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Sample records for systemic sclerosis lessons

  1. [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

  2. 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...

  3. Progressive systemic sclerosis in a child

    Directory of Open Access Journals (Sweden)

    Arun K De

    2013-01-01

    Full Text Available Systemic sclerosis is a clinically heterogeneous systemic disease affecting the connective tissues of skin, walls of blood vessels and internal organs like lung, heart and kidneys. Systemic sclerosis is very unusual in pediatric population. Children represent fewer than 10% of all cases. We report a case of 11 years old girl of progressive systemic sclerosis presenting with features of cutaneous sclerosis, microstomia, mask-like facies, sclerodactyly, esophageal dysmotility, Raynaud′s phenomenon, arthralgia and pulmonary fibrosis.

  4. Association between systemic lupus erythematosus and multiple sclerosis: lupoid sclerosis

    International Nuclear Information System (INIS)

    Medina, Yimy F; Martinez, Jose B; Fernandez, Andres R; Quintana, Gerardo; Restrepo, Jose Felix; Rondon, Federico; Gamarra, Antonio Iglesias

    2010-01-01

    Multiple sclerosis (MS) and Systemic Lupus Erythematosus (SLE) with/without antiphospholipid syndrome are autoimmune illnesses. It has been described in many occasions the association of these two illnesses and the clinical picture of MS with characteristics of laboratory of SLE. When they affect to the central nervous system they can make it in a defined form for each illness or they can also make it in interposed or combined form of the two illnesses what has been called lupoid sclerosis; making that in some cases difficult the differentiation of the two illnesses and therefore to address the treatment. We present four cases of lupoid sclerosis, discuss the clinical and laboratory characteristics of this entity and we make a differentiation of the multiple sclerosis with the neurological affectation of SLE especially for images and laboratory results.

  5. 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...

  6. 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.

  7. Treatment of Raynaud phenomenon in systemic sclerosis.

    Science.gov (United States)

    Sinnathurai, P; Schrieber, L

    2013-05-01

    Systemic sclerosis is a connective tissue disease characterised by microvascular injury and excessive fibrosis of the skin and internal organs. Most patients with this condition experience Raynaud phenomenon, usually as the earliest manifestation of disease. In addition to pain and functional impairment, Raynaud phenomenon can produce tissue ischaemia resulting in digital ulceration and gangrene. Current treatments have been only moderately successful in reducing the frequency and severity of Raynaud phenomenon in patients with systemic sclerosis. This review will address treatments available for Raynaud phenomenon in systemic sclerosis. © 2013 The Authors; Internal Medicine Journal © 2013 Royal Australasian College of Physicians.

  8. Erasmus Syndrome: Silicosis and Systemic Sclerosis.

    Science.gov (United States)

    Jain, Shubhra; Joshi, Vinod; Rathore, Yogendra S; Khippal, Narendra

    2017-01-01

    Several occupational hazards, especially exposure to silica, have been implicated as causal factors for the development of scleroderma-like disorders. Compared to other connective tissue disorders, silica-associated systemic sclerosis (SA-SS) is relatively rare. Silica-induced scleroderma is indistinguishable from idiopathic systemic sclerosis. However, the former expresses a high predisposition of pulmonary involvement and anti-Scl-70 antibody. We report the case of a 42-year-old male, stone cutter by occupation, who was diagnosed as simple chronic silicosis and developed systemic sclerosis.

  9. 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...... and ≤ 100 years was conducted, followed from 1997 to 2011 by individual-level linkage of nationwide registries. Multivariable adjusted Cox regression models were used to estimate the hazard ratios (HRs) for a composite cardiovascular disease endpoint. A total of 697 patients with localized scleroderma and 1......,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...

  10. HLA typing in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    M. Faré

    2011-09-01

    Full Text Available Objective: the aim of the study was to investigate the relationship between Systemic Sclerosis (SSc and HLA antigens, and to correlate these antigens with the clinical manifestations of the disease. Materials and methods: 55 patients were stratified according a to the cutaneous involvement b to the positivity of Scl- 70 and anticentromere antibody and c to the internal organ involvement, in particular we used HRCT to demonstrate lung fibrosis, echocardiography for the diagnosis of pulmonary hypertension, blood creatinine, urinalysis and arterial hypertension to demonstrate renal failure, and esophagus double-countrast barium swallow for the diagnosis of esophagopathy. The control group consisting of 2000 healthy Caucasian subjects was recruited from the same population. Results: the frequency of the antigens A23 (p=0.003, RR=3.69, B18 (p<0.0001, RR=3.57, and DR11 (p<0.0001, RR=6.18 was statistically increased in the patients population compared with the healthy controls. Although there is no any significant correlation between HLA antigens and different clinical subsets of scleroderma, antigens B18 and DR11 could be associated with more severe clinical features. Conclusions: the presence of a significant association between SSc and specific HLA antigens (A23, B18, and DR11 could link the HLA system with SSc.

  11. Targeted Therapy in Systemic Sclerosis

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    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.

  12. Selected methods of rehabilitation in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Agnieszka Gerkowicz

    2017-09-01

    Full Text Available Systemic sclerosis is a chronic connective tissue disease characterized by microvascular abnormalities, immune disturbances and progressive fibrosis of the skin and internal organs. Skin involvement may result in contractures, leading to marked loss of hand mobility, adversely affecting the performance of daily activities and decreasing the quality of life. Face involvement not only causes functional loss, but also lowers the self-esteem of patients. Increasing attention has recently been focused on the need to rehabilitate patients with systemic sclerosis in order to prevent the development of joint contractures and loss of mobility. The study presents a review of the current literature on rehabilitation possibilities in patients with systemic sclerosis, with a special focus on physiotherapy methods.

  13. 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

  14. 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...

  15. 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-ca...

  16. Esophageal transit scintigraphy in systemic sclerosis

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    Marek Chojnowski

    2016-11-01

    Full Text Available 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.

  17. Vascular Complications of Systemic Sclerosis during Pregnancy

    Directory of Open Access Journals (Sweden)

    Eliza F. Chakravarty

    2010-01-01

    Full Text Available Systemic sclerosis (SSc is a chronic autoimmune disorder characterized by progressive fibrosis of the skin and visceral tissues as well as a noninflammatory vasculopathy. Vascular disease in systemic sclerosis is a major cause of morbidity and mortality among nonpregnant patients with SSc and is even a bigger concern in the pregnant SSc patient, as the underlying vasculopathy may prevent the required hemodynamic changes necessary to support a growing pregnancy. Vascular manifestations including scleroderma renal crisis and pulmonary arterial hypertension should be considered relative contraindications against pregnancy due to the high associations of both maternal and fetal morbidity and mortality. In contrast, Raynaud's phenomenon may actually improve somewhat during pregnancy. Women with SSc who are considering a pregnancy or discover they are pregnant require evaluation for the presence and extent of underlying vasculopathy. In the absence of significant visceral vasculopathy, most women with SSc can expect to have reasonable pregnancy outcomes.

  18. Primary sclerosing cholangitis associated with systemic sclerosis.

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    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 significance of the association discussed. Images Figure 1 Figure 2 PMID:2041852

  19. Optical Elastography of Systemic Sclerosis Skin

    Science.gov (United States)

    2017-09-01

    have been tested in SSc, with varying success. Here, we advance a novel contact-independent noninvasive technique capable of micrometer/nanometer...1, the animal model of SSc has been successfully re-established. In addition, animals are being scheduled for the proposed treatment and monitoring...study. 15. SUBJECT TERMS Systemic Sclerosis, Imaging, Skin, Diagnostics, Animal Models, OCT, OCE 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

  20. Pro-angiogenic cytokines in systemic sclerosis

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    Ewa Robak

    2014-12-01

    Full Text Available Systemic sclerosis (SSc is a multifactorial connective tissue disease characterized by excessive and progressive fibrosis along with microvasculopathy due to poor vascular formation and repair. Despite a general increase in many potent angiogenic factors, the vasculopathy compensatory angiogenesis and vasculogenesis are impaired. In this review, we discuss the role of proangiogenic factors – VEGF, PlGF, endoglin, PDGF, endothelin-1, angiopoietins, SDF-1, uPAR – and the paradoxical paucity of an inadequate angiogenic response in SSc.

  1. Capillaroscopy 2016: new perspectives in systemic sclerosis

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    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.

  2. Clinical presentation in patients with systemic sclerosis

    International Nuclear Information System (INIS)

    Silvarino, R.; Rebella, M.; Alonso, J.; Cairoli, E.

    2009-01-01

    Introduction: systemic sclerosis is an autoimmune disease characterized by endothelial damage, and skin, vessel and internal organ fibrosis and inflammation. There are differences in terms of frequency, severity and prognosis for the different ethnic groups, what reinforces the importance of the study in each geographical region with the purpose of enabling early diagnosis of its incipient symptoms.Methods: we conducted a descriptive and retrospective study form March 2006 through March 2008, including patients with a final diagnosis of systemic sclerosis, who are treated at the Systemic Autoimmune Diseases Unit at the Clinicas Hospital. Results: 31 women were included in the study, average follow-up of patients was 39.2 months, and average age at the time of diagnosis was 47.6 years. Eleven patients (35,5) presented diffuse disease and 20 (64.5) of them evidenced limited disease. Thirty patients presented Raynaud's phenomenon. In 92 of cases capilaroscopy showed a sclerodermiform pattern. In terms of the respiratory system, we found interstitial pathology in 25 of cases, pulmonary arterial hypertension in 22.2 and are restrictive pattern in respiratory function studies in 35.5. Also, 67.7 presented digestive manifestations and 9.6 developed sclerodermic renal crisis. We found anti-nuclear antibodies (ANA) in 29 out of 31 patients (93,5) patients; 16 presented anticentromere antibodies and five anti-topoisomerasa-I antibodies. The four patients (12.9)who died during follow-up presented common elements such as diffuse sclerosis, digital ulcers and severe respiratory compromise. Conclusions: the clinical and immune characteristics found in our study were similar to those described in other series. Should there be no specific treatment, it is essential to perform regular assessment of visceral impact in order to control and delay complications which result in high morbimortality rates. (author) [es

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

    African Journals Online (AJOL)

    Congestive cardiac failure in a patient with systemic sclerosis: Case report and literature review. ... The presence of CCF in patients with SSe is a poor prognostic marker and cause of mortality and morbidity, ... not been reported in Nigerians. Keywords: Systemic sclerosis; Primary Cardiac Disease; Heart failure; Nigerians ...

  4. Brain magnetic resonance imaging findings in patients with systemic sclerosis.

    Science.gov (United States)

    Mohamed, Reem H A; Nassef, Amr A

    2010-02-01

    Systemic sclerosis is a multisystem disease where functional and structural abnormalities of small blood vessels prevail. Recently, transient ischemic attacks, ischemic stroke, and hemorrhages have been reported as primary consequence of vascular central nervous system affection in systemic sclerosis. Magnetic resonance imaging (MRI) is considered to be the most sensitive diagnostic technique for detecting symptomatic and asymptomatic lesions in the brain in cases of multifocal diseases. Evaluate brain changes in patients with systemic sclerosis using MRI. Thirty female patients with systemic sclerosis aged 27-61 years, with disease duration of 1-9 years and with no history of other systemic disease or cerebrovascular accidents, were enrolled. An age-matched female control group of 30 clinically normal subjects, underwent brain MR examination. Central nervous system involvement in the form of white matter hyperintense foci of variable sizes were found in significantly abundant forms in systemic sclerosis patients on MR evaluation than in the age-related control group, signifying a form of central nervous system vasculopathy. Such foci showed no definite correlation with disease duration, yet they showed significant correlation to severity of peripheral vascular disease, headaches, fainting attacks and depression in the group under study. Asymptomatic as well as symptomatic central nervous system ischemic vasculopathy is not uncommon in systemic sclerosis patients and MRI is considered a sensitive noninvasive screening tool for early detection of CNS involvement in patients with systemic sclerosis.

  5. Autoantibodies in systemic sclerosis: Unanswered questions

    Directory of Open Access Journals (Sweden)

    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.

  6. The Vascular Microenvironment and Systemic Sclerosis

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    Tracy Frech

    2010-01-01

    Full Text Available The role of the vascular microenvironment in the pathogenesis Systemic Sclerosis (SSc is appreciated clinically as Raynaud's syndrome with capillary nail bed change. This manifestation of vasculopathy is used diagnostically in both limited and diffuse cutaneous subsets of SSc, and is thought to precede fibrosis. The degree of subsequent fibrosis may also be determined by the vascular microenvironment. This paper describes why the vascular microenvironment might determine the degree of end-organ damage that occurs in SSc, with a focus on vascular cell senescence, endothelial progenitor cells (EPC including multipotential mesenchymal stem cells (MSC, pericytes, and angiogenic monocytes. An explanation of the role of EPC, pericytes, and angiogenic monocytes is important to an understanding of SSc pathogenesis. An evolving understanding of the vascular microenvironment in SSc may allow directed treatment.

  7. 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.

  8. Epigenetics: The Future Direction in Systemic Sclerosis.

    Science.gov (United States)

    Walczyk, M; Paradowska-Gorycka, A; Olesinska, M

    2017-12-01

    Systemic sclerosis (SSc) is an immune-mediated connective tissue disease of which the aetiology is still unclear. Previous genetic studies including candidate-gene studies and genomewide association studies have identified a number of genetic variations that confer risk to SSc. However, these variants, such as single nucleotide polymorphisms, cannot completely explain the SSc susceptibility and the diversity in the clinical symptoms of SSc patients. The contribution of epigenetic mechanisms as a link between genetics and environmental triggers represents promising field in understanding the pathogenesis of SSc. The aim of this review was to present the current knowledge on epigenetic mechanisms and highlight novel directions in diagnostic and therapeutical approaches. © 2017 The Foundation for the Scandinavian Journal of Immunology.

  9. Progressive Systemic sclerosis, manifested like malabsorption syndrome. Case report

    International Nuclear Information System (INIS)

    Ortiz Piza, Gabriel Jaime; Gonzalez Vasquez, Carlos Mario

    2005-01-01

    We report the case of a 32 year old woman whose first manifestation of systemic sclerosis was malabsorption syndrome. The small bowel series was the clue to the diagnosis, confirmed by laboratory tests and progression of the disease

  10. The endocannabinoid system and multiple sclerosis.

    Science.gov (United States)

    Baker, David; Pryce, Gareth

    2008-01-01

    Multiple sclerosis (MS) is a neurodegenerative disease that is characterised by repeated inflammatory/demyelinating events within the central nervous system (CNS). In addition to relapsing-remitting neurological insults, leading to loss of function, patients are often left with residual, troublesome symptoms such as spasticity and pain. These greatly diminish "quality of life" and have prompted some patients to self-medicate with and perceive benefit from cannabis. Recent advances in cannabinoid biology are beginning to support these anecdotal observations, notably the demonstration that spasticity is tonically regulated by the endogenous cannabinoid system. Recent clinical trials may indeed suggest that cannabis has some potential to relieve, pain, spasms and spasticity in MS. However, because the CB(1) cannabinoid receptor mediates both the positive and adverse effects of cannabis, therapy will invariably be associated with some unwanted, psychoactive effects. In an experimental model of MS, and in MS tissue, there are local perturbations of the endocannabinoid system in lesional areas. Stimulation of endocannabinoid activity in these areas either through increase of synthesis or inhibition of endocannabinoid degradation offers the positive therapeutic potential of the cannabinoid system whilst limiting adverse events by locally targeting the lesion. In addition, CB(1) and CB(2) cannabinoid receptor stimulation may also have anti-inflammatory and neuroprotective potential as the endocannabinoid system controls the level of neurodegeneration that occurs as a result of the inflammatory insults. Therefore cannabinoids may not only offer symptom control but may also slow the neurodegenerative disease progression that ultimately leads to the accumulation of disability.

  11. Gastrointestinal transit in patients with systemic sclerosis.

    Science.gov (United States)

    Fynne, Lotte; Worsøe, Jonas; Gregersen, Tine; Schlageter, Vincent; Laurberg, Søren; Krogh, Klaus

    2011-10-01

    Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis and collagen deposits. Gastrointestinal symptoms of SSc, including abdominal pain, bloating and discomfort, are common but diffuse and their pathophysiology remains obscure. To investigate the pathophysiology of abdominal pain and discomfort in individuals with SSc. A total of 15 individuals with SSc (13 women, median age 58 years), all suffering from diffuse abdominal symptoms, and 17 healthy volunteers (12 women, median age 52 years) were evaluated with the Motility Tracking System, MTS-1, measuring gastric emptying (GE) and velocity through the small intestine. SSc patients were also examined for bacterial overgrowth using the hydrogen breath test and with radiopaque markers to determine the total gastrointestinal transit time (GITT). Assessed with the MTS-1, the velocity through the proximal small intestine was significantly reduced in SSc patients (median 0.525 m/h, range 0.11-1.15) when compared to healthy subjects (median 0.91 m/h, range 0.51-1.74) (p = 0.02). Prolonged GE was found in 4 SSc patients (27%) but in none of the healthy volunteers (p = 0.04). Only 3 SSc patients (21%) had positive breath tests for small intestinal bacterial overgrowth. GITT was >3 days in 8 patients (53%). Slow small intestinal transit was associated with a prolonged GITT (p < 0.05). Velocity through the small intestine is significantly reduced in SSc patients with diffuse abdominal symptoms.

  12. 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.

  13. Gastro-intestinal involvement in systemic sclerosis

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    Saurabh Kedia

    2017-01-01

    Full Text Available The gastrointestinal (GI tract can be involved in up to 90% of patients with systemic sclerosis (SSc and is the leading cause of morbidity and third most common cause of mortality in these patients. The GI involvement can occur in the absence of cutaneous manifestations in 10% of patients. Vasculopathy, cellular and humoral immunity, and diffuse fibrosis are the principal pathogenetic mechanisms in SSc and begin with autoantibody-mediated neuronal damage followed by muscular damage and fibrosis. This leads to progressive dysmotility of the entire GI tract from mouth to anus and is responsible for the clinical manifestations including gastroesophageal reflux disease and dysphagia due to esophageal involvement, gastroparesis, small intestinal bacterial overgrowth and chronic intestinal pseudo-obstruction, and constipation due to colonic and fecal incontinence due to anorectal involvement. The clinical features resulting from the involvement of these organs often overlap and multiple areas may be involved simultaneously. The treatment remains mostly symptomatic because effective disease-modifying therapies are lacking. These patients are at a risk of malnutrition and nutritional screening, and thus rehabilitation is very important. Refractory cases require nutritional support in the form of enteral nutrition and/or home parenteral nutrition. Future research is needed in the pathogenesis, development of biomarkers for early identification of GI involvement at the asymptomatic stage, and targeted disease-modifying therapies, which can alter/halt the disease progression.

  14. Associations between Systemic Sclerosis and Thyroid Diseases

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    Poupak Fallahi

    2017-10-01

    Full Text Available We have reviewed scientific literature about the association of systemic sclerosis (SSc and thyroid disorders. A high incidence, and prevalence, of new cases of autoimmune thyroiditis (AT and/or hypothyroidism have been shown in sclerodermic patients (overall in the female gender. An association among a Th1 immune-predominance, low vitamin D levels, and AT have been also shown in SSc patients. Cases of Graves’ disease (GD have been described in SSc patients, too, according with the higher prevalence of thyroid autoimmunity. It has been also shown a higher prevalence of papillary thyroid cancer (PTC, in association with AT, in SSc patients. However, in order to confirm results about GD and thyroid cancer, studies in larger number of patients with SSc are needed. During the follow-up of SSc patients it would be appropriate to monitor carefully their thyroid status. The abovementioned data strongly suggest a periodic thyroid function follow-up in female SSc patients [showing a borderline high (although in the normal range thyroid-stimulating hormone level, antithyroid peroxidase antibody positivity, and a small thyroid with a hypoechoic pattern], and, when necessary, appropriate treatments. In conclusion, most of the studies show an association among SSc, AT, and hypothyroidism, such as an increased prevalence of TC overall in SSc patients with AT. Only few cases of GD have been also described in SSc.

  15. Early- versus Late-Onset Systemic Sclerosis

    Science.gov (United States)

    Alba, Marco A.; Velasco, César; Simeón, Carmen Pilar; Fonollosa, Vicent; Trapiella, Luis; Egurbide, María Victoria; Sáez, Luis; Castillo, María Jesús; Callejas, José Luis; Camps, María Teresa; Tolosa, Carles; Ríos, Juan José; Freire, Mayka; Vargas, José Antonio; Espinosa, Gerard

    2014-01-01

    Abstract Peak age at onset of systemic sclerosis (SSc) is between 20 and 50 years, although SSc is also described in both young and elderly patients. We conducted the present study to determine if age at disease onset modulates the clinical characteristics and outcome of SSc patients. The Spanish Scleroderma Study Group recruited 1037 patients with a mean follow-up of 5.2 ± 6.8 years. Based on the mean ± 1 standard deviation (SD) of age at disease onset (45 ± 15 yr) of the whole series, patients were classified into 3 groups: age ≤30 years (early onset), age between 31 and 59 years (standard onset), and age ≥60 years (late onset). We compared initial and cumulative manifestations, immunologic features, and death rates. The early-onset group included 195 patients; standard-onset group, 651; and late-onset, 191 patients. The early-onset group had a higher prevalence of esophageal involvement (72% in early-onset compared with 67% in standard-onset and 56% in late-onset; p = 0.004), and myositis (11%, 7.2%, and 2.9%, respectively; p = 0.009), but a lower prevalence of centromere antibodies (33%, 46%, and 47%, respectively; p = 0.007). In contrast, late-onset SSc was characterized by a lower prevalence of digital ulcers (54%, 41%, and 34%, respectively; p < 0.001) but higher rates of heart conduction system abnormalities (9%, 13%, and 21%, respectively; p = 0.004). Pulmonary hypertension was found in 25% of elderly patients and in 12% of the youngest patients (p = 0.010). After correction for the population effects of age and sex, standardized mortality ratio was shown to be higher in younger patients. The results of the present study confirm that age at disease onset is associated with differences in clinical presentation and outcome in SSc patients. PMID:24646463

  16. Tomography patterns of lung disease in systemic sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    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)

  17. 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.

  18. Gastric Antral Vascular Ectasia in Systemic Sclerosis: Current Concepts

    Directory of Open Access Journals (Sweden)

    Raphael Hernando Parrado

    2015-01-01

    Full Text Available Introduction. Gastric antral vascular ectasia (GAVE is a rare entity with unique endoscopic appearance described as “watermelon stomach.” It has been associated with systemic sclerosis but the pathophysiological changes leading to GAVE have not been explained and still remain uncertain. Methods. Databases Medline, Scopus, Embase, PubMed, and Cochrane were searched for relevant papers. The main search words were “Gastric antral vascular ectasia,” “Watermelon Stomach,” “GAVE,” “Scleroderma,” and “Systemic Sclerosis.” Fifty-four papers were considered for this review. Results. GAVE is a rare entity in the spectrum of manifestations of systemic sclerosis with unknown pathogenesis. Most patients with systemic sclerosis and GAVE present with asymptomatic anemia, iron deficiency anemia, or heavy acute gastrointestinal bleeding. Symptomatic therapy and endoscopic ablation are the first-line of treatment. Surgical approach may be recommended for patients who do not respond to medical or endoscopic therapies. Conclusion. GAVE can be properly diagnosed and treated. Early diagnosis is key in the management of GAVE because it makes symptomatic therapies and endoscopic approaches feasible. A high index of suspicion is critical. Future studies and a critical review of the current findings about GAVE are needed to understand the role of this condition in systemic sclerosis.

