. We present the case stories of two monozygote twins, who following a period of decreasing serum immunoglobulins developed primary central nervous system lymphomas. One twin had clinical and paraclinical features mimicking multiple sclerosis. Immunohistochemical investigations on biopsy tissue showed expression of the bcl-2 and p53 gene products, and Epstein-Barr virus (EBV) encoded small RNA's (EBER) indicating latent infection were detected in lymphoma cells using in situ hybridisation techniques. The pathogenetic role of EBV in oncogenesis is discussed.

  6. A 16-year Follow-up Case of Interstitial Pneumonia with Systemic Sclerosis-rheumatoid Arthritis Overlap Syndrome.

    Science.gov (United States)

    Yamakawa, Hideaki; Hagiwara, Eri; Yamanaka, Yumie; Ikeda, Satoshi; Sekine, Akimasa; Kitamura, Hideya; Baba, Tomohisa; Okudela, Koji; Iwasawa, Tae; Takemura, Tamiko; Ogura, Takashi

    2017-01-01

    Interstitial pneumonia is a common and major comorbidity affecting the prognosis of patients with systemic sclerosis (SSc). However, there are few reported cases of SSc-rheumatoid arthritis (RA) overlap-associated interstitial pneumonia. We herein report a case in which the clinical behavior and histopathology of interstitial pneumonia with SSc-RA overlap syndrome was followed over a long clinical course. When clinicians are deciding on the treatment strategy for patients with SSc-RA overlap syndrome-associated interstitial pneumonia, a pathological examination of a surgical lung biopsy may be useful.

  7. A multicenter, prospective, quasi-experimental evaluation study of a patient education program to foster multiple sclerosis self-management competencies.

    Science.gov (United States)

    Feicke, Janine; Spörhase, Ulrike; Köhler, Jürgen; Busch, Claudia; Wirtz, Markus

    2014-12-01

    To determine the impact of the self-management training program "S.MS" for new multiple sclerosis (MS) patients. Multicenter, prospective, quasi-experimental study with 31 MS patients in the intervention group (training program) and 33 participants in the control group (CG) (brochures). Data were collected before, after and 6 months after the interventions. Analysis of change was done by ANCOVA with repeated measurements. At baseline, participants in CG were younger at the time of diagnosis, suffered more frequently from relapsing-remitting MS and took more MS-medication on a permanent basis. The intervention had a stable significant effect on each dimension of self-management ability, on total self-management ability (ES=0.194, pmanagement abilities, anxiety and disease-specific quality of life in a quasi-experimental study design. Using RCT or CRT-designs would be desirable to further improve the evidence of treatment effectiveness. This study provides substantial evidence that "S.MS" fosters patients' self-management ability. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  8. UVA1 for diffuse cutaneous systemic sclerosis in a Fitzpatrick skin type VI patient: outcomes in the modified Rodnan skin score

    Directory of Open Access Journals (Sweden)

    Bárbara Roque Ferreira

    2017-04-01

    Full Text Available Introduction: Cutaneous sclerosis can lead to important mobility impairment. Ultraviolet (UV A1 phototherapy may improve skin sclerosis, although most of the studies have been with Caucasian patients. Material and Methods: A 44-year-old patient, Fitzpatrick skin type VI, was being followed up with the diagnosis of diffuse cutaneous systemic sclerosis. He had significant mobility impairment, especially of the right hand and arm. In 2015 he started UVA1 phototherapy daily, Monday until Friday (Waldmann® 7001 UVA cabin equipped with 40 Philips TL/10R lamps − spectral irradiation between 340 and 400 nm. The initial dose was 10 J/cm2, rapidly increased up to a steady dose of 35 J/cm2. Results: After 40 sessions of UVA1, active fingers flexion and abduction of the right arm significantly improved and the modified Rodnan skin score changed from 26 to 11. Conclusion: The modified Rodnan skin score is a practical and useful tool during the follow-up of patients with systemic sclerosis. UVA1 phototherapy improves cutaneous sclerosis, and the related mobility impairment, and a dose of 35 J/cm2 is effective, even in higher phototypes, having a good safety profile.

  9. Urotensinergic system genes in experimental subarachnoid hemorrhage.

    Science.gov (United States)

    Muñoz-Sánchez, M Á; Rodríguez-Rodríguez, A; Egea-Guerrero, J J; Gordillo-Escobar, E; Vilches-Arenas, Á; Carrillo-Vico, A; Guerrero, J M; Murillo-Cabezas, F

    2017-01-09

    Cerebral vasospasm, one of the main complications of subarachnoid hemorrhage (SAH), is characterized by arterial constriction and mainly occurs from day 4 until the second week after the event. Urotensin-II (U-II) has been described as the most potent vasoconstrictor peptide in mammals. An analysis is made of the serum U-II concentrations and mRNA expression levels of U-II, urotensin related peptide (URP) and urotensin receptor (UT) genes in an experimental murine model of SAH. An experimental study was carried out. Experimental operating room of the Biomedicine Institute of Seville (IBiS), Virgen del Rocío University Hospital (Seville, Spain). 96 Wistar rats: 74 SAH and 22 sham intervention animals. Day 1: blood sampling, followed by the percutaneous injection of 100μl saline (sham) or blood (SAH) into the subarachnoid space. Day 5: blood sampling, followed by sacrifice of the animals. Weight, early mortality, serum U-II levels, mRNA values for U-II, URP and UT. Serum U-II levels increased in the SAH group from day 1 (0.62pg/mL [IQR 0.36-1.08]) to day 5 (0.74pg/mL [IQR 0.39-1.43]) (p<0.05), though not in the sham group (0.56pg/mL [IQR 0.06-0.83] day 1; 0.37pg/mL [IQR 0.23-0.62] day 5; p=0.959). Between-group differences were found on day 5 (p<0.05). The ROC analysis showed that the day 5 serum U-II levels (AUC=0.691), URP mRNA (AUC=0.706) and UT mRNA (AUC=0.713) could discriminate between sham and SAH rats. The normal serum U-II concentration range in rats was 0.56pg/mL (IQR 0.06-0.83). The urotensinergic system is upregulated on day 5 in an experimental model of SAH. Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.

  10. Multiple sclerosis; Multiple Sklerose

    Energy Technology Data Exchange (ETDEWEB)

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P. [Universitaet des Saarlandes, Abteilung fuer Diagnostische und Interventionelle Neuroradiologie, Radiologische Klinik, Homburg/Saar (Germany); Shariat, K. [Universitaet des Saarlandes, Klinik fuer Neurochirurgie, Homburg/Saar (Germany); Kostopoulos, P. [Universitaet des Saarlandes, Klinik fuer Neurologie, Homburg/Saar (Germany)

    2008-06-15

    Multiple sclerosis is the most common chronic inflammatory disease of myelin with interspersed lesions in the white matter of the central nervous system. Magnetic resonance imaging (MRI) plays a key role in the diagnosis and monitoring of white matter diseases. This article focuses on key findings in multiple sclerosis as detected by MRI. (orig.) [German] Die Multiple Sklerose (MS) ist die haeufigste chronisch-entzuendliche Erkrankung des Myelins mit eingesprengten Laesionen im Bereich der weissen Substanz des zentralen Nervensystems. Die Magnetresonanztomographie (MRT) hat bei der Diagnosestellung und Verlaufskontrolle eine Schluesselrolle. Dieser Artikel befasst sich mit Hauptcharakteristika der MR-Bildbebung. (orig.)

  11. Experimental protocol of a randomized controlled clinical trial investigating exercise, subclinical atherosclerosis, and walking mobility in persons with multiple sclerosis.

    Science.gov (United States)

    Griffith, Garett; Klaren, Rachel E; Motl, Robert W; Baynard, Tracy; Fernhall, Bo

    2015-03-01

    This randomized controlled trial (RCT) will investigate the effects of a home-based aerobic exercise training regimen (i.e., cycle ergometry) on subclinical atherosclerosis and walking mobility in persons with multiple sclerosis (MS) and minimal disability. This RCT will recruit 54 men and women who have an Expanded Disability Status Scale characteristic of the 1st stage of MS (i.e., 0-4.0) to participate in a 3 month exercise or stretching intervention, with assessments of subclinical atherosclerosis and walking mobility conducted at baseline, week 6 (midpoint), and week 12 (conclusion) of the program. The exercise intervention will consist of 3 days/week of cycling, with a gradual increase of duration followed by an increase in intensity across the 3 month period. The attention-control condition will incorporate stretching activities and will require the same contact time commitment as the exercise condition. Both study groups will participate in weekly video chat sessions with study personnel in order to monitor and track program adherence. Primary outcomes will consist of assessments of vascular structure and function, as well as several walking tasks. Additional outcomes will include questionnaires, cardiorespiratory fitness assessment, and a 1-week free-living physical activity assessment. This investigation will increase understanding of the role of aerobic exercise as part of a treatment plan for managing subclinical atherosclerosis and improving walking mobility persons in the 1st stage of MS. Overall, this study design has the potential to lead to effective aerobic exercise intervention strategies for this population and improve program adherence. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. A computed tomographic imaging system for experimentation

    Science.gov (United States)

    Lu, Yanping; Wang, Jue; Liu, Fenglin; Yu, Honglin

    2008-03-01

    Computed tomography (CT) is a non-invasive imaging technique, which is widely applied in medicine for diagnosis and surgical planning, and in industry for non-destructive testing (NDT) and non-destructive evaluation (NDE). So, it is significant for college students to understand the fundamental of CT. In this work, A CT imaging system named CD-50BG with 50mm field-of-view has been developed for experimental teaching at colleges. With the translate-rotate scanning mode, the system makes use of a 7.4×10 8Bq (20mCi) activity 137Cs radioactive source which is held in a tungsten alloy to shield the radiation and guarantee no harm to human body, and a single plastic scintillator + photomultitude detector which is convenient for counting because of its short-time brightness and good single pulse. At same time, an image processing software with the functions of reconstruction, image processing and 3D visualization has also been developed to process the 16 bits acquired data. The reconstruction time for a 128×128 image is less than 0.1 second. High quality images with 0.8mm spatial resolution and 2% contrast sensitivity can be obtained. So far in China, more than ten institutions of higher education, including Tsinghua University and Peking University, have already applied the system for elementary teaching.

  13. Central nervous system infectious diseases mimicking multiple sclerosis: recognizing distinguishable features using MRI

    OpenAIRE

    Antonio Jose da Rocha; Ingrid Aguiar Littig; Renato Hoffmann Nunes; Charles Peter Tilbery

    2013-01-01

    The current diagnostic criteria for multiple sclerosis (MS) confirm the relevant role of magnetic resonance imaging (MRI), supporting the possibility of characterizing the dissemination in space (DIS) and the dissemination in time (DIT) in a single scan. To maintain the specificity of these criteria, it is necessary to determine whether T2/FLAIR visible lesions and the gadolinium enhancement can be attributed to diseases that mimic MS. Several diseases are included in the MS differential diag...

  14. Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS).

    Science.gov (United States)

    Herrick, Ariane L; Pan, Xiaoyan; Peytrignet, Sébastien; Lunt, Mark; Hesselstrand, Roger; Mouthon, Luc; Silman, Alan; Brown, Edith; Czirják, László; Distler, Jörg H W; Distler, Oliver; Fligelstone, Kim; Gregory, William J; Ochiel, Rachel; Vonk, Madelon; Ancuţa, Codrina; Ong, Voon H; Farge, Dominique; Hudson, Marie; Matucci-Cerinic, Marco; Balbir-Gurman, Alexandra; Midtvedt, Øyvind; Jordan, Alison C; Jobanputra, Paresh; Stevens, Wendy; Moinzadeh, Pia; Hall, Frances C; Agard, Christian; Anderson, Marina E; Diot, Elisabeth; Madhok, Rajan; Akil, Mohammed; Buch, Maya H; Chung, Lorinda; Damjanov, Nemanja; Gunawardena, Harsha; Lanyon, Peter; Ahmad, Yasmeen; Chakravarty, Kuntal; Jacobsen, Søren; MacGregor, Alexander J; McHugh, Neil; Müller-Ladner, Ulf; Riemekasten, Gabriela; Becker, Michael; Roddy, Janet; Carreira, Patricia E; Fauchais, Anne Laure; Hachulla, Eric; Hamilton, Jennifer; İnanç, Murat; McLaren, John S; van Laar, Jacob M; Pathare, Sanjay; Proudman, Susannah; Rudin, Anna; Sahhar, Joanne; Coppere, Brigitte; Serratrice, Christine; Sheeran, Tom; Veale, Douglas J; Grange, Claire; Trad, Georges-Selim; Denton, Christopher P

    2017-07-01

    The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed. NCT02339441. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  15. Earliest Phase of Systemic Sclerosis Typified by Increased Levels of Inflammatory Proteins in the Serum.

    Science.gov (United States)

    Cossu, Marta; van Bon, Lenny; Preti, Carlo; Rossato, Marzia; Beretta, Lorenzo; Radstake, Timothy R D J

    2017-08-31

    Patients with definite systemic sclerosis (SSc) who lack fibrotic features can be stratified into an intermediate stage of disease severity between preclinical/early SSc (EaSSc) and fibrotic subsets (limited cutaneous SSc [lcSSc] and diffuse cutaneous SSc [dcSSc]). The aim of the present study was to molecularly characterize nonfibrotic SSc and EaSSc on the basis of a broad panel of serum markers of inflammation and tissue damage, in order to increase the knowledge of the pathophysiologic mechanisms underlying SSc progression before the development of fibrosis. An 88-plex immunoassay was performed in serum samples from a discovery cohort composed of 21 patients with EaSSc (meeting the LeRoy and Medsger criteria), 15 with nonfibrotic SSc (meeting the American College of Rheumatology/European League Against Rheumatism 2013 classification criteria, without skin or lung fibrosis), and 11 healthy controls. Analyte concentrations that were consistently significantly different at the exploratory P value threshold of 0.1 were selected for replication analysis in a larger group composed of 47 patients with EaSSc, 48 with nonfibrotic SSc, and 43 healthy controls, as well as 51 patients with lcSSc and 35 with dcSSc. The value of the replicated molecules in predicting SSc progression (at a family-wise error rate of 0.05) was tested. Based on the results of the explorative analysis, 16 molecules were selected for testing in the replication set. The results showed that CXCL10, CXCL11, tumor necrosis factor receptor type II (TNFRII), and chitinase 3-like protein 1 levels were significantly increased in patients with EaSSc and those with nonfibrotic SSc as compared to healthy controls. The disease in patients with high concentrations of CXCL10 and TNFRII was also characterized by a faster rate of progression from EaSSc and from nonfibrotic SSc to worse disease stages. SSc patients with preclinical/early SSc and those with established, yet nonfibrotic, disease exhibit clear

  16. Mucocutaneous and demographic features of systemic sclerosis: A profile of 46 patients from Eastern India

    Directory of Open Access Journals (Sweden)

    Sudip Kumar Ghosh

    2012-01-01

    Full Text Available Background: Systemic sclerosis (SSc is a multisystem connective tissue disorder of uncertain etiology. The clinical picture is frequently dominated by prominent cutaneous manifestations that have diagnostic and prognostic significance. The objective of the present study was to find out the demographic profile and the relative frequencies and characteristics of different mucocutaneous features of SSc in a group of patients from eastern India. In addition, we sought to compare the frequency and pattern of the findings in the limited versus the diffuse variety of the disease. Materials and Methods:This was a cross-sectional, clinical observational study. Consecutive patients of SSc attending the dermatology O.P.D. of a tertiary care hospital of eastern India over 3 years were enrolled to the present study. Results:A total of 46 patients (41 females and 5 males; mean age 29.6±12.3 years of SSc were evaluated. Among mucocutaneous manifestations Raynaud′s phenomenon was present in 39 (84.8% patients. Other cutaneous features included dyspigmentation (40, 86.9%, sclerodactyly (38, 82.6%, inability to open the mouth (38,82.6%, mat-like telangiectasia (11,23.1%, fingertip ulceration and scarring (29,63%, cutaneous calcinosis (1,2.2%, digital gangrene in (2,4.3%, generalized pruritus (4,8.7%, cutaneous small vessel vasculitis (2,4.3%, chronic urticaria (2,4.3%, flexion contractures of the fingers (13,28.3%, and amputation of the digits (3,6.5%. Mucosal changes were observed in 10 (21.7% patients and nail changes were seen in 13 (28.2% patients. Diffuse cutaneous SSc was noted in 27 (58.7% patients and limited cutaneous SSc was seen in the remainder. Thirty-six (78.2% patients tested positive for ANA. Conclusion: The present study provides a snapshot of the spectrum of the demographic and mucocutaneous manifestations of SSc in the eastern Indian population. We have not observed any statistically significant differences between dcSSc and lcSSc in terms

  17. Intestinal dysbiosis is common in systemic sclerosis and associated with gastrointestinal and extraintestinal features of disease.

    Science.gov (United States)

    Andréasson, Kristofer; Alrawi, Zaid; Persson, Anita; Jönsson, Göran; Marsal, Jan

    2016-11-29

    Recent evidence suggests a link between autoimmunity and the intestinal microbial composition in several rheumatic diseases including systemic sclerosis (SSc). The objective of this study was to investigate the prevalence of intestinal dysbiosis in SSc and to characterise patients suffering from this potentially immunomodulatory deviation. This study consisted of 98 consecutive patients subject to in-hospital care. Stool samples were analysed for intestinal microbiota composition using a validated genome-based microbiota test (GA-map™ Dysbiosis Test, Genetic Analysis, Oslo, Norway). Gut microbiota dysbiosis was found present as per this standardised test. Patients were examined regarding gastrointestinal and extraintestinal manifestations of SSc by clinical, laboratory, and radiological measures including esophageal cineradiography, the Malnutrition Universal Screening Tool (MUST), levels of plasma transthyretin (a marker of malnutrition) and faecal (F-) calprotectin (a marker of intestinal inflammation). A majority (75.5%) of the patients exhibited dysbiosis. Dysbiosis was more severe (rs = 0.31, p = 0.001) and more common (p = 0.013) in patients with esophageal dysmotility. Dysbiosis was also more pronounced in patients with abnormal plasma levels of transthyretin (p = 0.045) or micronutrient deficiency (p = 0.009). In 19 patients at risk for malnutrition according to the MUST, 18 exhibited dysbiosis. Conversely, of the 24 patients with a negative dysbiosis test, only one was at risk for malnutrition. The mean ± SEM levels of F-calprotectin were 112 ± 14 and 45 ± 8 μg/g in patients with a positive and negative dysbiosis test, respectively. Dysbiosis was more severe in patients with skin telangiectasias (p = 0.020), pitting scars (p = 0.023), pulmonary fibrosis (p = 0.009), and elevated serum markers of inflammation (p dysbiosis did not correlate with age, disease duration, disease subtype, or extent of skin

  18. Serum interleukin-6 in systemic sclerosis and its correlation with disease parameters and cardiopulmonary involvement.

    Science.gov (United States)

    Abdel-Magied, Rasha A; Kamel, Shereen R; Said, Azza Farag; Ali, Hazem M; Abdel Gawad, Ehab A; Moussa, Mahmoud M

    2016-12-23

    To assess serum interleukin-6 (IL-6)level in patients with systemic sclerosis (SSc) and its correlations with European Scleroderma Study Group activity score (EUSTAR), Scleroderma Assessment Questionnaire (SAQ), disability index and cardiopulmonary involvement. Twenty SSc patients and 10 matched healthy controls were included. Serum IL-6 was measured in patients and controls. Disease activity, status,and disability were assessed.Cardiopulmonary involvement was evaluated by pulmonary function tests (PFTs), six minute walk test, echocardiography, and high resolution computed tomography (HRCT) of chest. Serum level of IL-6 was significantly higher in patients with SSc (6.3± 1.4pg/ml) versus healthy controls (3.2± 0.4pg/ml) (P=0.002). IL-6 level showed positive correlations with disease duration (r=0.49, P=0.03), EUSTAR score (r=0.64, P=0.002), Index of Respiratory Status "IRS" (r=0.46, P=0.001), Index of Musculoskeletal Status "IMSS" (r=0.45, P=0.049), Index of Vascular Status "IVS" (r=0.39, P=0.04), mean and peak of pulmonary artery pressure (r=0.44 & 0.55, P=0.02 & 0.002 respectively). Negative correlations of IL-6 level with DLCO% (r=-0.49, P=0.006),six minute walk distance (6MWD) (r=-0.52, P= 0.003) and right ventricle fraction area change (r=-0.48, P=0.03) were found, while there were strong positive correlations with HRCT-ground glass score (r=0.77, P=0.0001) and HRCT-fibrosis score (r=0.62, P=0.003). IL-6 level is increased in patients with SSc and significantly correlates with EUSTAR score, IRS, DLCO, 6MWD, HRCT scores, and echocardiographic abnormalities of the right side of the heart. These results support the role of IL-6 in the disease activity and in the development of cardiopulmonary manifestations in SSc patients.