  19. 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.

  20. Interstitial Lung disease in Systemic Sclerosis

    International Nuclear Information System (INIS)

    Ooi, G.C.; Mok, M.Y.; Tsang, K.W.T.; Khong, P.L.; Fung, P.C.W.; Chan, S.; Tse, H.F.; Wong, R.W.S.; Lam, W.K.; Lau, C.S.; Wong, Y.

    2003-01-01

    Purpose: To evaluate high-resolution CT (HRCT) parameters of inflammation and fibrosis in systemic sclerosis (SSc), for correlation with lung function, skin scores and exercise tolerance. Material and Methods: : 45 SSc patients (40 women, 48.5±13.4 years), underwent thoracic HRCT, lung function assessment, and modified Rodnan skin scores. Exercise tolerance was also graded. HRCT were scored for extent of 4 HRCT patterns of interstitial lung disease (ILD): ground glass opacification (GGO), reticular, mixed and honeycomb pattern in each lobe. Total HRCT score, inflammation index (GGO and mixed score) and fibrosis index (reticular and honeycomb scores) were correlated with lung function and clinical parameters. Results: ILD was present in 39/45 (86.7%) patients. Abnormal (<80% predicted) forced vital capacity (FVC), total lung capacity (TLC) and carbon monoxide diffusion factor (DLco) were detected in 30%, 22% and 46% of patients. Total HRCT score correlated with FVC (r=0.43, p=0.008), FEV1 (forced expiratory volume) (r=-0.37, p=0.03), TLC (r=-0.47, p=0.003), and DLCO (r=-0.43, p=0.008); inflammatory index with DLCO (r=-0.43, p=0.008) and exercise tolerance (r=-0.39, p < 0.05); and fibrosis index with FVC (r=-0.31, p=0.05) and TLC (r=-0.38, p=0.02). Higher total HRCT score, and inflammation and fibrosis indices were found in patients with abnormal lung function. Conclusion: Qualitative HRCT is able to evaluate inflammation and fibrosis, showing important relationships with diffusion capacity and lung volume, respectively

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Systemic Vasculitis During the Course of Systemic Sclerosis

    Science.gov (United States)

    Quéméneur, Thomas; Mouthon, Luc; Cacoub, Patrice; Meyer, Olivier; Michon-Pasturel, Ulrique; Vanhille, Philippe; Hatron, Pierre-Yves; Guillevin, Loïc; Hachulla, Eric

    2013-01-01

    Abstract Although the presence of antineutrophil cytoplasmic antibodies (ANCA) has been reported in patients with systemic sclerosis (SSc), the association of SSc and systemic vasculitis has rarely been described. We obtained information on cases of systemic vasculitis associated with SSc in France from the French Vasculitis Study Group and all members of the French Research Group on Systemic Sclerosis. We identified 12 patients with systemic vasculitis associated with SSc: 9 with ANCA-associated systemic vasculitis (AASV) and 3 with mixed cryoglobulinemia vasculitis (MCV). In all AASV patients, SSc was of the limited type. The main complication of SSc was pulmonary fibrosis. Only 2 patients underwent a D-penicillamine regimen before the occurrence of AASV. The characteristics of AASV were microscopic polyangiitis (n = 7) and renal limited vasculitis (n = 2). Anti-myeloperoxidase antibodies were found in 8 of the 9 patients. The Five Factor Score was above 1 in 3 of the 9 patients. Of the 3 patients with MCV, Sjögren syndrome was confirmed in 2. We compared our findings with the results of a literature review (42 previously reported cases of AASV with SSc). Although rare, vasculitis is a complication of SSc. AASV is the most frequent type, and its diagnosis can be challenging when the kidney is injured. Better awareness of this rare association could facilitate earlier diagnosis and appropriate management to reduce damage. PMID:23263715

  3. Historical problem areas: Lessons learned for expendable and reusable vehicle propulsion systems

    Science.gov (United States)

    Fester, Dale A.

    1991-01-01

    The following subject areas are covered: expendable launch vehicle lessons learned, upper stage/transfer vehicle lessons learned, shuttle systems - reuse, and reusable system issues and lessons learned.

  4. Treatment of systemic sclerosis: potential role for stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Wen Xiong

    2009-11-01

    Full Text Available Wen Xiong, Chris T DerkDivision of Rheumatology, Thomas Jefferson University, Philadelphia, PA, 19107, USAAbstract: Hematopoietic stem cell transplantation may “reset” the immune reconstitution and induce self tolerance of autoreactive lymphocytes, and has been explored in the treatments for systemic sclerosis. Phase I/II trials have shown a satisfactory risk benefit ratio. The true benefit will be identified by two ongoing prospective, randomized phase III trials. Multipotent mesenchymal stromal cells (MSCs possess antiproliferative, anti-inflammatory, and immunosuppressive properties. The use of MSCs has showed successful responses in patients with severe steroid-resistant acute graft versus host disease in phase II trials, and may be a potentially promising option for patients with systemic sclerosis.Keywords: scleroderma, systemic sclerosis, treatment, stem cells, transplant

  5. 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

  6. Very Large System Dynamics Models - Lessons Learned

    Energy Technology Data Exchange (ETDEWEB)

    Jacob J. Jacobson; Leonard Malczynski

    2008-10-01

    This paper provides lessons learned from developing several large system dynamics (SD) models. System dynamics modeling practice emphasize the need to keep models small so that they are manageable and understandable. This practice is generally reasonable and prudent; however, there are times that large SD models are necessary. This paper outlines two large SD projects that were done at two Department of Energy National Laboratories, the Idaho National Laboratory and Sandia National Laboratories. This paper summarizes the models and then discusses some of the valuable lessons learned during these two modeling efforts.

  7. Promoting Systems Thinking through Biology Lessons

    Science.gov (United States)

    Riess, Werner; Mischo, Christoph

    2010-04-01

    This study's goal was to analyze various teaching approaches within the context of natural science lessons, especially in biology. The main focus of the paper lies on the effectiveness of different teaching methods in promoting systems thinking in the field of Education for Sustainable Development. The following methods were incorporated into the study: special lessons designed to promote systems thinking, a computer-simulated scenario on the topic "ecosystem forest," and a combination of both special lessons and the computer simulation. These groups were then compared to a control group. A questionnaire was used to assess systems thinking skills of 424 sixth-grade students of secondary schools in Germany. The assessment differentiated between a conceptual understanding (measured as achievement score) and a reflexive justification (measured as justification score) of systems thinking. The following control variables were used: logical thinking, grades in school, memory span, and motivational goal orientation. Based on the pretest-posttest control group design, only those students who received both special instruction and worked with the computer simulation showed a significant increase in their achievement scores. The justification score increased in the computer simulation condition as well as in the combination of computer simulation and lesson condition. The possibilities and limits of promoting various forms of systems thinking by using realistic computer simulations are discussed.

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

    African Journals Online (AJOL)

    Case report. A 31 years old female patient from senafe with remote history of systemic sclerosis and recurrent hospital admissions presented to the ED of Orotta hospital with shortness of breath and altered mental status. She had generalized body weakness, and dry cough associated with chest pain. She also complained.

  9. 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,

  10. 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 ...

  11. 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 ...

  12. Immunochip Analysis Identifies Multiple Susceptibility Loci for Systemic Sclerosis

    NARCIS (Netherlands)

    Mayes, Maureen D.; Bossini-Castillo, Lara; Gorlova, Olga; Martin, Jose Ezequiel; Zhou, Xiaodong; Chen, Wei V.; Assassi, Shervin; Ying, Jun; Tan, Filemon K.; Arnett, Frank C.; Reveille, John D.; Guerra, Sandra; Terue, Maria; Carmona, Francisco David; Gregersen, Peter K.; Lee, Annette T.; Lopez-Isac, Elena; Ochoa, Eguzkine; Carreira, Patricia; Simeon, Carmen Pilar; Castellvi, Ivan; Angel Gonzalez-Gay, Miguel; Zhernakova, Alexandra; Padyukov, Leonid; Aarcon-Riquelme, Marta; Wijmenga, Cisca; Beretta, Lorenzo; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jorg H. W.; Voskuy, Alexandre E.; Schuerwegh, Annemie J.; Hesselstrand, Roger; Nordin, Annika; Airo, Paolo; Lunardi, Claudio; Shiels, Paul; van Laar, Jacob M.; Herrick, Ariane; Worthington, Jane; Denton, Christopher; Wigley, Fredrick M.; Hummers, Laura K.; Varga, John; Hinchcliff, Monique E.; Baron, Murray; Hudson, Marie; Pope, Janet E.; Furst, Daniel E.; Khanna, Dinesh; Phillips, Kristin; Schiopu, Elena; Segal, Barbara M.; Molitor, Jerry A.; Silver, Richard M.; Steen, Virginia D.; Simms, Robert W.; Lafyatis, Robert A.; Fessler, Barn I. J.; Frech, Tracy M.; AlKassab, Firas; Docherty, Peter; Kaminska, Elzbieta; Khalidi, Nader; Jones, Henry Niall; Markland, Janet; Robinson, David; Broen, Jasper; Radstake, Timothy R. D. J.; Fonseca, Carmen; Koeleman, Bobby P.; Martin, Javier

    2014-01-01

    In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic

  13. 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 tre...

  14. Very Early Systemic Sclerosis and Pre-systemic Sclerosis: Definition, Recognition, Clinical Relevance and Future Directions.

    Science.gov (United States)

    Bellando-Randone, Silvia; Matucci-Cerinic, Marco

    2017-09-18

    The approach to systemic sclerosis (SSc) has changed over the years with an increasing focus on the very early diagnosis of the disease. The terminology identifying patients in the early phase of SSc has been significantly confusing in the last three decades. The purpose of this article is to analyze how the concept of "very early SSc" has evolved over the years, which is the role of an early diagnosis and how early treat patients. Several attempts have been made over time, to create more sensitive and specific classification criteria to include the largest number of SSc patients, also in the earliest phase. An algorythm for the very early diagnosis of SSc was identified, diagnostic preliminary criteria proposed, and new 2013 ACR/EULAR SSc classification criteria published, including new items and adding emphasis to the vasculopathic manifestations. True biomarkers that could predict the disease evolution are still missing. Treat or not to treat patients in the earliest phases still remain a dilemma. For the moment, the only feasible clinical strategy in very early SSc remains a tight follow up program to detect in "real time" the early internal organ involvement which may allow an aggressive therapeutic agenda.

  15. An update on neuro-ophthalmology of multiple sclerosis: the visual system as a model to study multiple sclerosis.

    Science.gov (United States)

    Qureshi, Sara S; Beh, Shin C; Frohman, Teresa C; Frohman, Elliot M

    2014-06-01

    The purpose of this review is to familiarize the reader with the landscape of current neuro-ophthalmology research in the field of multiple sclerosis and to highlight important findings, directions of future research and advances in the clinical management of visual and ocular motor manifestations of multiple sclerosis. Research pertaining to the visual system in multiple sclerosis has identified new biomarkers of disease and is contributing to a better understanding of disease mechanisms. Progress has been made in the symptomatic management of visual manifestations of multiple sclerosis and visual outcome measures are now being included in clinical trials, with important quality of life ramifications. Perhaps the most prominent contribution from neuro-ophthalmology research in multiple sclerosis has been the establishment of the visual system as a model to study disease pathogenesis, and for the systematic, objective, and longitudinal detection and monitoring of protective and restorative neurotherapeutic strategies. The emergence of these sophisticated capabilities has been in large part due to the application of high speed, high definition, and objective methods for the elucidation of both the structure and function of visual system networks. Advances in neuro-ophthalmology research in multiple sclerosis have led to the establishment of the visual system as a model to objectively study disease pathogenesis, and for the identification of novel neurotherapeutic capabilities. With the prospects of myelin repair and neuroprotective agents increasingly becoming recognized as achievable goals, the validation and utility of new visual outcome measures quantifying changes in axonal integrity, myelin protection, and repair will likely prove invaluable.

  16. Lessons learned on digital systems safety

    International Nuclear Information System (INIS)

    Sivertsen, Terje

    2005-06-01

    A decade ago, in 1994, lessons learned from Halden research activities on digital systems safety were summarized in the reports HWR-374 and HWR-375, under the title 'A Lessons Learned Report on Software Dependability'. The reports reviewed all activities made at the Halden Project in this field since 1977. As such, the reports provide a wealth of information on Halden research. At the same time, the lessons learned from the different activities are made more accessible to the reader by being summarized in terms of results, conclusions and recommendations. The present report provides a new lessons learned report, covering the Halden Project research activities in this area from 1994 to medio 2005. As before, the emphasis is on the results, conclusions and recommendations made from these activities, in particular how they can be utilized by different types of organisations, such as licensing authorities, safety assessors, power companies, and software developers. The contents of the report have been edited on the basis of input from a large number of Halden work reports, involving many different authors. Brief summaries of these reports are included in the last part of the report. (Author)

  17. Motor Neuron Gene Therapy: Lessons from Spinal Muscular Atrophy for Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Tosolini, Andrew P; Sleigh, James N

    2017-01-01

    Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are severe nervous system diseases characterized by the degeneration of lower motor neurons. They share a number of additional pathological, cellular, and genetic parallels suggesting that mechanistic and clinical insights into one disorder may have value for the other. While there are currently no clinical ALS gene therapies, the splice-switching antisense oligonucleotide, nusinersen, was recently approved for SMA. This milestone was achieved through extensive pre-clinical research and patient trials, which together have spawned fundamental insights into motor neuron gene therapy. We have thus tried to distil key information garnered from SMA research, in the hope that it may stimulate a more directed approach to ALS gene therapy. Not only must the type of therapeutic (e.g., antisense oligonucleotide vs. viral vector) be sensibly selected, but considerable thought must be applied to the where , which , what , and when in order to enhance treatment benefit: to where (cell types and tissues) must the drug be delivered and how can this be best achieved? Which perturbed pathways must be corrected and can they be concurrently targeted? What dosing regime and concentration should be used? When should medication be administered? These questions are intuitive, but central to identifying and optimizing a successful gene therapy. Providing definitive solutions to these quandaries will be difficult, but clear thinking about therapeutic testing is necessary if we are to have the best chance of developing viable ALS gene therapies and improving upon early generation SMA treatments.

  18. Motor Neuron Gene Therapy: Lessons from Spinal Muscular Atrophy for Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Andrew P. Tosolini

    2017-12-01

    Full Text Available Spinal muscular atrophy (SMA and amyotrophic lateral sclerosis (ALS are severe nervous system diseases characterized by the degeneration of lower motor neurons. They share a number of additional pathological, cellular, and genetic parallels suggesting that mechanistic and clinical insights into one disorder may have value for the other. While there are currently no clinical ALS gene therapies, the splice-switching antisense oligonucleotide, nusinersen, was recently approved for SMA. This milestone was achieved through extensive pre-clinical research and patient trials, which together have spawned fundamental insights into motor neuron gene therapy. We have thus tried to distil key information garnered from SMA research, in the hope that it may stimulate a more directed approach to ALS gene therapy. Not only must the type of therapeutic (e.g., antisense oligonucleotide vs. viral vector be sensibly selected, but considerable thought must be applied to the where, which, what, and when in order to enhance treatment benefit: to where (cell types and tissues must the drug be delivered and how can this be best achieved? Which perturbed pathways must be corrected and can they be concurrently targeted? What dosing regime and concentration should be used? When should medication be administered? These questions are intuitive, but central to identifying and optimizing a successful gene therapy. Providing definitive solutions to these quandaries will be difficult, but clear thinking about therapeutic testing is necessary if we are to have the best chance of developing viable ALS gene therapies and improving upon early generation SMA treatments.

  19. Multiple Sclerosis

    Science.gov (United States)

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

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

    OpenAIRE

    M. Matucci- Cerinic; F. Braschi; A. Moggi Pignone; L. Amanzi; G. Fiori

    2011-01-01

    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 th...

  1. The role of platelets in the pathogenesis of systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Giuseppe A. eRamirez

    2012-06-01

    Full Text Available Systemic sclerosis (SSc is an inflammatory disease of unknown etiology characterized by widespread organ dysfunction due to fibrosis and ischemia. Its nebulous pathogenic background and the consequent absence of an etiological therapy prevent the adoption of satisfying treatment strategies, able to improve patients' quality of life and survival and stimulate researchers to identify a unifying pathogenic target. Platelets show a unique biological behavior, lying at the crossroads between vascular function, innate and adaptive immunity and regulation of cell proliferation. Consequently they are also emerging players in the pathogenesis of many inflammatory diseases, including systemic sclerosis. In the setting of SSc platelets are detectable in a persistent activated state, which is intimately linked to the concomitant presence of an injured endothelium and to the widespread activation of the innate and adaptive immune system. As a consistent circulating source of bioactive compounds platelets contribute to the development of many characteristic phenomena of SSc, such as fibrosis and impaired vascular tone.

  2. The Role of a Commander in Military Lessons Learned Systems

    Directory of Open Access Journals (Sweden)

    Zenon Waliński

    2015-06-01

    Full Text Available The aim of the paper is to investigate the role of a commander in military Lessons Learned systems. In order to achieve the aim, the paper presents (1 the architecture of the Lessons Learned capabilities in the U.S. Army, NATO and the Polish Armed Forces, (2 the commander’s role in the Lessons Learned process (3 the commander’s role in fostering Lessons Learned organisation culture. The paper is based on multiple case study analysis including Lessons Learned systems in NATO, the U.S. Army and the Polish Armed Forces.

  3. [The Multiple Sclerosis Documentation System MSDS. Discussion of a documentation standard for multiple sclerosis].

    Science.gov (United States)

    Pette, M; Eulitz, M

    2002-02-01

    The MSDS (multiple sclerosis documentation system) has been developed at the Department of Neurology, Technical University of Dresden, Germany, during the last 4 years. The first version of this database application has been in use since October 2000. The MSDS manages information on MS patients, their treating physicians, patient history (symptoms, other diseases, biographical history, family history, habits, medication), clinical signs, results of laboratory examinations (blood chemistry, autoantibodies, borrelia serology, evoked potentials, cranial and spinal cord magnetic resonance imaging), clinical scores relevant for MS, and biosamples. In principle, MSDS allows online data input and semiautomatically generates reports to all general practitioners and neurologists treating the respective patient. Patient information sheets and internal treatment guidelines are part of the system. During a 3-month evaluation, the first version of MSDS was tested at eight university multiple sclerosis ambulatory care units and one general neurology hospital. The overall judgement was favorable. Suggestions for changes and improvements, as well as practical experiences, were considered when developing MSDS 2.0, which will be available by the end of 2001.

  4. 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.

  5. Optimal management of digital ulcers in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Abraham S

    2015-06-01

    Full Text Available Shawn Abraham, Virginia SteenDivision of Rheumatology, Immunology, and Allergy, MedStar Georgetown University Hospital, Washington, DC, USAAbstract: Raynaud’s phenomenon and digital ulcerations are two common clinical features seen in patients with systemic sclerosis. They are painful and lead to significant morbidity and altered hand function within this patient population. While currently there are no US Food and Drug Administration (FDA-approved medications for the treatment of digital ulcerations in the United States, clinical trials have supported the use of pharmacologic and nonpharmacologic modalities in facilitating healing of existing digital ulcers and preventing formation of new ulcers. This article reviews the published data on these therapeutic options.Keywords: scleroderma, systemic sclerosis, Raynaud’s phenomenon, digital ulcers, treatment

  6. Pulmonary vasospasm in systemic sclerosis: noninvasive techniques for detection

    OpenAIRE

    Keir, Gregory J.; Nair, Arjun; Giannarou, Stamatia; Yang, Guang-Zhong; Oldershaw, Paul; Wort, S. John; MacDonald, Peter; Hansell, David M.; Wells, Athol U.

    2015-01-01

    In a subgroup of patients with systemic sclerosis (SSc), vasospasm affecting the pulmonary circulation may contribute to worsening respiratory symptoms, including dyspnea. Noninvasive assessment of pulmonary blood flow (PBF), utilizing inert-gas rebreathing (IGR) and dual-energy computed-tomography pulmonary angiography (DE-CTPA), may be useful for identifying pulmonary vasospasm. Thirty-one participants (22 SSc patients and 9 healthy volunteers) underwent PBF assessment with IGR and DE-CTPA ...

  7. 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...

  8. Psychiatric Symptoms and Quality of Life in Systemic Sclerosis

    OpenAIRE

    Mura, G; Bhat, Krishna M; Pisano, A; Licci, G; Carta, MG

    2012-01-01

    Introduction: Systemic sclerosis (SSc) is a rare conjunctive tissue disorder characterized by fibrosis of the skin and internal organs, and vascular obliteration phenomena. Patients with SSc often experience elevated symptoms of psychological distress, determined by the disfiguration, the pain, the fatigue sensation, and the difficult in daily life occupations. The characteristics of the disease may influence the perceived quality of life (QoL) in people with SSc. Methods: This is a narrative...

  9. Small intestinal bacterial overgrowth in patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Saara Rawn

    2017-01-01

    Full Text Available Small intestinal bacterial overgrowth (SIBO is common in patients with systemic sclerosis (SSc yet often goes underrecognized in clinical practice. In patients with SSc, untreated SIBO may result in marked morbidity and possible mortality. The pathogenesis of SIBO is multifactorial and relates to immune dysregulation, vasculopathy, and dysmotility. This article reviews various diagnostic approaches and therapeutic options for SIBO. Treatment modalities mainly include prokinetics, probiotics, and antibiotics.

  10. Abnormalities of small bowel and colon in systemic sclerosis

    International Nuclear Information System (INIS)

    Scutellari, P.N.; Cinotti, A.; Cavallari, L.; Orzincolo, C.; Dovigo, L.; Trotta, F.; Menegale, G.

    1990-01-01

    A series of 21 subjects (2 males and 19 females) affected with systemic sclerosis, was examined by small bowel (oral and intubation methods) and colon enema. The underlying process responsible for abnormalities in the small bowel and colon in systemic sclerosis is a variable and pacthy destruction of the muscularis propria, that produces the structural and functional changes detected on X-ray: Pathologic condition is the same affecting the esophagus. The scout film of the abdomen often reveals colonic distension and fecal impaction, so that it may be quite difficult to prepare adequately the patients for a barium enema. Peristalsis may be virtually absent in short segments, and transit time may be several time longer than that in normal patients. For these reasons, intestinal pseudo-obstruction may appear in systemic sclerosis. The observed radiographic changes are: 1) in the small bowel: a) dilatation of the gut, especially in its proximal portions (duodenum and jejunum), in which the valvulae conniventes are straightened, normal or thinned; b) presence of diverticula, 2-4 cm in diameter, with hemispherical shape without the neck-like opening into the bowel lumen; 2) in the colon, the characteristic finding is an increase in size of individual haustra, forming sacculations or pseudo-diverticula, usually on the antemesenteric border of the transverse colon, better demonstrated on post-evacuation film. Moreover, loss of colonic haustration is also observed associated to colonic elongation and dilatation

  11. Development of systemic lupus erythematosus in-patient with systemic sclerosis

    International Nuclear Information System (INIS)

    Martinez, Jose B; Medina, Yimmy F; Restrepo, Jose Felix; Rondon, Federico; Iglesias G, Antonio

    2005-01-01

    A 56 years old woman with systemic sclerosis consult by rapidly progressive deterioration of his pulmonary and renal function developing a superposition syndrome with systemic lupus erythematosus, unusual presentation that respond to high doses of corticosteroid and ciclophos- phamide. This is the first reported case in the literature of a superposition syndrome that begins with systemic sclerosis. The clinical finding, immunologic profile and its possible association are discussed

  12. 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.