  19. Measurement of upper limb ulcers in patients with systemic sclerosis: reproducibility and correlation with pain, function, and quality of life.

    Science.gov (United States)

    Toffolo, Sandra Regina; Furtado, Rita Nely Vilar; Klein, Adriana; Watanabe, Sandra; Andrade, Luis Eduardo Coelho; Natour, Jamil

    2008-01-01

    There are a large number of studies addressing the treatment and assessment of chronic ulcers. Despite the fact that ischemic ulcers are frequent and difficult to manage in cases of systemic sclerosis, there is minimal literature on assessment measures regarding these wounds or on their reproducibility. The aim of this study was to investigate intraobserver and interobserver reproducibility regarding ulcer dimension measurements in patients with systemic sclerosis. Correlations between pain, upper limb function, pinch strength, and quality of life were also determined. A prospective 11-week follow-up study was carried out to assess active upper limb ulcers. Ulcer diameter, ulcer area, and interobserver reproducibility were performed weekly. Quality of life (Medical Outcomes Study 36-Item Short-Form Health Survey), upper limb function (disabilities of the arm, shoulder, and hand), pinch strength, pain, visual analog scale, and intraobserver reproducibility were assessed at baseline, 3, 7, and 11 weeks. Fifty-one active ulcers were recorded. Larger ulcer diameter, smaller ulcer diameter, and ulcer area demonstrated excellent intraobserver (r > .81, p .76, p ulcer dimension and visual analog scale scores for pain (r = .42; p or= .40; p ulcers were reproducible in patients with SSc and correlated to other variables of interest for these wounds.

  20. Genetic variants of chemokine receptor CCR7 in patients with systemic lupus erythematosus, Sjogren's syndrome and systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Stanke Frauke

    2007-06-01

    Full Text Available Abstract Background The chemokine receptor CCR7 is a key organizer of the immune system. Gene targeting in mice revealed that Ccr7-deficient animals are severely impaired in the induction of central and peripheral tolerance. Due to these defects, Ccr7-deficient mice spontaneously develop multi-organ autoimmunity showing symptoms similar to those observed in humans suffering from connective tissue autoimmune diseases. However, it is unknown whether mutations of CCR7 are linked to autoimmunity in humans. Results DNA samples were collected from 160 patients suffering from connective tissue autoimmune disease (Sjogren's syndrome, n = 40; systemic lupus erythematosus, SLE, n = 20 and systemic sclerosis, n = 100 and 40 health subjects (n = 40. All participants in this study were of German descent. Samples were screened for single nucleotide polymorphisms (SNP by sequencing the coding region of the CCR7 gene as well asthe exon flaking intron sites and parts of the regions encoding for the 5'- and 3'-UTR. CCR7 variants were rare. We identified six different sequence variants, which occurred in heterozygosis. The identified SNP were observed at position -60 C/T (observed 1x, +6,476 A/G (7x, +6,555 C/T (15x, +6,560 C/T (6x, +10,440 A/G (3x and +11,475 C/A (1x. Four of these variants (+6,476 A/G, +6,555 C/T, +6,560 C/T and +10,440 A/G display allelic frequencies between 1% and 5 % and were present in both patients and control groups. The variants +6,476 A/G, +6,555 C/T, +6,560 C/T are located in the intron 2, while the +10,440 A/G variant corresponds to a silent mutation in exon 3. The variants -60 C/T and +11,475 C/A which are located at the 5'-UTR and 3-UTR respectively, display allelic frequencies below 1%. No correlation between these variants and the autoimmune diseases investigated could be observed. However, reporter gene expression assay demonstrated that the mutation at the -60 C/T position in homozygosis leads to reduced luciferase activity

  1. Systems level analysis of systemic sclerosis shows a network of immune and profibrotic pathways connected with genetic polymorphisms.

    Directory of Open Access Journals (Sweden)

    J Matthew Mahoney

    2015-01-01

    Full Text Available Systemic sclerosis (SSc is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6-12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes using a gene-gene interaction network, and place the genetic risk loci in the context of the intrinsic subsets. To identify gene expression modules common to three independent datasets from three different clinical centers, we developed a consensus clustering procedure based on mutual information of partitions, an information theory concept, and performed a meta-analysis of these genome-wide gene expression datasets. We created a gene-gene interaction network of the conserved molecular features across the intrinsic subsets and analyzed their connections with SSc-associated genetic polymorphisms. The network is composed of distinct, but interconnected, components related to interferon activation, M2 macrophages, adaptive immunity, extracellular matrix remodeling, and cell proliferation. The network shows extensive connections between the inflammatory- and fibroproliferative-specific genes. The network also shows connections between these subset-specific genes and 30 SSc-associated polymorphic genes including STAT4, BLK, IRF7, NOTCH4, PLAUR, CSK, IRAK1, and several human leukocyte antigen (HLA genes. Our analyses suggest that the gene expression changes underlying the SSc subsets may be long-lived, but mechanistically interconnected

  2. Polymorphism of keratin 1 associates with systemic lupus erythematosus and systemic sclerosis in a south Chinese population.

    Science.gov (United States)

    Luo, Weiguang; Zhou, Bin; Luo, Qizhi; Fang, Huilong; Zuo, Xiaoxia; Zou, Yizhou

    2017-01-01

    Both systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) diseases are related to the genetic and environmental factors, causing damage to the skin. The mutations of keratin 1 gene (KRT1) were reported to associate with skin diseases. The single-nucleotide polymorphism (SNP, rs14024) and the indel polymorphism (cds-indel, rs267607656), consisting mostly of the common haplotypes and could be used for genotyping of KRT1. We used the PCR with sequence specific primers (PCR-SSP) to determine the genotype of KRT1 in 164 SLE, 99 SSc patients, and 418 healthy controls. The results showed that the mutant with G at SNP rs14024 was associated with the high risk to SLE (p = 6.48×10-5) and SSc (p = 8.75×10-5), while the deletion allele at rs267607656 was associated with the low risk to SSc (p = 4.89×10-4) comparing to the normal controls. Haplogenotype, Del-/MU+ was associated with high susceptibility to SLE (OR = 1.87, p = 0.001) and SSc (OR = 2.29, p = 2.34×10-4). In contrast, the Haplogenotype Del+/MU- was associated with resistance to SLE (OR = 0.35, p = 6.24×10-5) and SSc (OR = 0.34, p = 0.001). This study demonstrates that the variations in KRT1 and the specific polymorphism of KRT1 in this Chinese Han population are associated with autoimmune diseases SLE and SSc. Typing KRT1 might be helpful to identify SLE and SSc patients.

  3. Limb apraxia in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Rapaić Dragan

    2014-01-01

    Full Text Available Background/Aim. There are almost no studies on apraxia in people with multiple sclerosis. Although the white matter is damaged in MS, it is not the only location in which the pathological changes are present. Demyelinated lesions in the cortex have recently been recognized as important components of multiple sclerosis pathology. The aim of this study was to determine whether apraxia is present among people with MS, and the importance of demographic characteristics and impairment of functional systems at conceptualization and execution of movements. Methods. The experimental group consisted of 30 patients, mean age 51.34 ± 7.70 years. The patients in the experimental group were diagnosed with MS according to the McDonald criteria. The control group consisted of 30 healthy subjects, mean age 50.30 ± 10.47 years. For research purposes, we used the following instruments: Questionnaire for Collecting Demographic Data, Kurtzke Functional Systems Scores, Waterloo-Sunnybrook Apraxia Battery (WatAB. Execution of motion tasks that are a part of the Watwere incorporated in the System for the Observation and Analysis of Motor Behavior. Results. Our study showed that limb apraxia was common in people with MS. Apraxia was present during pantomime in 26.70% of the patients, and during the imitation of movements in 44.80% of the patients. Gender, age, education level, duration of disease and a form of MS did not determine the quality of conceptualization and execution of movements. The time elapsed from the last exacerbation was a determinant of quality of executed movements. Impairments of functional systems predicted impairments of movement execution. The expanded disability scale score correlated with the severity of apraxia. Conclusion. Our study confirm the presence of apraxia in MS. It is necessary to carry out further studies using functional magnetic resonance imaging, as well as the conduct longitudinal studies to determine the precise structure of

  4. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, Egon; Stenager, E N; Knudsen, Lone

    1994-01-01

    In a cross-sectional study of 117 randomly selected patients (52 men, 65 women) with definite multiple sclerosis, it was found that 76 percent were married or cohabitant, 8 percent divorced. Social contacts remained unchanged for 70 percent, but outgoing social contacts were reduced for 45 percent......, need for structural changes in home and need for pension became greater with increasing physical handicap. No significant differences between gender were found. It is concluded that patients and relatives are under increased social strain, when multiple sclerosis progresses to a moderate handicap...

  5. The interferon type I signature is present in systemic sclerosis before overt fibrosis and might contribute to its pathogenesis through high BAFF gene expression and high collagen synthesis

    NARCIS (Netherlands)

    Brkic, Z.; Bon, L. van; Cossu, M.; Helden-Meeuwsen, C.G. van; Vonk, M.C.; Knaapen, H.; Berg, W. van den; Dalm, V.A.; Daele, P.L. van; Severino, A.; Maria, N.I.; Guillen, S.; Dik, W.A.; Beretta, L.; Versnel, M.A.; Radstake, T.

    2016-01-01

    BACKGROUND: Interferon (IFN) signature has been reported in definite systemic sclerosis (SSc) but it has not been characterised in early SSc (EaSSc). We aim at characterising IFN type I signature in SSc before overt skin fibrosis develops. METHODS: The expression of 11 IFN type I inducible genes was

  6. Cross-sectional study of soluble selectins, fractions of circulating microparticles and their relationship to lung and skin involvement in systemic sclerosis

    DEFF Research Database (Denmark)

    Iversen, Line V; Ullman, Susanne; Østergaard, Ole

    2015-01-01

    BACKGROUND: Endothelial damage and activation may play central roles in the pathogenesis of systemic sclerosis (SSc) and are reflected by microparticles (MPs) and soluble selectins. The objective of this study was to determine if these potential biomarkers are associated with specific organ invol...

  7. A rare polymorphism in the gene for Toll-like receptor 2 is associated with systemic sclerosis phenotype and increases the production of inflammatory mediators.

    NARCIS (Netherlands)

    Broen, J.C.A.; Bossini-Castillo, L.; Bon, L. van; Vonk, M.C.; Knaapen, H.K.A.; Beretta, L.; Rueda, B.; Hesselstrand, R.; Herrick, A.; Worthington, J.; Hunzelman, N.; Denton, C.P.; Fonseca, C.; Riemekasten, G.; Kiener, H.P.; Scorza, R.; Simeon, C.P.; Ortego-Centeno, N.; Gonzalez-Gay, M.A.; Airo, P.; Coenen, M.J.H.; Martin, J.; Radstake, T.R.D.J.

    2012-01-01

    OBJECTIVE: To investigate whether polymorphisms in Toll-like receptor (TLR) genes, previously reported to be associated with immune-mediated diseases, are involved in systemic sclerosis (SSc). METHODS: We genotyped 14 polymorphisms in the genes for TLRs 2, 4, 7, 8, and 9 in a discovery cohort

  8. Polymorphisms in the interleukin 4, interleukin 13, and corresponding receptor genes are not associated with systemic sclerosis and do not influence gene expression

    NARCIS (Netherlands)

    Broen, J.C.; Dieude, P.; Vonk, M.C.; Beretta, L.; Carmona, F.D.; Herrick, A.; Worthington, J.; Hunzelmann, N.; Riemekasten, G.; Kiener, H.; Scorza, R.; Simeon, C.P.; Fonollosa, V.; Spanish Systemic Sclerosis, G.; Carreira, P.; Ortego-Centeno, N.; Gonzalez-Gay, M.A.; Airo, P.; Coenen, M.J.; Tsang, K.; Aliprantis, A.O.; Martin, J.; Allanore, Y.; Radstake, T.R.

    2012-01-01

    OBJECTIVE: Polymorphisms in the genes encoding interleukin 4 (IL4), interleukin 13 (IL13), and their corresponding receptors have been associated with multiple immune-mediated diseases. Our aim was to validate these previous observations in patients with systemic sclerosis (SSc) and scrutinize the

  9. Appearance self-esteem in systemic sclerosis--subjective experience of skin deformity and its relationship with physician-assessed skin involvement, disease status and psychological variables.

    NARCIS (Netherlands)

    Lankveld, W.G.J.M. van; Vonk, M.C.; Teunissen, H.; Hoogen, F.H.J. van den

    2007-01-01

    OBJECTIVES: To determine the importance of skin deformity in systemic sclerosis (SSc) relative to other disease stressors and to find psychological correlates of appearance self-esteem (ASE) after controlling for disease status. METHODS: Disease-related stressors, symptoms, physical and

  10. Mir-155 is overexpressed in systemic sclerosis fibroblasts and is required for NLRP3 inflammasome-mediated collagen synthesis during fibrosis

    NARCIS (Netherlands)

    Artlett, C.M. (Carol M.); Sassi-Gaha, S. (Sihem); J.L. Hope (Jennifer); Feghali-Bostwick, C.A. (Carol A.); P.D. Katsikis (Peter D.)

    2017-01-01

    textabstractBackground: Despite the important role that microRNAs (miRNAs) play in immunity and inflammation, their involvement in systemic sclerosis (SSc) remains poorly characterized. miRNA-155 (miR-155) plays a role in pulmonary fibrosis and its expression can be induced with interleukin (IL)-1β.

  11. Phase I/II trial of autologous stem cell transplantation in systemic sclerosis: procedure related mortality and impact on skin disease.

    NARCIS (Netherlands)

    Binks, M.; Passweg, J.R.; Furst, D.E.; McSweeney, P.; Sullivan, K.; Besenthal, C.; Finke, J.; Peter, H.H.; Laar, J.A. van; Breedveld, F.C.; Fibbe, W.; Farge, D.; Gluckman, E.; Locatelli, F.; Martini, A.; Hoogen, F.J.A. van den; Putte, L.B.A. van de; Schattenberg, A.V.M.B.; Arnold, R.; Bacon, P.A.; Emery, P.; Espigado, I.; Hertenstein, B.; Hiepe, F.; Kashyap, A.; Kotter, I.; Marmont, A.; Martinez, A.; Pascual, M.J.; Gratwohl, A.; Prentice, H.G.; Black, G.C.M.; Tyndall, A.

    2001-01-01

    BACKGROUND: Systemic sclerosis (SSc, scleroderma) in either its diffuse or limited skin forms has a high mortality when vital organs are affected. No treatment has been shown to influence the outcome or significantly affect the skin score, though many forms of immunosuppression have been tried.

  12. A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations.

    NARCIS (Netherlands)

    Bossini-Castillo, L.; Martin, J.E.; Broen, J.; Gorlova, O.; Simeon, C.P.; Beretta, L.; Vonk, M.C.; Callejas, J.L.; Castellvi, I.; Carreira, P.; Garcia-Hernandez, F.J.; Fernandez Castro, M.; Coenen, M.J.H.; Riemekasten, G.; Witte, T.; Hunzelmann, N.; Kreuter, A.; Distler, J.H.; Koeleman, B.P.; Voskuyl, A.E.; Schuerwegh, A.J.; Palm, O.; Hesselstrand, R.; Nordin, A.; Airo, P.; Lunardi, C.; Scorza, R.; Shiels, P.; Laar, J.M. van; Herrick, A.; Worthington, J.; Denton, C.; Tan, F.K.; Arnett, F.C.; Agarwal, S.K.; Assassi, S.; Fonseca, C.; Mayes, M.D.; Radstake, T.R.D.J.; Martin, J.

    2012-01-01

    A single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in a previously published genome-wide association study (GWAS) in systemic sclerosis (SSc). Aiming to reveal the possible implication of the IL12RB2 gene in SSc, we conducted a follow-up study of this

  13. A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort

    NARCIS (Netherlands)

    Bossini-Castillo, L.; Broen, J.C.; Simeon, C.P.; Beretta, L.; Vonk, M.C.; Ortego-Centeno, N.; Espinosa, G.; Carreira, P.; Camps, M.T.; Navarrete, N.; Gonzalez-Escribano, M.F.; Vicente-Rabaneda, E.; Rodriguez, L.; Tolosa, C.; Roman-Ivorra, J.A.; Gomez-Gracia, I.; Garcia-Hernandez, F.J.; Castellvi, I.; Gallego, M.; Fernandez-Nebro, A.; Garcia-Portales, R.; Egurbide, M.V.; Fonollosa, V.; Pena, P.G. de la; Pros, A.; Gonzalez-Gay, M.A.; Hesselstrand, R.; Riemekasten, G.; Witte, T.J.M. de; Coenen, M.J.H.; Koeleman, B.P.; Houssiau, F.; Smith, V.; Keyser, F. de; Westhovens, R.; Langhe, E. De; Voskuyl, A.E.; Schuerwegh, A.J.; Chee, M.M.; Madhok, R.; Shiels, P.; Fonseca, C.; Denton, C.; Claes, K.; Padykov, L.; Nordin, A.; Palm, O.; Lie, B.A.; Airo, P.; Scorza, R.; Laar, J.M. van; Hunzelmann, N.; Kreuter, A.; Herrick, A.; Worthington, J.; Radstake, T.R.D.J.; Martin, J.; Rueda, B.

    2011-01-01

    OBJECTIVES: The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features. METHODS: A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four

  14. [SCLEROSIS: LOCAL AND GENERAL PATTERNS OF DEVELOPMENT].

    Science.gov (United States)

    Kats, Ya A; Parkhonyuk, E V

    2015-01-01

    Sclerosis is a final substrate and outcome of structural lesions of different organs and tissues in various pathological conditions, such as hypertensive disease, coronaty heart disease, chronic obstructive pulmonary disease, systemic lupus erythematosus, rheumatoid arthritis, systemic scleroderma, etc. Not infrequently it as a determinant of severity and unfavourable outcome of the disease. Elucidation of general patterns of the development of sclerosis requires an integrated approach to the systemic analysis of clinical, genetic, biochemical, and morphological characteristics whereas a local analysis reveals peculiarities of formation of sclerosis in individual patients. Such combination permits to use methods of predictive-preventive personified medicine for planning the treatment of sclerosis.

  15. Genetics Home Reference: multiple sclerosis

    Science.gov (United States)

    ... Share: Email Facebook Twitter Home Health Conditions Multiple sclerosis Multiple sclerosis Printable PDF Open All Close All Enable Javascript ... Profile National Multiple Sclerosis Society: What is Multiple Sclerosis? Orphanet: Multiple sclerosis Patient Support and Advocacy Resources (5 links) ...

  16. Experimental Design and Data Analysis Issues Contribute to Inconsistent Results of C-Bouton Changes in Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Dukkipati, S Shekar; Chihi, Aouatef; Wang, Yiwen; Elbasiouny, Sherif M

    2017-01-01

    The possible presence of pathological changes in cholinergic synaptic inputs [cholinergic boutons (C-boutons)] is a contentious topic within the ALS field. Conflicting data reported on this issue makes it difficult to assess the roles of these synaptic inputs in ALS. Our objective was to determine whether the reported changes are truly statistically and biologically significant and why replication is problematic. This is an urgent question, as C-boutons are an important regulator of spinal motoneuron excitability, and pathological changes in motoneuron excitability are present throughout disease progression. Using male mice of the SOD1-G93A high-expresser transgenic (G93A) mouse model of ALS, we examined C-boutons on spinal motoneurons. We performed histological analysis at high statistical power, which showed no difference in C-bouton size in G93A versus wild-type motoneurons throughout disease progression. In an attempt to examine the underlying reasons for our failure to replicate reported changes, we performed further histological analyses using several variations on experimental design and data analysis that were reported in the ALS literature. This analysis showed that factors related to experimental design, such as grouping unit, sampling strategy, and blinding status, potentially contribute to the discrepancy in published data on C-bouton size changes. Next, we systematically analyzed the impact of study design variability and potential bias on reported results from experimental and preclinical studies of ALS. Strikingly, we found that practices such as blinding and power analysis are not systematically reported in the ALS field. Protocols to standardize experimental design and minimize bias are thus critical to advancing the ALS field.

  17. Multiple Sclerosis.

    Science.gov (United States)

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on multiple sclerosis is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  18. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Jensen, K

    1988-01-01

    Forty-two (12%) of a total of 366 patients with multiple sclerosis (MS) had psychiatric admissions. Of these, 34 (81%) had their first psychiatric admission in conjunction with or after the onset of MS. Classification by psychiatric diagnosis showed that there was a significant positive correlation...