  13. 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.

  14. Increased risk of acute myocardial infarction in systemic sclerosis: a nationwide population-based study.

    Science.gov (United States)

    Chu, Szu-Ying; Chen, Yi-Ju; Liu, Chia-Jen; Tseng, Wei-Cheng; Lin, Ming-Wei; Hwang, Chian-Yaw; Chen, Chih-Chiang; Lee, Ding-Dar; Chen, Tzeng-Ji; Chang, Yun-Ting; Wang, Wen-Jen; Liu, Han-Nan

    2013-11-01

    Systemic sclerosis is a life-threatening autoimmune disease characterized by vasculopathy, which results in myocardial involvement in an extremely high percentage of patients. Nevertheless, there have been no large-scale epidemiological studies about the risk of acute myocardial infarction in patients with systemic sclerosis. The aims of this study were to evaluate the hazard ratio (HR) and risk factors of acute myocardial infarction in patients with systemic sclerosis, as well as to compare the risks of acute myocardial infarction among systemic sclerosis patients taking different immunosuppressors. The study cohort included 1344 patients with systemic sclerosis and 13,440 (1:10) age-, sex-, and comorbidity-matched controls during the period between 1997 and 2006, from the National Health Insurance Research Database. We compared the risk of acute myocardial infarction between patients with systemic sclerosis and controls and calculated the adjusted HRs for acute myocardial infarction in systemic sclerosis patients taking immunosuppressors and not taking immunosuppressors. The incidence rates of acute myocardial infarction were 535 and 313 cases per 100,000 person-years for systemic sclerosis cohort and reference cohort, respectively (P systemic sclerosis was found to be an independent risk factor for acute myocardial infarction (HR 2.45). Other risk factors included hypertension (HR 2.08) and diabetes (HR 2.14). The multivariate adjusted HR for acute myocardial infarction did not decrease among the systemic sclerosis patients taking systemic steroids, penicillamine, cyclophosphamide, azathioprine, methotrexate, or cyclosporine. Systemic sclerosis is independently associated with an increased risk of acute myocardial infarction. Immunosuppressors do not lower the risk of acute myocardial infarction in our study. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Brain MRI screening showing evidences of early central nervous system involvement in patients with systemic sclerosis.

    Science.gov (United States)

    Mohammed, Reem Hamdy A; Sabry, Yousriah Y; Nasef, Amr A

    2011-05-01

    Systemic sclerosis is a multisystem autoimmune collagen disease where structural and functional abnormalities of small blood vessels prevail. Transient ischemic attacks, ischemic stroke, and hemorrhage have been reported as primary consequence of vascular central nervous system affection in systemic sclerosis. Magnetic resonance imaging is considered to be the most sensitive diagnostic technique for detecting symptomatic and asymptomatic lesions in the brain in cases of multifocal diseases. The objective of this study is to detect subclinical as well as clinically manifest cerebral vasculopathy in patients with systemic sclerosis using magnetic resonance imaging. As much as 30 female patients with systemic sclerosis aged 27-61 years old, with disease duration of 1-9 years and with no history of other systemic disease or cerebrovascular accidents, were enrolled. Age-matched female control group of 30 clinically normal subjects, underwent brain magnetic resonance examination. Central nervous system (CNS) involvement in the form of white matter hyperintense foci of variable sizes were found in significantly abundant forms in systemic sclerosis patients on magnetic resonance evaluation than in age-related control group, signifying a form of CNS vasculopathy. Such foci showed significant correlation to clinical features of organic CNS lesion including headaches, fainting attacks and organic depression as well as to the severity of peripheral vascular disease with insignificant correlation with disease duration. In conclusion, subclinical as well as clinically manifest CNS ischemic vasculopathy is not uncommon in systemic sclerosis patients and magnetic resonance imaging is considered a sensitive noninvasive screening tool for early detection of CNS involvement in patients with systemic sclerosis.

  16. The role of information system in multiple sclerosis management

    Science.gov (United States)

    Ajami, Sima; Ahmadi, Golchehreh; Etemadifar, Masoud

    2014-01-01

    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. PMID:25709660

  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. Association of systemic sclerosis and psoriatic arthritis: a case report

    Directory of Open Access Journals (Sweden)

    A. Musio

    2011-09-01

    Full Text Available The association of Systemic Sclerosis (SSc and Psoriatic Arthritis (PsA is unfrequent; only few cases are reported in literature. We describe a case of a patient with SSc following the onset of PsA. The disease begun with tenosynovitis, polyarthritis in association with psoriasis. After two years, Raynaud’s phenomenon and sclerodactyly appeared, and, later, pulmonary interstizial fibrosis and esophageal dysfunction. The existence of a common pathogenesis of the two diseases, SSc and PsA, is discussed.

  19. 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....

  20. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  2. The Joint Lessons Learned System and Interoperability

    Science.gov (United States)

    1989-06-02

    should not be artificially separated. 4 8 That lesson would not be learned here. Another lesson which was learned, however, was that interservice... artificially high level of support masked the continuing rivalry between the Army and Air Force over mission priorities. 6 4 In spite of Air Force...knowledge concerning joint interoperability issues and lessons learned activities. -72- MAP 2 Central African Republic Sudan sangu . Bo"oo Cameroon tuie

  3. 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

  4. Incidence and predictors of cutaneous manifestations during the early course of systemic sclerosis

    DEFF Research Database (Denmark)

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

    2016-01-01

    OBJECTIVES: To longitudinally map the onset and identify risk factors for skin sclerosis and digital ulcers (DUs) in patients with systemic sclerosis (SSc) from an early time point after the onset of Raynaud's phenomenon (RP) in the European Scleroderma Trials and Research (EUSTAR) cohort. METHOD...

  5. 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.

  6. Measurement of cold challenge responses in primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis.

    Science.gov (United States)

    O'Reilly, D; Taylor, L; el-Hadidy, K; Jayson, M I

    1992-01-01

    Using computed thermography continuous temperature recordings were made before and after cold challenge of the fingers of control subjects and patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis. Basal skin temperature measurements (Tpre) were significantly lower in patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis than in the controls. Temperatures immediately after cold challenge (T0) were significantly lower in patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis than in controls. The lag phase before the start of temperature recovery (Tlag) was significantly greater in patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis than in control subjects. The maximum recovery index (R%) was significantly less in patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis than in controls. The maximum rate of change of temperature during the rapid phase of rewarming (Gmax) was significantly greater in controls than in patients with primary Raynaud's phenomenon and Raynaud's phenomenon associated with systemic sclerosis. Discriminant analysis showed that the dynamic parameters of rewarming (Tlag, Gmax, and R%) showed greater variation between the patients with primary Raynaud's phenomenon and those with Raynaud's phenomenon associated with systemic sclerosis than did Tpre or T0. This method of analysis of cold challenge will be used in studies of the effects of treatment of Raynaud's phenomenon. PMID:1466594

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

    Directory of Open Access Journals (Sweden)

    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

  8. Prolonged Barium-Impaction Ileus in Two Lung Transplant Recipients With Systemic Sclerosis: Case Report.

    Science.gov (United States)

    Tokman, S; Hays, S R; Leard, L E; Bush, E L; Kukreja, J; Kleinhenz, M E; Golden, J A; Singer, J P

    2015-12-01

    Lung transplantation can be a life-saving measure for people with end-stage lung disease from systemic sclerosis. However, outcomes of lung transplantation may be compromised by gastrointestinal manifestations of systemic sclerosis, which can involve any part of the gastrointestinal tract. Esophageal and gastric disease can be managed by enteral feeding with the use of a gastrojejunal feeding tube. In this report, we describe the clinical courses of 2 lung transplant recipients with systemic sclerosis who experienced severe and prolonged barium-impaction ileus after insertion of a percutaneous gastrojejunal feeding tube. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. 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

  10. Vascular Alterations and Sexual Function in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    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.

  11. 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.

  12. Registry Evaluation of Digital Ulcers in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    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. Cardiac tamponade preceding skin involvement in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    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.

  14. Alemtuzumab in Multiple Sclerosis: Lessons from Social Media in Enhancing Patient Care.

    Science.gov (United States)

    Rath, Louise; Vijiaratnam, Nirosen; Skibina, Olga

    2017-01-01

    Alemtuzumab is a monoclonal antibody that has been approved for the treatment of relapsing-remitting multiple sclerosis (MS). Alemtuzumab is associated with infusion reactions and potential autoimmune complications. Patient education and understanding are crucial to favorable outcomes. Our objective was to observe communication on a peer-to-peer Facebook group for content, accuracy of posts, and number of "likes" per post and to compare shared themes to current approved prescribing information and educational modules. We identified a Facebook group specific to alemtuzumab in MS. A 14-day window was observed. Posts were classified as "sharing" or "seeking information." Content analysis was used for information-seeking posts. Accuracy of replies was compared with product prescribing information. We reviewed 458 posts. Members contemplating receiving or currently receiving alemtuzumab primarily used Facebook for information gathering (54.6%), followed by seeking emotional support and sharing personal experiences (45.4%). Most shared experiences (83.6%) were positive. Themes for information were predominantly consistent with standard protocols. Complications discussed included infection (15.50%), bone pain (11.80%), immune thrombocytopenia (8.07%), and fatigue (7.46%). Accuracy of replies was consistent with product information except for immune thrombocytopenia. Some patients with MS look to online groups for discussion, peer support, and information. Although written guidelines on the studied home page reinforce that online discussion "does not replace medical advice," inaccurate information does occur. Health-care providers' reviews of these online sites allow insight into the real-world experiences of patients receiving alemtuzumab, with potential for modification of educational approaches by health-care professionals.

  15. Towards a lessons learned system for critical software

    International Nuclear Information System (INIS)

    Andrade, J.; Ares, J.; Garcia, R.; Pazos, J.; Rodriguez, S.; Rodriguez-Paton, A.; Silva, A.

    2007-01-01

    Failure can be a major driver for the advance of any engineering discipline and Software Engineering is no exception. But failures are useful only if lessons are learned from them. In this article we aim to make a strong defence of, and set the requirements for, lessons learned systems for safety-critical software. We also present a prototype lessons learned system that includes many of the features discussed here. We emphasize that, apart from individual organizations, lessons learned systems should target industrial sectors and even the Software Engineering community. We would like to encourage the Software Engineering community to use this kind of systems as another tool in the toolbox, which complements or enhances other approaches like, for example, standards and checklists

  16. Towards a lessons learned system for critical software

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, J. [University of A Coruna. Campus de Elvina, s/n. 15071, A Coruna (Spain)]. E-mail: jag@udc.es; Ares, J. [University of A Coruna. Campus de Elvina, s/n. 15071, A Coruna (Spain)]. E-mail: juanar@udc.es; Garcia, R. [University of A Coruna. Campus de Elvina, s/n. 15071, A Coruna (Spain)]. E-mail: rafael@udc.es; Pazos, J. [Technical University of Madrid. Campus de Montegancedo, s/n. 28660, Boadilla del Monte, Madrid (Spain)]. E-mail: jpazos@fi.upm.es; Rodriguez, S. [University of A Coruna. Campus de Elvina, s/n. 15071, A Coruna (Spain)]. E-mail: santi@udc.es; Rodriguez-Paton, A. [Technical University of Madrid. Campus de Montegancedo, s/n. 28660, Boadilla del Monte, Madrid (Spain)]. E-mail: arpaton@fi.upm.es; Silva, A. [Technical University of Madrid. Campus de Montegancedo, s/n. 28660, Boadilla del Monte, Madrid (Spain)]. E-mail: asilva@fi.upm.es

    2007-07-15

    Failure can be a major driver for the advance of any engineering discipline and Software Engineering is no exception. But failures are useful only if lessons are learned from them. In this article we aim to make a strong defence of, and set the requirements for, lessons learned systems for safety-critical software. We also present a prototype lessons learned system that includes many of the features discussed here. We emphasize that, apart from individual organizations, lessons learned systems should target industrial sectors and even the Software Engineering community. We would like to encourage the Software Engineering community to use this kind of systems as another tool in the toolbox, which complements or enhances other approaches like, for example, standards and checklists.

  17. Pulmonary involvement in systemic sclerosis: A clinical profile

    Directory of Open Access Journals (Sweden)

    A S Deepa

    2016-01-01

    Full Text Available Background: Systemic sclerosis is a generalized disorder of connective tissue affecting skin and internal organs. Lung involvement accounts for significant morbidity and is a leading cause of mortality in patients. Objectives: This study intends to study the frequency of occurrence of pulmonary involvement in progressive systemic sclerosis (PSS and to describe the clinical and radiological picture of pulmonary involvement in PSS. Materials and Methods: This was a descriptive cross-sectional study. A detailed history, modified Rodnan score, clinical examination, routine investigation, antinuclear antibody, immuno biot, chest X-ray (CXR, pulmonary function test (PFT, and 6 min walk test (6MWT were performed on all patients. High resolution computed tomography was done on those who consented. Results: Hundred subjects with PSS were included in the study; 90 were females and 10 were males. Common presenting complaints were skin thickening in 98% and Raynaud's phenomenon in 98%. Skin thickening of digits beyond metacarpo phalangeal was seen in 98%, face and neck in 92%, and hands in 92%. Chest wall thickening was seen in 40 subjects (40%. 90 (90% of the studied subjects had pulmonary involvement, longer duration of disease was significantly associated with pulmonary involvement (P < 0.05. Dyspnea, cough, bilateral crepitations, CXR, Borg score, and Rodnan score was found to be significantly associated with severe pulmonary involvement (P < 0.05. Conclusion: The prevalence of pulmonary involvement in this cohort study was 90%. Almost 1/3rd of patients, that is 29 (29% were detected to have pulmonary involvement despite being asymptomatic for respiratory complaints, hence early screening and evaluation is recommended. PFT and 6MWT are noninvasive, cost-effective, and easily available screening tests which can be used in resource-limited settings.

  18. Sacral nerve stimulation for faecal incontinence due to systemic sclerosis

    Science.gov (United States)

    Kenefick, N J; Vaizey, C J; Nicholls, R J; Cohen, R; Kamm, M A

    2002-01-01

    Background: Faecal incontinence occurs in over one third of patients with systemic sclerosis. The aetiology is multifactorial. Conventional treatment is often unsuccessful. Sacral nerve stimulation is a new effective treatment for resistant faecal incontinence. Aims: To evaluate sacral nerve stimulation in patients with systemic sclerosis. Patients: Five women, median age 61 years (30–71), with scleroderma associated faecal incontinence were evaluated. All had failed maximal conventional treatment. Median number of preoperative weekly episodes of incontinence was 15 (7–25), median duration of incontinence was five years (5–9), and scleroderma 13 years (4–29). Methods: All patients were screened with temporary stimulation. Those who benefited underwent permanent implantation. At baseline and after stimulation a bowel diary, the SF-36 quality of life assessment, endoanal ultrasound, and anorectal physiology were performed. Results: Four patients were continent at a median follow up of 24 months (6–60). One patient failed temporary stimulation and was not permanently implanted. The weekly episodes of incontinence decreased from 15, 11, 23, and 7 to 0. Urgency resolved (median time to defer <1 minute (0–1) v 12.5 minutes (5–15)). Quality of life, especially social function, improved. Endoanal ultrasound showed an atrophic internal anal sphincter (median width 1.0 mm (0–1.6)). Anorectal physiology showed an increase in median resting pressure (37 pre v 65 cm H2O post) and squeeze pressure (89 v 105 cm H2O). Stimulation produced enhanced rectal sensitivity to distension. There were no major complications. Conclusions: Sacral nerve stimulation is a safe and effective treatment for resistant faecal incontinence secondary to scleroderma. The benefit is maintained in the medium term. PMID:12427794

  19. The role of B cells in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Marina D Kraaij

    2008-09-01

    Full Text Available Marina D Kraaij, Jacob M van LaarMusculoskeletal Research Group, Institute of Cellular Medicine, School of Clinical Medical Sciences, Newcastle University, Newcastle upon Tyne NE2 4HH, United KingdomAbstract: Systemic sclerosis (SSc is a connective disease characterized by features of autoimmunity, vasculopathy, inflammation, and fibrosis. The disease typically starts with Raynaud’s phenomenon, followed by skin thickening in the extremities due to inflammation and fibrosis. Fibrosis results from excessive collagen production by fibroblasts, which constitutes the final common pathway of complex cellular interactions including B cells. Several studies have indicated that B cells may play a role in SSc. Lesional skin infiltrates from SSc patients consist of a variety of cells, including eosinophils, neutrophils, lymphocytes, plasma cells, and macrophages. Autoantibodies of several specificities are present in the serum of SSc patients of which antitopoisomerase 1 is the most common, and evidence has been gathered for a potential pathogenic role of some autoantibodies, eg, anti-PDGF antibodies. The blood of SSc patients contains an increased proportion of naïve B cells but a decreased proportion of memory B cells. Furthermore, serum levels of interleukin-6, an important pro-inflammatory cytokine, have been shown to correlate with skin fibrosis. Animal models of SSc have provided more in-depth information on the role of B lymphocytes, eg, through disruption of B cell function. In this review we will discuss the evidence that B cells are involved in the pathogenesis of SSc.Keywords: B lymphocyte, systemic sclerosis, fibrosis

  20. Oral and periodontal manifestations associated with systemic sclerosis: A case series and review

    OpenAIRE

    Rekha Jagadish; Dhoom Singh Mehta; P Jagadish

    2012-01-01

    Systemic sclerosis is a rare connective tissue disorder with a wide range of oral manifestations. This case series reports significant oral and periodontal changes and also makes an attempt to correlate oral and systemic findings in these patients which enable the clinician for a better diagnosis and evolve a comprehensive treatment plan. Six patients with a known diagnosis of systemic sclerosis were included. After obtaining the patient's informed consent, relevant medical history, oral mani...

  1. 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

  2. Multiple sclerosis

    International Nuclear Information System (INIS)

    Grunwald, I.Q.; Kuehn, A.L.; Backens, M.; Papanagiotou, P.; Shariat, K.; Kostopoulos, P.

    2008-01-01

    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.) [de

  3. 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

  4. [Systemic sclerosis and occupational exposures: About a case in a driller-powderman].

    Science.gov (United States)

    Boulanger, M; Bienvenu, B; Marquignon, M-F; Letourneux, M; Clin, B

    2015-08-01

    Erasmus' syndrome is the association between systemic sclerosis and silica exposure. We report a case of this syndrome in a driller-powderman exposed to silica and nitro compounds contained in explosives. Physiopathology and etiologies of systemic sclerosis are still not well known. However, nitric oxide, a product of nitro compounds metabolism, is involved in the physiopathology of the disease: it seems thus licit to wonder about the consequences of an uncontrolled occupational exposure to nitric oxide on the vascular function, already damaged by systemic sclerosis. To a wider extent, our report highlights the importance of a comprehensive and detailed collection of occupational exposures for patients diagnosed with systemic sclerosis. Copyright © 2014 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  5. 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...

  6. Need for online information and support of patients with Systemic Sclerosis

    NARCIS (Netherlands)

    van der Vaart, R.; Repping-Wuts, Han; Drossaert, Constance H.C.; Taal, Erik; Knaapen-Hans, Hanneke K.A.; van de Laar, Mart A F J

    2013-01-01

    Objective Interactive health communication applications (IHCAs) offer interesting possibilities to support systemic sclerosis (SSc) patients, since SSc is an uncommon, severe disease that needs a multidisciplinary treatment. This study aimed to investigate patients' needs for a hospital-based IHCA.

  7. Designing an Electronic Patient Management System for Multiple Sclerosis: Building a Next Generation Multiple Sclerosis Documentation System.

    Science.gov (United States)

    Kern, Raimar; Haase, Rocco; Eisele, Judith Christina; Thomas, Katja; Ziemssen, Tjalf

    2016-01-08

    Technologies like electronic health records or telemedicine devices support the rapid mediation of health information and clinical data independent of time and location between patients and their physicians as well as among health care professionals. Today, every part of the treatment process from diagnosis, treatment selection, and application to patient education and long-term care may be enhanced by a quality-assured implementation of health information technology (HIT) that also takes data security standards and concerns into account. In order to increase the level of effectively realized benefits of eHealth services, a user-driven needs assessment should ensure the inclusion of health care professional perspectives into the process of technology development as we did in the development process of the Multiple Sclerosis Documentation System 3D. After analyzing the use of information technology by patients suffering from multiple sclerosis, we focused on the needs of neurological health care professionals and their handling of health information technology. Therefore, we researched the status quo of eHealth adoption in neurological practices and clinics as well as health care professional opinions about potential benefits and requirements of eHealth services in the field of multiple sclerosis. We conducted a paper-and-pencil-based mail survey in 2013 by sending our questionnaire to 600 randomly chosen neurological practices in Germany. The questionnaire consisted of 24 items covering characteristics of participating neurological practices (4 items), the current use of network technology and the Internet in such neurological practices (5 items), physicians' attitudes toward the general and MS-related usefulness of eHealth systems (8 items) and toward the clinical documentation via electronic health records (4 items), and physicians' knowledge about the Multiple Sclerosis Documentation System (3 items). From 600 mailed surveys, 74 completed surveys were returned

  8. Incidence and prevalence of systemic sclerosis in Campo Grande, State of Mato Grosso do Sul, Brazil.

    Science.gov (United States)

    Horimoto, Alex Magno Coelho; Matos, Erica Naomi Naka; Costa, Márcio Reis da; Takahashi, Fernanda; Rezende, Marcelo Cruz; Kanomata, Letícia Barrios; Locatelli, Elisangela Possebon Pradebon; Finotti, Leandro Tavares; Maegawa, Flávia Kamy Maciel; Rondon, Rosa Maria Ribeiro; Machado, Natália Pereira; Couto, Flávia Midori Arakaki Ayres Tavares do; Figueiredo, Túlia Peixoto Alves de; Ovidio, Raphael Antonio; Costa, Izaias Pereira da

    Systemic sclerosis is an autoimmune disease which shows extreme heterogeneity in its clinical presentation and that follows a variable and unpredictable course. Although some discrepancies in the incidence and prevalence rates between geographical regions may reflect methodological differences in the definition and verification of cases, they may also reflect true local differences. To determine the prevalence and incidence of systemic sclerosis in the city of Campo Grande, state capital of Mato Grosso do Sul (MS), Brazil, during the period from January to December 2014. All health care services of the city of Campo Grande - MS with attending in the specialty of Rheumatology were invited to participate in the study through a standardized form of clinical and socio-demographic assessment. Physicians of any specialty could report a suspected case of systemic sclerosis, but necessarily the definitive diagnosis should be established by a rheumatologist, in order to warrant the standardization of diagnostic criteria and exclusion of other diseases resembling systemic sclerosis. At the end of the study, 15 rheumatologists reported that they attended patients with systemic sclerosis and sent the completed forms containing epidemiological data of patients. The incidence rate of systemic sclerosis in Campo Grande for the year 2014 was 11.9 per million inhabitants and the prevalence rate was 105.6 per million inhabitants. Systemic sclerosis patients were mostly women, white, with a mean age of 50.58 years, showing the limited form of the disease with a mean duration of the disease of 8.19 years. Regarding laboratory tests, 94.4% were positive for antinuclear antibody, 41.6% for anti-centromere antibody and 19.1% for anti-Scl70; anti-RNA Polymerase III was performed in 37 patients, with 16.2% positive. The city of Campo Grande, the state capital of MS, presented a lower incidence/prevalence of systemic sclerosis in comparison with those numbers found in US studies and close

  9. 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.