  19. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Knudsen, L; Jensen, K

    1994-01-01

    In a cross-sectional study of 94 patients (42 males, 52 females) with definite multiple sclerosis (MS) in the age range 25-55 years, the correlation of neuropsychological tests with the ability to read TV-subtitles and with the use of sedatives is examined. A logistic regression analysis reveals...

  20. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Knudsen, L; Jensen, K

    1991-01-01

    In a cross-sectional investigation of 116 patients with multiple sclerosis, the social and sparetime activities of the patient were assessed by both patient and his/her family. The assessments were correlated to physical disability which showed that particularly those who were moderately disabled...

  1. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Jensen, K

    1990-01-01

    An investigation on the correlation between ability to read TV subtitles and the duration of visual evoked potential (VEP) latency in 14 patients with definite multiple sclerosis (MS), indicated that VEP latency in patients unable to read the TV subtitles was significantly delayed in comparison...

  2. Analysis of killer cell immunoglobulin-like receptors (KIRs) and their HLA ligand genes polymorphisms in Iranian patients with systemic sclerosis.

    Science.gov (United States)

    Mahmoudi, Mahdi; Fallahian, Faranak; Sobhani, Soheila; Ghoroghi, Shima; Jamshidi, Ahmadreza; Poursani, Shiva; Dolati, Masoumeh; Hosseinpour, Zahra; Gharibdoost, Farhad

    2017-04-01

    Genetic factors have a great role in the pathogenesis of autoimmune diseases by cooperating with environmental stimuli. Killer immunoglobulin-like receptors (KIRs) are cell surface proteins on NK cells whose association with major histocompatibility complex-I regulates their killing function. The aim of this study was to provide information on the possible association between KIR and human leukocyte antigen (HLA) genes with systemic sclerosis disease in Iranian population. A total of 279 systemic sclerosis patients and 451 healthy controls were enrolled in this case-control study in order to determine the presence or absence of 19 KIR genes and 6 specific HLA class I ligands. DNA was analyzed by polymerase chain reaction using the specific sequence primer method (PCR-SSP). Among 11 discovered KIR genotypes, 6 genotypes showed a considerable role and 4 genotypes could preclude the risk of systemic sclerosis (SSc) disease. The gene-gene interactions were also analyzed, and significant confounding effects were seen between involved genes in these two combinations: "KIR3DL1; HLA-BW4-Thr80" and "KIR3DL1 -HLA-BW4-A1." None of single KIR genes showed significant effect on the risk of SSc. We conclude that there is an important relationship between KIR genes and their HLA ligands with incidence rate of systemic sclerosis in Iranian population. The powerful role of a number of discovered KIR/HLA compounds such as activating KIR genotype 3 and HLA-BW4-A1 confirmed the provocative hypothesis of the interplay between activating or inhibitory KIR genes with HLA ligands as a critical index of systemic sclerosis predisposition.

  3. Angiotensin II type 1 and 2 receptors and lymphatic vessels modulate lung remodeling and fibrosis in systemic sclerosis and idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Parra, Edwin Roger; Ruppert, Aline Domingos Pinto; Capelozzi, Vera Luiza

    2014-01-01

    To validate the importance of the angiotensin II receptor isotypes and the lymphatic vessels in systemic sclerosis and idiopathic pulmonary fibrosis. We examined angiotensin II type 1 and 2 receptors and lymphatic vessels in the pulmonary tissues obtained from open lung biopsies of 30 patients with systemic sclerosis and 28 patients with idiopathic pulmonary fibrosis. Their histologic patterns included cellular and fibrotic non-specific interstitial pneumonia for systemic sclerosis and usual interstitial pneumonia for idiopathic pulmonary fibrosis. We used immunohistochemistry and histomorphometry to evaluate the number of cells in the alveolar septae and the vessels stained by these markers. Survival curves were also used. We found a significantly increased percentage of septal and vessel cells immunostained for the angiotensin type 1 and 2 receptors in the systemic sclerosis and idiopathic pulmonary fibrosis patients compared with the controls. A similar percentage of angiotensin 2 receptor positive vessel cells was observed in fibrotic non-specific interstitial pneumonia and usual interstitial pneumonia. A significantly increased percentage of lymphatic vessels was present in the usual interstitial pneumonia group compared with the non-specific interstitial pneumonia and control groups. A Cox regression analysis showed a high risk of death for the patients with usual interstitial pneumonia and a high percentage of vessel cells immunostained for the angiotensin 2 receptor in the lymphatic vessels. We concluded that angiotensin II receptor expression in the lung parenchyma can potentially control organ remodeling and fibrosis, which suggests that strategies aimed at preventing high angiotensin 2 receptor expression may be used as potential therapeutic target in patients with pulmonary systemic sclerosis and idiopathic pulmonary fibrosis.

  4. Comorbidity of Bipolar Disorder and Multiple Sclerosis: A Case Report

    Directory of Open Access Journals (Sweden)

    Necla Keskin

    2013-08-01

    Full Text Available Multiple sclerosis is a chronic demyelinating disease of a central nervous system. Neuropsychiatric symptoms are common in multiple sclerosis and bipolar disorder is one of the most common psychiatric disorders that coexist with multiple sclerosis. Manic episodes may be the first presenting symptom of multiple sclerosis as comorbid pathology or as an adverse effect of pharmacotherapies used in multiple sclerosis. The comorbidity of bipolar disorder and multiple sclerosis is well-proven but its etiology is not known and investigated accurately. Recent studies support a common genetic susceptibility. Management of bipolar disorder in multiple sclerosis is based on evidence provided by case reports and treatment should be individualized. In this report, the association between bipolar disorder and multiple sclerosis, epidemiology, ethiology and treatment is discussed through a case had diagnosed as multiple sclerosis and had a manic episode with psychotic features. [Cukurova Med J 2013; 38(4.000: 832-836

  5. Impaired quality of life in patients with systemic sclerosis compared to the general population and chronic dermatoses.

    Science.gov (United States)

    Bretterklieber, Agnes; Painsi, Clemens; Avian, Alexander; Wutte, Nora; Aberer, Elisabeth

    2014-09-02

    Systemic sclerosis (SSc) is a rare and potentially life threatening autoimmune disorder. The burden of disease compared to other dermatoses is unknown. The purpose of this study was to assess both the quality of life in patients with SSc and the variables that are associated with poor quality of life. Forty-one patients with systemic sclerosis (29 limited, 2 diffuse, 10 undifferentiated forms) were assessed with respect to their health status and compared to published data for the normal population, SSc patients from other studies, and patients with chronic skin diseases. For the most part, our SSc patients had better outcomes in all 8 dimensions of the SF-36 than SSc patients from other studies, and poorer scores than the healthy population and those with occupational contact dermatitis, ichthyosis, non-melanoma skin cancer, contact dermatitis, atopic eczema, chronic nail disease, vitiligo, health care workers with work-related disease, and those with other chronic skin diseases, but significantly better scores for mental health than those with nail disease, vitiligo, and health-care workers. Patients with atopic dermatitis, psoriasis and pemphigus had significantly poorer mean scores in social function and mental health than SSc patients. Patients with pemphigus were also significantly impaired in their physical and emotional roles. Patients with systemic lupus erythematosus (SLE) had the significantly poorest mean scores for QoL in all 8 domains except bodily pain and emotional role. Besides SLE, SSc is one of the most severe chronic dermatologic diseases in terms of reduced QoL. Since SSc cannot be cured, treatment strategies should include therapeutic interventions such as psychotherapy, social support, physiotherapy, and spiritual care. Their beneficial effects could be studied in future.

  6. Diagnostic challenges in combined multiple sclerosis and centronuclear myopathy

    DEFF Research Database (Denmark)

    Olsen, D.B.; Langkilde, Annika Reynberg; Schmalbruch, H

    2000-01-01

    The first case of combined centronuclear myopathy and multiple sclerosis is reported. The difficulties of diagnosing multiple sclerosis in patients with muscular disorders associated with the central nervous system involvement are discussed...

  7. Accelerated Course of Experimental Autoimmune Encephalomyelitis in PD-1-Deficient Central Nervous System Myelin Mutants

    Science.gov (United States)

    Kroner, Antje; Schwab, Nicholas; Ip, Chi Wang; Ortler, Sonja; Göbel, Kerstin; Nave, Klaus-Armin; Mäurer, Mathias; Martini, Rudolf; Wiendl, Heinz

    2009-01-01

    It is assumed that the onset and course of autoimmune inflammatory central nervous system (CNS) disorders (eg, multiple sclerosis) are influenced by factors that afflict immune regulation as well as CNS vulnerability. We challenged this concept experimentally by investigating how genetic alterations that affect myelin (primary oligodendrocyte damage in PLPtg mice) and/or T-cell regulation (deficiency of PD-1) influence both the onset and course of an experimental autoimmune CNS inflammatory disease [MOG35-55-induced experimental autoimmune encephalomyelitis (EAE)]. We observed that double pathology was associated with a significantly earlier onset of disease, a slight increase in the neurological score, an increase in the number of infiltrating cells, and enhanced axonal degeneration compared with wild-type mice and the respective, single mutant controls. Double-mutant PLPtg/PD-1−/− mice showed an increased production of interferon-γ by CNS immune cells at the peak of disease. Neither PD-1 deficiency nor oligodendropathy led to detectable spread of antigenic MHC class I- or class II-restricted epitopes during EAE. However, absence of PD-1 clearly increased the propensity of T lymphocytes to expand, and the number of clonal expansions reliably reflected the severity of the EAE disease course. Our data show that the interplay between immune dysregulation and myelinopathy results in a stable exacerbation of actively induced autoimmune CNS inflammation, suggesting that the combination of several pathological issues contributes significantly to disease susceptibility or relapses in human disease. PMID:19443704

  8. In systemic sclerosis, anxiety and depression assessed by hospital anxiety depression scale are independently associated with disability and psychological factors.

    Science.gov (United States)

    Del Rosso, Angela; Mikhaylova, Svetlana; Baccini, Marco; Lupi, Ilaria; Matucci Cerinic, Marco; Maddali Bongi, Susanna

    2013-01-01

    Anxious and depressive symptoms are frequent in Systemic Sclerosis (SSc). Our objective is to assess their prevalence and association with district and global disability and psychological variables. 119 SSc patients were assessed by Hospital Anxiety Depression Scale (HADS). Clinical depression and anxiety were defined for HADS score cutoff ≥ 8. Patients were assessed for psychological symptoms (RSES, COPE-NIV), hand (HAMIS, CHFDS, fist closure, and hand opening) and face disability (MHISS, mouth opening), global disability, and fatigue (HAQ, FACIT). Both depression and anxiety in SSc are 36%. Depressive patients with comorbid anxiety have higher HADS-D score than patients with depression only (P = 0.001). HADS-A and -D are positively correlated with global disability, hands and mouth disability, fatigue, self-esteem and avoidance coping strategy, and, only HADS-A, also with social support (P anxiety correlate to local and global disabilities and psychological characteristics. Depressive patients with comorbid anxiety have higher level of depressive symptoms.

  9. Gradual progression of intrapulmonary lymph nodes associated with usual interstitial pneumonia in progressive systemic sclerosis on chest radiographs and CT

    Energy Technology Data Exchange (ETDEWEB)

    Ohm, Joon Young; Chung, Myung Hee; Kim, Seon Mun [The Catholic Univ. of Korea, Seoul (Korea, Republic of); Kim, Yong Hyun [The Catholic Univ. of Korea, Bucheon (Korea, Republic of)

    2012-10-15

    A 40 year old female visited the clinic for evaluation of Raynaud's phenomenon for a period of four years. The initial chest radiograph showed a fine reticular density and ground glass opacity with lower lobe predominance. These findings are consistent interstitial fibrosis. Additionally, high resolution CT showed multiple, small, coexisting nodular opacities, ranging from 3 to 7 mm in size in both lungs. These nodules grew up to 1.5 cm and showed moderate enhancement. Because of the rareness of intrapulmonary lymph node in patient of progressive systemic sclerosis, we couldn't exclude the possibility of malignancy. These nodules are turned out to be intrapulmonary lymph nodes on video assisted thoracoscopic lung biopsy.

  10. Impact of hand and face disabilities on global disability and quality of life in systemic sclerosis patients.

    Science.gov (United States)

    Maddali-Bongi, S; Del Rosso, A; Mikhaylova, S; Francini, B; Branchi, A; Baccini, M; Matucci-Cerinic, M

    2014-01-01

    In systemic sclerosis (SSc), the frequent involvement of hand and face leads to their disability. We aimed to assess influence of hand and face disability on global disability and Health related Quality of life (HRQoL). 119 SSc patients were assessed for global disability by HAQ, HRQoL, by SF36; hand disability by HAMIS, CHFDS, fist closure and hand opening measures; face disability by MHISS and mouth opening measure. Diffuse SSc (dSSc) patients present higher HAQ, lower Summary Physical Index (SPI) of SF36, major hand disability at hand (higher HAMIS, CHFDS, fist closure, lower hand opening) and face (lower mouth opening, higher MHISS) than lSSc patients (pdisability, and lower HRQoL in SPI than lSSc patients. Local disabilities, assessed by CHDFS and MHISS, are independently related to global disability and HRQoL.

  11. Translation, cross-cultural adaptation, and validation of the Mouth Handicap in Systemic Sclerosis questionnaire (MHISS) into the Dutch language.

    Science.gov (United States)

    Schouffoer, A A; Strijbos, E; Schuerwegh, A J M; Mouthon, L; Vliet Vlieland, T P M

    2013-11-01

    The Mouth Handicap in Systemic Sclerosis (MHISS) is a French-generic questionnaire evaluating mouth-opening restriction, dryness, and esthetic concerns. The aim of this study was to translate and adapt the MHISS questionnaire into the Dutch language and evaluate its psychometric properties. The MHISS was translated according to international guidelines, field-tested among 16 systemic sclerosis (SSc) patients, and adapted. Subsequently, the Dutch MHISS was administered to 52 SSc patients visiting the outpatient or day patient clinic of a university hospital and readministered after 2 weeks. Internal consistency was tested by computing Cronbach's alpha. Test-retest reliability was determined by computing the intraclass correlation coefficient (ICC) and validity by determining associations with measures of overall functioning (Health Assessment Questionnaire (HAQ)), maximum mouth opening (MMO, in millimeter), subjective xerostomia (visual analog scale), and objective xerostomia (Saxon test). Patients had mean ± standard deviation (SD) age and disease duration of 55 ± 21 and 7.2 ± 7.3 years. Twenty-seven (52 %) patients had diffuse cutaneous SSc. The mean Dutch MHISS score was 17.5 (SD 10.0) with Cronbach's alpha being 0.862. Dutch MHISS scores differed significantly between patients with high and low disability levels (HAQ, MMO, and subjective and objective xerostomia divided according to the median; paired t test). Spearman rank correlations with HAQ (r = 0.599, p = 0.000), MMO (r = -0.518, p = 0.000), and subjective xerostomia (r = 0.536, p = 0.000) were moderate; correlation with objective xerostomia did not reach statistical significance. The ICC was 0.94. The Dutch version of the MHISS demonstrated good psychometric properties and is useful in assessing mouth disability in SSc patients.

  12. Scleroderma-polymyositis overlap syndrome versus idiopathic polymyositis and systemic sclerosis: a descriptive study on clinical features and myopathology.

    Science.gov (United States)

    Bhansing, Kavish J; Lammens, Martin; Knaapen, Hanneke K A; van Riel, Piet L C M; van Engelen, Baziel G M; Vonk, Madelon C

    2014-05-13

    The objective was to characterize the clinical and myopathologic features of patients with scleroderma-polymyositis (SSc-PM) overlap compared with a population of patients with systemic sclerosis (SSc) and polymyositis (PM). A three-way comparison of patients with SSc-PM overlap (n = 25) with patients with SSc (n = 397) and PM (n = 40) on clinical and myopathologic features and causes of death. One neuropathologist blinded for the diagnosis evaluated all recent available muscle biopsies. Biopsies were scored for presence of inflammation, necrotic muscle fibers, rimmed vacuoles, fibrosis, and immunohistochemical staining. Clinical or myopathologic characteristics were compared by using the χ(2) test or one-way analysis of variance (ANOVA). The prevalence of SSc-PM overlap in the Nijmegen Systemic Sclerosis cohort was 5.9%. The mortality was 32% (eight of 25) in SSc-PM, of which half was related to cardiac diseases. The prevalence of pulmonary fibrosis was significantly increased in SSc-PM (83%) (P = 0.04) compared with SSc (49%) and PM (53%). SSc or myositis-specific antibodies were nearly absent in the SSc-PM group. In almost all biopsies (96%) of SSc-PM patients, necrotic muscle fibers were present, which was significantly increased compared with PM patients (P = 0.02). Patients with SSc-PM have increased prevalence of pulmonary fibrosis and cardiac disease as the cause of death compared with patients with SSc and PM . In addition, we found that necrotizing muscle fibers with inflammation characterize SSc-PM overlap in muscle biopsies. Further research should focus on underlying mechanisms causing necrosis, inflammation, and fibrosis and their relation to pulmonary involvement and mortality in patients with SSc-PM overlap.

  13. Sexual function in Italian women with systemic sclerosis is affected by disease-related and psychological concerns.

    Science.gov (United States)

    Maddali Bongi, Susanna; Del Rosso, Angela; Mikhaylova, Svetlana; Baccini, Marco; Matucci Cerinic, Marco

    2013-10-01

    In patients with systemic sclerosis (SSc), sexual function is somewhat impaired. Our aim was to evaluate sexual function in women with SSc in comparison to controls, and to investigate the association with sociodemographic and disease characteristics, and physical and psychological variables. Forty-six women with SSc and 46 healthy women were assessed for sociodemographic characteristics and gynecological development and administered the Female Sexual Function Index (FSFI), Medical Outcomes Study Short Form-36 (SF-36), Health Assessment Questionnaire (HAQ), Hospital Anxiety and Depression Scale (HADS), Rosenberg Self-Esteem Scale, Coping Orientation to Problems Experienced-New Italian Version, and Functional Assessment of Chronic Illness Therapy-Fatigue Scale. Patients were also assessed for disease duration and subset, Female Sexual Function in SSc, Hand Mobility in Scleroderma test (HAMIS), Cochin Hand Functional Disability Scale, Mouth Handicap in Systemic Sclerosis Scale (MHISS), Disability Sexual and Body Esteem Scale (PDSBE); and fist closure, hand opening, and mouth opening. In patients with SSc, only FSFI desire subscale score was significantly lower (p = 0.035) versus controls. Total FSFI score, similar to controls, was related with Medical Outcomes Study Short Form-36 mental component, HAQ (p = 0.022), MHISS (p = 0.038), and HAMIS (p = 0.037). In SSc, the main factors independently associated with sexual functioning were vaginal dryness [regression coefficient (B) = -0.72; p sexual function, although not different from controls, is influenced by specific disease-related and psychological concerns. Thus it should be included in patient evaluations and assessed in daily clinical practice.

  14. Echocardiography may help detect pulmonary vasculopathy in the early stages of pulmonary artery hypertension associated with systemic sclerosis.

    Science.gov (United States)

    Serra, Walter; Chetta, Alfredo; Santilli, Daniele; Mozzani, Flavio; Dall'Aglio, Pier Paolo; Olivieri, Dario; Cattabiani, Maria Alberta; Ardissino, Diego; Gherli, Tiziano

    2010-07-05

    Pulmonary arterial hypertension (PAH) in patients with systemic sclerosis is associated with a poor prognosis, but this can be improved by early disease detection. Abnormal pulmonary and cardiac function can be detected early by means of echocardiography, whereas right heart catheterization is usually performed later. The purpose of this prospective study was to detect early the presence of pulmonary artery vasculopathy in patients with verified systemic sclerosis without significant pulmonary fibrosis, normal lung volumes and a mildly reduced lung diffusion capacity of carbon monoxide (DLCO). Nineteen consecutive female NYHA class I-II patients with scleroderma and a PAPs of 0.05 was considered significant. Right heart catheterization detected PAH in 15/19 patients; mean PAP was 30.5 mm/Hg and RVP 3.6 UW. Coronary angiography of the patients aged more than 55 years showed some evidence of significant coronary artery disease. Echocardiography showed high systolic PAP values (46 +/- 8 mmHg), whereas right ventricular function was normal (TAPSE 23 +/- 3 mm), and in line with the NYHA class. ACTpo was reduced in the patients with a systolic PAP of 0.001) and positively correlated with DLCO (p > 0.001) and the hemodynamic data.There was a good correlation between ACTpo and PVR (hemodynamic data) (r = -0615; p > 0.01). Although they need to be confirmed by studies of larger series of patients, our findings suggest that, in comparison with hemodynamic data, non-invasive echocardiographic measurements are an excellent means of identifying early-stage PAH.

  15. Diagnostic challenges in combined multiple sclerosis and centronuclear myopathy

    DEFF Research Database (Denmark)

    Olsen, D.B.; Langkilde, Annika Reynberg; Schmalbruch, H

    2000-01-01

    The first case of combined centronuclear myopathy and multiple sclerosis is reported. The difficulties of diagnosing multiple sclerosis in patients with muscular disorders associated with the central nervous system involvement are discussed......The first case of combined centronuclear myopathy and multiple sclerosis is reported. The difficulties of diagnosing multiple sclerosis in patients with muscular disorders associated with the central nervous system involvement are discussed...

  16. Effect of 12-Week Pilates Trainning on EDSS in Women Suffering fromMultiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Z Shanazari

    2013-04-01

    Full Text Available Abstract Background & aim: Multiple sclerosis is a debilitating disease that strikes the immune system. Multiple sclerosis is a chronic disease which debilitates the nervous system. The study was evaluated the effects of Pilates exercise on women with physical disabilities suffering from multiple sclerosis for 12 weeks .The aim of this study was to investigating the effects of Pilates trainning on EDSS of women suffering from Multiple Sclerosis (MS for 12 weeks. Methods: In the present clinical trial study, 38 patients age 20-40 years (mean disease duration of 8±2 years with multiple sclerosis grade 0-4.5 were selected. The Patients were randomly divided into two groups: experimental and control groups. The training program for pilates, 12 weeks, three sessions a week, with each session consisting of 60 minutes. Patients' physical disability was measured using Krutzke Expanded Disability Status Scale, before and after exercise. Data were analyzed by ANCOVA test. Results: Physical disability scores before and after the exercise in intervention was 47.1 and 37 and in the control group, was 93.1 and 43.1 respectively, which was significantly different in the intervention group before and after training (p<0.05. Conclusion: Pilates training improves the physical disability of MS patients. Therefore, this exercise can be used as a complementary treatment alongside drug treatments. Key Words: Multiple Sclerosis, Women, Pilates, EDSS

  17. Multiple sclerosis after infectious mononucleosis

    DEFF Research Database (Denmark)

    Nielsen, Trine Rasmussen; Rostgaard, Klaus; Nielsen, Nete Munk

    2007-01-01

    BACKGROUND: Infectious mononucleosis caused by the Epstein-Barr virus has been associated with increased risk of multiple sclerosis. However, little is known about the characteristics of this association. OBJECTIVE: To assess the significance of sex, age at and time since infectious mononucleosis......, and attained age to the risk of developing multiple sclerosis after infectious mononucleosis. DESIGN: Cohort study using persons tested serologically for infectious mononucleosis at Statens Serum Institut, the Danish Civil Registration System, the Danish National Hospital Discharge Register, and the Danish...... Multiple Sclerosis Registry. SETTING: Statens Serum Institut. PATIENTS: A cohort of 25 234 Danish patients with mononucleosis was followed up for the occurrence of multiple sclerosis beginning on April 1, 1968, or January 1 of the year after the diagnosis of mononucleosis or after a negative Paul...

  18. Immune surveillance of the central nervous system in multiple sclerosis– Relevance for therapy and experimental models

    Science.gov (United States)

    Hussain, Rehana Z.; Hayardeny, Liat; Cravens, Petra C.; Yarovinsky, Felix; Eagar, Todd N.; Arellano, Benjamine; Deason, Krystin; Castro-Rojas, Cyd; Stüve, Olaf

    2015-01-01

    Treatment of central nervous system (CNS) autoimmune disorders frequently involves the reduction, or depletion of immune-competent cells. Alternatively, immune cells are being sequestered away from the target organ by interfering with their movement from secondary lymphoid organs, or their migration into tissues. These therapeutic strategies have been successful in multiple sclerosis (MS), the most prevalent autoimmune inflammatory disorder of the CNS. However, many of the agents that are currently approved or in clinical development also have severe potential adverse effects that stem from the very mechanisms that mediate their beneficial effects by interfering with CNS immune surveillance. This review will outline the main cellular components of the innate and adaptive immune system that participate in host defense and maintain immune surveillance of the CNS. Their pathogenic role in MS and its animal model experimental autoimmune encephalomyelitis (EAE) is also discussed. Furthermore, an experimental model is introduced that may assist in evaluating the effect of therapeutic interventions on leukocyte homeostasis and function within the CNS. This model or similar models may become a useful tool in the repertoire of pre-clinical tests of pharmacological agents to better explore their potential for adverse events. PMID:25282087

  19. Central nervous system infectious diseases mimicking multiple sclerosis: recognizing distinguishable features using MRI

    Directory of Open Access Journals (Sweden)

    Antonio Jose da Rocha

    2013-09-01

    Full Text Available The current diagnostic criteria for multiple sclerosis (MS confirm the relevant role of magnetic resonance imaging (MRI, supporting the possibility of characterizing the dissemination in space (DIS and the dissemination in time (DIT in a single scan. To maintain the specificity of these criteria, it is necessary to determine whether T2/FLAIR visible lesions and the gadolinium enhancement can be attributed to diseases that mimic MS. Several diseases are included in the MS differential diagnosis list, including diseases with exacerbation, remitting periods and numerous treatable infectious diseases, which can mimic the MRI features of MS. We discuss the most relevant imaging features in several infectious diseases that resemble MS and examine the primary spatial distributions of lesions and the gadolinium enhancement patterns related to MS. Recognizing imaging "red flags" can be useful for the proper diagnostic evaluation of suspected cases of MS, facilitating the correct differential diagnosis by assessing the combined clinical, laboratory and MR imaging information.

  20. Interferon-beta increases systemic BAFF levels in multiple sclerosis without increasing autoantibody production

    DEFF Research Database (Denmark)

    Hedegaard, Chris J; Sellebjerg, Finn; Krakauer, Martin

    2011-01-01

    Background: Treatment with interferon-beta (IFN-beta) increases B-cell activating factor of the TNF family (BAFF) expression in multiple sclerosis (MS), raising the concern that treatment of MS patients with IFN-beta may activate autoimmune B cells and stimulate the production of MS......-enhanced lesions. The patients were followed for up to 26 months, during which the BAFF levels remained elevated without association to increased disease activity. IFN-beta therapy caused an increase in plasma BAFF levels after both 3 and 6 months of therapy (p ...% decrease in IgG anti-MBP autoantibodies (p treatment BAFF levels correlate with high disability scores in MS, suggesting that high BAFF expression is a negative prognostic marker. Despite its known beneficial effects, IFN...

  1. Incidences and Risk Factors of Organ Manifestations in the Early Course of Systemic Sclerosis: A Longitudinal EUSTAR Study.

    Directory of Open Access Journals (Sweden)

    Veronika K Jaeger

    Full Text Available Systemic sclerosis (SSc is a rare and clinically heterogeneous autoimmune disorder characterised by fibrosis and microvascular obliteration of the skin and internal organs. Organ involvement mostly manifests after a variable period of the onset of Raynaud's phenomenon (RP. We aimed to map the incidence and predictors of pulmonary, cardiac, gastrointestinal (GI and renal involvement in the early course of SSc.In the EUSTAR cohort, patients with early SSc were identified as those who had a visit within the first year after RP onset. Incident SSc organ manifestations and their risk factors were assessed using Kaplan-Meier methods and Cox regression analysis.Of the 695 SSc patients who had a baseline visit within 1 year after RP onset, the incident non-RP manifestations (in order of frequency were: skin sclerosis (75% GI symptoms (71%, impaired diffusing capacity for monoxide40mmHg (14%, and renal crisis (3%. In the heart, incidence rates were highest for diastolic dysfunction, followed by conduction blocks and pericardial effusion. While the main baseline risk factor for a short timespan to develop FVC impairment was diffuse skin involvement, for PAPsys>40mmHg it was higher patient age. The main risk factors for incident cardiac manifestations were anti-topoisomerase autoantibody positivity and older age. Male sex, anti-RNA-polymerase-III positivity, and older age were risk factors associated with incident renal crisis.In SSc patients presenting early after RP onset, approximately half of all incident organ manifestations occur within 2 years and have a simultaneous rather than a sequential onset. These findings have implications for the design of new diagnostic and therapeutic strategies aimed to 'widen' the still very narrow 'window of opportunity'. They may also enable physicians to counsel and manage patients presenting early in the course of SSc more accurately.

  2. Relationship between Body Mass Composition, Bone Mineral Density, Skin Fibrosis and 25(OH Vitamin D Serum Levels in Systemic Sclerosis.

    Directory of Open Access Journals (Sweden)

    Addolorata Corrado

    Full Text Available A reduced bone mineral density (BMD is observed in several rheumatic autoimmune diseases, including Systemic Sclerosis (SSc; nevertheless, data concerning the possible determinants of bone loss in this disease are not fully investigated. The aim of this study is to evaluate the relationship between BMD, body mass composition, skin sclerosis and serum Vitamin D levels in two subsets of SSc patients. 64 post-menopausal SSc patients, classified as limited cutaneous (lcSSc or diffuse cutaneous (dcSSc SSc, were studied. As control, 35 healthy post-menopausal women were recruited. Clinical parameters were evaluated, including the extent of skin involvement. BMD at lumbar spine, hip, femoral neck and body mass composition were determined by dual-energy X-ray absorptiometry. Serum calcium, phosphorus, alkaline phosphatase, urine pyridinium cross-links, intact parathyroid hormone and 25-hydroxyvitamin D (25OHD were measured. BMD at spine, femoral neck and total hip was significantly lower in SSc patients compared to controls. In dcSSc subset, BMD at spine, femoral neck and total hip was significantly lower compared to lcSSc. No differences in both fat and lean mass were found in the three study groups even if patients with dcSSc showed a slightly lower total body mass compared to healthy controls. Total mineral content was significantly reduced in dSSc compared to both healthy subjects and lcSSc group. Hypovitaminosis D was observed both in healthy post-menopausal women and in SSc patients, but 25OHD levels were significantly lower in dcSSc compared to lcSSc and inversely correlated with the extent of skin thickness. These results support the hypothesis that the extent of skin involvement in SSc patients could be an important factor in determining low circulating levels of 25OHD, which in turn could play a significant role in the reduction of BMD and total mineral content.

  3. Curriculum system for experimental teaching in optoelectronic information

    Science.gov (United States)

    Di, Hongwei; Chen, Zhenqiang; Zhang, Jun; Luo, Yunhan

    2017-08-01

    The experimental curriculum system is directly related to talent training quality. Based on the careful investigation of the developing request of the optoelectronic information talents in the new century, the experimental teaching goal and the content, the teaching goal was set to cultivate students' innovative consciousness, innovative thinking, creativity and problem solving ability. Through straightening out the correlation among the experimental teaching in the main courses, the whole structure design was phased out, as well as the hierarchical curriculum connotation. According to the ideas of "basic, comprehensive, applied and innovative", the construction of experimental teaching system called "triple-three" was put forward for the optoelectronic information experimental teaching practice.

  4. Multiple sclerosis

    OpenAIRE

    Nylander, Alyssa; Hafler, David A.

    2012-01-01

    Multiple sclerosis (MS) is a multifocal demyelinating disease with progressive neurodegeneration caused by an autoimmune response to self-antigens in a genetically susceptible individual. While the formation and persistence of meningeal lymphoid follicles suggest persistence of antigens to drive the continuing inflammatory and humoral response, the identity of an antigen or infectious agent leading to the oligoclonal expansion of B and T cells is unknown. In this review we examine new paradig...

  5. Low cost experimental software defined radio system

    OpenAIRE

    Baldwin, Gerard; Ruiz, Livia; Barrandon, Ludovic; Farrell, Ronan

    2007-01-01

    This paper documents the design of a low cost experimental SDR Platform as a research tool. In order to keep costs to a minimum and provide the maximum flexibility a processor-less architecture is chosen. All signal processing is carried out using a standard notebook computer. The platform consists of four hardware elements. These are baseband transmitter board, baseband receiver board, RF transmitter board and RF receiver board. The baseband transmitter board consists of a USB 2....

  6. Uric acid in multiple sclerosis

    NARCIS (Netherlands)

    Koch, M; De Keyser, J

    Peroxynitrite, a reactive oxidant formed by the reaction of nitric oxide with superoxide at sites of inflammation in multiple sclerosis (MS), is capable of damaging tissues and cells. Uric acid, a natural scavenger of peroxynitrite, reduces inflammatory demyelination in experimental allergic

  7. Thermoregulation in multiple sclerosis

    OpenAIRE

    Davis, Scott L.; Wilson, Thad E.; White, Andrea T.; Frohman, Elliot M.

    2010-01-01

    Multiple sclerosis (MS) is a progressive neurological disorder that disrupts axonal myelin in the central nervous system. Demyelination produces alterations in saltatory conduction, slowed conduction velocity, and a predisposition to conduction block. An estimated 60–80% of MS patients experience temporary worsening of clinical signs and neurological symptoms with heat exposure. Additionally, MS may produce impaired neural control of autonomic and endocrine functions. This review focuses on f...

  8. Experimental analysis of humanistic systems in decision making ...

    African Journals Online (AJOL)

    Experimental analysis of humanistic systems in decision making. ... Journal of Applied Science and Technology ... Computational techniques for generating intuitionistic fuzzy random numbers (IFRNs) for the formulation of test problems in the management of humanistic systems have been developed and implemented.

  9. Experimental Evaluation of Mountain Bike Suspension Systems

    Directory of Open Access Journals (Sweden)

    J. Titlestad

    2003-01-01

    Full Text Available A significant distinction between competitive mountain bikes is whether they have a suspension system. Research studies indicate that a suspension system gives advantages, but it is difficult to quantify the benefits because they depend on so many variables, including the physiology and psychology of the cyclist, the roughness of the track and the design of the suspension system. A laboratory based test rig has been built that allows the number of variables in the system to be reduced and test conditions to be controlled. The test rig simulates regular impacts of the rear wheel with bumps in a rolling road. The physiological variables of oxygen consumption and heart rate were measured, together with speeds and forces at various points in the system. Physiological and mechanical test results both confirm a significant benefit in using a suspension system on the simulated rough track, with oxygen consumption reduced by around 30 % and power transmitted through the pedals reduced by 30 % to 60 %.

  10. Infratentorial lesion volume correlates with sensory functional system in multiple sclerosis patients: a 3.0-Tesla MRI study.

    Science.gov (United States)

    Quattrocchi, C C; Cherubini, A; Luccichenti, G; Grasso, M G; Nocentini, U; Beomonte Zobel, B; Sabatini, U

    2010-02-01

    This study sought to correlate lesion volume in infratentorial areas using 3.0-T proton-density (PD)-weighted images with disability scales and appropriate functional system scores in patients with multiple sclerosis (MS). We examined 20 consecutive patients (13 women and 7 men) with a median age of 47 years (range 26-70). Neurological examination included the Expanded Disability Status Scale and its functional systems, the Barthel Index (BI) and the Rivermead Mobility Index (RMI). MRI scans were performed on a system operating at 3.0 T using a quadrature birdcage head coil. Acquired images imported as Digital Imaging and Communication in Medicine (DICOM) files, and the region of interest (ROI) files were converted to Neuroimaging Informatics Technology Initiative (NIfTI) format and normalised to the Montreal Neurological Institute (MNI) standard template. An automated segmentation algorithm was used to distinguish between supratentorial and infratentorial areas. Normalisation to the magnetisation-prepared rapid acquisition with gradient echo (MPRAGE) T1-weighted sequence allowed lesion volume estimation in the different anatomical areas. A significant correlation was found between infratentorial lesion volume and the sensory functional system score (rho=0.76, p=0.002). No significant correlation was found between supratentorial lesion volume and Expanded Disability Status Scale (EDSS), RMI and BI scores. The described method, by means of anatomical assignment of MS lesions, allows detection of significant correlation coefficients between clinical and MRI lesion burden in MS patients at the infratentorial level.

  11. Impaired neurosteroid synthesis in multiple sclerosis

    Science.gov (United States)

    Noorbakhsh, Farshid; Ellestad, Kristofor K.; Maingat, Ferdinand; Warren, Kenneth G.; Han, May H.; Steinman, Lawrence; Baker, Glen B.

    2011-01-01

    High-throughput technologies have led to advances in the recognition of disease pathways and their underlying mechanisms. To investigate the impact of micro-RNAs on the disease process in multiple sclerosis, a prototypic inflammatory neurological disorder, we examined cerebral white matter from patients with or without the disease by micro-RNA profiling, together with confirmatory reverse transcription–polymerase chain reaction analysis, immunoblotting and gas chromatography-mass spectrometry. These observations were verified using the in vivo multiple sclerosis model, experimental autoimmune encephalomyelitis. Brains of patients with or without multiple sclerosis demonstrated differential expression of multiple micro-RNAs, but expression of three neurosteroid synthesis enzyme-specific micro-RNAs (miR-338, miR-155 and miR-491) showed a bias towards induction in patients with multiple sclerosis (P micro-RNAs revealed suppression of enzyme transcript and protein levels in the white matter of patients with multiple sclerosis (P micro-RNA target knockdown experiments (P micro-RNAs by in situ hybridization in the brains of patients with or without multiple sclerosis. Levels of important neurosteroids, including allopregnanolone, were suppressed in the white matter of patients with multiple sclerosis (P micro-RNAs, miR-338 and miR-155, accompanied by diminished expression of neurosteroidogenic enzymes and allopregnanolone, was also observed in the brains of mice with experimental autoimmune encephalomyelitis (P < 0.05). Allopregnanolone treatment of the experimental autoimmune encephalomyelitis mouse model limited the associated neuropathology, including neuroinflammation, myelin and axonal injury and reduced neurobehavioral deficits (P < 0.05). These multi-platform studies point to impaired neurosteroidogenesis in both multiple sclerosis and experimental autoimmune encephalomyelitis. The findings also indicate that allopregnanolone and perhaps other neurosteroid

  12. Rapidly progressive systemic sclerosis with a fatal outcome in male patients

    Directory of Open Access Journals (Sweden)

    Małgorzata Widuchowska

    2010-02-01

    Full Text Available Objectives: Retrospective analysis of clinical outcomes of malepatients with particularly severe and rapidly progressive diffusesystemic sclerosis (SSc with a fatal outcome with emphasis onorgan involvement and results of diagnostic tests, and tentativedistinction of a subgroup of especially progressive SSc. Material and methods: In the last few years among patients withSSc hospitalized in our centres, five patients with particularlyrapidly progressive disease were distinguished. Despiteaggressive treatment, the disease led to a fatal outcome ina short time. Their clinical history and results of diagnostic testswere evaluated. Results: All of them were smokers and three of them did not stopsmoking after the diagnosis. Laboratory findings revealed hightitres of Scl70 antibodies and enhanced erythrocytesedimentation rate (ESR in all of the patients. Most of them hadincreased serum creatine kinase (CK values. During the diseaserapidly progressive severe organ involvement was observed(pulmonary fibrosis, renal failure, cardiac failure, pulmonaryarterial hypertension. The skin thickening increased rapidly andthey died within 12-24 months after the first signs of skinthickening. Acute cardiac failure was the cause of death. Conclusions: The described cases suggest possible distinction ofa subset of a subgroup of patients with a particularly severe and rapidly progressive disease. It might be a population of patientswith the following characteristics: males over 40 years of agewith high titres of anti-Scl70 antibodies and elevated serum CKlevels. This is consistent with the presently published data onfactors associated with fatal prognosis in patients with SSc.

  13. Cortical injury in multiple sclerosis; the role of the immune system

    Directory of Open Access Journals (Sweden)

    Walker Caroline A

    2011-12-01

    Full Text Available Abstract The easily identifiable, ubiquitous demyelination and neuronal damage that occurs within the cerebral white matter of patients with multiple sclerosis (MS has been the subject of extensive study. Accordingly, MS has historically been described as a disease of the white matter. Recently, the cerebral cortex (gray matter of patients with MS has been recognized as an additional and major site of disease pathogenesis. This acknowledgement of cortical tissue damage is due, in part, to more powerful MRI that allows detection of such injury and to focused neuropathology-based investigations. Cortical tissue damage has been associated with inflammation that is less pronounced to that which is associated with damage in the white matter. There is, however, emerging evidence that suggests cortical damage can be closely associated with robust inflammation not only in the parenchyma, but also in the neighboring meninges. This manuscript will highlight the current knowledge of inflammation associated with cortical tissue injury. Historical literature along with contemporary work that focuses on both the absence and presence of inflammation in the cerebral cortex and in the cerebral meninges will be reviewed.