  10. [The treatment of skin ulcers in patients with systemic sclerosis].

    Science.gov (United States)

    Fiori, G; Amanzi, L; Moggi Pignone, A; Braschi, F; Matucci-Cerinic, M

    2004-01-01

    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 easily make an ulcer chronic 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 sclerodermic 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.

  11. Motor System Plasticity and Compensation in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. A critical view on cardiovascular risk in systemic sclerosis.

    Science.gov (United States)

    Psarras, Antonios; Soulaidopoulos, Stergios; Garyfallos, Alexandros; Kitas, George; Dimitroulas, Theodoros

    2017-01-01

    Systemic Sclerosis (SSc) is an autoimmune disorder characterized by microvascular injury and diffuse fibrosis of the skin and internal organs. While macrovascular disease and higher risk for cardiovascular events are well documented in other systemic rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus, the presence and extent of atherosclerosis among patients with SSc is yet to be established. Primary cardiac involvement, due to impairment of coronary microvascular circulation and myocardial fibrosis, considerably affects prognosis and life expectancy of individuals with SSc, representing one of the leading causes of death in this population. On the other hand the existence and prevalence of atherosclerotic coronary disease remains an issue of debate as studies comparing structural and morphological markers of atherosclerosis and cardiovascular events between SSc patients and the general population have yielded controversial results. The aim of this review is to summarize recent literature about the prevalence of cardiovascular disease in SSc, review the surrogate markers of CVD that have been evaluated and examine whether common pathogenic mechanisms exist between SSc and macrovascular disease.

  14. Presentation of pain in patients suffering from systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Janković Katarina

    2016-01-01

    Full Text Available Introduction: Systemic sclerosis (SSc is a chronic autoimmune disease with very heterogeneous clinical manifestations. There are not many studies which directly research the pain experienced by patients with SSc. Aim: Evaluation of pain in patients with verified systemic sclerosis; making comparison in the two subsets of SSc (diffuse and limited and in the anti-centromere antibodies (ACA and anti-topoisomerase-I antibodies (ATA detected in patients. Material and methods: The study group included 42 patients with SSc. The research was conducted at the Institute of Rheumatology in Belgrade. Each patient was asked to complete the questionnaire, which included the questions about frequency, location and intensity of the pain. Two statistical methodologies were used in the data analysis: descriptive and analytical statistics. Results: Most of the patients (93% confirmed they had some kind of pain . Arthralgia was the most common pain symptom (78,6%, 29 (69% suffered from pain during Raynaud phenomenon, the back pain was found in 20 (47,6%, a headache in 13 (31%, the chest pain in 10 (23,8%, odynophagia in 9 (21,4% and in 8 (19% patients painful digital ulcers. The pain from digital ulcers was rated as the most intensive with the average value of 8,5/10. The patients with diffuse subset of SSc had a higher average intensity score of arthralgia (7,6, compared to those with limited SSc (5,5. The statistically significant difference in the frequency and intensity of the pain in the patients with anti-topoisomerase-I antibodies and the patients with anti-centromere antibodies was not found. Conclusion: Most of the patients suffer from some kind of pain. The most common pain was arthralgia, and the most intensive one was from digital ulcers, although it was the rarest. The pain frequency and intensity were not significantly different in patients with anti-topoisomerase-I and anti-centromere antibodies. There was a statisticaly significant difference in the

  15. [Botulinum toxin type A contribution in the treatment of Raynaud's phenomenon due to systemic sclerosis].

    Science.gov (United States)

    Serri, J; Legré, R; Veit, V; Guardia, C; Gay, A-M

    2013-12-01

    Raynaud's phenomenon is a vasospastic disorder of the extremities that can lead, in the hands, to pain, disability, ischemic ulcers and digital chronic ischemia. Medical and surgical current treatments are not fully effective while causing side effects. Recent studies have emphasized the value of botulinum toxin type A (BTX A) in the management of primary Raynaud's phenomenon. The originality of Raynaud's syndrome secondary to systemic sclerosis is to combine both arterial vasospasm and sclerosis of the arterial wall, what is supposed to reduce BTX A effects. The purpose of this work is to evaluate BTX A efficiency in patients with Raynaud's phenomenon secondary to systemic sclerosis. We performed a prospective study for 12 months. Patients with severe Raynaud's phenomenon due to systemic sclerosis were injected with BTX A in the two hands. Evolution of ischemic ulcers, QuickDASH Score, O2 partial pressure, pain were measured before and 30 days after injection. We treated 18 patients. Thirty days after injection, we noticed a complete healing of ulcers, QuickDASH Score was improved from 39.4 to 20, as the O2 partial pressure from 16 to 42 mmHg and the pain from VNS from 6/10 to 2/10. BTX A appears to improve significantly Raynaud's phenomenon symptomatology in patients with systemic sclerosis despite the component of arterial sclerosis. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  16. Fecal incontinence in systemic sclerosis is secondary to neuropathy.

    Science.gov (United States)

    Thoua, Nora M; Abdel-Halim, Mostafa; Forbes, Alastair; Denton, Chris P; Emmanuel, Anton V

    2012-04-01

    Systemic sclerosis (SSc) is a chronic multi-system autoimmune disorder with gastrointestinal tract (GIT) involvement in up to 90% of patients and anorectal involvement occurs in up to 50% of patients. The pathogenesis of gastrointestinal abnormalities may be both myogenic and neurogenic. We aimed to identify which anorectal physiological abnormalities correlate with clinical symptoms and thus understand the pathophysiology of anorectal involvement in SSc. In total, 44 SSc patients (24 symptomatic (Sx) (fecal incontinence) and 20 asymptomatic (ASx)) and 20 incontinent controls (ICs) were studied. Patients underwent anorectal manometry, rectal mucosal blood flow (RMBF), rectal compliance (barostat), and rectoanal inhibitory reflex assessment (RAIR). Anal squeeze pressure was lower in the IC group compared with both the ASx and Sx groups (IC: 46.95 (30-63.9)) vs. ASx: 104.6 (81-128.3) vs. (Sx: 121.4 (101.3-141.6); P ASx: 6.7 (5.7-7.7) vs. IC: 8.5 (6.5-10.4); P ASx and in 1/20 IC patients. Fecal incontinence in SSc is related to neuropathy as suggested by absent RAIR and higher anal sensory threshold and is related less so to sphincter atrophy and rectal fibrosis.

  17. Plasma D-dimer concentration in patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Montagnana Martina

    2006-01-01

    Full Text Available Abstract Background Systemic sclerosis (SSc is an autoimmune disorder of the connective tissue characterized by widespread vascular lesions and fibrosis. Little is known so far on the activation of the hemostatic and fibrinolytic systems in SSc, and most preliminary evidences are discordant. Methods To verify whether SSc patients might display a prothrombotic condition, plasma D-dimer was assessed in 28 consecutive SSc patients and in 33 control subjects, matched for age, sex and environmental habit. Results and discussion When compared to healthy controls, geometric mean and 95% confidence interval (IC95% of plasma D-dimer were significantly increased in SSc patients (362 ng/mL, IC 95%: 361–363 ng/mL vs 229 ng/mL, IC95%: 228–231 ng/mL, p = 0.005. After stratifying SSc patients according to disease subset, no significant differences were observed between those with limited cutaneous pattern and controls, whereas patients with diffuse cutaneous pattern displayed substantially increased values. No correlation was found between plasma D-dimer concentration and age, sex, autoantibody pattern, serum creatinine, erythrosedimentation rate, nailfold videocapillaroscopic pattern and pulmonary involvement. Conclusion We demonstrated that SSc patients with diffuse subset are characterized by increased plasma D-dimer values, reflecting a potential activation of both the hemostatic and fibrinolytic cascades, which might finally predispose these patients to thrombotic complications.

  18. Association of TRPM Channel Gene Polymorphisms with Systemic Sclerosis.

    Science.gov (United States)

    Oztuzcu, Serdar; Onat, Ahmet M; Pehlivan, Yavuz; Alibaz-Oner, Fatma; Donmez, Salim; Cetin, Gozde Y; Yolbas, Servet; Bozgeyik, Ibrahim; Yilmaz, Neslihan; Ozgen, Metin; Cagatay, Yonca; Kisacik, Bunyamin; Koca, Suleyman S; Pamuk, Omer Nuri; Sayarlioglu, Mehmet; Direskeneli, Haner; Demiryurek, Abdullah T

    2015-01-01

    Systemic sclerosis (SSc) is an inflammatory disease characterized by vascular abnormalities and fibrosis. The aim of the present study was to investigate the possible role of transient receptor potential melastatin (TRPM) channel genes in the susceptibility and phenotype expression of SSc. A total of 339 patients with SSc and 302 healthy controls were studied. Genomic DNA was extracted from leukocytes of the peripheral blood, and 25 single nucleotide polymorphisms in the TRPM channel genes were analyzed by the BioMark HD dynamic array system. There were marked increases in the CC genotype (94.7% vs 81.8%, pTRPM5 rs34551253 (Ala456Thr) polymorphism in SSc patients when compared to controls. TRPM3 gene rs1328142 polymorphism was also markedly associated with disease phenotype. However, no associations with the other 23 polymorphisms studied were found. This is the first study to examine the involvement of TRPM channel gene variations on the risk of SSc incidence. Our results suggest roles of TRPM3 and TRPM5 gene variants in the susceptibility to or clinical expression of SSc in the Turkish population. Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  19. 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.

  20. Penile involvement in Systemic Sclerosis: New Diagnostic and Therapeutic Aspects

    Directory of Open Access Journals (Sweden)

    Antonio Aversa

    2010-01-01

    Full Text Available Systemic Sclerosis (SSc is a connective tissue disorder featuring vascular alterations and an immunological activation leading to a progressive and widespread fibrosis of several organs such as the skin, lung, gastrointestinal tract, heart, and kidney. Men with SSc are at increased risk of developing erectile dysfunction (ED because of the evolution of early microvascular tissutal damage into corporeal fibrosis. The entity of penile vascular damage in SSc patients has been demonstrated by using Duplex ultrasonography and functional infra-red imaging and it is now clear that this is a true clinical entity invariably occurring irrespective of age and disease duration and constituting the ‘‘sclerodermic penis’’. Once-daily phosphodiesterase type-5 (PDE5 inhibitors improve both sexual function and vascular measures of cavernous arteries by improving surrogate markers of endothelial dysfunction, that is, plasma endothelin-1 and adrenomedullin levels, which may play a potential role in preventing progression of penile fibrosis and ED. Also, the beneficial effect of long-term PDE5i add-on therapy to SSc therapy in the treatment of Raynaud's phenomenon is described.

  1. Gastrointestinal mucosal abnormalities using videocapsule endoscopy in systemic sclerosis.

    Science.gov (United States)

    Marie, I; Antonietti, M; Houivet, E; Hachulla, E; Maunoury, V; Bienvenu, B; Viennot, S; Smail, A; Duhaut, P; Dupas, J-L; Dominique, S; Hatron, P-Y; Levesque, H; Benichou, J; Ducrotté, P

    2014-07-01

    To date, there are no large studies on videocapsule endoscopy in systemic sclerosis (SSc). Consequently, the prevalence and features of gastrointestinal mucosal abnormalities in SSc have not been determined. To determine both prevalence and characteristics of gastrointestinal mucosal abnormalities in unselected patients with SSc, using videocapsule endoscopy. To predict which SSc patients are at risk of developing potentially bleeding gastrointestinal vascular mucosal abnormalities. Videocapsule endoscopy was performed on 50 patients with SSc. Prevalence of gastrointestinal mucosal abnormalities was 52%. Potentially bleeding vascular mucosal lesions were predominant, including: watermelon stomach (34.6%), gastric and/or small intestinal telangiectasia (26.9%) and gastric and/or small intestinal angiodysplasia (38.5%). SSc patients with gastrointestinal vascular mucosal lesions more often exhibited: limited cutaneous SSc (P = 0.06), digital ulcers (P = 0.05), higher score of nailfold videocapillaroscopy (P = 0.0009), anaemia (P = 0.02), lower levels of ferritin (P correlation between gastrointestinal vascular mucosal lesions and presence of severe extra-digestive vasculopathy (digital ulcers and higher nailfold videocapillaroscopy scores). This latter supports the theory that SSc-related diffuse vasculopathy is responsible for both cutaneous and digestive vascular lesions. Therefore, we suggest that nailfold videocapillaroscopy may be a helpful test for managing SSc patients. In fact, nailfold videocapillaroscopy score should be calculated routinely, as it may result in identification of SSc patients at higher risk of developing potentially bleeding gastrointestinal vascular mucosal lesions. © 2014 John Wiley & Sons Ltd.

  2. Pulmonary vasospasm in systemic sclerosis: noninvasive techniques for detection.

    Science.gov (United States)

    Keir, Gregory J; Nair, Arjun; Giannarou, Stamatia; Yang, Guang-Zhong; Oldershaw, Paul; Wort, S John; MacDonald, Peter; Hansell, David M; Wells, Athol U

    2015-09-01

    In a subgroup of patients with systemic sclerosis (SSc), vasospasm affecting the pulmonary circulation may contribute to worsening respiratory symptoms, including dyspnea. Noninvasive assessment of pulmonary blood flow (PBF), utilizing inert-gas rebreathing (IGR) and dual-energy computed-tomography pulmonary angiography (DE-CTPA), may be useful for identifying pulmonary vasospasm. Thirty-one participants (22 SSc patients and 9 healthy volunteers) underwent PBF assessment with IGR and DE-CTPA at baseline and after provocation with a cold-air inhalation challenge (CACh). Before the study investigations, participants were assigned to subgroups: group A included SSc patients who reported increased breathlessness after exposure to cold air (n = 11), group B included SSc patients without cold-air sensitivity (n = 11), and group C patients included the healthy volunteers. Median change in PBF from baseline was compared between groups A, B, and C after CACh. Compared with groups B and C, in group A there was a significant decline in median PBF from baseline at 10 minutes (-10%; range: -52.2% to 4.0%; P CACh. There was no significant difference in median PBF change between groups B or C at any time point and no change in pulmonary perfusion on DE-CTPA. Reduction in pulmonary blood flow following CACh suggests that pulmonary vasospasm may be present in a subgroup of patients with SSc and may contribute to worsening dyspnea on exposure to cold.

  3. Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis

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    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.

  4. Circulating angiostatin serum level in patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Zofia Gerlicz-Kowalczuk

    2017-12-01

    Full Text Available Introduction : Systemic sclerosis (SSc is achronic connective tissue disease characterized by microangiopathy with inadequate angiogenesis. Angiostatin (AS is a potent antiangiogenic factor specifically inhibiting proliferation and inducing apoptosis of vascular endothelial cells. Aim : To evaluate the level of angiostatin in the serum of patients with SSc. Material and methods : Serum levels of AS were measured in 20 SSc patients and 12 healthy controls. Results : A statistically significant difference in the serum levels of AS in SSc patients was observed compared to the control group (636.51 vs. 869.20 ng/ml; p = 0.012. Significant correlations between limited and disseminated SSc (lSSc/dSSc were not found, however, a difference between lSSc and the control group was demonstrated (620.00 vs. 869.20 ng/ml; p = 0.011. The serum level of AS was not associated positively with organ changes caused by SSc. However, a statistically significant lower serum level of AS was observed in patients with SSc and no esophageal (p = 0.008 or pulmonary changes (p = 0.007 compared to the control group. Conclusions : Our results reveal significant differences in AS level in SSc patients compared to the healthy controls, and suggest that a low level of AS may occur as a result of impaired angiogenesis.

  5. Screening and management of pulmonary arterial hypertension in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Vivek Nagaraja

    2017-01-01

    Full Text Available Systemic sclerosis-associated pulmonary hypertension (SSc-PH and pulmonary arterial (PA hypertension (SSc-PAH are well-recognized manifestations. SSc-PH is a hemodynamic observation, and it is important to identify underlying etiology. SSc patients commonly have mixed etiology for SSc-PH due to interstitial lung disease, PAH, and left heart disease. SSc-PAH is associated with high morbidity and mortality. Early detection of PAH through routine screening improves survival in patients with SSc. Right heart catheterization is mandatory to diagnose PAH. SSc-PAH patients should be managed by a multidisciplinary team comprising of rheumatologist, pulmonologist, cardiologist, and physiotherapist. Various pharmacotherapy options to treat SSc-PAH are derived from the idiopathic PAH management. Upfront or sequential combination therapy of PAH-specific drugs seems to confer a clinical benefit compared to monotherapy. Cardiopulmonary rehabilitation should be considered as a part of the management plan. Lung transplantation is a consideration in patients who are not responding to pharmacotherapy. Although the long-term prognosis of SSc-PAH has been historically poor, the landscape is gradually changing with early detection and institution of treatment.

  6. Plants and Photosynthesis: Level III, Unit 3, Lesson 1; The Human Digestive System: Lesson 2; Functions of the Blood: Lesson 3; Human Circulation and Respiration: Lesson 4; Reproduction of a Single Cell: Lesson 5; Reproduction by Male and Female Cells: Lesson 6; The Human Reproductive System: Lesson 7; Genetics and Heredity: Lesson 8; The Nervous System: Lesson 9; The Glandular System: Lesson 10. Advanced General Education Program. A High School Self-Study Program.

    Science.gov (United States)

    Manpower Administration (DOL), Washington, DC. Job Corps.

    This self-study program for the high-school level contains lessons in the following subjects: Plants and Photosynthesis; The Human Digestive System; Functions of the Blood; Human Circulation and Respiration; Reproduction of a Single Cell; Reproduction by Male and Female Cells; The Human Reproductive System; Genetics and Heredity; The Nervous…

  7. 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.

  8. 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.

  9. Hand and wrist involvement in systemic sclerosis: US features.

    Science.gov (United States)

    Freire, Véronique; Bazeli, Ramin; Elhai, Muriel; Campagna, Raphaël; Pessis, Éric; Avouac, Jérôme; Allanore, Yannick; Drapé, Jean-Luc; Guérini, Henri

    2013-12-01

    To characterize ultrasonographic (US) features in the hand of patients with systemic sclerosis (SSc) and to evaluate the sensitivity of US in the detection of calcinosis and acroosteolysis. The local ethics committee approved this study, and oral informed consent was obtained. A total of 44 consecutive patients with SSc (34 women; mean age, 56.1 years ± 12.1 [standard deviation]; 10 men; mean age, 45.0 years ± 14.0) and 30 healthy control subjects (20 women; mean age, 46.3 years ± 12.1; 10 men; mean age, 39.6 years ± 10.8) were included between October 2010 and December 2011. Bilateral US, including Doppler assessment of the wrists, hands, and fingers, was performed, and presence of synovitis, tenosynovitis with or without a layered appearance, calcifications, acroosteolysis, and distal vascularization was recorded. Radiography of both hands was performed to assess for acroosteolysis and calcinosis. Frequency of US features, sensitivity of US for calcinosis and acroosteolysis, and respective confidence intervals were calculated. Synovitis was found in 17 patients (39%). Tenosynovitis was found in 12 patients (27%), and it had a layered pattern in 15 (41%) of 37 cases. Calcinosis was found in 17 patients (39%) with US, with a sensitivity of 89%. Acroosteolysis was found in nine (20%) patients with US and in 10 (23%) patients with radiography, with 90% sensitivity for US. Distal vascularization was detected in 26 patients (59%) and 30 control subjects (100%) and was in contact with the acroosteolysis bed in seven (78%) of nine patients with SSc. US can be used to assess features of SSc, including synovitis, tenosynovitis, calcinosis, acroosteolysis, and distal vascularization and is sensitive for calcinosis and acroosteolysis detection. A layered pattern (similar to the appearance of an artichoke heart) of tenosynovitis was seen commonly. Online supplemental material is available for this article. © RSNA, 2013.

  10. Low bone density in systemic sclerosis. A systematic review.

    Science.gov (United States)

    Omair, Mohammed A; Pagnoux, Christian; McDonald-Blumer, Heather; Johnson, Sindhu R

    2013-11-01

    The effect of systemic sclerosis (SSc) on bone density is not well understood. Through systematic review of the literature, the objectives of this study were to synthesize data about the prevalence of low bone mineral density (BMD), risk factors for low BMD, and occurrence of fracture and fracture-related mortality in SSc. A search was conducted of MEDLINE (1948-2012), Evidence Based Medicine Reviews (1991-2012), EMBASE (1980-2012), and CINAHL (1981-2012). Abstracts were screened to identify studies that evaluated low BMD in patients with SSc. Two investigators independently used a standardized form to abstract prevalence of osteopenia and osteoporosis (OP); risk factors for low BMD, BMD measurements, frequency of fracture, and fracture-related mortality. Screening of 1032 citations identified 19 articles. Fifteen studies compared patients with SSc to controls. Most patients were white, female (prevalence 74%-100%), and postmenopausal (prevalence 45.9%-100%). The prevalence of low BMD and OP was 27%-53.3% and 3%-51.1%, respectively. Ten studies reported a lower BMD in patients with SSc compared to matched controls, whereas 2 studies reported no difference. Candidate risk factors for low BMD in SSc include family history of OP, age, menopause, diffuse subtype, presence of internal organ involvement, low vitamin D levels, and calcinosis. However, the studies supporting these factors were conflicting. Fracture rate ranged between 0% and 38%. No study reported OP-related fracture mortality. The data suggest that patients with SSc are at risk of low BMD and fracture, especially when other risk factors for OP are present. The interaction of SSc manifestations, traditional OP risk factors, and clinically relevant outcomes is complex and warrants further research.

  11. Gastric involvement in systemic sclerosis: a prospective study.

    Science.gov (United States)

    Marie, I; Levesque, H; Ducrotté, P; Denis, P; Hellot, M F; Benichou, J; Cailleux, N; Courtois, H

    2001-01-01

    This study aims to assess the prevalence of gastric electrical activity dysfunction with cutaneous electrogastrography (EGG), disturbances of gastric emptying function using radiopaque pellets, and gastric endoscopic abnormalities in patients with systemic sclerosis (SSc). We also investigate for an association between EGG and gastric-emptying data with clinical manifestations and esophageal motor disturbances. Fasting and postprandial gastric electrical activity was studied in 22 consecutive patients with SSc (17 with and 5 without clinical gastric manifestations) and 22 age- and sex-matched healthy subjects. Gastric emptying of radiopaque pellets and gastroscopy were also performed in SSc patients. The prevalence of EGG disturbances was as high as 81.82% in SSc patients. SSc patients exhibited, compared with controls, higher median percentage of dominant frequency in bradygastria during the fasting period and lower median values for postprandial electrical power and postprandial to fasting ratio for electrical power. Gastric emptying of radiopaque pellets was delayed in 11 SSc patients, and gastroscopy demonstrated "watermelon stomach" in 3 SSc patients. No correlation was found between the severity of gastric impairment and clinical presentation, SSc duration and subsets, and esophageal manometric impairment. Our study underlines the high frequency of gastric dysfunction in SSc patients. It suggests the usefulness of EGG in SSc in noninvasively detecting disorders of gastric electrical activity at an early stage and symptomatic patients with gastroparesis (because there was a correlation between values of postprandial to fasting ratio for electrical power of watermelon stomach diagnosis should be excluded in SSc patients presenting with gastrointestinal hemorrhage or with anemia related to iron deficiency.

  12. 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

  13. 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.

  14. 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.

  15. Oral and periodontal manifestations associated with systemic sclerosis: A case series and review.

    Science.gov (United States)

    Jagadish, Rekha; Mehta, Dhoom Singh; Jagadish, P

    2012-04-01

    Systemic sclerosis is a rare connective tissue disorder with a wide range of oral manifestations. This case series reports significant oral and periodontal changes and also makes an attempt to correlate oral and systemic findings in these patients which enable the clinician for a better diagnosis and evolve a comprehensive treatment plan. Six patients with a known diagnosis of systemic sclerosis were included. After obtaining the patient's informed consent, relevant medical history, oral manifestations including periodontal findings and oral hygiene index simplified index were recorded. In these patients, oral changes included restricted mouth opening and, resorption of the mandible. The periodontal changes observed were gingival recession, absence or minimal gingival bleeding on probing, and widened periodontal ligament space, radiographically. Patients with systemic sclerosis often show wide range of oral manifestations, which is of major concern for the dentist.

  16. Oral and periodontal manifestations associated with systemic sclerosis: A case series and review

    Directory of Open Access Journals (Sweden)

    Rekha Jagadish

    2012-01-01

    Full Text Available Systemic sclerosis is a rare connective tissue disorder with a wide range of oral manifestations. This case series reports significant oral and periodontal changes and also makes an attempt to correlate oral and systemic findings in these patients which enable the clinician for a better diagnosis and evolve a comprehensive treatment plan. Six patients with a known diagnosis of systemic sclerosis were included. After obtaining the patient′s informed consent, relevant medical history, oral manifestations including periodontal findings and oral hygiene index simplified index were recorded. In these patients, oral changes included restricted mouth opening and, resorption of the mandible. The periodontal changes observed were gingival recession, absence or minimal gingival bleeding on probing, and widened periodontal ligament space, radiographically. Patients with systemic sclerosis often show wide range of oral manifestations, which is of major concern for the dentist.

  17. 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.

  18. 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

  19. Endothelin Receptor Antagonists for the Treatment of Raynaud's Phenomenon and Digital Ulcers in Systemic Sclerosis

    Science.gov (United States)

    Arefiev, Kait; Fiorentino, David F.; Chung, Lorinda

    2011-01-01

    Systemic sclerosis is a connective tissue disease characterized by fibrosis of the skin, internal organs, and widespread vasculopathy. Raynaud's phenomenon and digital ulcers are vascular manifestations of this disease and cause significant morbidity. Current treatments are only moderately effective in reducing the severity of Raynaud's in a portion of patients and typically do not lead to substantial benefit in terms of the healing or prevention of digital ulcers. Several studies have evaluated the efficacy of targeting the vasoconstrictor endothelin-1 for the treatment of systemic sclerosis-associated vascular disease. The purpose of this paper is to summarize the published studies and case reports evaluating the efficacy of endothelin receptor antagonists in the treatment of Raynaud's phenomenon and digital ulcers associated with systemic sclerosis. PMID:22121371

  20. Endothelin Receptor Antagonists for the Treatment of Raynaud's Phenomenon and Digital Ulcers in Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    Kait Arefiev

    2011-01-01

    Full Text Available Systemic sclerosis is a connective tissue disease characterized by fibrosis of the skin, internal organs, and widespread vasculopathy. Raynaud's phenomenon and digital ulcers are vascular manifestations of this disease and cause significant morbidity. Current treatments are only moderately effective in reducing the severity of Raynaud's in a portion of patients and typically do not lead to substantial benefit in terms of the healing or prevention of digital ulcers. Several studies have evaluated the efficacy of targeting the vasoconstrictor endothelin-1 for the treatment of systemic sclerosis-associated vascular disease. The purpose of this paper is to summarize the published studies and case reports evaluating the efficacy of endothelin receptor antagonists in the treatment of Raynaud's phenomenon and digital ulcers associated with systemic sclerosis.

  1. Gallium-67 uptake by the thyroid associated with progressive systemic sclerosis

    International Nuclear Information System (INIS)

    Sjoberg, R.J.; Blue, P.W.; Kidd, G.S.

    1989-01-01

    Although thyroidal uptake of gallium-67 has been described in several thyroid disorders, gallium-67 scanning is not commonly used in the evaluation of thyroid disease. Thyroidal gallium-67 uptake has been reported to occur frequently with subacute thyroiditis, anaplastic thyroid carcinoma, and thyroid lymphoma, and occasionally with Hashimoto's thyroiditis and follicular thyroid carcinoma. A patient is described with progressive systemic sclerosis who, while being scanned for possible active pulmonary involvement, was found incidentally to have abnormal gallium-67 uptake only in the thyroid gland. Fine needle aspiration cytology of the thyroid revealed Hashimoto's thyroiditis. Although Hashimoto's thyroiditis occurs with increased frequency in patients with progressive systemic sclerosis, thyroidal uptake of gallium-67 associated with progressive systemic sclerosis has not, to our knowledge, been previously described. Since aggressive thyroid malignancies frequently are imaged by gallium-67 scintigraphy, fine needle aspiration cytology of the thyroid often is essential in the evaluation of thyroidal gallium-67 uptake

  2. Retinoic acid for treatment of systemic sclerosis and morphea: A literature review.

    Science.gov (United States)

    Thomas, Renee M; Worswick, Scott; Aleshin, Maria

    2017-03-01

    Systemic sclerosis and morphea are connective tissue diseases characterized by tightening, thickening, and hardening of the skin, leading to significant morbidity. Unfortunately, current treatment options have limited efficacy for many patients. Cutaneous manifestations of these diseases arise from excess collagen deposition and fibrosis in the skin, through pathogenic mechanisms which have yet to be extensively detailed at the causal immune and cellular levels. Research elucidating the mechanism of action of retinoic acid on collagen production in the skin and case series highlighting the success of retinoic acid on the skin manifestations of systemic sclerosis and on morphea demonstrate its promise as a treatment. Herein they will briefly review the treatment options for both systemic sclerosis and morphea, and will discuss the potential of retinoic acid as a therapy and the supporting evidence from the literature, highlighting the previously published basic science and clinical studies investigating the role of retinoic acid in the treatment of sclerotic skin diseases. © 2016 Wiley Periodicals, Inc.

  3. 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,

  4. Relationship between disease characteristics and orofacial manifestations in systemic sclerosis: Canadian Systemic Sclerosis Oral Health Study III.

    Science.gov (United States)

    Baron, Murray; Hudson, Marie; Tatibouet, Solène; Steele, Russell; Lo, Ernest; Gravel, Sabrina; Gyger, Geneviève; El Sayegh, Tarek; Pope, Janet; Fontaine, Audrey; Masetto, Ariel; Matthews, Debora; Sutton, Evelyn; Thie, Norman; Jones, Niall; Copete, Maria; Kolbinson, Dean; Markland, Janet; Nogueira, Getulio; Robinson, David; Fritzler, Marvin; Gornitsky, Mervyn

    2015-05-01

    Systemic sclerosis (SSc; scleroderma) is associated with decreased saliva production and interincisal distance, more missing teeth, and periodontal disease. We undertook this study to determine the clinical correlates of SSc with these oral abnormalities. Subjects were recruited from the Canadian Scleroderma Research Group cohort. Detailed dental and clinical examinations were performed according to standardized protocols. Associations between dental abnormalities and selected clinical and serologic manifestations of SSc were examined. One hundred sixty-three SSc subjects were included: 90% women, mean ± SD age 56 ± 11 years, mean ± SD disease duration 14 ± 8 years, 72% with limited cutaneous disease, and 28% with diffuse cutaneous disease. Decreased saliva production was associated with Sjögren's syndrome-related autoantibodies (β = -43.32; 95% confidence interval [95% CI] -80.89, -5.75), but not with disease severity (β = -2.51; 95% CI -8.75, 3.73). Decreased interincisal distance was related to disease severity (β = -1.02; 95% CI -1.63, -0.42) and the modified Rodnan skin thickness score (β = -0.38; 95% CI -0.53, -0.23). The number of missing teeth was associated with decreased saliva production (relative risk [RR] 0.97; 95% CI 0.94, 0.99), worse hand function (RR 1.52; 95% CI 1.13, 2.02), and the presence of gastroesophageal reflux disease (GERD; RR 1.68 [95% CI 1.14, 2.46]). No clinical or serologic variables were correlated with periodontal disease. In SSc, diminished interincisal distance is related to overall disease severity. Decreased saliva production is related to concomitant Sjögren's syndrome antibodies. Tooth loss is associated with poor upper extremity function, GERD, and decreased saliva. The etiology of excess periodontal disease is likely multifactorial and remains unclear. © 2015, American College of Rheumatology.

  5. Systemic sclerosis biomarkers discovered using mass-spectrometry-based proteomics: a systematic review.

    Science.gov (United States)

    Bălănescu, Paul; Lădaru, Anca; Bălănescu, Eugenia; Băicuş, Cristian; Dan, Gheorghe Andrei

    2014-08-01

    Systemic sclerosis (SSc) is an autoimmune disease with incompletely known physiopathology. There is a great challenge to predict its course and therapeutic response using biomarkers. To critically review proteomic biomarkers discovered from biological specimens from systemic sclerosis patients using mass spectrometry technologies. Medline and Embase databases were searched in February 2014. Out of the 199 records retrieved, a total of 20 records were included, identifying 116 candidate proteomic biomarkers. Research in SSc proteomic biomarkers should focus on biomarker validation, as there are valuable mass-spectrometry proteomics studies in the literature.

  6. 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.

  7. [Silica-associated systemic sclerosis occurring after an occupational exposure to arc welding].

    Science.gov (United States)

    Alaya, Zeineb; Kalboussi, Houda; Osman, Walid; Naouar, Nader; Zeglaoui, Héla; Bouajina, Elyès

    2016-01-01

    Crystalline silica-associated systemic sclerosis can occur in people operating arc welding. Diffuse scleroderma was diagnosed in a 57-year old plumber-welder suffering from inflammatory polyarthralgias, Raynaud's phenomenon, sclerodactyly, diffuse cutaneous scleroderma, telangiectasias, esophageal damage, pulmonary arterial hypertension and pulmonary fibrosis associated with the presence of anti-nucleosome antibodies. During his professional activity the patient was frequently exposed to high atmospheric concentrations of crystalline silica generated by arc-welding. The diagnosis of Erasmus syndrome associated with systemic sclerosis and pulmonary silicosis was retained. A report of work-related illness (table 17 in Tunisia) was made.

  8. 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

  9. An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis

    DEFF Research Database (Denmark)

    Denton, C P; Engelhart, M; Tvede, N

    2008-01-01

    /kg). Clinical assessment included skin sclerosis score, scleroderma health assessment questionnaire, self-reported functional score and physician global visual analogue scale. Collagen turnover, skin biopsy analysis and full safety evaluation were performed. RESULTS: There was no significant change in skin......AIM: The safety and potential efficacy of a chimaeric anti-tumour necrosis factor alpha monoclonal antibody (infliximab) were examined in diffuse cutaneous systemic sclerosis (dcSSc). METHODS: A 26-week open-label pilot study in which 16 cases of dcSSc received five infusions of infliximab (5 mg.......025). CONCLUSION: In dcSSc infliximab did not show clear benefit at 26 weeks but was associated with clinical stabilisation and a fall in two laboratory markers of collagen synthesis. The frequency of suspected infusion reactions may warrant additional immunosuppression in any future studies in systemic sclerosis....

  10. 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...

  11. Scheduling lessons learned from the Autonomous Power System

    Science.gov (United States)

    Ringer, Mark J.

    1992-01-01

    The Autonomous Power System (APS) project at NASA LeRC is designed to demonstrate the applications of integrated intelligent diagnosis, control, and scheduling techniques to space power distribution systems. The project consists of three elements: the Autonomous Power Expert System (APEX) for Fault Diagnosis, Isolation, and Recovery (FDIR); the Autonomous Intelligent Power Scheduler (AIPS) to efficiently assign activities start times and resources; and power hardware (Brassboard) to emulate a space-based power system. The AIPS scheduler was tested within the APS system. This scheduler is able to efficiently assign available power to the requesting activities and share this information with other software agents within the APS system in order to implement the generated schedule. The AIPS scheduler is also able to cooperatively recover from fault situations by rescheduling the affected loads on the Brassboard in conjunction with the APEX FDIR system. AIPS served as a learning tool and an initial scheduling testbed for the integration of FDIR and automated scheduling systems. Many lessons were learned from the AIPS scheduler and are now being integrated into a new scheduler called SCRAP (Scheduler for Continuous Resource Allocation and Planning). This paper will service three purposes: an overview of the AIPS implementation, lessons learned from the AIPS scheduler, and a brief section on how these lessons are being applied to the new SCRAP scheduler.

  12. 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.

  13. Update of EULAR recommendations for the treatment of systemic sclerosis.

    Science.gov (United States)

    Kowal-Bielecka, Otylia; Fransen, Jaap; Avouac, Jerome; Becker, Mike; Kulak, Agnieszka; Allanore, Yannick; Distler, Oliver; Clements, Philip; Cutolo, Maurizio; Czirjak, Laszlo; Damjanov, Nemanja; Del Galdo, Francesco; Denton, Christopher P; Distler, Jörg H W; Foeldvari, Ivan; Figelstone, Kim; Frerix, Marc; Furst, Daniel E; Guiducci, Serena; Hunzelmann, Nicolas; Khanna, Dinesh; Matucci-Cerinic, Marco; Herrick, Ariane L; van den Hoogen, Frank; van Laar, Jacob M; Riemekasten, Gabriela; Silver, Richard; Smith, Vanessa; Sulli, Alberto; Tarner, Ingo; Tyndall, Alan; Welling, Joep; Wigley, Frederic; Valentini, Gabriele; Walker, Ulrich A; Zulian, Francesco; Müller-Ladner, Ulf

    2017-08-01

    The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help

  14. 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

    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 po...

  15. Human parvovirus B19 (B19V) infection in systemic sclerosis patients

    DEFF Research Database (Denmark)

    Zakrzewska, K.; Corcioli, F.; Carlsen, Karen Marie

    2009-01-01

    BACKGROUND: Our previous reports suggested a possible association between parvovirus B19 (B19V) infection and systemic sclerosis (SSc), based on higher prevalence of B19V DNA in SSc patients in respect to controls. METHODS: In the present study, to further evaluate the differences in the pattern...

  16. 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...

  17. Assessment of light touch sensation in the hands of systemic sclerosis patients

    Directory of Open Access Journals (Sweden)

    Paula Gabriel Silva

    2014-09-01

    Full Text Available INTRODUCTION: Systemic sclerosis is a relatively rare connective tissue disorder characterized by severe and progressive fibrosis of the skin. Due to the current lack of available information on this subject, the aim of the present study was to assess light touch sensations in the hands of patients with systemic sclerosis. METHODS: We completed a cross-sectional comparative study. Light touch sensations were evaluated in 30 individuals, including 15 patients with systemic sclerosis who exhibited changes in the dermis of their hands without loss of the distal phalanx and 15 subjects who did not exhibit changes in the upper limbs (control group. The groups were age- and sex-matched. Tactile sensory evaluations were performed using the Semmes-Weinstein monofilament test and the two-point discrimination test. RESULTS: Statistically significant differences were found between groups in the monofilament test. The study group had lower scores across all points of the hand when compared with the control group. Differences were also found when dominant and non-dominant hands were compared (p<0.05. Statistically significant differences were found between groups for a subset of the assessed points in the two-point discrimination test. CONCLUSIONS: The results of a monofilament test showed that tactile sensation, specifically light touch and deep pressure sensations, is altered in the hands of systemic sclerosis patients.

  18. 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...

  19. Altered B lymphocyte homeostasis and functions in systemic sclerosis.

    Science.gov (United States)

    Forestier, Alexandra; Guerrier, Thomas; Jouvray, Mathieu; Giovannelli, Jonathan; Lefèvre, Guillaume; Sobanski, Vincent; Hauspie, Carine; Hachulla, Eric; Hatron, Pierre-Yves; Zéphir, Hélène; Vermersch, Patrick; Labalette, Myriam; Launay, David; Dubucquoi, Sylvain

    2018-03-01

    Beyond the production of autoantibodies, B-cells are thought to play a role in systemic sclerosis (SSc) by secreting proinflammatory/profibrotic cytokines. B-cells are a heterogeneous population with different subsets distinguished by their phenotypes and cytokine production. Data about B-cell subsets, cytokine production and intracellular pathways leading to this production are scarce in SSc. The aim of our study was to describe B-cell homeostasis, activation, proliferation, cytokine production in B-cells and serum and B-cell intracellular signaling pathways in SSc. We hypothezided that B-cell homeostasis and cytokine production were altered in SSc and could be explained by serum cytokine as well as by intracellular signaling pathway abnormalities. Forty SSc patients and 20 healthy controls (HC) were prospectively included. B-cell subsets were determined by flow cytometry using CD19, CD21, CD24, CD38, CD27, IgM and IgD. CD25, CD80, CD95, HLA-DR were used to assess B-cell activation. Intracellular production of IL-10 and IL-6 were assessed by flow cytometry after TLR9 and CD40 stimulation. IL-6, IL-10, Ki67, Bcl2 mRNA were quantified in B-cells. Cytokine production was also assessed in sera and supernatants of B-cell culture, using a multiplex approach. Signaling pathways were studied through phosphorylation of mTOR, ERK, STAT3, STAT5 using a flow cytometry approach. We found that SSc patients exhibited an altered peripheral blood B-cell subset distribution, with decreased memory B-cells but increased proportion of naive and CD21 Lo CD38 Lo B-cell subsets. We observed an increased expression of activation markers (CD80, CD95, HLA-DR) on some B-cell subsets, mainly the memory B-cells. Secretion of IL-6, BAFF and CXCL13 were increased in SSc sera. There was no correlation between the peripheral blood B-cell subsets and the serum concentrations of these cytokines. After stimulation, we observed a lower proportion of IL-10 and IL-6 producing B-cells in SSc. Finally, we

  20. 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.

  1. 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.

  2. Lessons learned from the Autonomous Power System

    Science.gov (United States)

    Ringer, Mark J.; Quinn, Todd M.; Merolla, Anthony

    1992-01-01

    The Autonomous Power System (APS) project at the NASA Lewis Research Center is designed to demonstrate the applications of integrated intelligent diagnosis, control and scheduling techniques to space power distribution systems. The project consists of three elements: the Autonomous Power Expert System (APEX) for Fault Diagnosis, Isolation, and Recovery (FDIR); the Autonomous Intelligent Power Scheduler (AIPS) to efficiently assign activities start times and resources; and power hardware (Brassboard) to emulate a space-based power system. The APS project had been through one design iteration. Each of the three elements of the APS project has been designed, tested, and integrated into a complete working system. After these three portions were completed, an evaluation period was initiated. Each piece of the system was critiqued based on individual performance as well as the ability to interact with the other portions of the APS project. These critiques were then used to determine guidelines for new and improved components of the APS system.

  3. System 80+{trademark} standard design incorporates radiation protection lessons learned

    Energy Technology Data Exchange (ETDEWEB)

    Crom, T.D.; Naugle, C.L. [Duke Engineering & Services, Inc., Charlotte, NC (United States); Turk, R.S. [ABB Combustion Engineering Nuclear Power, Windsor, CT (United States)

    1995-03-01

    Many lessons have been learned from the current generation of nuclear plants in the area of radiation protection. The following paper will outline how the lessons learned have been incorporated into the design and operational philosophy of the System 80+{trademark} Standard Design currently under development by ABB Combustion Engineering (ABB-CE) with support from Duke Engineering and Services, Inc. and Stone and Webster Engineering Corporation in the Balance-of-Plant design. The System 80+{trademark} Standard Design is a complete nuclear power plant for national and international markets, designed in direct response to utility needs for the 1990`s, and scheduled for Nuclear Regulatory Commission (NRC) Design Certification under the new standardization rule (10 CFR Part 52). System 80+{trademark} is a natural extension of System 80{sup R} technology, an evolutionary change based on proven Nuclear Steam Supply System (NSSS) in operation at Palo Verde in Arizona and under construction at Yonggwang in the Republic of Korea. The System 80+{trademark} Containment and much of the Balance of Plant design is based upon Duke Power Company`s Cherokee Plant, which was partially constructed in the late 1970`s, but, was later canceled (due to rapid declined in electrical load growth). The System 80+{trademark} Standard Design meets the requirements given in the Electric Power Research Institute (EPRI) Advanced Light Water Reactor (ALWR) Requirements Document. One of these requirements is to limit the occupational exposure to 100 person-rem/yr. This paper illustrates how this goal can be achieved through the incorporation of lessons learned, innovative design, and the implementation of a common sense approach to operation and maintenances practices.

  4. Lessons Learned from the Puerto Rico Battery Energy Storage System

    Energy Technology Data Exchange (ETDEWEB)

    BOYES, JOHN D.; DE ANA, MINDI FARBER; TORRES, WENCESLANO

    1999-09-01

    The Puerto Rico Electric Power Authority (PREPA) installed a distributed battery energy storage system in 1994 at a substation near San Juan, Puerto Rico. It was patterned after two other large energy storage systems operated by electric utilities in California and Germany. The U.S. Department of Energy (DOE) Energy Storage Systems Program at Sandia National Laboratories has followed the progress of all stages of the project since its inception. It directly supported the critical battery room cooling system design by conducting laboratory thermal testing of a scale model of the battery under simulated operating conditions. The Puerto Rico facility is at present the largest operating battery storage system in the world and is successfully providing frequency control, voltage regulation, and spinning reserve to the Caribbean island. The system further proved its usefulness to the PREPA network in the fall of 1998 in the aftermath of Hurricane Georges. The owner-operator, PREPA, and the architect/engineer, vendors, and contractors learned many valuable lessons during all phases of project development and operation. In documenting these lessons, this report will help PREPA and other utilities in planning to build large energy storage systems.

  5. Discovering Architectures from Running Systems: Lessons Learned

    National Research Council Canada - National Science Library

    Yan, Hong; Aldrich, Jonathan; Garlan, David; Kazman, Rick; Schmerl, Bradley

    2004-01-01

    .... In addition, this report describes the current implementation of a tool, called DiscoTect, that uses these mappings, and it shows how DiscoTect can highlight inconsistencies between implementations and architectures. Furthermore, two case studies are provided that illustrate how DiscoTect works and how it can be applied to real-world systems.

  6. CONTRACT LABOUR SYSTEM AND LESSONS FOR POST ...

    African Journals Online (AJOL)

    Shiweda

    2017-02-02

    Feb 2, 2017 ... Various historians have written on contract labour system in. Namibia and have analysed the origins of the institutionalized structure of labour exploitation, central to colonial power and profit (see Clarence-Smith & Moorsom 1975;. Katjavivi 1988; Emmett 1999; Stals 1967). The literature highlights the ...

  7. 'Chronic cerebrospinal venous insufficiency' in multiple sclerosis. Is multiple sclerosis a disease of the cerebrospinal venous outflow system?

    International Nuclear Information System (INIS)

    Wattjes, M.P.; Doepp, F.; Bendszus, M.; Fiehler, J.

    2011-01-01

    Chronic impaired venous outflow from the central nervous system has recently been claimed to be associated with multiple sclerosis (MS) pathology. This resulted in the term chronic cerebrospinal venous insufficiency (CCSVI) in MS. The concept of CCSVI is based on sonography studies showing that impaired venous outflow leading to pathological reflux is almost exclusively present in MS patients but not in healthy controls. Based on these findings, a new pathophysiological concept has been introduced suggesting that chronic venous outflow obstruction and venous reflux in the CNS result in pathological iron depositions leading to inflammation and neurodegeneration. The theory of CCSVI in MS has rapidly generated tremendous interest in the media and among patients and the scientific community. In particular, the potential shift in treatment concepts possibly leading to an interventional treatment approach including balloon angioplasty and venous stent placement is currently being debated. However, results from recent studies involving several imaging modalities have raised substantial concerns regarding the CCSVI concept in MS. In this review article, we explain the concept of CCSVI in MS and discuss this hypothesis in the context of MS pathophysiology and imaging studies which have tried to reproduce or refute this theory. In addition, we draw some major conclusions focusing in particular on the crucial question as to whether interventional treatment options are expedient. In conclusion, the present conclusive data confuting the theory of CCSVI in MS should lead to reluctance with respect to the interventional treatment of possible venous anomalies in MS patients. (orig.)