  14. Assessment of autonomic nervous system dysfunction in multiple sclerosis and the association with clinical disability

    Directory of Open Access Journals (Sweden)

    Nilufer Kale

    2009-06-01

    Full Text Available Background: Recent studies have reported autonomic dysfunction (AD in multiple sclerosis (MS, bladder and/or bowel dysfunction, orthostatic hypotension, and cardiac adaptation disorders have been observed in a wide range (15-80%. The primary aim of this study is to investigate the frequency and association of AD in MS patients, assessed by sympathetic skin reaction (SSR and a symptoms questionnaire. The secondary aims of this study are to study the association of AD and disease disability assessed by expanded disability status scale (EDSS, as well as disease duration. Design and Methods: 100 clinically definite MS patients were evaluated for ANS dysfunction by use of an autonomic symptoms questionnaire and SSR testing. The relationship between these methods, AD and disease-related parameters, such as the expanded disability status scale (EDSS and disease duration were all evaluated. Results: 65% of the patients presented with AD and 29% of these patients had abnormal SSR results. MS patients with high EDSS values (EDSS >4 and longer disease duration were more likely to have ANS dysfunction (p less than 0.0001. Conclusions. ANS dysfunction is not uncommon in CDMS patients and thus noninvasive investigations of AD are warranted to optimize AD evaluation and disease management.

  15. Innate Immunity in Systemic Sclerosis – Role of Toll-Like Receptors, Interferon, and the Potential Impact of Vitamin D

    Directory of Open Access Journals (Sweden)

    Ruxandra Ionescu

    2014-07-01

    Full Text Available Systemic sclerosis (SSc is an autoimmune disease in which vascular damage and immune activation leads to excessive accumulation of extracellular matrix in the skin and internal organs. Although the focus has been on adaptive immunity in SSc, recent data suggest that innate immunity is critically important. The innate immune system, the first-line barrier against pathogens, modulates mechanisms which activate adaptive immunity. Dysregulation of the innate immune system and toll-like receptors (TLRs may link immune abnormalities and fibrosis in SSc. TLR signalling pathways might induce production of Type I interferon (IFN and other cytokines, and represent one of the mechanisms that initiate and develop autoimmunity and subsequent fibrosis. Vitamin D displays many immunomodulatory effects on both innate and adaptive immune responses. Active vitamin D will produce signals via vitamin D receptor and influences TLR stimulation, IFN response, and antimicrobial peptide production. Vitamin D deficiency has been associated with many autoimmune disorders, and can influence clinical phenotype and immune disorders in SSc patients.

  16. Effectiveness and safety of oxycodone/naloxone in the management of chronic pain in patients with systemic sclerosis with recurrent digital ulcers: two case reports

    Directory of Open Access Journals (Sweden)

    Ughi N

    2016-03-01

    Full Text Available Nicola Ughi, Chiara Crotti, Francesca Ingegnoli Division of Rheumatology, Department of Clinical Sciences and Community Health, Gaetano Pini Institute, The University of Milan, Milan, Italy Abstract: Digital ulcers (DUs are a severe and frequent clinical feature of patients with systemic sclerosis (SSc. The presence of DUs may cause severe pain and often lead to impairment of patient’s functional activities and health-related quality of life. Moreover, poor patient cooperation during the wound care procedure due to pain may be associated with a negative outcome of DU healing. Therefore, pain management has a key role in patients with SSc. These two case reports describe the effectiveness and safety of oxycodone/naloxone in patients with SSc complicated by painful chronic DUs. Such a therapy has provided pain relief and consequently an increased compliance during redressing wounds. Keywords: oxycodone, naloxone, systemic sclerosis, pain, digital ulcer, scleroderma, analgaesia, wound healing, opioids, calcinosis, UCLA-SCTC GIT 2.0

  17. Glatiramer Acetate in Treatment of Multiple Sclerosis: A Toolbox of Random Co-Polymers for Targeting Inflammatory Mechanisms of both the Innate and Adaptive Immune System?

    Directory of Open Access Journals (Sweden)

    Thomas Vorup-Jensen

    2012-11-01

    Full Text Available Multiple sclerosis is a disease of the central nervous system, resulting in the demyelination of neurons, causing mild to severe symptoms. Several anti-inflammatory treatments now play a significant role in ameliorating the disease. Glatiramer acetate (GA is a formulation of random polypeptide copolymers for the treatment of relapsing-remitting MS by limiting the frequency of attacks. While evidence suggests the influence of GA on inflammatory responses, the targeted molecular mechanisms remain poorly understood. Here, we review the multiple pharmacological modes-of-actions of glatiramer acetate in treatment of multiple sclerosis. We discuss in particular a newly discovered interaction between the leukocyte-expressed integrin αMβ2 (also called Mac-1, complement receptor 3, or CD11b/CD18 and perspectives on the GA co-polymers as an influence on the function of the innate immune system.

  18. Tuberous sclerosis complex

    Directory of Open Access Journals (Sweden)

    Alexander Jerman

    2014-05-01

    Full Text Available Tuberous sclerosis complex is a genetic disorder with a characteristic development of a benign tumorous growth in various tissues. Clinical picture is very heterogeneous, resulting in difficult diagnosis and unrecognized patients. In this article, we present pathophysiological basis for understanding the clinical picture and the diagnosis of tuberous sclerosis complex. The skin, central nervous system, kidneys and heart are the most commonly affected sites. The disease course is progressive. Although the great majority of lesions are benign, life expectancy and quality of life are affected by their secondary impact. Until recently, the therapy has been only symptomatic, but nowadays the inhibitors of mTOR complex, such as everolimus, are efficient in reducing the growth of tumors.

  19. Bronchoalveoloar lavage fluid cytokines and chemokines as markers and predictors for the outcome of interstitial lung disease in systemic sclerosis patients

    OpenAIRE

    Schmidt, Katrin; Martinez-Gamboa, Lorena; Meier, Susan; Witt, Christian; Meisel, Christian; Hanitsch, Leif G.; Becker, Mike O; Huscher, Doerte; Burmester, Gerd R; Riemekasten, Gabriela

    2009-01-01

    Introduction Interstitial lung disease (ILD) is a frequent manifestation of systemic sclerosis (SSc), and cytokines can contribute to the disease pathology. The aim of the current study was to identify specific changes in cytokine levels that may serve as disease markers and possible targets for therapy. Methods Cytokines were measured with bioplex analysis in 38 bronchoalveolar fluids (BALFs) from 32 SSc patients (27 with alveolitis and 11 without alveolitis) and 26 control patients. In the ...

  20. Systemic Inflammation in Progressive Multiple Sclerosis Involves Follicular T-Helper, Th17- and Activated B-Cells and Correlates with Progression

    DEFF Research Database (Denmark)

    Romme Christensen, Jeppe; Börnsen, Lars; Ratzer, Rikke

    2013-01-01

    Pathology studies of progressive multiple sclerosis (MS) indicate a major role of inflammation including Th17-cells and meningeal inflammation with ectopic lymphoid follicles, B-cells and plasma cells, the latter indicating a possible role of the newly identified subset of follicular T-helper (TFH...... a pathogenic role of systemic inflammation in progressive MS. These observations may have implications for the treatment of progressive MS....

  1. Experimental OAI-Based Digital Library Systems

    Science.gov (United States)

    Nelson, Michael L. (Editor); Maly, Kurt (Editor); Zubair, Mohammad (Editor); Rusch-Feja, Diann (Editor)

    2002-01-01

    The objective of Open Archives Initiative (OAI) is to develop a simple, lightweight framework to facilitate the discovery of content in distributed archives (http://www.openarchives.org). The focus of the workshop held at the 5th European Conference on Research and Advanced Technology for Digital Libraries (ECDL 2001) was to bring researchers in the area of digital libraries who are building OAI based systems so as to share their experiences, problems they are facing, and approaches they are taking to address them. The workshop consisted of invited talks from well-established researchers working in building OAI based digital library system along with short paper presentations.

  2. Proton spectroscopy study of the masseter in patients with systemic sclerosis; Analise do masseter, por espectroscopia de proton, em pacientes com esclerose sistemica

    Energy Technology Data Exchange (ETDEWEB)

    Marcucci, Marcelo [Hospital Heliopolis - SUS, Sao Paulo, SP (Brazil). Servico de Estomatologia e Cirurgia Buco Maxilo Facial], e-mail: marcucci21@gmail.com; Abdala, Nitamar [Universidade Federal de Sao Paulo (UNIFESP/EPM), SP (Brazil). Dept. de Diagnostico por Imagem

    2009-05-15

    Objective: To evaluate metabolite concentration in the masseter of patients with systemic sclerosis, by analyzing creatine, choline, lipid and lactate levels, and correlating them with the presence of mandibular osteolysis. Materials and methods: The sample included 25 individuals, 15 of them with diagnosis of systemic sclerosis, divided into two groups according to the presence (group I) or absence (group II) of osteolysis, and 10 healthy individuals (group III, control). All of them were submitted to proton magnetic resonance spectroscopy with PRESS sequence and 3D acquisition. Results: Metabolite analysis showed that the creatine and lipid levels were the same for the three groups. Patients in group I presented higher levels of choline when compared with group III. On the other hand, lower lactate levels were observed in groups I and II when compared with the healthy individuals. Creatine/lipid and choline/lactate ratios were the same in the three groups. Conclusion: Lower lactate levels were observed in the patients with systemic sclerosis (groups I and II). Choline levels were increased in the patients with mandibular osteolysis (group I). Creatine/choline, lipid/lactate and choline/lipid ratios were different among the three groups. Further studies are necessary to understand the role played by the masseter in the development of mandibular osteolysis. (author)

  3. [Screening for pulmonary arterial hypertension in patients with systemic sclerosis: Comparison of DETECT algorithm to decisions of a multidisciplinary team, in a competence centre].

    Science.gov (United States)

    Coirier, V; Lescoat, A; Fournet, M; Cazalets, C; Coiffier, G; Jouneau, S; Chabanne, C; Jégo, P

    2017-08-01

    Pulmonary arterial hypertension (PAH) is a severe complication of systemic sclerosis and detecting PAH efficiently remains challenging. The DETECT study has offered in 2013 a composite screening tool for PAH. The objective of our study was to compare the indication of right heart catheterisation (RHC) as suggested by the DETECT algorithm with the decisions of a multidisciplinary team. This prospective monocentric non-interventional study consecutively included systemic sclerosis patients when data required to apply DETECT algorithm were available. We evaluate the number of RHC as requested by this algorithm and confronted it with the indications of RHC suggested by a multidisciplinary group blinded for the result of DETECT algorithm. In total, 117 systemic sclerosis patients were included. When DETECT algorithm was applied to all patients, RHC was suggested by this algorithm for 70 patients, whereas only 15 indications were required by the multidisciplinary group; among those patients only 7 had PAH. When DETECT algorithm was applied only to the 42 patients with DLCOalgorithm is able to efficiently detect all PAH patients finally diagnosed by our multidisciplinary team. However, it increases by 3 the number of RHC that should be performed. Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  4. Comprometimento pulmonar na esclerose sistêmica: revisão de casos Pulmonary involvement in systemic sclerosis: cases review

    Directory of Open Access Journals (Sweden)

    Marcel Koenigkam Santos

    2006-06-01

    Full Text Available OBJETIVO: Rever e avaliar os padrões de alterações encontrados em exames de imagem de pacientes com comprometimento pulmonar da esclerose sistêmica. MATERIAIS E MÉTODOS: Foram retrospectivamente estudados os exames de radiografia simples e tomografia computadorizada de alta resolução de 23 pacientes com esclerose sistêmica. RESULTADOS: Na radiografia simples, o padrão reticular em bases pulmonares foi predominante, tendo sido verificado em 18 pacientes (78,2%. A tomografia computadorizada de alta resolução evidenciou lesão pulmonar em todos os pacientes estudados, encontrando-se faveolamento em nove pacientes (39,1%, opacidades em vidro fosco associadas a opacidades reticulares em oito (34,7%, predomínio de opacidades reticulares em cinco (21,7% e vidro fosco em um paciente (4,3%. CONCLUSÃO: O padrão de anormalidades tomográficas possui boa correlação com os achados histopatológicos, diferenciando padrões predominantemente inflamatórios de fibróticos, com os padrões inflamatórios estando associados a uma resposta superior ao tratamento. Dessa maneira, observou-se alteração sugestiva de fibrose na maior parte dos casos (faveolamento e opacidades reticulares somando 60,8%, porém com boa parte apresentando padrões sugestivos de processo inflamatório.OBJECTIVE: To review and evaluate the patterns of imaging examinations findings of lung disease in patients with systemic sclerosis. MATERIALS AND METHODS: Plain x-rays and high-resolution computed tomography studies of 23 patients with systemic sclerosis were retrospectively analyzed. RESULTS: At plain x-rays, pulmonary disease with reticular pattern had higher prevalence, appearing in 18 patients (78.2%. High-resolution computed tomography showed lung involvement in the whole group of patients, with honeycombing in nine patients (39.1%, ground-glass opacities associated with reticular opacities in eight patients (34.7%, predominance of reticular opacities in five (21

  5. Echocardiography may help detect pulmonary vasculopathy in the early stages of pulmonary artery hypertension associated with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Serra Walter

    2010-07-01

    Full Text Available Abstract Background Pulmonary arterial hypertension (PAH in patients with systemic sclerosis is associated with a poor prognosis, but this can be improved by early disease detection. Abnormal pulmonary and cardiac function can be detected early by means of echocardiography, whereas right heart catheterization is usually performed later. Objectives The purpose of this prospective study was to detect early the presence of pulmonary artery vasculopathy in patients with verified systemic sclerosis without significant pulmonary fibrosis, normal lung volumes and a mildly reduced lung diffusion capacity of carbon monoxide (DLCO. Methods Nineteen consecutive female NYHA class I-II patients with scleroderma and a PAPs of 2. They all underwent complete Doppler echocardiography, CPET, a pulmonary ventilation test (carbon monoxide lung diffusion, DLCO, HRCT. To investigate PAH by means of complete resting Doppler echocardiography estimates of systolic pulmonary artery pressure (PAPs derived from tr icuspid regurgitation, mean PAP derived from pulmonary regurgitation, pulmonary vessel resistance (PVR derived from the acceleration time of the pulmonary outflow tract (ACTpo, and right ventricular function derived from tricuspid annular plane systolic excursion (TAPSE. Right heart catheterisation was conducted only, if pulmonary hypertension was suggested by echocardiography and an abnormal ventilator test. The data are given as mean values ± SD, unless otherwise stated. The correlations between the variables were analysed using Pearson's r coefficient, and the predictive value of the variables was calculated using linear regression analysis. A p value of > 0.05 was considered significant. Results Right heart catheterization detected PAH in 15/19 patients; mean PAP was 30.5 mm/Hg and RVP 3.6 UW. Coronary angiography of the patients aged more than 55 years showed some evidence of significant coronary artery disease. Echocardiography showed high systolic PAP

  6. Low socioeconomic status (measured by education) and outcomes in systemic sclerosis: data from the Canadian Scleroderma Research Group.

    Science.gov (United States)

    Mansour, Samah; Bonner, Ashley; Muangchan, Chayawee; Hudson, Marie; Baron, Murray; Pope, Janet E

    2013-04-01

    In systemic lupus erythematosus, socioeconomic status (SES) affects outcomes. SES can modify outcomes by altering timing of access to care and adherence. It is unknown whether SES affects systemic sclerosis (SSc) outcomes. Disease can affect income and cause work disability, thus education (completed long before SSc onset) may be a proxy for SES. The Canadian Scleroderma Research Group collects annual data on patients with SSc. Baseline data were used from a prevalent cohort. Education was stratified by whether participants completed high school. Regression models assessed effects of education on organ complications and survival. In our study, 1145 patients with SSc had 11.0 ± 9.5 years' disease duration; 86% were women, with a mean age of 55.4 ± 12.1 years. About one-quarter did not complete high school; this was more common in older patients (p education on mortality; whereas mortality was related to age, diffuse cutaneous SSc (dcSSc) subset, elevated pulmonary arterial (PA) pressure on echocardiography, low forced vital capacity expressed as percentage of predicted, and proteinuria (similar in the dcSSc subset and in limited cutaneous SSc), mortality was increased in older patients, those with elevated PA pressure, and those with low DLCO. Completing less education than high school was not associated with a worse prognosis in SSc after adjustment for confounding characteristics.

  7. EPICS: Experimental Physics and Industrial Control System

    Science.gov (United States)

    Epics Development Team

    2013-02-01

    EPICS is a set of software tools and applications developed collaboratively and used to create distributed soft real-time control systems for scientific instruments such as particle accelerators and telescopes. Such distributed control systems typically comprise tens or even hundreds of computers, networked together to allow communication between them and to provide control and feedback of the various parts of the device from a central control room, or even remotely over the internet. EPICS uses Client/Server and Publish/Subscribe techniques to communicate between the various computers. A Channel Access Gateway allows engineers and physicists elsewhere in the building to examine the current state of the IOCs, but prevents them from making unauthorized adjustments to the running system. In many cases the engineers can make a secure internet connection from home to diagnose and fix faults without having to travel to the site. EPICS is used by many facilities worldwide, including the Advanced Photon Source at Argonne National Laboratory, Fermilab, Keck Observatory, Laboratori Nazionali di Legnaro, Brazilian Synchrotron Light Source, Los Alamos National Laboratory, Australian Synchrotron, and Stanford Linear Accellerator Center.

  8. Translational Mini-Review Series on B cell subsets in disease. B cells in multiple sclerosis: drivers of disease pathogenesis and Trojan horse for Epstein-Barr virus entry to the central nervous system?

    Science.gov (United States)

    Meier, U-C; Giovannoni, G; Tzartos, J S; Khan, G

    2012-01-01

    The recent success of therapies directed at B cells has highlighted their potential as central players in multiple sclerosis (MS) pathogenesis. Exciting new data showed that B cell depletion led to reduced clinical and magnetic resonance imaging (MRI) evidence of disease activity. However, the mechanisms of action remain unknown, but could involve autoantibody production, antigen presentation and/or cytokine production by B cells. Another exciting line of investigation in the field of MS comes from latent infection of memory B cells by Epstein-Barr virus (EBV). These cells are hijacked as 'Trojan horses' and 'smuggle' the virus into the central nervous system (CNS). Thus, these new anti B cell treatments will also be likely to have anti-viral effects. We briefly review recent findings in the field of MS pathogenesis, and highlight promising new targets for therapeutic intervention in MS. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

  9. The experimental optical burst switching system

    Science.gov (United States)

    Li, Xinwan; Chen, Jian-Ping; Wu, Guiling; Wang, Hui; Lu, Jialin; Ye, Ailun

    2005-02-01

    The first optical burst switching (OBS) system has been demonstrated in China, which includes three edge routers and one core-node. A kind of fast wavelength selective optical switching was used in the system. The core OBS node consists of a kind of wavelength selective optical switch we developed. It consists of two SOA switches and one wavelength selective thin film filter with centre wavelength at one wavelength. There are one input optical fiber and two output fibers, each fiber carries two wavelengths. The Dell PE2650 servers act as the edge OBS routers. The wavelength of each data channel is located in C-band and the bit rate is at 1.25Gbps. The control channel uses bit rate of 100Mbps at wavelength of 1310 nm. A novel effective scheme for Just-In-Time (JIT) protocol was proposed and implemented. OBS services, such as Video on Demand (VOD) and file transfer protocol (FTP), have been demonstrated. Assembling and scheduling methods that are capable to guarantee the QoS (quality of service) of the transported service are studied.

  10. Experimental evidence for mixed reality states in an interreality system.

    Science.gov (United States)

    Gintautas, Vadas; Hübler, Alfred W

    2007-05-01

    We present experimental data on the limiting behavior of an interreality system comprising a virtual horizontally driven pendulum coupled to its real-world counterpart, where the interaction time scale is much shorter than the time scale of the dynamical system. We present experimental evidence that, if the physical parameters of the simplified virtual system match those of the real system within a certain tolerance, there is a transition from an uncorrelated dual reality state to a mixed reality state of the system in which the motion of the two pendula is highly correlated. The region in parameter space for stable solutions has an Arnold tongue structure for both the experimental data and a numerical simulation. As virtual systems better approximate real ones, even weak coupling in other interreality systems may produce sudden changes to mixed reality states.

  11. Energy management of DSL systems: Experimental findings

    KAUST Repository

    Guenach, Mamoun

    2013-12-01

    We present a measurement study of the energy consumption of an operator-side digital subscriber line (DSL) board under various conditions of data rate and power spectral density, with and without vectoring. The results highlight practical opportunities and challenges for optimizing rate-power-stability tradeoffs in DSL access systems, complementing simulation-based studies focused on energy reduction through spectral optimization. We validate models for line board consumption that can be tied with line driver consumption based on the aggregate transmit power of each line, and demonstrate that near-optimal rate-power-stability tradeoffs can be obtained through external line management of data rate, Signal-to-Noise-Ratio margin and power spectral density parameters. © 2013 IEEE.