  8. Rituximab-induced neutropenia in a patient with inflammatory myopathy and systemic sclerosis overlap disease.

    Science.gov (United States)

    Akram, Qasim; Roberts, Mark; Oddis, Chester; Herrick, Arianne; Chinoy, Hector

    2016-01-01

    Rituximab (RTX) is a monoclonal chimeric antibody directed against the CD20 antigen of B lymphocytes. Late onset neutropenia (LON) is a recognised complication of rituximab usually occurring 4 weeks after the last dose and is reported in both haematological and rheumatological conditions. However, it has never been described in a patient with myositis and systemic sclerosis overlap disease. We describe a case of LON in a 54-year-old man who was diagnosed with myositis and then systemic sclerosis overlap disease. It resolved within 7 days, and the patient did not suffer neutropenic sepsis or any other complications. We propose similar mechanisms for LON as described in other conditions and routine blood monitoring in such patients.

  9. Silica-associated limited systemic sclerosis after occupational exposure to calcined diatomaceous earth.

    Science.gov (United States)

    Moisan, Stéphanie; Rucay, Pierre; Ghali, Alaa; Penneau-Fontbonne, Dominique; Lavigne, Christian

    2010-10-01

    Silica-associated systemic sclerosis can occur in persons using calcined diatomaceous earth for filtration purpose. A limited systemic sclerosis was diagnosed in a 52-year-old male winegrower who had a combination of Raynaud's phenomenon, oesophageal dysfunction, sclerodactyly and telangectasia. The anti-centromere antibodies titre was 1/5000. The patient was frequently exposed to high atmospheric concentrations of calcined diatomaceous earth when performing the filtration of wines. Calcined diatomaceous earth is almost pure crystalline silica under the cristobalite form. The diagnosis of silica-associated limited systemic sclerosis after exposure to calcined diatomaceous earth was made. The patient's disease met the medical, administrative and occupational criteria given in the occupational diseases list 22 bis of the agriculture Social Security scheme and thence was presumed to be occupational in origin, without need to be proved. The diagnosis of occupational disease had been recognized by the compensation system of the agricultural health insurance. Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  10. Evaluation of quatitative scintigraphic method in diagnosis of esophagic involvement of Progressive Systemic Sclerosis

    International Nuclear Information System (INIS)

    Von Muehlen, C.A.

    1985-01-01

    Twenty patients with Progressive Systemic Sclerosis are studied by scintigraphic methodology. The esophageal transit method is used for liquid and solid meals. The results are compared with the ones of a control group, without or not gastrintestinal problems but without autoimmune diasese. 99 sup(m)Tc-sulfurcolloid is used as labelling compound. The studies were done in supine and orthostatical position. (M.A.C.) [pt

  11. 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...

  12. Human Systems Integration in Practice: Constellation Lessons Learned

    Science.gov (United States)

    Zumbado, Jennifer Rochlis

    2012-01-01

    NASA's Constellation program provided a unique testbed for Human Systems Integration (HSI) as a fundamental element of the Systems Engineering process. Constellation was the first major program to have HSI mandated by NASA's Human Rating document. Proper HSI is critical to the success of any project that relies on humans to function as operators, maintainers, or controllers of a system. HSI improves mission, system and human performance, significantly reduces lifecycle costs, lowers risk and minimizes re-design. Successful HSI begins with sufficient project schedule dedicated to the generation of human systems requirements, but is by no means solely a requirements management process. A top-down systems engineering process that recognizes throughout the organization, human factors as a technical discipline equal to traditional engineering disciplines with authority for the overall system. This partners with a bottoms-up mechanism for human-centered design and technical issue resolution. The Constellation Human Systems Integration Group (HSIG) was a part of the Systems Engineering and Integration (SE&I) organization within the program office, and existed alongside similar groups such as Flight Performance, Environments & Constraints, and Integrated Loads, Structures and Mechanisms. While the HSIG successfully managed, via influence leadership, a down-and-in Community of Practice to facilitate technical integration and issue resolution, it lacked parallel top-down authority to drive integrated design. This presentation will discuss how HSI was applied to Constellation, the lessons learned and best practices it revealed, and recommendations to future NASA program and project managers. This presentation will discuss how Human Systems Integration (HSI) was applied to NASA's Constellation program, the lessons learned and best practices it revealed, and recommendations to future NASA program and project managers on how to accomplish this critical function.

  13. Altered Dermal Fibroblasts in Systemic Sclerosis Display Podoplanin and CD90.

    Science.gov (United States)

    Nazari, Banafsheh; Rice, Lisa M; Stifano, Giuseppina; Barron, Alexander M S; Wang, Yu Mei; Korndorf, Tess; Lee, Jungeun; Bhawan, Jag; Lafyatis, Robert; Browning, Jeffrey L

    2016-10-01

    Tissue injury triggers the activation and differentiation of multiple cell types to minimize damage and initiate repair processes. In systemic sclerosis, these repair processes appear to run unchecked, leading to aberrant remodeling and fibrosis of the skin and multiple internal organs, yet the fundamental pathological defect remains unknown. We describe herein a transition wherein the abundant CD34(+) dermal fibroblasts present in healthy human skin disappear in the skin of systemic sclerosis patients, and CD34(-), podoplanin(+), and CD90(+) fibroblasts appear. This transition is limited to the upper dermis in several inflammatory skin diseases, yet in systemic sclerosis, it can occur in all regions of the dermis. In vitro, primary dermal fibroblasts readily express podoplanin in response to the inflammatory stimuli tumor necrosis factor and IL-1β. Furthermore, we show that on acute skin injury in both human and murine settings, this transition occurs quickly, consistent with a response to inflammatory signaling. Transitioned fibroblasts partially resemble the cells that form the reticular networks in organized lymphoid tissues, potentially linking two areas of fibroblast research. These results allow for the visualization and quantification of a basic stage of fibroblast differentiation in inflammatory and fibrotic diseases in the skin. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  14. A recombinant topoisomerase I used for autoantibody detection in sera from patients with systemic sclerosis.

    Science.gov (United States)

    Verheijen, R; Van den Hoogen, F; Beijer, R; Richter, A; Penner, E; Habets, W J; van Venrooij, W J

    1990-04-01

    We report the expression of a cDNA clone encoding 695 carboxyl-terminal amino acids of human DNA topoisomerase I (topoI) in Escherichia coli. More than 96% of the anti-HeLa topoI-positive sera from patients with a connective tissue disease displayed also an immunoreactivity with this recombinant protein (the HTopoA protein). Sera from patients with a definite diagnosis systemic sclerosis and reacting with HeLa topoI, all reacted with the HTopoA protein as well. Sera from patients with systemic sclerosis that did not contain anti-topoI antibodies (about 30% of the systemic sclerosis sera), as concluded from HeLa immunoblot, displayed also no immunoreactivity with our recombinant antigen. By expressing different fragments of HTopoA, we were able to assign at least three different autoimmune epitope regions on the HTopoA protein and we show that over a period of 5 years the amount of anti-topoI antibodies against these regions may fluctuate.

  15. [Multiple sclerosis management system 3D. Moving from documentation towards management of patients].

    Science.gov (United States)

    Schultheiss, T; Kempcke, R; Kratzsch, F; Eulitz, M; Pette, M; Reichmann, H; Ziemssen, T

    2012-04-01

    The increasing therapeutic options for relapsing-remitting multiple sclerosis require a specific treatment and risk management to recognize the individual response as well as potential side effects. To switch from pure MS documentation to MS management by implementing a new multiple sclerosis management and documentation tool may be of importance. This article presents the novel computer-based patient management system "multiple sclerosis management system 3D" (MSDS 3D). MSDS 3D allows documentation and visualization of visit schedules and mandatory examinations via defined study modules by integration of data input from patients, attending physicians and MS nurses. It provides forms for the documentation of patient visits as well as clinical and diagnostic findings. Information is collected via interactive touch screens. A specific module which is part of MSDS 3D's current version allows the monthly monitoring of patients under treatment with natalizumab. A checklist covering clinical signs of progressive multifocal leukoencephalopathy (PML) and a detailed questionnaire about the handling of natalizumab in practice have additionally been added. The MS patient management system MSDS 3D has successfully been implemented and is currently being evaluated in a multi-centre setting. Advanced assessment of patient data may allow improvements in clinical practice and research work. The addition of a checklist and a questionnaire into the natalizumab module may support the recognition of PML during its early, treatable course.

  16. Proton spectroscopy study of the masseter in patients with systemic sclerosis

    International Nuclear Information System (INIS)

    Marcucci, Marcelo; Abdala, Nitamar

    2009-01-01

    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)

  17. [Autonomic nervous system alteration in multiple sclerosis patients with urinary symptoms. Clinical, urodynamic and cardiovascular study].

    Science.gov (United States)

    Amarenco, G; Raibaut, P; Hubeaux, K; Jousse, M; Sheikh Ismaël, S; Lapeyre, E

    2013-12-01

    To assess symptoms related to autonomic nervous system alteration in a population of patients suffering from multiple sclerosis (MS) and presenting with urinary symptoms. We investigated 65 patients (mean age 47.5 years) suffering from MS, and presenting with urological dysfunction by means of symptom scores, urodynamic investigation, cardiovascular autonomic function tests (orthostatic hypotension testing, Valsalva test, deep breath test, cold pressor test) and sympathetic skin responses. Forty-five (69%) patients suffered from overactive bladder, 48 (73%) from voiding dysfunction, 14 (21%) from urinary retention and 13 (20%) from fecal incontinence. Urodynamic investigation demonstrated overactive detrusor in 46 (70%) cases, and underactive detrusor in four (6%) cases. Twenty-five (38%) patients had dysautonomia without correlation neither with clinical or urodynamic data, nor gravity of multiple sclerosis (EDSS). In this series, the prevalence of dysautonomia was high in patients suffering from MS and presenting with urinary disorders. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  18. 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.

  19. Demographic and clinical features of autoimmune thyroid disorder in Japanese patients with systemic sclerosis.

    Science.gov (United States)

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

    2014-12-01

    Autoimmune thyroid disorders (AITD) are characterized by the impairment of the thyroid gland as a result of systemic or organ-specific autoimmune disorders, and the presence of antithyroid autoantibodies, such as antithyroglobulin antibody (AbTg) and antithyroid peroxidase antibody (AbTPO). Several studies have reported the association of AITD with systemic sclerosis (SSc). However, none of those studies analyzed the association between AITD and skin sclerosis in SSc patients. The aim of this study was to examine the demographic and clinical features of SSc patients with AITD treated in our department. Of a total of 210 SSc patients, we identified 30 with AITD (14.3%), including 29 with Hashimoto's disease (13.8%) and one patient with Graves' disease (0.5%), indicating that hypothyroidism was more common among SSc patients with AITD. All patients with AITD were female, and anticentromere antibody positivity, the complication of Sjögren's syndrome, severe facial skin sclerosis and atrophy of the thyroid gland were significantly prevalent in SSc patients with AITD. SSc patients with such clinical features may be at high risk of AITD and require regular follow up of thyroid function including ultrasonography and the examination of serum hormone levels to start an early treatment. © 2014 Japanese Dermatological Association.

  20. Central nervous system remyelination in culture — A tool for multiple sclerosis research

    Science.gov (United States)

    Zhang, Hui; Jarjour, Andrew A.; Boyd, Amanda; Williams, Anna

    2011-01-01

    Multiple sclerosis is a demyelinating disease of the central nervous system which only affects humans. This makes it difficult to study at a molecular level, and to develop and test potential therapies that may change the course of the disease. The development of therapies to promote remyelination in multiple sclerosis is a key research aim, to both aid restoration of electrical impulse conduction in nerves and provide neuroprotection, reducing disability in patients. Testing a remyelination therapy in the many and various in vivo models of multiple sclerosis is expensive in terms of time, animals and money. We report the development and characterisation of an ex vivo slice culture system using mouse brain and spinal cord, allowing investigation of myelination, demyelination and remyelination, which can be used as an initial reliable screen to select the most promising remyelination strategies. We have automated the quantification of myelin to provide a high content and moderately-high-throughput screen for testing therapies for remyelination both by endogenous and exogenous means and as an invaluable way of studying the biology of remyelination. PMID:21515259

  1. Central nervous system remyelination in culture--a tool for multiple sclerosis research.

    Science.gov (United States)

    Zhang, Hui; Jarjour, Andrew A; Boyd, Amanda; Williams, Anna

    2011-07-01

    Multiple sclerosis is a demyelinating disease of the central nervous system which only affects humans. This makes it difficult to study at a molecular level, and to develop and test potential therapies that may change the course of the disease. The development of therapies to promote remyelination in multiple sclerosis is a key research aim, to both aid restoration of electrical impulse conduction in nerves and provide neuroprotection, reducing disability in patients. Testing a remyelination therapy in the many and various in vivo models of multiple sclerosis is expensive in terms of time, animals and money. We report the development and characterisation of an ex vivo slice culture system using mouse brain and spinal cord, allowing investigation of myelination, demyelination and remyelination, which can be used as an initial reliable screen to select the most promising remyelination strategies. We have automated the quantification of myelin to provide a high content and moderately-high-throughput screen for testing therapies for remyelination both by endogenous and exogenous means and as an invaluable way of studying the biology of remyelination. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. 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

  3. Novel Neuroprotective Multicomponent Therapy for Amyotrophic Lateral Sclerosis Designed by Networked Systems.

    Directory of Open Access Journals (Sweden)

    Mireia Herrando-Grabulosa

    Full Text Available Amyotrophic Lateral Sclerosis is a fatal, progressive neurodegenerative disease characterized by loss of motor neuron function for which there is no effective treatment. One of the main difficulties in developing new therapies lies on the multiple events that contribute to motor neuron death in amyotrophic lateral sclerosis. Several pathological mechanisms have been identified as underlying events of the disease process, including excitotoxicity, mitochondrial dysfunction, oxidative stress, altered axonal transport, proteasome dysfunction, synaptic deficits, glial cell contribution, and disrupted clearance of misfolded proteins. Our approach in this study was based on a holistic vision of these mechanisms and the use of computational tools to identify polypharmacology for targeting multiple etiopathogenic pathways. By using a repositioning analysis based on systems biology approach (TPMS technology, we identified and validated the neuroprotective potential of two new drug combinations: Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine. In addition, we estimated their molecular mechanisms of action in silico and validated some of these results in a well-established in vitro model of amyotrophic lateral sclerosis based on cultured spinal cord slices. The results verified that Aliretinoin and Pranlukast, and Aliretinoin and Mefloquine promote neuroprotection of motor neurons and reduce microgliosis.

  4. 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.

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

    International Nuclear Information System (INIS)

    Kim, Ho Kyun; Lee, Hui Joong

    2013-01-01

    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.

  6. A systemic sclerosis and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci

    Science.gov (United States)

    Martin, Jose-Ezequiel; Assassi, Shervin; Diaz-Gallo, Lina-Marcela; Broen, Jasper C.; Simeon, Carmen P.; Castellvi, Ivan; Vicente-Rabaneda, Esther; Fonollosa, Vicente; Ortego-Centeno, Norberto; González-Gay, Miguel A.; Espinosa, Gerard; Carreira, Patricia; Camps, Mayte; Sabio, Jose M.; D'alfonso, Sandra; Vonk, Madelon C.; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; Kreuter, Alexander; Witte, Torsten; Riemekasten, Gabriella; Hunzelmann, Nicolas; Airo, Paolo; Beretta, Lorenzo; Scorza, Raffaella; Lunardi, Claudio; Van Laar, Jacob; Chee, Meng May; Worthington, Jane; Herrick, Arianne; Denton, Christopher; Fonseca, Carmen; Tan, Filemon K.; Arnett, Frank; Zhou, Xiaodong; Reveille, John D.; Gorlova, Olga; Koeleman, Bobby P.C.; Radstake, Timothy R.D.J.; Vyse, Timothy; Mayes, Maureen D.; Alarcón-Riquelme, Marta E.; Martin, Javier

    2013-01-01

    Systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) are two archetypal systemic autoimmune diseases which have been shown to share multiple genetic susceptibility loci. In order to gain insight into the genetic basis of these diseases, we performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication stage including additional SSc and SLE cohorts. This increased the sample size to a total of 21 109 (6835 cases and 14 274 controls). We selected for replication 19 SNPs from the GWAS data. We were able to validate KIAA0319L (P = 3.31 × 10−11, OR = 1.49) as novel susceptibility loci for SSc and SLE. Furthermore, we also determined that the previously described SLE susceptibility loci PXK (P = 3.27 × 10−11, OR = 1.20) and JAZF1 (P = 1.11 × 10−8, OR = 1.13) are shared with SSc. Supporting these new discoveries, we observed that KIAA0319L was overexpressed in peripheral blood cells of SSc and SLE patients compared with healthy controls. With these, we add three (KIAA0319L, PXK and JAZF1) and one (KIAA0319L) new susceptibility loci for SSc and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity. PMID:23740937

  7. Lessons learned on the Ground Test Accelerator control system

    Energy Technology Data Exchange (ETDEWEB)

    Kozubal, A.J.; Weiss, R.E.

    1994-09-01

    When we initiated the control system design for the Ground Test Accelerator (GTA), we envisioned a system that would be flexible enough to handle the changing requirements of an experimental project. This control system would use a developers` toolkit to reduce the cost and time to develop applications for GTA, and through the use of open standards, the system would accommodate unforeseen requirements as they arose. Furthermore, we would attempt to demonstrate on GTA a level of automation far beyond that achieved by existing accelerator control systems. How well did we achieve these goals? What were the stumbling blocks to deploying the control system, and what assumptions did we make about requirements that turned out to be incorrect? In this paper we look at the process of developing a control system that evolved into what is now the ``Experimental Physics and Industrial Control System`` (EPICS). Also, we assess the impact of this system on the GTA project, as well as the impact of GTA on EPICS. The lessons learned on GTA will be valuable for future projects.

  8. Improvement of peripheral artery disease with Sildenafil and Bosentan combined therapy in a patient with limited cutaneous systemic sclerosis

    Science.gov (United States)

    Omarjee, Loukman; Fontaine, Cedric; Mahe, Guillaume; Jaquinandi, Vincent

    2017-01-01

    Abstract Rationale: Sildenafil, a phosphodiesterase-5-inhibitor and Bosentan, an endothelin-1-receptor antagonist combined therapy could have beneficial effect in systemic sclerosis (SSc) patients with peripheral artery disease. Patient concerns: We report a case of a 48-year-old Black woman, who developed severe left limb claudication and walking limitation following a left femoropopliteal bypass occlusion in 2014. She was a heavy smoker and had a history of right middle cerebral artery ischemic stroke and bilateral Raynaud phenomenon. Diagnoses: According to the American College of Rheumatology/European League Against Rheumatism-2013 criteria, diagnosis of limited cutaneous SSc was retained with macrovascular lesions. She was referred for investigation of left limb claudication on treadmill using transcutaneous oxygen pressure measurement during exercise to argue for the vascular origin of the walking impairment. She had a severe left limb ischemia and the maximum walking distance (MWD) she reached was 118 m in March 2015 despite the medical optimal treatment and walking rehabilitation. Interventions: Sildenafil, 20 mg tid, was introduced due to active digital ulcers. In July 2015, the MWD increased to 288 m, then to 452 m in December 2015. Adding Bosentan to Sildenafil to prevent recurrent digital ulcers resulted in an MWD of 1576 m. Outcomes: Recently, the patient is treated with the combined therapy. She has no more pain during walking and his quality of life has improved. Lessons: Sildenafil and Bosentan combined therapy was associated in our case with an improvement of MWD without adverse effect. Further clinical trials are necessary to confirm our original observation. PMID:28640077

  9. Dexamethasone pulse therapy in patients of systemic sclerosis: Is it a viable proposition? A study from kashmir

    Directory of Open Access Journals (Sweden)

    Sameem Farah

    2010-01-01

    Full Text Available Background: Systemic sclerosis is a multisystemic autoimmune disorder. Intravenous dexamethasone pulse therapy has been used since 1998. Aim: The aim was to report the beneficial effects of dexamethasone pulse in patients of systemic sclerosis vis-á-vis the side effects. Materials and Methods: Forty-seven patients of systemic sclerosis were included. After looking at the history and physical examination, the patients were submitted to various relevant investigations. Clinical scoring of the patient was done at baseline and 6-month interval according to Furst′s organ indices score. Results: A total of 47 patients of systemic sclerosis were included (45 females, 2 males. In majority, acrosclerosis was seen. Severe sclerosis and contractures were seen in two patients. Moderate proteinuria, restrictive lung disease, dysphagia, and valvular heart involvement were seen. A total of 13 patients on dexamethasone pulse therapy developed tuberculosis. Improvement in skin scoring and decreased severity of Raynaud′s phenomenon was seen. No improvement in dysphagia, severe vascular symptoms, or restrictive lung disease was seen. Conclusion: Thus, beneficial effects of dexamethasone pulse therapy seem to be merely cosmetic.

  10. Lessons learned from the MIT Tara control and data system

    International Nuclear Information System (INIS)

    Gaudreau, M.P.J.; Sullivan, J.D.; Fredian, T.W.; Irby, J.H.; Karcher, C.A.; Rameriz, R.A.; Sevillano, E.; Stillerman, J.A.; Thomas, P.

    1987-10-01

    The control and data system of the MIT Tara Tandem Mirror has worked successfully throughout the lifetime of the experiment (1983 through 1987). As the Tara project winds down, it is appropriate to summarize the lessons learned from the implementation and operation of the control and data system over the years and in its final form. The control system handled ∼2400 I/0 points in real time throughout the 5 to 10 minute shot cycle while the data system, in near real time, handled ∼1000 signals with a total of 5 to 7 Mbytes of data each shot. The implementation depended upon a consistent approach based on separating physics and engineering functions and on detailed functional diagrams with narrowly defined cross communication. This paper is a comprehensive treatment of the principal successes, residual problems, and dilemmas that arose from the beginning until the final hardware and software implementation. Suggestions for future systems of either similar size or of larger scale such as CIT are made in the conclusion. 11 refs., 1 fig

  11. 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

  12. Bilateral vocal fold immobility in a patient with overlap syndrome rheumatoid arthritis/systemic sclerosis.

    Science.gov (United States)

    Ingegnoli, Francesca; Galbiati, Valentina; Bacciu, Andrea; Zeni, Silvana; Fantini, Flavio

    2007-10-01

    Bilateral vocal fold immobility (BVFI) can be the result of a primary disorder or as an iatrogenic complication of surgery or intubation. Laryngeal involvement can be a rare complication of connective tissue disorders and it usually occurs in association with other symptoms and signs that indicate active disease. We present a case of BVFI in a patient with an overlap syndrome rheumatoid arthritis/systemic sclerosis, referred to our division because of dysphonia and dyspnea. The video-laryngostroboscopy showed the presence of BVFI. Physical examination, blood tests, lung and neck high resolution computed tomography scans did not demonstrate significant abnormalities. She was treated with pulses of intravenous methylprednisolone with slow improvement.

  13. 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 tissue injury, stress and some neurodegenerative diseases, which have been postulated to play a neuroprotective role. In fact, MT-I+II-deficient mice are more susceptible to developing experimental autoimmune encephalomyelitis (EAE), and treatment of Lewis rats with Zn-MT-II reduces EAE severity. We show...

  14. Risk factors for severity and manifestations in systemic sclerosis and prediction of disease course.

    Science.gov (United States)

    Becker, Mike O; Riemekasten, Gabriela

    2016-01-01

    Systemic sclerosis (SSc, or scleroderma) is a rheumatic disease with distinct features that encompass autoimmunity, vascular lesions (vasculopathy) and tissue fibrosis. The disease has a high morbidity and mortality compared with other rheumatic diseases. This review discusses risk factors and markers that predict the disease course and the occurrence of disease manifestations, with an emphasis on major organ involvement. In addition, risk factors will be described that are associated with mortality in SSc patients. The review addresses the impact of recent developments on screening, diagnosis and risk stratification as well as the need for further research where data are lacking.

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

    African Journals Online (AJOL)

    Background: Dysphagia is common in inflammatory myopathies and usually responds to corticosteroids. Severe dysphagia requiring feeding by percutaneous endoscopic gastrostomy is associated with significant morbidity and high mortality. Clinical case: A 56-year old African Black woman initially presented with systemic ...

  16. [Treatment and course of a man with systemic sclerosis before and after hematopoetic blood stem cell transplantation].

    Science.gov (United States)

    Blank, N; Lorenz, H M

    2013-09-01

    A 66-year-old patient presented in our clinic with increasing painful swelling of his hands, whole body stiffness, weight loss and dyspnoea upon exercise. The physical examination revealed a marked skin sclerosis of hands, extremities and the face. Fist closure was impossible. Pulmonary CT scan showed lung fibrosis and ground glass opacities. Antinuclear antibodies and antibodies against Scl70 were positive. CRP, LDH, NT-Pro-BNP were elevated. A diffuse cutaneous systemic sclerosis with an active interstitial pneumonia and lung fibrosis was diagnosed. Three pulses of cyclophosphamide 1.4 g every three weeks were ineffective to halt the progression of skin sclerosis, joint contractures and decline of pulmonary function. Mobilisation chemotherapy was initialized and blood stem cells were harvested. Blood stem cells were reinfused after myeloablative chemotherapy with melphalan. A maintainance therapy with mycophenolic acid was initiated after recovery of hematopoiesis. Six months after blood stem cell transplantation a decrease of skin sclerosis and an increasing recovery of joint mobility and physical strength was observed. Patients with a progressive systemic sclerosis and further risk factors should be treated with high-dose chemotherapy with blood stem cell transplantation before organ function is severely compromised. In cases with contraindications against cyclophosphamide or anti-thymocyte-globulin melphalan can be discussed as an alternative. © Georg Thieme Verlag KG Stuttgart · New York.

  17. 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

  18. 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.

  19. Reduced levels of S-nitrosothiols in plasma of patients with systemic sclerosis and Raynaud's phenomenon

    Science.gov (United States)

    Kundu, Devi; Abraham, David; Black, Carol M.; Denton, Christopher P.; Bruckdorfer, K. Richard

    2014-01-01

    Objective S-Nitrosothiols (RSNOs) are bioactive forms of nitric oxide which are involved in cell signalling and redox regulation of vascular function. Circulating S-nitrosothiols are predominantly in the form of S-nitrosoalbumin. In this study plasma concentrations of S-nitrosothiols were measured in patients with systemic sclerosis (SSc) where NO metabolism is known to be abnormal. Patients and methods Venous blood was collected from 16 patients with Raynaud's phenomenon (RP), 45 with systemic sclerosis (SSc) (34 patients had limited SSc (IcSSc) and 11 diffuse cutaneous disease (dcSSc)). Twenty six healthy subjects were used as controls. Plasma S-nitrosothiol concentrations were measured by chemiluminescence. The measurements were related to the extent of biological age, capillary/skin scores and disease duration. Results Plasma RSNO levels in patients with Raynaud's phenomenon (RP) and in those with SSc was significantly lower compared to the concentrations in control subjects. In SSc, plasma S-nitrosothiols were often below the level of detection (1nM). Conclusions Low S-nitrosothiol concentrations were observed in the blood of patients with SSc and patients with RP indicating a profound disturbance of nitric oxide metabolism. PMID:25446164

  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....... Juvenile-onset SSc showed scleroderma pattern more frequently than adult-onset SSc (93.3% and 88%). The OR was 2.44 and 95% CI 0.57-10.41. An active scleroderma pattern was present in 58% of juvenile- and 61% of adult-onset SSc. The OR was 0.91 and 95% CI 0.28-2.93. The late scleroderma pattern was present...... 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. 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.

  2. Multiple sclerosis documentation system (MSDS): moving from documentation to management of MS patients.

    Science.gov (United States)

    Ziemssen, Tjalf; Kempcke, Raimar; Eulitz, Marco; Großmann, Lars; Suhrbier, Alexander; Thomas, Katja; Schultheiss, Thorsten

    2013-09-01

    The long disease duration of multiple sclerosis and the increasing therapeutic options require a individualized therapeutic approach which should be carefully documented over years of observation. To switch from MS documentation to an innovative MS management, new computer- and internet-based tools could be implemented as we could demonstrate with the novel computer-based patient management system "multiple sclerosis management system 3D" (MSDS 3D). MSDS 3D allows documentation and management of visit schedules and mandatory examinations via defined study modules by integration of data input from various sources (patients, attending physicians and MS nurses). It provides forms for the documentation of patient visits as well as clinical and diagnostic findings. Information can be collected via interactive touch screens. Specific modules allow the management of highly efficacious treatments as natalizumab or fingolimod. MSDS can be used to transfer the documented data to databases as, e.g. the registry of the German MS society or REGIMS. MSDS has already been implemented successfully in clinical practice and is currently being evaluated in a multicenter setting. High-quality management and documentation are crucial for improvements in clinical practice and research work.

  3. Physiologic abnormalities of cardiac function in progressive systemic sclerosis with diffuse scleroderma

    International Nuclear Information System (INIS)

    Follansbee, W.P.; Curtiss, E.I.; Medsger, T.A. Jr.; Steen, V.D.; Uretsky, B.F.; Owens, G.R.; Rodnan, G.P.

    1984-01-01

    To investigate cardiopulmonary function in progressive systemic sclerosis with diffuse scleroderma, we studied 26 patients with maximal exercise and redistribution thallium scans, rest and exercise radionuclide ventriculography, pulmonary-function testing, and chest roentgenography. Although only 6 patients had clinical evidence of cardiac involvement, 20 had abnormal thallium scans, including 10 with reversible exercise-induced defects and 18 with fixed defects (8 had both). Seven of the 10 patients who had exercise-induced defects and underwent cardiac catheterization had normal coronary angiograms. Mean resting left ventricular ejection fraction and mean resting right ventricular ejection fraction were lower in patients with post-exercise left ventricular thallium defect scores above the median (59 +/- 13 per cent vs. 69 +/- 6 per cent, and 36 +/- 12 per cent vs. 47 +/- 7 per cent, respectively). The authors conclude that in progressive systemic sclerosis with diffuse scleroderma, abnormalities of myocardial perfusion are common and appear to be due to a disturbance of the myocardial microcirculation. Both right and left ventricular dysfunction appear to be related to this circulatory disturbance, suggesting ischemically mediated injury

  4. Implementing a regional oncology information system: approach and lessons learned.

    Science.gov (United States)

    Evans, W K; Ashbury, F D; Hogue, G L; Smith, A; Pun, J

    2014-10-01

    Paper-based medical record systems are known to have major problems of inaccuracy, incomplete data, poor accessibility, and challenges to patient confidentiality. They are also an inefficient mechanism of record-sharing for interdisciplinary patient assessment and management, and represent a major problem for keeping current and monitoring quality control to facilitate improvement. To address those concerns, national, regional, and local health care authorities have increased the pressure on oncology practices to upgrade from paper-based systems to electronic health records. Here, we describe and discuss the challenges to implementing a region-wide oncology information system across four independent health care organizations, and we describe the lessons learned from the initial phases that are now being applied in subsequent activities of this complex project. The need for change must be shared across centres to increase buy-in, adoption, and implementation. It is essential to establish physician leadership, commitment, and engagement in the process. Work processes had to be revised to optimize use of the new system. Culture change must be included in the change management strategy. Furthermore, training and resource requirements must be thoroughly planned, implemented, monitored, and modified as required for effective adoption of new work processes and technology. Interfaces must be established with multiple existing electronic systems across the region to ensure appropriate patient flow. Periodic assessment of the existing project structure is necessary, and adjustments are often required to ensure that the project meets its objectives. The implementation of region-wide oncology information systems across different health practice locations has many challenges. Leadership is essential. A strong, collaborative information-sharing strategy across the region and with the supplier is essential to identify, discuss, and resolve implementation problems. A structure

  5. Cannabinoids inhibit fibrogenesis in diffuse systemic sclerosis fibroblasts.

    Science.gov (United States)

    Garcia-Gonzalez, Estrella; Selvi, Enrico; Balistreri, Epifania; Lorenzini, Sauro; Maggio, Roberta; Natale, Maria-Rita; Capecchi, Pier-Leopoldo; Lazzerini, Pietro-Enea; Bardelli, Marco; Laghi-Pasini, Franco; Galeazzi, Mauro

    2009-09-01

    It has been demonstrated that the endocannabinoid system is up-regulated in pathologic fibrosis and that modulation of the cannabinoid receptors might limit the progression of uncontrolled fibrogenesis. The aim of this study was to investigate whether the synthetic cannabinoid receptor agonist WIN55,212-2 could modulate fibrogenesis in an in vitro model of dcSSc. The expression of cannabinoid receptors CB1 and CB2 was assessed in dcSSc fibroblasts and healthy control fibroblasts. To investigate the effect of WIN55,212-2 on dcSSc fibrogenesis, we studied type I collagen, profibrotic cytokines, fibroblast transdifferentiation into myofibroblasts, apoptotic processes and activation of the extracellular signal-related kinase 1/2 pathway prior to and after the treatment with the synthetic cannabinoid at increasing concentrations. Both CB1 and CB2 receptors were over-expressed in dcSSc fibroblasts compared with healthy controls. WIN55,212-2 caused a reduction in extracellular matrix deposition and counteracted several behavioural abnormalities of scleroderma fibroblasts including transdifferentiation into myofibroblasts and resistance to apoptosis. The anti-fibrogenic effect of WIN55,212-2 was not reverted by selective cannabinoid antagonists. Our preliminary findings suggest that cannabinoids are provided with an anti-fibrotic activity, thereby possibly representing a new class of agents targeting fibrosis diseases.

  6. Progressive multiple sclerosis: from pathogenic mechanisms to treatment.

    Science.gov (United States)

    Correale, Jorge; Gaitán, María I; Ysrraelit, María C; Fiol, Marcela P

    2017-03-01

    During the past decades, better understanding of relapsing-remitting multiple sclerosis disease mechanisms have led to the development of several disease-modifying therapies, reducing relapse rates and severity, through immune system modulation or suppression. In contrast, current therapeutic options for progressive multiple sclerosis remain comparatively disappointing and challenging. One possible explanation is a lack of understanding of pathogenic mechanisms driving progressive multiple sclerosis. Furthermore, diagnosis is usually retrospective, based on history of gradual neurological worsening with or without occasional relapses, minor remissions or plateaus. In addition, imaging methods as well as biomarkers are not well established. Magnetic resonance imaging studies in progressive multiple sclerosis show decreased blood-brain barrier permeability, probably reflecting compartmentalization of inflammation behind a relatively intact blood-brain barrier. Interestingly, a spectrum of inflammatory cell types infiltrates the leptomeninges during subpial cortical demyelination. Indeed, recent magnetic resonance imaging studies show leptomeningeal contrast enhancement in subjects with progressive multiple sclerosis, possibly representing an in vivo marker of inflammation associated to subpial demyelination. Treatments for progressive disease depend on underlying mechanisms causing central nervous system damage. Immunity sheltered behind an intact blood-brain barrier, energy failure, and membrane channel dysfunction may be key processes in progressive disease. Interfering with these mechanisms may provide neuroprotection and prevent disability progression, while potentially restoring activity and conduction along damaged axons by repairing myelin. Although most previous clinical trials in progressive multiple sclerosis have yielded disappointing results, important lessons have been learnt, improving the design of novel ones. This review discusses mechanisms involved

  7. Heritage Systems Engineering Lessons from NASA Deep Space Missions

    Science.gov (United States)

    Barley, Bryan; Newhouse, Marilyn; Clardy, Dennon

    2010-01-01

    In the design and development of complex spacecraft missions, project teams frequently assume the use of advanced technology systems or heritage systems to enable a mission or reduce the overall mission risk and cost. As projects proceed through the development life cycle, increasingly detailed knowledge of the advanced and heritage systems within the spacecraft and mission environment identifies unanticipated technical issues. Resolving these issues often results in cost overruns and schedule impacts. The National Aeronautics and Space Administration (NASA) Discovery & New Frontiers (D&NF) Program Office at Marshall Space Flight Center (MSFC) recently studied cost overruns and schedule delays for 5 missions. The goal was to identify the underlying causes for the overruns and delays, and to develop practical mitigations to assist the D&NF projects in identifying potential risks and controlling the associated impacts to proposed mission costs and schedules. The study found that optimistic hardware/software inheritance and technology readiness assumptions caused cost and schedule growth for all five missions studied. The cost and schedule growth was not found to be the result of technical hurdles requiring significant technology development. The projects institutional inheritance and technology readiness processes appear to adequately assess technology viability and prevent technical issues from impacting the final mission success. However, the processes do not appear to identify critical issues early enough in the design cycle to ensure project schedules and estimated costs address the inherent risks. In general, the overruns were traceable to: an inadequate understanding of the heritage system s behavior within the proposed spacecraft design and mission environment; an insufficient level of development experience with the heritage system; or an inadequate scoping of the systemwide impacts necessary to implement an advanced technology for space flight applications

  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......), was developed to study fatigue in MS. It can continuously measure electrocardiogram, body-skin temperature, electromyogram and motions of feet. The goal of this study is to test the ability of distinguishing fatigued MS patients from healthy subjects by the use of FAMOS. This paper presents the realization...... 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. Radioimmunoassay determination of urinary prostaglandins in patients with progressive systemic sclerosis

    International Nuclear Information System (INIS)

    Ramirez P, P.; Erbessd, M.L.; Mares, G.; Recinos, G.; Graef S, A.; Lavalle, C.

    1985-01-01

    The results of urinary determinations of E-2 prostaglandines by radioimmunoassay (RIA) in 24-hour urine are presented for three groups: progressive systemic sclerotic patients with normotension and with elevated or normal APR, progressive systemic sclerotic patients with hypertension and with normal or low APR, control group of normal subjects. In a recent report of progressive systemic sclerosis in patients we demonstrated changes in the urine concentratrion of APR levels, sodium excretion and in total blood volume. Based on these findings we felt the need to perform quantifications of E-2 prostaglandines (PGE-2) in 24-hour recently taken urine samples stored at 70 0 and measure the sodium amounts excreted in the urine. We concluded that urinary determination of E-2 prostaglandines was the most suitable for our study as it allowed the establishment of relationships between APR, aldosterone and metabolic sodium balance. (author)

  10. Reservation Application System Of Private Lesson At Easyspeak Denpasar Based On Web And Android

    Directory of Open Access Journals (Sweden)

    Ferry yudhitama putra

    2016-06-01

    Full Text Available Abstract— English Private lessons institutes are now widely facilitates a person to develop English skills in speaking and writing. Currently the service users private lessons English book private lessons manually, that is by coming directly to the place as well as through the telephone service, but with the operator even then still have difficulties in user validation that requires a long time. To facilitate the user in terms of the reservation, then the system will be built based on web and Android. Development of private lessons reservation application built with PHP and Java programming language using CodeIgniter framework on the web side , while on the Android using Eclipse tools , and MySQL as database storage media . Applications reservation private lessons has several functions to make a reservation time and tutor can be done by the student of Easyspeak and on the side of the tutor application can provide information about the student will be taught , as well as on the side of the operator to provide ease in setting booking private lessons because it computerized not manually as before. Applications reservation private lessons are also equipped with a reminder or reminders are made on the side of Android apps , using alarmmanager system.

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

    International Nuclear Information System (INIS)

    Martin, Abraham; Szczupak, Boguslaw; Arrieta, Ander; Vazquez-Villoldo, Nuria; Soria, Federico N.; Domercq, Maria; Matute, Carlos; Gomez-Vallejo, Vanessa; Llop, Jordi; Padro, Daniel; Plaza-Garcia, Sandra; Reese, Torsten

    2016-01-01

    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 - 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-[ 18 F]Fluoro-2-deoxy-D-glucose ([ 18 F]FDG), [ 11 C]-(R)-1-(2-chlorophenyl)-N-methyl-N-1(1-methylpropyl) -3-isoquinolinecarbox amide ([ 11 C]PK11195) and (4S)-4-(3- 18 F-fluoropropyl)-L-glutamate ([ 18 F]FSPG) were carried out during the course of experimental autoimmune encephalomyelitis (EAE) induction in rats. [ 18 F]FSPG showed a significant increase of system xc - 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, [ 18 F]FDG did not show significant changes in glucose metabolism throughout central nervous system and [ 11 C]PK11195 evidenced a significant increase of microglial/macrophage activation in spinal cord and cerebellum 2 weeks after EAE induction. Therefore, [ 18 F]FSPG showed a major capacity to discriminate regions of the central nervous system affected by the MS in comparison to [ 18 F]FDG and [ 11 C]PK11195. Additionally, clodronate-treated rats showed a depletion in microglial population and [ 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 - could become a valuable tool for the diagnosis and treatment evaluation of MS. (orig.)

  12. 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

  13. 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+

  14. 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.

  15. 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.; et al.,

    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

  16. 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

  17. Distinct evolution of TLR-mediated dendritic cell cytokine secretion in patients with limited and diffuse cutaneous systemic sclerosis.

    NARCIS (Netherlands)

    Bon, L. van; Popa, C.; Huibens, R.J.F.; Vonk, M.C.; York, M.; Simms, R.; Hesselstrand, R.; Wuttge, D.M.; Lafyatis, R.; Radstake, T.R.D.J.

    2010-01-01

    BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease and accumulating evidence suggests a role for Toll-like receptor (TLR)-mediated activation of dendritic cells (DCs). OBJECTIVE: To map TLR-mediated cytokine responses of DCs from patients with SSc. METHODS: 45 patients with SSc were

  18. Critical finger ischemia and myocardial fibrosis development after sudden interruption of sildenafil treatment in a systemic sclerosis patient.

    Science.gov (United States)

    Bruni, C; Bellando-Randone, S; Gargani, L; Picano, E; Pingitore, A; Matucci-Cerinic, M; Guiducci, S

    2016-09-09

    Systemic sclerosis (SSc) is a connective tissue disease frequently associated with Raynaud's Phenomenon (RP). Among possible pharmacological treatments, phosphodiesterase 5 inhibitors are considered in cases of severe non -responsive RP. We present the case of a male SSc patient wh presented with critical finger ischemia and concomitant appearance of myocardial fibrosis after sudden interruption of sildenafil treatment.

  19. 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...

  20. 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

  1. Exercise echocardiography for the assessment of pulmonary hypertension in systemic sclerosis: a systematic review.

    Science.gov (United States)

    Baptista, Rui; Serra, Sara; Martins, Rui; Teixeira, Rogério; Castro, Graça; Salvador, Maria João; Pereira da Silva, José António; Santos, Lèlita; Monteiro, Pedro; Pêgo, Mariano

    2016-07-02

    Pulmonary arterial hypertension (PAH) complicates the course of systemic sclerosis (SSc) and is associated with poor prognosis. The elevation of systolic pulmonary arterial pressure (sPAP) during exercise in patients with SSc with normal resting haemodynamics may anticipate the development of PAH. Exercise echocardiography (ExEcho) has been proposed as a useful technique to identify exercise-induced increases in sPAP, but it is unclear how to clinically interpret these findings. In this systematic review, we summarize the available evidence on the role of exercise echocardiography to estimate exercise-induced elevations in pulmonary and left heart filling pressures in patients with systemic sclerosis. We conducted a systematic review of the literature using MEDLINE, Cochrane Library and Web of Knowledge, using the vocabulary terms: ('systemic sclerosis' OR 'scleroderma') AND ('exercise echocardiography') AND ('pulmonary hypertension'). Studies including patients with SSc without a prior diagnosis of PAH, and subjected to exercise echocardiography were included. All searches were limited to English and were augmented by review of bibliographic references from the included studies. The quality of evidence was assessed by the Effective Public Health Practice Project system. We identified 15 studies enrolling 1242 patients, who were mostly middle-aged and female. Several exercise methods were used (cycloergometer, treadmill and Master's two step), with different protocols and positions (supine, semi-supine, upright); definition of a positive test also varied widely. Resting estimated sPAP levels varied from 18 to 35 mm Hg, all in the normal range. The weighted means for estimated sPAP were 22.2 ± 2.9 mmHg at rest and 43.0 ± 4.3 mmHg on exercise; more than half of the studies reported mean exercise sPAP ≥40 mmHg. The assessment of left ventricular diastolic function on peak exercise was reported in a minority of studies; however, when assessed, surrogate

  2. 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 ...

  3. Two faces of the same coin: Raynaud phenomenon and digital ulcers in systemic sclerosis.

    Science.gov (United States)

    Galluccio, Felice; Matucci-Cerinic, Marco

    2011-03-01

    Systemic sclerosis (SSc) is characterized by wide-spread fibrosis, activation of immune system with production of autoantibodies and extensive vascular damage. Raynaud's phenomenon (RP) and digital ulcers (DU) represent two faces of the same coin in SSc vasculopathy. RP, the earliest manifestation of the vascular involvement, is due to an excessive vasospasm of digital arteries, precapillary arterioles and cutaneous arteriovenous shunts, usually in response to cold exposure or other stimuli. DU are a severe complication of microvessel involvement and also of the persistent vasospasm of RP. Thus, the management of RP and DU requires a multimodal approach using a combination of pharmacological, non-pharmacological, and surgical treatments. Currently, the treatment of these complications represents a great challenge for all physicians. Copyright © 2010 Elsevier B.V. All rights reserved.

  4. 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.