  12. Trichuris suis secrete products that reduce disease severity in a multiple sclerosis model

    DEFF Research Database (Denmark)

    Hansen, Christine Soholm; Hasseldam, Henrik; Bacher, Idahella Hyldgaard

    2017-01-01

    Multiple sclerosis is a chronic inflammatory central nervous system (CNS) disease, which affects about 1 in 1000 individuals in the western world. It has been suggested that this relatively high prevalence is linked to a high level of hygiene, i.e. a reduced exposure to various microorganisms....... suis ova as well as of intraperitoneal administration of T. suis excretory/secretory products on the development and progression of experimental autoimmune encephalomyelitis – an animal model that shares clinical and pathological characteristics with multiple sclerosis. Intraperitoneal administration...

  13. Prevalence and Severity of Depression and Anxiety in Patients With Systemic Sclerosis: An Epidemiologic Survey and Investigation of Clinical Correlates.

    Science.gov (United States)

    Faezi, Seyedeh Tahereh; Paragomi, Pedram; Shahali, Ashraf; Akhlaghkhah, Maryam; Akbarian, Mahmood; Akhlaghi, Maassoomeh; Kheirandish, Masoumeh; Gharibdoost, Farhad

    2017-03-01

    Systemic sclerosis (SSc) is a chronic multisystem connective tissue disorder with detrimental impact on quality of life. Patients with SSc face emotional distress and frequently meet criteria for a psychiatric disorder. However, the pattern of psychiatric manifestations may vary according to socioethnic background. We investigated the prevalence of depressive and anxiety symptoms and examined their association with sociodemographic and clinical factors in Iranian SSc patients. Depressive and anxiety symptoms were evaluated by Beck Depression Inventory and Cattell questionnaire in 114 SSc patients. The associations between sociodemographic and clinical factors and depressive/anxiety symptoms were examined via multivariate analysis. The prevalence of depressive symptoms was 68.4%. There was a significant association between depressive symptoms and pulmonary and gastrointestinal manifestations. Also, diffuse SSc patients were more prone to depressive symptoms. Mean Rodnan scores were significantly higher in patients with depressive symptoms in comparison with subjects with no depressive symptoms. The prevalence of anxiety symptoms was 23.6%. Anxiety symptoms were not associated with demographic characteristics, SSc subtype, disease duration, Rodnan score, other clinical features, and previous history of depression in the patients or their family. The coincidence of anxiety and depression was 82.8%. Depressive and anxiety symptoms are prevalent among Iranian SSc population. The depressive symptoms showed correlation with pulmonary and gastrointestinal involvement, as well as diffuse SSc subtype.

  14. Pulmonary magnetic resonance imaging is similar to chest tomography in detecting inflammation in patients with systemic sclerosis.

    Science.gov (United States)

    Müller, Carolina de Souza; Warszawiak, Danny; Paiva, Eduardo Dos Santos; Escuissato, Dante Luiz

    Interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are prevalent complications of systemic sclerosis (SSc) and are currently the leading causes of death related to the disease. The accurate recognition of these conditions is therefore of utmost importance for patient management. A study was carried out with 24 SSc patients being followed at the Rheumatology Department of the Hospital de Clínicas of Universidade Federal do Paraná (UFPR) and 14 healthy volunteers, with the objective of evaluating the usefulness of lung magnetic resonance imaging (MRI) when assessing ILD in SS patients. The results obtained with lung MRI were compared to those obtained by computed tomography (CT) of the chest, currently considered the examination of choice when investigating ILD in SS patients. The assessed population was predominantly composed of women with a mean age of 50 years, limited cutaneous SS, and a disease duration of approximately 7 years. In most cases, there was agreement between the findings on chest CT and lung MRI. Considering it is a radiation-free examination and capable of accurately identifying areas of lung tissue inflammatory involvement, lung MRI showed to be a useful examination, and further studies are needed to assess whether there is an advantage in using lung MRI instead of chest CT when assessing ILD activity in SS patients. Copyright © 2017 Elsevier Editora Ltda. All rights reserved.

  15. Balance deficit with opened or closed eyes reveals involvement of different structures of the central nervous system in multiple sclerosis.

    Science.gov (United States)

    Prosperini, Luca; Petsas, Nikolaos; Raz, Eytan; Sbardella, Emilia; Tona, Francesca; Mancinelli, Chiara Rosa; Pozzilli, Carlo; Pantano, Patrizia

    2014-01-01

    To evaluate whether balance deficit in patients with multiple sclerosis (MS), as assessed with eyes opened (EO) and closed (EC), is associated with damage of different structures of the central nervous system (CNS). Fifty patients with MS and 20 healthy controls (HCs) underwent static posturography to calculate the body's center of pressure displacement (COP path) with EO and EC. They were scanned using a 3.0T magnet to obtain PD/T2 and 3D-T1-weighted images of the brain and spinal cord. We determined the mid-sagittal cerebellum area (MSCA) and upper cervical cord cross-sectional area (UCCA). We also measured the patients' lesion volumes (T2-LVs) on the whole brain and at different infratentorial levels. MS patients had wider COP paths with both EO and EC (p Balance deficit in MS was related to atrophy of both the cerebellum and spinal cord, but the extent of COP path under the two different conditions (EO or EC) implied different patterns of damage in the CNS.

  16. Efficacy of connective tissue massage and Mc Mennell joint manipulation in the rehabilitative treatment of the hands in systemic sclerosis.

    Science.gov (United States)

    Bongi, Susanna Maddali; Del Rosso, Angela; Galluccio, Felice; Sigismondi, Fabrizio; Miniati, Irene; Conforti, M Letizia; Nacci, Francesca; Cerinic, Marco Matucci

    2009-10-01

    Rehabilitation may contribute to the management of systemic sclerosis (SSc) dealing with disabilities due to hand involvement. The aim of this study is to evaluate the efficacy of a rehabilitation programme based on the combination of connective tissue massage and Mc Mennell joint manipulation specifically conceived for SSc patients' hands. Forty SSc patients were enrolled: 20 (interventional group) were treated for a 9-week period (twice a week, 1 h per session) with a combination of connective tissue massage, Mc Mennell joint manipulation and home exercise programme, and 20 (control group) were assigned only to home exercise programme. Patients of both groups were assessed at baseline (T0), after 9 week (T1) and at a 9 weeks follow-up (T2). They were evaluated for quality of life by SF-36 and Health Assessment Questionnaire (HAQ), hands involvement by Hand Mobility in Scleroderma (HAMIS) test, Cochin hand functional disability scale and the measurements of ROM. In the interventional group, fist closure, HAMIS test and Cochin hand functional disability scale improved at the end of the treatment (p Mental Synthetic Index (MSI) of SF-36 scores (HAQ and PSI, p manipulation and home exercise programme is effective in the rehabilitative treatment of SSc hands. This combined treatment may lead to an improvement of hand function and quality of life.

  17. Concepts of functioning and health important to people with systemic sclerosis: a qualitative study in four European countries

    Science.gov (United States)

    Stamm, Tanja A; Mattsson, Malin; Mihai, Carina; Stöcker, Juliane; Binder, Alexa; Bauernfeind, Bettina; Stummvoll, Georg; Gard, Gunvor; Hesselstrand, Roger; Sandqvist, Gunnel; Draghicescu, Oana; Gherghe, Ana Maria; Voicu, Malina; Machold, Klaus P; Distler, Oliver; Smolen, Josef S; Boström, Carina

    2011-01-01

    Objective To describe the experiences of people with systemic sclerosis (SSc) in different European countries of functioning and health and to link these experiences to the WHO International Classification of Functioning, Disability and Health (ICF) to develop a common understanding from a bio-psycho-social perspective. Method A qualitative multicentre study with focus-group interviews was performed in four European countries: Austria, Romania, Sweden and Switzerland. The qualitative data analysis followed a modified form of ‘meaning condensation’ and the concepts that emerged in the analysis were linked to the ICF. Results 63 people with SSc participated in 13 focus groups. In total, 86 concepts were identified. 32 (37%) of these were linked to the ICF component body functions and structures, 21 (24%) to activities and participation, 26 (30%) to environmental factors, 6 (7%) to personal factors and 1 (1%) to the health condition itself. 19 concepts (22%) were identified in all four countries and included impaired hand function, household activities, paid work, drugs, climate and coldness, support from others and experiences with healthcare institutions, non-pharmacological treatment, social security and benefits. Conclusion Concepts identified in all four countries could be used for guiding clinical assessment, as well as interdisciplinary team care and rheumatological rehabilitation for patients with SSc. For a full understanding of the aspects of the disease that were most relevant to people with SSc, people with SSc from multiple countries needed to be involved. PMID:21540204

  18. Lidocaine controls pain and allows safe wound bed preparation and debridement of digital ulcers in systemic sclerosis: a retrospective study.

    Science.gov (United States)

    Braschi, Francesca; Bartoli, Francesca; Bruni, Cosimo; Fiori, Ginevra; Fantauzzo, Claudia; Paganelli, Lucia; De Paulis, Amato; Rasero, Laura; Matucci-Cerinic, M

    2017-01-01

    In Systemic Sclerosis (SSc), digital ulcers (DU) are painful, difficult to heal, and frequently infected. To reduce the risk of bacterial infection and to prevent chronicity, it is essential to carefully remove necrotic tissue from DU, with maximum patient comfort. Debridement, although very efficacious, is invasive and causes local pain: lidocaine is a local anesthetic commonly used as to fight pain during debridement procedures. The aim of the study was to evaluate the efficacy of lidocaine 4 % in pain control during debridement procedure of DU in SSc. One hundred eight DU characterized by pain Numeric Rating Scale (NRS) >3/10 before starting the procedure were treated with lidocaine 4 % (lidocaine cloridrate 200 mg in 5 ml of injecting solution). Pain was measured with NRS (0-10) before starting debridement, after 15 min of lidocaine application and at the end of the procedure. In DU, in respect to baseline (mean NRS 6.74 ± 2.96), pain after application of lidocaine 4 % for 15 min was significantly lower (mean NRS 2.83 ± 2.73) (p lidocaine were observed. In SSc, topical application of lidocaine 4 % significantly reduces pain, allowing a safe debridement procedure, thus improving the management of DU.

  19. Treatment of digital ulcers in systemic sclerosis: Case series study of thirteen patients and discussion on outcome.

    Science.gov (United States)

    Abuowda, Yahia; Almeida, Raquel Sousa; Oliveira, Ana Alves; Pego, Petra; Santos, Cristina; Matos-Costa, João

    2017-05-01

    In systemic sclerosis (SSc), digital ulcers (DU) are debilitating and recurrent. They are markers of prognosis and are associated with disability and mortality. Treatment strategies have been developed to block the proposed mechanisms of this complication. Clinical description of a population of SSc patients with DU, treatment, complications and outcome. Analysis of 48 SSc patients meeting 2013 ACR-EULAR criteria, followed between 1999-2015; 13 patients had DU. Treatment protocol applied included cycles of 21 days of alprostadil, which can be repeated in the absence of DU healing. After DU healing, bosentan was initiated. DU healing was achieved with intravenous prostanoid in 12 patients; seven patients required repeated treatment for DU healing. Twelve patients were later treated with bosentan; three of them experienced recurrence of DU, while one was anti-B2-GPI positive. Four patients had soft tissue loss and three other suffered digital amputation, these being late diagnosis. Younger patients and early referrals had better outcomes. Endothelin receptor antagonist toxicity should be monitored, particularly in patients previously exposed to hepatotoxic drugs.

  20. The enhanced liver fibrosis test: a clinical grade, validated serum test, biomarker of overall fibrosis in systemic sclerosis.

    Science.gov (United States)

    Abignano, Giuseppina; Cuomo, Giovanna; Buch, Maya H; Rosenberg, William M; Valentini, Gabriele; Emery, Paul; Del Galdo, Francesco

    2014-02-01

    The absence of a serological surrogate outcome measure of fibrosis in systemic sclerosis (SSc) is a major deficiency for intervention studies and clinical management. An algorithm including the serum concentration of procollagen-III aminoterminal-propeptide, tissue inhibitor of matrix metalloproteinase-1 and hyaluronic acid, has recently been validated as predictive of severity and clinical outcome in chronic liver diseases (enhanced liver fibrosis (ELF) test) and implemented as a clinical grade test available for physicians. We evaluated the ELF test as a surrogate outcome measure in SSc. The ELF score was determined blindly in 210 patients with SSc. Results were correlated with clinical, functional and instrumental variables including disease severity, activity and disability. The ELF test was above normal range in 83% of SSc patients (175/210). The ELF score showed a significant correlation (pfibrosis in SSc and with overall disease activity, severity and HAQ-DI. The specific correlation with fibrosis and its face validity, together with the feasibility of the test, warrant its further development as a surrogate outcome measure of fibrosis in SSc.

  1. [Late-onset systemic sclerosis: A retrospective study of 27 patients diagnosed after the age of 70].

    Science.gov (United States)

    Achille, A; Journeau, L; Espitia, O; Connault, J; Espitia-Thibault, A; Durant, C; Perrin, F; Pistorius, M-A; Néel, A; Hamidou, M; Agard, C

    2017-12-08

    The aim of this study was to describe special features of patients with systemic sclerosis (SSc) diagnosed after the age of 70. This is a retrospective study of patients aged above 70 years at the time of diagnosis of SSc and followed at an internal medicine unit between 2000 and 2015. Co-morbidities and clinical characteristics were analyzed, as well as survival at 1, 2 and 3 years. Of 246 patients, 27 (11%) were included (89% women, 96% Caucasians, age 78.3±4.5 years). Synchronous cancer was noted in 3 patients. SSc was mostly limited cutaneous only (24/27), with telangiectasia (63%), gastroesophageal reflux (59%) and digital ulcers (22%), and was associated with anti-centromere antibody (69%). Interstitial lung disease was not frequent (29%). Pulmonary arterial hypertension (PAH) was suspected at diagnosis of SSc in 14 cases (52%), but only 5 patients had undergone heart catheterization, with severe PAH in 3 cases. Survival at 1 and 3 years was 85.2% and 66.7%, and was worse in the case of suspected PAH, at 78.6% and 57.1% respectively. Cases of SSc diagnosed after 70 years are mostly limited cutaneous forms. Suspicion of PAH is frequent, and PAH may be the main initial sign of the disease for patients at this age. There may be association with synchronous cancer. Survival is poor. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. Telangiectasis in CREST syndrome and systemic sclerosis: correlation of clinical and pathological features with response to pulsed dye laser treatment.

    Science.gov (United States)

    Halachmi, Shlomit; Gabari, Osama; Cohen, Sarit; Koren, Romelia; Amitai, Dan Ben; Lapidoth, Moshe

    2014-01-01

    Telangiectasia are cardinal features of systemic sclerosis (SS) and calcinosis, Raynaud's syndrome, esophageal motility, sclerodactyly, telangiectasias (CREST) syndrome. The etiology of telangiectasia in these syndromes is unknown, but vascular dysfunction has been proposed. However, the telangiectasia of CREST have anecdotally been considered relatively resistant to pulse dye laser (PDL), the treatment of choice for classic telangiectasia. The study was designed to test whether SS/CREST telangiectasia require more treatments than sporadic telangiectasia and to identify clinical and histological features that could explain such an effect. Nineteen skin biopsies from patients with SS or CREST and 10 control biopsies were examined and compared for features that may predict a differential response to PDL. Sixteen cases of SS or CREST treated with PDL between 1997 and 2007 were evaluated and response to treatment was compared with 20 patients with sporadic telangiectasis. Relative to normal skin, CREST/scleroderma telangiectasia exhibited thickened vessels in 17 out of 19 sections and thickened collagen fibers in the reticular or deep dermis in all sections. The number of treatments required to clear SS/CREST telangiectasia was approximately twofold higher. SS/CREST telangiectasia are more resistant to PDL but can be effectively cleared with more treatments.

  3. KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor

    Science.gov (United States)

    2012-01-01

    Introduction Potassium voltage-gated channel shaker-related subfamily member 5 (KCNA5) is implicated in vascular tone regulation, and its inhibition during hypoxia produces pulmonary vasoconstriction. Recently, a protective association of the KCNA5 locus with systemic sclerosis (SSc) patients with pulmonary arterial hypertension (PAH) was reported. Hence, the aim of this study was to replicate these findings in an independent multicenter Caucasian SSc cohort. Methods The 2,343 SSc cases (179 PAH positive, confirmed by right-heart catheterization) and 2,690 matched healthy controls from five European countries were included in this study. Rs10744676 single-nucleotide polymorphism (SNP) was genotyped by using a TaqMan SNP genotyping assay. Results Individual population analyses of the selected KCNA5 genetic variant did not show significant association with SSc or any of the defined subsets (for example, limited cutaneous SSc, diffuse cutaneous SSc, anti-centromere autoantibody positive and anti-topoisomerase autoantibody positive). Furthermore, pooled analyses revealed no significant evidence of association with the disease or any of the subsets, not even the PAH-positive group. The comparison of PAH-positive patients with PAH-negative patients showed no significant differences among patients. Conclusions Our data do not support an important role of KCNA5 as an SSc-susceptibility factor or as a PAH-development genetic marker for SSc patients. PMID:23270786

  4. Artifactual Hypoglycaemia in Systemic Sclerosis and Raynaud’s Phenomenon: A Clinical Case Report and Short Review

    Directory of Open Access Journals (Sweden)

    RH Bishay

    2016-01-01

    Full Text Available Background. Artifactual hypoglycaemia, defined as a discrepancy between glucometer (capillary and plasma glucose levels, may lead to overtreatment and costly investigations. It is not infrequently observed in patients with Raynaud’s phenomenon due to vascular capillary distortion, yet this is clinically underappreciated. Case Report. We report a 76-year-old woman with systemic sclerosis and Raynaud’s phenomenon, who presented with upper gastrointestinal bleeding and found to have concomitant persistent hypoglycaemia (1.0–2.7mmol/L on a point-of-care glucometer in the absence hypoglycaemic symptoms. She underwent a 2-week hospital admission, repeated glucose monitoring, hydrocortisone replacement and dextrose infusions, with consequent hyperglycaemia on plasma measurements. Clinically, she did not satisfy Whipple’s triad and radiological investigations failed to identify pituitary or pancreatic pathology. A 72-hour fast was negative for hyperinsulinaemia or exogenous insulin use and her sulphonylurea metabolite urinary screen was negative. Discussion. Treatment of low capillary blood glucose is usually met with clinical impetus to treat, even when hypoglycaemic symptoms are lacking. The correct diagnosis may have been achieved had there been an observation of her cold hands, scleroderma facies, and consideration of the likely distorted peripheral microvasculature. Early identification of this presumably rare clinical scenario may have prevented overtreatment, altered methods of monitoring, and avoided unnecessary investigations.

  5. Serum Neuroinflammatory Disease-Induced Central Nervous System Proteins Predict Clinical Onset of Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Itay Raphael

    2017-07-01

    Full Text Available There is an urgent need in multiple sclerosis (MS patients to develop biomarkers and laboratory tests to improve early diagnosis, predict clinical relapses, and optimize treatment responses. In healthy individuals, the transport of proteins across the blood–brain barrier (BBB is tightly regulated, whereas, in MS, central nervous system (CNS inflammation results in damage to neuronal tissues, disruption of BBB integrity, and potential release of neuroinflammatory disease-induced CNS proteins (NDICPs into CSF and serum. Therefore, changes in serum NDICP abundance could serve as biomarkers of MS. Here, we sought to determine if changes in serum NDICPs are detectable prior to clinical onset of experimental autoimmune encephalomyelitis (EAE and, therefore, enable prediction of disease onset. Importantly, we show in longitudinal serum specimens from individual mice with EAE that pre-onset expression waves of synapsin-2, glutamine synthetase, enolase-2, and synaptotagmin-1 enable the prediction of clinical disease with high sensitivity and specificity. Moreover, we observed differences in serum NDICPs between active and passive immunization in EAE, suggesting hitherto not appreciated differences for disease induction mechanisms. Our studies provide the first evidence for enabling the prediction of clinical disease using serum NDICPs. The results provide proof-of-concept for the development of high-confidence serum NDICP expression waves and protein biomarker candidates for MS.

  6. Gut microbiome and multiple sclerosis.

    Science.gov (United States)

    Bhargava, Pavan; Mowry, Ellen M

    2014-10-01

    The commensal flora that lives in the human gut is a unique ecosystem that has evolved over millennia with human beings. The importance of the microbiota in various bodily functions is gradually becoming more apparent. Besides the gut microbiome playing a role in bowel-related disorders, a role in metabolic and autoimmune disorders is becoming clearer. The gut bacteria play a role in educating the immune system and hence may be a player in the development of multiple sclerosis. We examine the different sources of information linking the gut microbiota to multiple sclerosis and examine the future avenues for utilizing the knowledge of the gut microbiome to potentially treat and prevent multiple sclerosis.

  7. Primary Lateral Sclerosis

    Science.gov (United States)

    ... When symptoms begin, PLS may be mistaken for amyotrophic lateral sclerosis (ALS) or spastic paraplegia. Most neurologists follow an ... When symptoms begin, PLS may be mistaken for amyotrophic lateral sclerosis (ALS) or spastic paraplegia. Most neurologists follow an ...

  8. National Multiple Sclerosis Society

    Science.gov (United States)

    ... Have you met? d Our Healthcare Voice National Multiple Sclerosis Society International Progressive MS Alliance live from Paris ... Persist for Years October 25, 2017 View All Multiple Sclerosis News & Press View All Clinical Trial Alerts Every ...

  9. Multiple sclerosis - discharge

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/patientinstructions/000129.htm Multiple sclerosis - discharge To use the sharing features on this ... doctor has told you that you have multiple sclerosis (MS). This disease affects the brain and spinal ...

  10. Depression and Multiple Sclerosis

    Science.gov (United States)

    ... navigation Skip to content Menu Navigation National Multiple Sclerosis Society Sign In In Your Area Donate Donate ... MS What Causes MS? Who Gets MS? Multiple Sclerosis FAQs Types of MS Related Conditions Symptoms & Diagnosis ...

  11. Fatigue and Multiple Sclerosis

    Science.gov (United States)

    ... navigation Skip to content Menu Navigation National Multiple Sclerosis Society Sign In In Your Area Donate Donate ... MS What Causes MS? Who Gets MS? Multiple Sclerosis FAQs Types of MS Related Conditions Symptoms & Diagnosis ...

  12. Clinical diagnosis of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    ZHANG Xing-hu

    2012-04-01

    Full Text Available Multiple sclerosis (MS is an inflammatory demyelinating disease in central nervous system. The etiology is still unknown. The pathogenesis may be related to autoimmune response. Clinical features are dissemination in time (multiple attacks and dissemination in space (multifocal episode. The common used examinations including brain or spinal MRI, CSF analysis and evoked potentials. The latest diagnostic criteria is McDonald criteria published in 2010. It is now accepted that neuromyelitis optica (NMO is different from MS in clinical, pathology, imaging and so on. Due to the diversity in clinical manifestation and the lack of specific biological parameters, the diagnosis of multiple sclerosis is still challenging.

  13. Increased mitochondrial content in remyelinated axons: implications for multiple sclerosis

    Science.gov (United States)

    Zambonin, Jessica L.; Zhao, Chao; Ohno, Nobuhiko; Campbell, Graham R.; Engeham, Sarah; Ziabreva, Iryna; Schwarz, Nadine; Lee, Sok Ee; Frischer, Josa M.; Turnbull, Doug M.; Trapp, Bruce D.; Lassmann, Hans; Franklin, Robin J. M.

    2011-01-01

    Mitochondrial content within axons increases following demyelination in the central nervous system, presumably as a response to the changes in energy needs of axons imposed by redistribution of sodium channels. Myelin sheaths can be restored in demyelinated axons and remyelination in some multiple sclerosis lesions is extensive, while in others it is incomplete or absent. The effects of remyelination on axonal mitochondrial content in multiple sclerosis, particularly whether remyelination completely reverses the mitochondrial changes that follow demyelination, are currently unknown. In this study, we analysed axonal mitochondria within demyelinated, remyelinated and myelinated axons in post-mortem tissue from patients with multiple sclerosis and controls, as well as in experimental models of demyelination and remyelination, in vivo and in vitro. Immunofluorescent labelling of mitochondria (porin, a voltage-dependent anion channel expressed on all mitochondria) and axons (neurofilament), and ultrastructural imaging showed that in both multiple sclerosis and experimental demyelination, mitochondrial content within remyelinated axons was significantly less than in acutely and chronically demyelinated axons but more numerous than in myelinated axons. The greater mitochondrial content within remyelinated, compared with myelinated, axons was due to an increase in density of porin elements whereas increase in size accounted for the change observed in demyelinated axons. The increase in mitochondrial content in remyelinated axons was associated with an increase in mitochondrial respiratory chain complex IV activity. In vitro studies showed a significant increase in the number of stationary mitochondria in remyelinated compared with myelinated and demyelinated axons. The number of mobile mitochondria in remyelinated axons did not significantly differ from myelinated axons, although significantly greater than in demyelinated axons. Our neuropathological data and findings in

  14. Short-Term Pulmonary Function Trends Are Predictive of Mortality in Interstitial Lung Disease Associated With Systemic Sclerosis.

    Science.gov (United States)

    Goh, Nicole S; Hoyles, Rachel K; Denton, Christopher P; Hansell, David M; Renzoni, Elisabetta A; Maher, Toby M; Nicholson, Andrew G; Wells, Athol U

    2017-08-01

    To determine the prognostic value of pulmonary function test (PFT) trends at 1 and 2 years in interstitial lung disease (ILD) associated with systemic sclerosis (SSc). The prognostic significance of PFT trends at 1 year (n = 162) and 2 years (n = 140) was examined against 15-year survival in patients with SSc-associated ILD. PFT trends, expressed as continuous change and as categorical change in separate analyses, were examined against mortality in univariate and multivariate models. SSc-associated ILD was defined at presentation as either limited lung fibrosis or extensive lung fibrosis, using the United Kingdom Raynaud's and Scleroderma Association severity staging system. One-year PFT trends were predictive of mortality only in patients with extensive lung fibrosis: categorical change in the forced vital capacity (FVC), alone or in combination with categorical change in the diffusing capacity for carbon monoxide (DLco), had greater prognostic significance than continuous change in the FVC or trends in other PFT variables. Taking into account both prognostic value and sensitivity to change, the optimal definition of progression for trial purposes was an FVC and DLco composite end point, consisting of either an FVC decline from baseline of ≥10% or an FVC decline of 5-9% in association with a DLco decline of ≥15%. At 2 years, gas transfer trends had the greatest prognostic significance, in the whole cohort and in those with limited lung fibrosis. However, in patients with extensive lung fibrosis, the above-defined FVC and DLco composite end point was the strongest prognostic determinant. Larger changes in the FVC:DLco ratio than in the carbon monoxide transfer coefficient were required to achieve prognostic significance. Based on linkages to long-term outcomes, these findings provide support for use of routine spirometry and gas transfer monitoring in patients with SSc-associated ILD, with further evaluation of a composite FVC and DLco end point

  15. Optimization of a murine and human tissue model to recapitulate dermal and pulmonary features of systemic sclerosis.

    Directory of Open Access Journals (Sweden)

    Tomoya Watanabe

    Full Text Available The murine bleomycin (BLM-induced fibrosis model is the most widely used in systemic sclerosis (SSc studies. It has been reported that systemic delivery of BLM via continuous diffusion from subcutaneously implanted osmotic minipumps can cause fibrosis of the skin, lungs, and other internal organs. However, the mouse strain, dosage of BLM, administration period, and additional important features differ from one report to the next. In this study, by employing the pump model in C57BL/6J mice, we show a dose-dependent increase in lung fibrosis by day 28 and a transient increase in dermal thickness. Dermal thickness and the level of collagen in skin treated with high-dose BLM was significantly higher than in skin treated with low dose BLM or vehicle. A reduction in the thickness of the adipose layer was noted in both high and low dose groups at earlier time points suggesting that the loss of the fat layer precedes the onset of fibrosis. High-dose BLM also induced dermal fibrosis and increased expression of fibrosis-associated genes ex vivo in human skin, thus confirming and extending the in vivo findings, and demonstrating that a human organ culture model can be used to assess the effect of BLM on skin. In summary, our findings suggest that the BLM pump model is an attractive model to analyze the underlying mechanisms of fibrosis and test the efficacy of potential therapies. However, the choice of mouse strain, duration of BLM administration and dose must be carefully considered when using this model.

  16. Left Ventricular Mass and Intrarenal Arterial Stiffness as Early Diagnostic Markers in Cardiorenal Syndrome Type 5 due to Systemic Sclerosis.

    Science.gov (United States)

    Gigante, Antonietta; Barilaro, Giuseppe; Barbano, Biagio; Romaniello, Antonella; Di Mario, Francesca; Quarta, Silvia; Gasperini, Maria Ludovica; Di Lazzaro Giraldi, Gianluca; Laviano, Alessandro; Amoroso, Antonio; Cianci, Rosario; Rosato, Edoardo

    2016-02-01

    Cardiorenal syndrome type 5 (CRS-5) includes a group of conditions characterized by a simultaneous involvement of the heart and kidney in the course of a systemic disease. Systemic sclerosis (SSc) is frequently involved in the etiology of acute and chronic CRS-5 among connective tissue diseases. In SSc patients, left ventricular mass (LVM) can be used as a marker of nutritional status and fibrosis, while altered intrarenal hemodynamic parameters are suggestive of early kidney involvement. Forty-two consecutive patients with a diagnosis of SSc without cardiac and/or renal impairment were enrolled to assess whether cardiac muscle mass can be related to arterial stiffness. Thirty subjects matched for age and sex were also enrolled as healthy controls (HC). All patients performed echocardiography and renal ultrasound. Doppler indices of intrarenal stiffness and echocardiographic indices of LVM were significantly increased in SSc patients compared to HC. A positive correlation exists between LVM/body surface area and pulsatile index (p < 0.05, r = 0.36), resistive index (p < 0.05, r = 0.33) and systolic/diastolic ratio (p < 0.05, r = 0.38). Doppler indices of intrarenal stiffness and LVM indices were significantly higher in SSc patients with digital ulcers than in SSc patients without a digital ulcer history. SSc is characterized by the presence of microvascular and multiorgan injury. An early cardiac and renal impairment is very common. LVM and intrarenal arterial stiffness can be considered as early markers of CRS onset. The clinical use of these markers permits a prompt identification of organ damage. An early diagnosis allows the appropriate setting of pharmacological management, by slowing disease progression. © 2016 S. Karger AG, Basel.

  17. Quadrivalent HPV vaccination and risk of multiple sclerosis and other demyelinating diseases of the central nervous system.

    Science.gov (United States)

    Scheller, Nikolai Madrid; Svanström, Henrik; Pasternak, Björn; Arnheim-Dahlström, Lisen; Sundström, Karin; Fink, Katharina; Hviid, Anders

    2015-01-06

    Case reports have suggested a link between human papillomavirus (HPV) vaccination and development of multiple sclerosis and other demyelinating diseases. To investigate if quadrivalent HPV (qHPV) vaccination is associated with an increased risk of multiple sclerosis and other demyelinating diseases. Using nationwide registers we identified a cohort of all females aged 10 years to 44 years in Denmark and Sweden, followed up from 2006 to 2013, information on qHPV vaccination, and data on incident diagnoses of multiple sclerosis and other demyelinating diseases. The primary analysis used a cohort design including vaccinated and unvaccinated study participants. A secondary analysis used a self-controlled case-series design including only cases. Both analyses used a 2-year risk period following vaccination. Information on qHPV vaccination was obtained through the national vaccination and prescription registers. The primary outcomes were multiple sclerosis and a composite end point of other demyelinating diseases. Incidence rate ratios were estimated using Poisson regression, comparing rates of events in the 2-year risk periods following vaccination and in unvaccinated time periods. The study included 3,983,824 females, among whom 789,082 received a total of 1,927,581 qHPV vaccine doses. During follow-up, 4322 multiple sclerosis cases and 3300 cases of other demyelinating diseases were identified, of which 73 and 90, respectively, occurred within the risk period. In the cohort analysis, there was no increased risk of multiple sclerosis (crude incidence rates, 6.12 events/100,000 person-years [95% CI, 4.86-7.69] and 21.54 events/100,000 person-years [95% CI, 20.90-22.20] for the vaccinated and unvaccinated periods; adjusted rate ratio, 0.90 [95% CI, 0.70-1.15]) or other demyelinating diseases (crude incidence rates, 7.54 events/100,000 person-years [95% CI, 6.13-9.27] and 16.14 events/100,000 person-years [95% CI, 15.58-16.71]; adjusted rate ratio, 1.00 [95% CI, 0

  18. Experimental analyses of dynamical systems involving shape memory alloys

    DEFF Research Database (Denmark)

    Enemark, Søren; Savi, Marcelo A.; Santos, Ilmar F.

    2015-01-01

    The use of shape memory alloys (SMAs) in dynamical systems has an increasing importance in engineering especially due to their capacity to provide vibration reductions. In this regard, experimental tests are essential in order to show all potentialities of this kind of systems. In this work, SMA...... springs are incorporated in a dynamical system that consists of a one degree of freedom oscillator connected to a linear spring and a mass, which is also connected to the SMA spring. Two types of springs are investigated defming two distinct systems: a pseudoelastic and a shape memory system......-tension of the springs. This article shows several experimental tests that allow one to obtain a general comprehension of the dynamical behaviour of SMA systems. Results show the general thermo-mechanical behaviour of SMA dynamical systems and the obtained conclusions can be applied in distinct situations as in rotor...

  19. The genetic basis of amyotrophic lateral sclerosis: recent breakthroughs

    Directory of Open Access Journals (Sweden)

    Eykens C

    2015-10-01

    Full Text Available Caroline Eykens,1,2 Wim Robberecht1–31Research Group Experimental Neurology, Department of Neurosciences, KU Leuven – University of Leuven, Leuven, Belgium; 2Laboratory of Neurobiology, Vesalius Research Center, VIB, Leuven, Belgium; 3Department of Neurology, University Hospitals Leuven, Leuven, BelgiumAbstract: Deciphering the genetic architecture of amyotrophic lateral sclerosis (ALS, an adult-onset neurodegenerative disorder of the motor neuron system, is important to understand the etiology of this fatal disease as well as to develop customized ALS therapies based on the patient's genetic fingerprint. In this review, we discuss the genetic basis of ALS, and attempt to link the causal genes to three highly interrelated pathogenic mechanisms: dysproteostasis, RNA dysregulation, and axon dysfunction. In addition, we address the clinical and biological implications of these genetic findings. Furthermore, we explore to what extent genetic knowledge can be converted into targeted and personalized treatments.Keywords: amyotrophic lateral sclerosis, frontotemporal dementia, genetics, disease modifiers, personalized medicine

  20. Development of experimental systems for material sciences under microgravity

    Science.gov (United States)

    Tanii, Jun; Obi, Shinzo; Kamimiyata, Yotsuo; Ajimine, Akio

    1988-01-01

    As part of the Space Experiment Program of the Society of Japanese Aerospace Companies, three experimental systems (G452, G453, G454) have been developed for materials science studies under microgravity by the NEC Corporation. These systems are to be flown as Get Away Special payloads for studying the feasibility of producing new materials. Together with the experimental modules carrying the hardware specific to the experiment, the three systems all comprise standard subsystems consisting of a power supply, sequence controller, temperature controller, data recorder, and video recorder.

  1. Stiffness analysis and experimental validation of robotic systems

    Science.gov (United States)

    Carbone, Giuseppe

    2011-06-01

    Stiffness can be considered of primary importance in order to guarantee the successful use of any robotic system for a given task. Therefore, this paper proposes procedures for carrying out both numerical and experimental estimations of stiffness performance for multibody robotic systems. The proposed numerical procedure is based on models with lumped parameters for deriving the Cartesian stiffness matrix. Stiffness performance indices are also proposed for comparing stiffness performance. Then, an experimental procedure for the evaluation stiffness performance is proposed as based on a new measuring system named as Milli-CATRASYS (Milli Cassino Tracking System) and on a trilateration technique. Cases of study are reported to show the soundness and engineering feasibility of both the proposed numerical formulation for stiffness analysis and experimental validation of stiffness performance.

  2. Mechanisms of immunotherapeutic intervention by anti-CD40L (CD154) antibody in an animal model of multiple sclerosis

    NARCIS (Netherlands)

    Howard, L.M.; Miga, A.J.; Vanderlugt, C.L.; Dal Canto, M.C.; Laman, J.D.; Noelle, R.J.; Miller, S.D.

    1999-01-01

    Relapsing experimental autoimmune encephalomyelitis (R-EAE) in the SJL mouse is a Th1-mediated autoimmune demyelinating disease model for human multiple sclerosis and is characterized by infiltration of the central nervous system (CNS) by Th1 cells and macrophages. Disease relapses are mediated by T

  3. Pediatric Multiple sclerosis

    OpenAIRE

    Gkampeta, Anastasia; Pavlidou, Efterpi; Saravakos, Panagiotis; Pavlou, Evangelos

    2013-01-01

    Multiple sclerosis (MS) is considered as the major cause of acquired neurological insult in young adults and the most common demyelinating disease of the central nervous system (CNS). It is an inflammatory disease characterized by multiple areas of demyelination, rupture of the blood-brain barrier and diffused disorder of the white matter. MS is relatively rare in childhood. However, 3-10% of children develop the first episode of MS before the 16th year of age. Diagnosis of MS in childhood re...

  4. Tuberous sclerosis Anaesthetic considerations

    African Journals Online (AJOL)

    QuickSilver

    Tuberous sclerosis. Anaesthetic considerations. Tuberous sclerosis. Tuberous sclerosis(TS) was first described by Bourneville in. 1880.1 TS is said to be one of the commonest autosomal domi- nant diseases. Epidemiological studies report an incidence rang- ing between1:10000 to 1:170000.2,3 Two gene loci have been ...

  5. Childhood Multiple Sclerosis: A Review

    Science.gov (United States)

    Waldman, Amy; O'Connor, Erin; Tennekoon, Gihan

    2006-01-01

    Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS) that is increasingly recognized as a disease that affects children. Similar to adult-onset MS, children present with visual and sensory complaints, as well as weakness, spasticity, and ataxia. A lumbar puncture can be helpful in diagnosing MS when…

  6. Neuromyelitis optica and multiple sclerosis

    DEFF Research Database (Denmark)

    Bennett, J. L.; de Seze, J.; Lana-Peixoto, M.

    2015-01-01

    Neuromyelitis optica (NMO) is an inflammatory autoimmune disease of the central nervous system that preferentially targets the optic nerves and spinal cord. The clinical presentation may suggest multiple sclerosis (MS), but a highly specific serum autoantibody against the astrocytic water channel...

  7. Hippocampal Sclerosis: Causes and Prevention.

    Science.gov (United States)

    Walker, Matthew Charles

    2015-06-01

    Hippocampal sclerosis is the commonest cause of drug-resistant epilepsy in adults, and is associated with alterations to structures and networks beyond the hippocampus.In addition to being a cause of epilepsy, the hippocampus is vulnerable to damage from seizure activity. In particular, prolonged seizures (status epilepticus) can result in hippocampal sclerosis. The hippocampus is also vulnerable to other insults including traumatic brain injury, and inflammation. Hippocampal sclerosis can occur in association with other brain lesions; the prevailing view is that it is probably a secondary consequence. In such instances, successful surgical treatment usually involves the resection of both the lesion and the involved hippocampus. Experimental data have pointed to numerous neuroprotective strategies to prevent hippocampal sclerosis. Initial neuroprotective strategies aimed at glutamate receptors may be effective, but later, metabolic pathways, apoptosis, reactive oxygen species, and inflammation are involved, perhaps necessitating the use of interventions aimed at multiple targets. Some of the therapies that we use to treat status epilepticus may neuroprotect. However, prevention of neuronal death does not necessarily prevent the later development of epilepsy or cognitive deficits. Perhaps, the most important intervention is the early, aggressive treatment of seizure activity, and the prevention of prolonged seizures. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  8. Identification of potential biomarkers in Multiple Sclerosis

    NARCIS (Netherlands)

    V. Singh (Vaibhav)

    2015-01-01

    markdownabstractAbstract Multiple sclerosis (MScl) is an inflammatory, autoimmune, demyelinating disease of the central nervous system (CNS). Thesis describes the identification of potential MScl biomarker research, with emphasis on distinguishing subtypes, first event of CNS demyelination in

  9. Experimental system of ejected electron spectroscopy with ECR ion source

    Energy Technology Data Exchange (ETDEWEB)

    Kitazawa, Sin-iti [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    1995-09-01

    The experiment of analyzing energy spectrum of electrons ejected from multiple electron capture process on ion-atom collision is carried out using ECR (Electron Cyclotron Resonance) ion source. An old collision system using gas atoms as target and a new system using vapour atoms are developed. In this report, the developments and exploitations of the experimental systems for the ejected electron spectroscopy with ECR Ion source are presented. (author).

  10. Symptoms of depression and anxiety in Serbian patients with systemic sclerosis: impact of disease severity and socioeconomic factors.

    Science.gov (United States)

    Ostojic, Predrag; Zivojinovic, Sladjana; Reza, Tamara; Damjanov, Nemanja

    2010-08-01

    This study aimed to assess symptoms of depression and anxiety in Serbian patients with systemic sclerosis (SSc) and to estimate the impact of disease severity and socioeconomic factors on development of depression and anxiety in SSc. Thirty-five patients with SSc and 30 age- and gender-matched healthy individuals participated. Symptoms of depression and anxiety were evaluated using the Beck's depression inventory and Zung's anxiety self-assessment scale. We estimated the impact of gender, age, economic status, marital status, disease duration, disease subset (limited or diffuse), and some clinical features on development of depressive symptoms and anxiety in patients with SSc. Symptoms of depression were found in 68.6% of patients (compared with 23.3% in the control group), were more frequent in patients with longer disease duration and in female and older patients, and were more common in unemployed and retired patients than in employed individuals. No differences in anxiety and depressive symptoms was noticed between patients with limited and diffuse SSc or those with or without restrictive lung disease, pulmonary hypertension, finger-tip ulcers, and heart involvement. Symptoms of depression were associated with severe pain. Symptoms of anxiety were found in 80% of patients compared with 13.3% of healthy individuals and were equally as frequent in patients of different gender, age, socioeconomic status, and disease duration and severity. Symptoms of depression and anxiety are common in Serbian patients with SSc. Depressive symptoms depended mostly on socioeconomic factors, disease duration, and pain intensity, whereas disease severity had no significant impact on development of depressive symptoms and anxiety.

  11. Nintedanib inhibits macrophage activation and ameliorates vascular and fibrotic manifestations in the Fra2 mouse model of systemic sclerosis.

    Science.gov (United States)

    Huang, Jingang; Maier, Christiane; Zhang, Yun; Soare, Alina; Dees, Clara; Beyer, Christian; Harre, Ulrike; Chen, Chih-Wei; Distler, Oliver; Schett, Georg; Wollin, Lutz; Distler, Jörg H W

    2017-11-01

    Nintedanib is an inhibitor targeting platelet-derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor tyrosine kinases that has recently been approved for the treatment of idiopathic pulmonary fibrosis. The aim of this study was to analyse the effects of nintedanib in the fos-related antigen-2 (Fra2) mouse model of systemic sclerosis (SSc). The effects of nintedanib on pulmonary arterial hypertension with proliferation of pulmonary vascular smooth muscle cells (PVSMCs) and luminal occlusion, on microvascular disease with apoptosis of microvascular endothelial cells (MVECs) and on fibroblast activation with myofibroblast differentiation and accumulation of extracellular matrix were analysed. We also studied the effects of nintedanib on the levels of key mediators involved in the pathogenesis of SSc and on macrophage polarisation. Nintedanib inhibited proliferation of PVSMCs and prevented thickening of the vessel walls and luminal occlusion of pulmonary arteries. Treatment with nintedanib also inhibited apoptosis of MVECs and blunted the capillary rarefaction in Fra2-transgenic mice. These effects were associated with a normalisation of the serum levels of vascular endothelial growth factor in Fra2 mice on treatment with nintedanib. Nintedanib also effectively blocked myofibroblast differentiation and reduced pulmonary, dermal and myocardial fibrosis in Fra2-transgenic mice. The antifibrotic effects of nintedanib were associated with impaired M2 polarisation of monocytes and reduced numbers of M2 macrophages. Nintedanib targets core features of SSc in Fra2-transgenic mice and ameliorates histological features of pulmonary arterial hypertension, destructive microangiopathy and pulmonary and dermal fibrosis. These data might have direct implications for the ongoing phase III clinical trial with nintedanib in SSc-associated interstitial lung disease. © Article author(s) (or their employer(s) unless otherwise

  12. PerSSception: A Survey of Patients with Systemic Sclerosis and Their Perceptions of the Quality of Their Primary Care

    Science.gov (United States)

    Toci, Ashley L.; Hyer, J. Madison; Silver, Richard M.; Nietert, Paul J; Hant, Faye N.

    2016-01-01

    Background Among patients with systemic sclerosis (SSc), early recognition of potentially life-threatening organ involvement is critical. Because prompt recognition of early signs of organ involvement can dramatically alter a patient’s outcome, it is crucial that patients and primary care providers (PCPs) recognize these symptoms. We conducted a survey of SSc patients regarding their perceptions of the quality of their primary care, and whether or not they perceive the quality of their primary care to be impaired by their scleroderma diagnosis. Methods A mail survey was sent to 525 patients with SSc seen at the Medical University of South Carolina. Questionnaire items addressed demographics and perceptions of their quality of their primary care. Results Of n=140 respondents, most (74.5%) did not feel as though their diagnosis of SSc has resulted in barriers to appropriate or satisfactory care, and most (81.3%) answered that they had not ever felt as though their medical concerns were not being addressed because they had SSc. Perceptions of barriers were significantly (p<0.05) associated with female gender and younger age, along with poorer overall quality of care and satisfaction with their primary care. Conclusions Most SSc patients value the quality of their primary care. However, some SSc patients feel that their PCPs do not adequately monitor their blood pressure, reflux symptoms, or shortness of breath. These results highlight the importance of PCPs in the overall care of SSc patients and the need for continued education regarding close monitoring of signs/symptoms suggestive of possible life-threatening internal organ involvement. PMID:27140701

  13. Long-term efficacy of B cell depletion therapy on lung and skin involvement in diffuse systemic sclerosis.

    Science.gov (United States)

    Bosello, Silvia L; De Luca, Giacomo; Rucco, Manuela; Berardi, Giorgia; Falcione, Matteo; Danza, Francesco Maria; Pirronti, Tommaso; Ferraccioli, Gianfranco

    2015-02-01

    To assess the long-term efficacy and safety of single and multiple courses of rituximab therapy in systemic sclerosis (SSc) patients with and without lung disease. A total of 20 SSc patients with a diffuse disease were treated with rituximab. At baseline and during follow-up the lung involvement was evaluated with pulmonary function tests (FVC and DLCO) and with lung high-resolution computed tomography (HRCT). The skin score, activity, and severity indices improved significantly after 12 months and at final follow-up compared to baseline. After 12 months, there was a significant increase of FVC and TLC compared to baseline (p = 0.024 and p = 0.005, respectively), while the mean DLCO value remained stable. Considering the last available follow-up in six patients with restrictive lung disease at baseline, two patients (33.3%) experienced an increase of more than 10% of FVC, one patient had a decrease of FVC >10%, while in three patients FVC remained stable (50%). After the mean follow-up of 48.5 ± 20.4 months, among the patients with normal lung parameters at baseline, FVC remained stable in 12 (85.7%) and in one patient (14.3%) it increased by more than 10%. At the final follow-up, the alveolar and interstitial HRCT scores remained stable in more than 80% of patients, both in patients with and without restrictive lung disease at baseline. Anti-CD20 B cell depletion therapy is effective on skin involvement but seems also to preserve the pulmonary function, as supported by a stable or improved FVC and stable interstitial score, suggesting a possible role of rituximab as a modifying therapy overall in early diffuse SSc. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Anticardiolipin and anti-beta2 glycoprotein I antibodies and lupus-like anticoagulant: prevalence and significance in systemic sclerosis.

    Science.gov (United States)

    Marie, I; Jouen, F; Hellot, M-F; Levesque, H

    2008-01-01

    It has been suggested that both anticardiolipin (aCL) and anti-beta(2) glycoprotein I (abeta(2)GPI) antibodies may play a critical role in the pathogenesis of systemic sclerosis (SSc)-related vascular impairment. To evaluate the prevalence of aCL and abeta(2)GPI antibodies and lupus-like anticoagulant (LAC) in patients with SSc and healthy controls. We also investigated a possible relationship between clinical and biological variables of patients with SSc and the presence of aCL/abeta(2)GPI antibodies and/or LAC. Measurements of aCL and abeta(2)GPI antibodies, and LAC were performed in 69 consecutive patients with SSc and 69 age- and sex-matched controls. Clinical and biological findings were compared between patients with and without antiphospholipid antibodies. aCL and abeta(2)GPI antibodies and/or LAC were detected in 13 (19%) of 69 consecutive patients with SSc; in the healthy control group, aCL antibody was found in only one (2%) subject (P = 0.0007). None of the healthy controls had abeta(2)GPI antibody and/or LAC. Moreover, pitting scars, pulmonary arterial hypertension, macrovascular involvement as well as severity of capillary impairment (using nailfold videocapillaroscopy) were more frequent in SSc patients with aCL/abeta(2)GPI antibodies and/or LAC compared with those without. Our findings suggest that antiphospholipid antibodies may have a role in the genesis of vascular involvement related to SSc. Finally, the assessment of antiphospholipid antibodies (aCL and abeta(2)GPI antibodies, as well as LAC) may contribute to a better recognition of clinical features in patients with SSc; in essence, the patients with aCL/abeta(2)GPI antibodies and/or LAC may require close monitoring of vascular changes, including in particular pulmonary arterial hypertension and digital infarcts.

  15. Therapeutic Targeting of TAZ and YAP by Dimethyl Fumarate in Systemic Sclerosis Fibrosis.

    Science.gov (United States)

    Toyama, Tetsuo; Looney, Agnieszka P; Baker, Brendon M; Stawski, Lukasz; Haines, Paul; Simms, Robert; Szymaniak, Aleksander D; Varelas, Xaralabos; Trojanowska, Maria

    2018-01-01

    Systemic sclerosis (scleroderma, SSc) is a devastating fibrotic disease with few treatment options. Fumaric acid esters, including dimethyl fumarate (DMF, Tecfidera; Biogen, Cambridge, MA), have shown therapeutic effects in several disease models, prompting us to determine whether DMF is effective as a treatment for SSc dermal fibrosis. We found that DMF blocks the profibrotic effects of transforming growth factor-β (TGFβ) in SSc skin fibroblasts. Mechanistically, we found that DMF treatment reduced nuclear localization of transcriptional coactivator with PDZ binding motif (TAZ) and Yes-associated protein (YAP) proteins via inhibition of the phosphatidylinositol 3 kinase/protein kinase B (Akt) pathway. In addition, DMF abrogated TGFβ/Akt1 mediated inhibitory phosphorylation of glycogen kinase 3β (GSK3β) and a subsequent β-transducin repeat-containing proteins (βTRCP) mediated proteasomal degradation of TAZ, as well as a corresponding decrease of TAZ/YAP transcriptional targets. Depletion of TAZ/YAP recapitulated the antifibrotic effects of DMF. We also confirmed the increase of TAZ/YAP in skin biopsies from patients with diffuse SSc. We further showed that DMF significantly diminished nuclear TAZ/YAP localization in fibroblasts cultured on a stiff surface. Importantly, DMF prevented bleomycin-induced skin fibrosis in mice. Together, our work demonstrates a mechanism of the antifibrotic effect of DMF via inhibition of Akt1/GSK3β/TAZ/YAP signaling and confirms a critical role of TAZ/YAP in mediating the profibrotic responses in dermal fibroblasts. This study supports the use of DMF as a treatment for SSc dermal fibrosis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. Novel Ideas: The Increased Skin Viscoelasticity - A Possible New Fifth Sign for the Very Early Diagnosis of Systemic Sclerosis.

    Science.gov (United States)

    Dobrev, Hristo

    2013-01-01

    Diagnosis of systemic sclerosis (SSc) at very early stage could allow starting an appropriate therapy and improving the patient outcome. Skin involvement is often the first non-Raynaud's phenomenon (RP) symptom. Its uncovering may play an important role for the initial diagnosis. To introduce a simplified method for non-invasive evaluation of skin mechanical properties in patients with clinically evident or suspected SSc. A total of 94 patients and 162 healthy subjects were studied. According to clinical and nailfold videocapillaroscopy findings the patients were divided into four groups: 20 with edematous phase of SSc (group 1), 28 with indurative phase of SSc (group 2), 26 with suspected secondary RP (group 3), and 20 with primary RP (group 4). Mechanical properties of the volar forearm skin were evaluated using a non-invasive suction device (Cutometer) equipped with 2-mm diameter probe. The skin mechanical parameters analyzed were distensibility (Uf), elasticity (Ua/Uf) and viscoelasticity (Uv/Ue). Skin distensibility was reduced and skin viscoelasticity increased in group 1-3 compared to age matched healthy controls. There were no significant changes in skin elasticity. Mechanical parameters in group 4 were normal. Comparison of individual patient's values with population 95% confidence intervals of the mean showed increased skin viscoelasticity in group 1 (100%), group 2 (93%), and group 3 (81%), whereas the incidence in group 4 was 10%. Noninvasive method applied is appropriate for objective and quantitative evaluation of sclerodermatous skin. In combination with nailfold videocapillaroscopy it could be predictive in pre-scleroderma patients. The increased skin viscoelasticity parameter could be proposed as the possible new fifth sign for the very early diagnosis of SSc.

  17. Validation of the UCLA Scleroderma Clinica Trial Gastrointestinal Tract Instrument version 2.0 for systemic sclerosis.

    Science.gov (United States)

    Baron, Murray; Hudson, Marie; Steele, Russell; Lo, Ernest

    2011-09-01

    The University of California at Los Angeles (UCLA) Scleroderma Clinical Trial Consortium GI Tract Instrument (UCLA SCTC GITI) was recently developed to measure gastrointestinal tract disease in systemic sclerosis (SSc). Our study assesses the internal consistency and validity of the instrument in a different population than was used in the original study. A sample of 113 consecutive patients with SSc from the Canadian Scleroderma Research Group (CSRG) Registry completed the UCLA SCTC GITI, a self-administered questionnaire with 7 scales and an overall score. Reliability was evaluated using Cronbach's alpha coefficient and validity was determined by testing multiple constructs. Our subjects were slightly older than the original cohort, and had less formal education and less diffuse cutaneous disease. The overall score of the instrument correlated well with the GI scale of the Health Assessment Questionnaire for the Spondyloarthropathies (GI-S-HAQ; r = 0.58, p < 0.001) and the total number of GI symptoms (r = 0.77, p < 0.001). Each subscale correlated well with the GI-S-HAQ. The individual scales and the overall score were able to differentiate between categorical groupings of the GI-S-HAQ. The scale scores differentiated well those patients with clinical involvement of the corresponding GI problem. Multiple linear regression adjusting for age, disease duration, sex, and ethnicity showed that the UCLA SCTC GITI had a significant association with both the physical component summary and the mental component summary of the Medical Outcomes Study Short-Form 36 questionnaire. Our study confirms that the UCLA SCTC GITI version 2.0 will be a useful tool for assessing the role of GI involvement in SSc, even in a population with substantially different characteristics than the subjects originally tested.

  18. Functional alterations of the ubiquitin-proteasome system in motor neurons of a mouse model of familial amyotrophic lateral sclerosis.

    Science.gov (United States)

    Cheroni, Cristina; Marino, Marianna; Tortarolo, Massimo; Veglianese, Pietro; De Biasi, Silvia; Fontana, Elena; Zuccarello, Laura Vitellaro; Maynard, Christa J; Dantuma, Nico P; Bendotti, Caterina

    2009-01-01

    In familial and sporadic amyotrophic lateral sclerosis (ALS) and in rodent models of the disease, alterations in the ubiquitin-proteasome system (UPS) may be responsible for the accumulation of potentially harmful ubiquitinated proteins, leading to motor neuron death. In the spinal cord of transgenic mice expressing the familial ALS superoxide dismutase 1 (SOD1) gene mutation G93A (SOD1G93A), we found a decrease in constitutive proteasome subunits during disease progression, as assessed by real-time PCR and immunohistochemistry. In parallel, an increased immunoproteasome expression was observed, which correlated with a local inflammatory response due to glial activation. These findings support the existence of proteasome modifications in ALS vulnerable tissues. To functionally investigate the UPS in ALS motor neurons in vivo, we crossed SOD1G93A mice with transgenic mice that express a fluorescently tagged reporter substrate of the UPS. In double-transgenic Ub(G76V)-GFP /SOD1G93A mice an increase in Ub(G76V)-GFP reporter, indicative of UPS impairment, was detectable in a few spinal motor neurons and not in reactive astrocytes or microglia, at symptomatic stage but not before symptoms onset. The levels of reporter transcript were unaltered, suggesting that the accumulation of Ub(G76V)-GFP was due to deficient reporter degradation. In some motor neurons the increase of Ub(G76V)-GFP was accompanied by the accumulation of ubiquitin and phosphorylated neurofilaments, both markers of ALS pathology. These data suggest that UPS impairment occurs in motor neurons of mutant SOD1-linked ALS mice and may play a role in the disease progression.

  19. Evaluation of endothelial function in patients with limited systemic sclerosis by use of brachial artery Doppler ultrasound.

    Science.gov (United States)

    Fernandes, Tatiana Melo; Bica, Blanca Elena Gomes; Villela, Nivaldo Ribeiro; Salles, Elizabeth Figueiredo; Azevedo, Mario Newton Leitão de; Papi, José Angelo de Souza; Martins, Rosângela Aparecida Gomes

    2012-08-01

    The aim of this study was to compare the brachial artery endothelium-dependent and endothelium-independent dilating responses in patients with limited systemic sclerosis (LSSc) with those of healthy subjects of the same gender, age and color. Twenty adult, non-obese, non-smoker, non-diabetic, non-dyslipidemic, and non-hypertensive women, who fulfilled the American College of Rheumatology criteria for the diagnosis of SSc, were submitted to right brachial artery Doppler ultrasound. The vasodilating responses were analyzed as follows: the endothelium-dependent dilating response, after a 5-minute ischemia in the right arm; and the endothelium-independent dilating response, after administering 300 mcg of nitroglycerin (NTG) sublingually. The results were compared with the response obtained in healthy subjects. Brachial artery longitudinal diameter was significantly low at baseline 1: 3.57 ± 0.52 mm and 3.93 ± 0.39 mm for the LSSc group and the control group, respectively, P = 0.005. The vascular reactivity after the ischemia/reactive hyperemia and the NTG showed no significant difference between the groups (8.60 ± 5.45 mm vs. 9.26 ± 5.91 mm and 25.01 ± 12.55 mm vs. 19.59 ± 7.94 mm for the LSSc and control groups, respectively). Also, no statistically significant difference was found between red blood cell velocity (RBCV) after reactive hyperemia and NTG (110.2 ± 43.86 cm/s vs. 102.0 ± 25.89 cm/s and 63.80 ± 17.69 cm/s vs. 65.4 ± 12.90 cm/s in the LSSc and control groups, respectively). Although the LSSc group showed lower brachial artery diameter, the endothelium-dependent and the endothelium-independent dilating responses were preserved in both groups.

  20. Comprehensive immune profiling reveals substantial immune system alterations in a subset of patients with amyotrophic lateral sclerosis.

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    Michael P Gustafson

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal neurodegenerative disease with a median lifespan of 2-3 years after diagnosis. There are few meaningful treatments that alter progression in this disease. Preclinical and clinical studies have demonstrated that neuroinflammation may play a key role in the progression rate of ALS. Despite this, there are no validated biomarkers of neuroinflammation for use in clinical practice or clinical trials. Biomarkers of neuroinflammation could improve patient management, provide new therapeutic targets, and possibly help stratify clinical trial selection and monitoring. However, attempts to identify a singular cause of neuroinflammation have not been successful. Here, we performed multi-parameter flow cytometry to comprehensively assess 116 leukocyte populations and phenotypes from lymphocytes, monocytes, and granulocytes in a cohort of 80 ALS patients. We identified 32 leukocyte phenotypes that were altered in ALS patients compared to age and gender matched healthy volunteers (HV that included phenotypes of both inflammation and immune suppression. Unsupervised hierarchical clustering and principle component analysis of ALS and HV immunophenotypes revealed two distinct immune profiles of ALS patients. ALS patients were clustered into a profile distinct from HVs primarily due to differences in a multiple T cell phenotypes, CD3+CD56+ T cells and HLA-DR on monocytes. Patients clustered into an abnormal immune profile were younger, more likely to have a familial form of the disease, and survived longer than those patients who clustered similarly with healthy volunteers (344 weeks versus 184 weeks; p = 0.012. The data set generated from this study establishes an extensive accounting of immunophenotypic changes readily suitable for biomarker validation studies. The extensive immune system changes measured in this study indicate that normal immune homeostatic mechanisms are disrupted in ALS patients, and that