  5. The systemic lupus erythematosus IRF5 risk haplotype is associated with systemic sclerosis.

    Directory of Open Access Journals (Sweden)

    F David Carmona

    Full Text Available 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 this

  6. 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

  7. Isolated pulmonary veno-occlusive disease and pulmonary arterial thrombosis in systemic sclerosis – a lethal combination

    Directory of Open Access Journals (Sweden)

    Arun Jeevagan

    2010-05-01

    Full Text Available Arun JeevaganGeneral Medicine, Ipswich NHS Hospital, UKBackground: Isolated pulmonary hypertension secondary to systemic sclerosis is not uncommon. Our patient with systemic sclerosis presented with a very aggressive form of pulmonary hypertension due to a lethal combination of pulmonary veno-occlusive disease (PVOD and pulmonary arterial thrombosis. This combined presentation has never before been reported in medical literature.Case report: A 75-year-old woman with a 4-month history of atypical chest pains was admitted with a 3-week history of worsening symptoms of shortness of breath, reduced exercise tolerance, and bilateral pitting edema. On examination she had thickened skin in her hands, telangiectasia on her face, maculopapular rash in her legs, raised jugular venous pressure, and bilateral pitting edema. Her autoimmune profile revealed positive anticentromere antibodies, and her echocardiogram showed right ventricular systolic pressure of 91 mmHg. She also had renal impairment secondary to hypoperfusion. A diagnosis of isolated pulmonary hypertension secondary to limited systemic sclerosis was made. As she was clinically improving on slow diuretic infusion and awaiting transfer to a specialist center for management of pulmonary hypertension, our patient died due to cardiopulmonary arrest. Her postmortem revealed that she died of a combination of PVOD and pulmonary arteriopathy due to thrombosis.Conclusion: This is clearly a unique case both in presentation and difficulty of management. Pulmonary vasodilators used in therapy of pulmonary arteriopathy can be detrimental in patients with PVOD. There is no definitive investigation, curative treatment, or management, that exists for a combination of PVOD and pulmonary arteriopathy due to thrombosis secondary to systemic sclerosis.Keywords: pulmonary veno-occlusive disease, pulmonary arterial hypertension, systemic sclerosis, pulmonary arteriopathy with thrombosis

  8. lessons from tuberous sclerosis complex

    African Journals Online (AJOL)

    example here is the relationship between trisomy 21 (Down syndrome) and high rates of Alzheimer's disease, which led to the discovery of the molecular basis of ... Treatment is often inadequate or wrong. For example, a recent case report[13] in the SAMJ was clearly a case of an adolescent with TSC, facial angiofibromas ...

  9. Therapeutic hypothermia after cardiac arrest in a patient with systemic sclerosis and Raynaud phenomenon.

    Science.gov (United States)

    Bakal, Keren; Danckers, Mauricio; Denson, Joshua L; Sauthoff, Harald

    2015-02-01

    Therapeutic hypothermia favorably impacts neurologic outcomes in patients after cardiopulmonary arrest, although the appropriate target temperature is less clear. Its safety profile in patients with systemic sclerosis (SSc) and Raynaud phenomenon (RP), who may be at increased risk for ischemic complications, has not been addressed in the literature, to our knowledge. Digital lesions are commonly seen in patients with SSc, and cold-induced myocardial ischemia has also been reported. We describe a case of a man with SSc, RP, and digital ulcers who underwent therapeutic hypothermia after cardiopulmonary arrest. He regained full neurologic function, and except for digital necrosis, no hypothermia-associated adverse events were observed. Other risk factors for ischemia, such as cocaine use, may have contributed to the development of the digital necrosis. However, clinicians should be aware of the risk for ischemic complications in patients with SSc and RP when considering the appropriate target temperature after cardiopulmonary arrest.

  10. Neuropathic pain in Systemic Sclerosis patients: A cross-sectional study.

    Science.gov (United States)

    Sousa-Neves, Joana; Cerqueira, Marcos; Santos-Faria, Daniela; Afonso, Carmo; Teixeira, Filipa

    2018-01-31

    To investigate if patients with Systemic Sclerosis (SSc) show a higher prevalence of neuropathic pain (NP) in comparison with controls. To study the relationship between clinical variables of the disease and NP among SSc patients. 48 patients and 45 controls were included. Presence of NP was assessed applying the DN4 "Douleur Neuropathique en 4 Questions" questionnaire. Different clinical variables were also assessed in patients. Statistical analysis included parametric, nonparametric tests and multivariate logistic regression. NP was significantly higher in SSc patients (56.2% vs 13.3%, pNP (pNP in SSc patients and controls. These findings should raise the awareness of the clinician to recognize and address the presence of NP in these patients, especially in those with severe skin involvement. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  11. 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.

  12. Potential control of multiple sclerosis by cannabis and the endocannabinoid system.

    Science.gov (United States)

    Pryce, Gareth; Baker, David

    2012-08-01

    For many years, multiple sclerosis (MS) patients have been self-medicating with illegal street cannabis to alleviate symptoms associated with MS. Data from animal models of MS and clinical studies have supported the anecdotal data that cannabis can improve symptoms such as limb spasticity, which are commonly associated with progressive MS, by the modulation of excessive neuronal signalling. This has lead to cannabis-based medicines being approved for the treatment of pain and spasticity in MS for the first time. Experimental studies into the biology of the endocannabinoid system have revealed that cannabinoids have activity, not only in symptom relief but also potentially in neuroprotective strategies which may slow disease progression and thus delay the onset of symptoms such as spasticity. This review appraises the current knowledge of cannabinoid biology particularly as it pertains to MS and outlines potential future therapeutic strategies for the treatment of disease progression in MS.

  13. Analysis of an immunodominant epitope of topoisomerase I in patients with systemic sclerosis.

    Science.gov (United States)

    Meesters, T M; Hoet, M; van den Hoogen, F H; Verheijen, R; Habets, W J; van Venrooij, W J

    1992-05-01

    In this paper an immunodominant epitope of Topoisomerase I is described. An epitope expression sublibrary was constructed from Topoisomerase I cDNA. The subclones were screened with an antiserum from a patient with systemic sclerosis (SSc). The positive clones defined one immunodominant B cell epitope (epitope III), which was located at the carboxyterminal part of the protein. The epitope, 52 amino acids in length, neither contains the p30gag sequence nor the suggested active site Tyr-723, both presumed antibody recognition sites. More than 70% of our anti-TopoI sera recognize this epitope III, indicating that it is a major recognition site of the anti-TopoI autoantibodies in SSc sera. DNA relaxation experiments show that all sera that recognize epitope III and most sera with antibodies to other epitopes inhibit Topoisomerase I activity.

  14. Microvascular damage evaluation in systemic sclerosis: the role of nailfold videocapillaroscopy and laser techniques

    Directory of Open Access Journals (Sweden)

    B. Ruaro

    2017-12-01

    Full Text Available Microvascular damage and a decrease in peripheral blood perfusion are typical features of systemic sclerosis (SSc with serious clinical implications, not only for a very early diagnosis, but also for disease progression. Nailfold videocapillaroscopy is a validated and safe imaging technique able to detect peripheral capillary morphology, as well as to classify and to score any nailfold abnormalities into different microangiopathy patterns. Capillaroscopic analysis is now included in the ACR/EULAR classification criteria for SSc. The decrease in peripheral blood perfusion is usually associated with microvascular damage in SSc, which may be studied by different methods. Several of these make use of safe laser technologies. This paper focuses on these new clinical aspects to assess SSc microvascular impairment.

  15. CD16-positive circulating monocytes and fibrotic manifestations of systemic sclerosis.

    Science.gov (United States)

    Lescoat, Alain; Lecureur, Valérie; Roussel, Mikael; Sunnaram, Béatrice Ly; Ballerie, Alice; Coiffier, Guillaume; Jouneau, Stéphane; Fardel, Olivier; Fest, Thierry; Jégo, Patrick

    2017-07-01

    The objective of this study is to assess the association of clinical manifestations of systemic sclerosis (SSc) with the absolute count of circulating blood monocyte subpopulations according to their membrane expression of CD16. Forty-eight consecutive patients fulfilling the 2013 ACR/EULAR classification criteria for SSc were included in this cross-sectional study. CD16+ monocyte absolute count was defined by flow cytometry and confronted to the clinical characteristics of SSc patients. Twenty-three healthy donors (HD) were randomly selected for comparison. SSc patients had an increased number of total circulating blood monocytes compared to HD (p skin fibrosis evaluated by the modified Rodnan skin score (p manifestations of SSc and their role in the pathogenesis of fibrosis in this autoimmune disorder should therefore be further considered.

  16. Risk of ischemic stroke in patients with systemic sclerosis: A systematic review and meta-analysis.

    Science.gov (United States)

    Ungprasert, Patompong; Sanguankeo, Anawin; Upala, Sikarin

    2016-01-01

    Several chronic inflammatory disorders, such as rheumatoid arthritis and idiopathic inflammatory myositis, have been shown to increase risk of ischemic stroke but the data on systemic sclerosis (SSc) remains unclear. We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing risk of ischemic stroke in patients with SSc versus non-SSc participants. Pooled risk ratio and 95% confidence intervals (CIs) were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. Four retrospective cohort studies were identified and included in our data analysis. We found a statistically significant elevated ischemic stroke risk in patients with SSc with a pooled risk ratio of 1.68 (95% CI, 1.26-2.24). The statistical heterogeneity was moderate with an I(2) of 69%. Our study demonstrated a statistically significant increased ischemic stroke risk among patients with SSc.

  17. 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

    2018-03-01

    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.

  18. 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

  19. The clinical significance of antibody determination to cyclic citrullinated peptides in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Stamenković Bojana

    2012-01-01

    Full Text Available Introduction. Anti-citrullinated peptides antibodies (ACPA are present in 80% of sera of rheumatoid arthritis (RA patients with high specificity for diagnosis and prediction for the development of early erosive arthritis. A few studies have reported a low frequency ACPA in systemic sclerosis (SSc patients with the presence of arthritis. Objective. The aim of our study was to determine the frequency of ACPA in systemic sclerosis (SSc patients, their correlation with clinical manifestations and radiographic features. Methods. The study included 82 patients with SSc, mean age 54.4 years, 59 with the limited (lSSc and 23 with the diffuse (dSSc form of the disease. The control group included 28 healthy age and sex matched subjects. ACPA and rheumatoid factor (RF were determined in all SSc patients and healthy subjects in whom standard radiography of hands and wrists was also done. Results. The presence of ACPA was detected in 11 (13.4% of SSc patients. Their level was not increased in any of the controls. Positive RF was found in 15.9% of SSc patients. Arthritis was present in 17.1%, as well as marginal bone erosions. There was a statistically significant association between positive ACPA and arthritis (p<0.0001 and positive ACPA and marginal bone erosions (p=0.0002. Conclusion. The research confirmed the correlation between ACPA with clinical signs of arthritis and radiographic damage of hand joints. ACPA is a useful diagnostic marker in the identification of SSc patients with arthritis and anatomic bone damage enabling the use of adequate therapy in order to prevent joint damage and poor quality of life.

  20. Hand Impairment in Systemic Sclerosis: Various Manifestations and Currently Available Treatment.

    Science.gov (United States)

    Young, Amber; Namas, Rajaie; Dodge, Carole; Khanna, Dinesh

    2016-09-01

    Systemic sclerosis (SSc) is an autoimmune disease initially recognized by hand involvement due to characteristic Raynaud's phenomenon (RP), puffy hands, skin thickening, and contractures resembling claw deformities. SSc contributes to hand impairment through inflammatory arthritis, joint contractures, tendon friction rubs (TFRs), RP, digital ulcers (DU), puffy hands, skin sclerosis, acro-osteolysis, and calcinosis. These manifestations, which often co-exist, can contribute to difficulty with occupational activities and activities of daily living (ADL), which can result in impaired quality of life. However, despite this knowledge, most diagnostic and treatment principles in SSc are focused on visceral manifestations due to known associations with morbidity and mortality. Treatment of inflammatory arthritis is symptom based and involves corticosteroids ≤10mg daily, methotrexate, tumor necrosis factor inhibitors, tocilizumab, and abatacept. Small joint contractures are managed by principles of occupational hand therapy and rarely surgical procedures. TFRs may be treated similar to inflammatory arthritis with corticosteroids. All patients with RP and DU should keep digits covered and warm and avoid vasoconstrictive agents. Pharmacologic management of RP begins with use of calcium channel blockers, but additional agents that may be considered are fluoxetine and phosphodiesterase 5 (PDE5) inhibitors. DU management also involves vasodilators including calcium channel blockers and PDE5 inhibitors; bosentan has also been shown to prevent DU. In patients with severe RP and active DU, intravenous epoprostenol or iloprost can be used and surgical procedures, such as botulinum injections and digital sympathectomies, may be considered. For those with early diffuse cutaneous SSc needing immunosuppression for skin sclerosis, methotrexate or mycophenolate mofetil can be used, but the agent of choice depends on co-existing manifestations, such as inflammatory arthritis and/or lung

  1. Lesson Plan on Comparative Political Systems: Compare and Contrast the Presidential Election System of the USA to the Parliamentary Election System of Hungary.

    Science.gov (United States)

    O'Connell, Daniel W.

    This lesson describes the current government of Hungary and its underlying political and electoral systems. The lesson is structured with: (1) background on the parliamentary model of government, political parties, and Hungary's unique electoral system; (2) a summary of the six major political parties in Hungary and voter information for the 1990…

  2. 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,

  3. 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,

  4. 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.)

  5. The circulating cell-free microRNA profile in systemic sclerosis is distinct from both healthy controls and systemic lupus erythematosus

    DEFF Research Database (Denmark)

    Steen, Samantha O; Iversen, Line V; Carlsen, Anting Liu

    2015-01-01

    OBJECTIVE: To evaluate the expression profile of cell-free circulating microRNA (miRNA) in systemic sclerosis (SSc), healthy controls (HC), and systemic lupus erythematosus (SLE). METHODS: Total RNA was purified from plasma and 45 different, mature miRNA were measured using quantitative PCR assays...

  6. Lesson Learning at JPL

    Science.gov (United States)

    Oberhettinger, David

    2011-01-01

    A lessons learned system is a hallmark of a mature engineering organization A formal lessons learned process can help assure that valuable lessons get written and published, that they are well-written, and that the essential information is "infused" into institutional practice. Requires high-level institutional commitment, and everyone's participation in gathering, disseminating, and using the lessons

  7. A systems view and lessons from the ongoing Ebola Virus disease ...

    African Journals Online (AJOL)

    This article analyses the on-going (2014) Ebola Virus Disease (EVD) outbreak in West Africa from a systems perspective; and draws out lessons for West Africa in general and Ghana in particular. Keywords: Ebola Virus Disease, West Africa , Ghana , Systems , Prevention and Control ...

  8. National Training Course. Emergency Medical Technician. Paramedic. Instructor's Lesson Plans. Module V. Respiratory System.

    Science.gov (United States)

    National Highway Traffic Safety Administration (DOT), Washington, DC.

    This instructor's lesson plan guide on the respiratory system is one of fifteen modules designed for use in the training of emergency medical technicians (paramedics). Five units of study are presented: (1) anatomy and physiology of the respiratory system; (2) pathophysiology assessment of the patient; (3) pathophysiology and management of…

  9. Clinical and diagnostic significance of activity of enzymes participating in endoergic reactions of patients systemic lupus erythematosus and systemic sclerosis

    Directory of Open Access Journals (Sweden)

    LA Zborovskaya

    2004-01-01

    Full Text Available Objective. To improve quality of diagnosis of systemic lupus erythematosus (SLE and systemic sclerosis (SS. Material and methods. 30 pts with SLE and 30 with SS were included. Besides complex clinical, instrumental and laboratory examination activity and isoenzymes of succinate dehydrogenase (SDG, fumarate hydrase (FH, malate dehydrogenase (MDG, cytochrome oxidase (CO were evaluated trice (at admission, after two weeks and at discharge with original methods. 30 healthy persons were included in the control group. Results. SLE and SS pts had significant changes of energy metabolism enzymes depended on clinical features of the disease. Enzyme indices at minimal activity of SLE and SS were more informative than most of traditional laboratory tests. Comparative analysis of enzyme indices in SLE and SS pts revealed some features with along with clinical, instrumental and traditional laboratory data should be consider in diagnosis of these diseases. Enzyme indices correlated with changes of pts clinical state what allow to use them as criteria of treatment efficacy.

  10. [Evaluation of the equilibrium system in patients with multiple sclerosis based on qualitative assessment with videonystagmography].

    Science.gov (United States)

    Kenig, Dagmara; Kantor, Ireneusz; Jurkiewicz, Dariusz

    2005-09-01

    Multiple sclerosis (SM) is the most frequent inflammatory-demyelinating disease of central nervous system. The character of SM disease provokes that its most frequent symptoms are vertigo, equilibrium disorders and ataxia. Objective method of vertigo estimation is evaluation of the nystagmus via videonystagmography registration (VNG). This examination allows to simultaneously assess the vertical and horizontal component of the nystagmus. It is considered that mainly the vertical nystagmus is characteristic to equilibrium system impairments of the central nervous system, caused also by SM. The study was carried out on 40 patients (28 women, 12 men) with SM diagnosed as a result of neurological examination. 7 patients (17.5%) suffered from sham - movement vertigo, while 33 patients (82.5%) suffered from instability of posture and walking deviation. The videonystagmography examination resulted in the following: deviation of the eye movement was recorded in 26 patients (65%) during either in saccadic test and in smooth pursuit test, optokinetic nystagmus recorded: dissymetric and variable amplitude result in 24 patients (60%), presence of vertical nystagmus component in 30 patients (75%), positional test: directional-changable nystagmus in 8 patients (20%), pendular nystagmus in 4 patients (10%), presence of vertical nystagmus component in 31 patients (77.5%), caloric test: impairments of one of the labyrinth recorded in 12 patients (30%). SM is still the diagnostic and therapeutic problem. During the mentioned tests we have found the quantitative and qualitative changes in VNG recordings. This may be helpful in SM diagnosis, mainly during its early stages.

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

    Science.gov (United States)

    Yu, Fei; Bilberg, Arne; Stenager, Egon; Rabotti, Chiara; Zhang, Bin; Mischi, Massimo

    2012-12-01

    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), was developed to study fatigue in MS. It can continuously measure electrocardiogram, body-skin temperature, electromyogram and motions of feet. The goal of this study is to test the ability of distinguishing fatigued MS patients from healthy subjects by the use of FAMOS. This paper presents the realization 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 differences between fatigued MS patients and healthy controls. In conclusion, the FAMOS enables continuous data acquisition and estimation of multiple physiological and functional parameters. It provides a new, flexible and objective approach to study fatigue in MS, which can distinguish between fatigued MS patients and healthy controls. The usability and reliability of the FAMOS should however be further improved and validated through larger clinical trials.

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

    International Nuclear Information System (INIS)

    Yu, Fei; Bilberg, Arne; Zhang, Bin; Stenager, Egon; Rabotti, Chiara; Mischi, Massimo

    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), was developed to study fatigue in MS. It can continuously measure electrocardiogram, body-skin temperature, electromyogram and motions of feet. The goal of this study is to test the ability of distinguishing fatigued MS patients from healthy subjects by the use of FAMOS. This paper presents the realization 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 differences between fatigued MS patients and healthy controls. In conclusion, the FAMOS enables continuous data acquisition and estimation of multiple physiological and functional parameters. It provides a new, flexible and objective approach to study fatigue in MS, which can distinguish between fatigued MS patients and healthy controls. The usability and reliability of the FAMOS should however be further improved and validated through larger clinical trials. (paper)

  13. Effect of Deep oscillation and Biofeedback on subjective perception of disease and tissue findings in systemic sclerosis

    OpenAIRE

    Sporbeck, Birte

    2011-01-01

    INTRODUCTION: Systemic sclerosis (SSc) is a rare multisystemic autoimmune disease characterised by a broad spectrum of clinical manifestations including different forms of musculoskeletal involvement, skin and vascular changes, as well as internal organ complications. In the therapeutic management of SSc physiotherapy obtained a high value, as skin and joint findings are easily accessible for rehabilitation techniques. They are widely used in clinical practice but to date only a few investiga...

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

    Directory of Open Access Journals (Sweden)

    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.

  15. In systemic sclerosis, anxiety and depression assessed by hospital anxiety depression scale are independently associated with disability and psychological factors.

    OpenAIRE

    Del Rosso, A; Mikhaylova, S; Baccini, M; Lupi, I; Matucci Cerinic, M; Maddali Bongi, S

    2013-01-01

    Background. 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. Methods. 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 d...

  16. 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

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

    Science.gov (United States)

    Horimoto, Alex Magno Coelho; da Costa, Izaias Pereira

    2016-01-01

    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. 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. 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. 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 SSc/RA overlap. Comparing the clinical manifestations among the

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

    Science.gov (United States)

    Horimoto, Alex Magno Coelho; Costa, Izaias Pereira da

    2015-03-04

    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 to 97% of patients with SSc. 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. 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. 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 to 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 SSc/RA overlap. Comparing the clinical manifestations among

  19. Cardiac involvement in undifferentiated connective tissue disease at risk for systemic sclerosis (otherwise referred to as very early-early systemic sclerosis): a TDI study.

    Science.gov (United States)

    D'Alto, Michele; Riccardi, Antonella; Argiento, Paola; Di Stefano, Ilaria; Romeo, Emanuele; Iacono, Agostino Mattera; D'Andrea, Antonello; Fasano, Serena; Sanduzzi, Alessandro; Bocchino, Marialuisa; Docimo, Ludovico; Tolone, Salvatore; Russo, Maria Giovanna; Valentini, Gabriele

    2017-10-09

    Undifferentiated connective tissue disease at risk for systemic sclerosis (UCTD-risk-SSc), otherwise referred to as very early-early SSc, is a condition characterized by Raynaud's phenomenon with serum SSc marker autoantibodies and/or typical capillaroscopic findings and unsatisfying classification criteria for the disease. The aim of the present study was to assess the prevalence of right (RV) or left ventricular (LV) systolic and/or diastolic dysfunction by standard echocardiography and tissue Doppler imaging (TDI). Thirty patients with UCTD-risk-SSc (28 female, mean age 47 ± 13 years, range 21-70) and 30 age- and sex-matched controls underwent cardiac assessment by standard echocardiography and TDI. UCTD-risk-SSc patients and controls did not show any difference at standard echocardiography. Despite results falling within the respective normal ranges, TDI pointed out a mild impairment of LV and RV diastolic (E m 15 ± 4 vs. 19 ± 5, p = 0.0004; E/E m 6.1 ± 1.7 vs. 4.8 ± 1.2, p = 0.001; E t 14 ± 3 vs. 16 ± 2, p = 0.02; E t /A t 0.9 ± 0.4 vs. 1.3 ± 0.3, p = 0.002; E/E t 3.5 ± 1.2 vs. 4.2 ± 0.9, p = 0.02) and systolic function (S m 13 ± 3 vs. 15 ± 2 cm/s, p risk-SSc patients as compared to controls. Notably, a statistically significant difference also emerged in the prevalence of TDI detected E'/A' t , (71% of UCTD-risk-SSc patients vs. 19% of controls; p risk-SSc patients show a previously unrecognized, mild biventricular systolic and diastolic dysfunction as compared to controls. The pathophysiologic meaning as well the predictive value of developing overt SSc await to be elucidated.

  20. Clinical significance of changes of plasma endothelial vasoactive factors contents after treatment in patients with systemic sclerosis (SSc)

    International Nuclear Information System (INIS)

    Wang Chunxi; Han Li'na; Yao Di; Wang Taihan

    2005-01-01

    Objective: To investigate the relationship between endothelial vasoactive factors and development of systemic sclerosis (SSc). Methods: Blood circulating endothelial cell count (CEC, with density gradient precipitation method); plasma endothelin (ET), thromboxane B 2 (TXB 2 ), 6-keto-prostaglandin F 1α concentrations (all above three with RIA); nitric oxide (NO) contents (with Griss method) and plasma intercellular adhesion molecule-1 (ICAM-1), p-selectin (P-S) contents (with ELISA) were measured in 52 patients with systemic sclerosis (SSc) both before and after treatment with prostaglandin E1 and 30 controls. Results: Plasma ET, TXB 2 , ICAM-1, P-S contents and CEC were significantly higher and plasma NO, 6-K-PGF 1α contents were significantly lower in all the patients with SSc before treatment than those in the controls, After treatment, the patients with satisfactory responses (n=33) had the abnormal plasma values of these parameters greatly corrected (vs before treatment P<0.05, P<0.01); while poorly responding patients had the plasma values little changed. Conclusion: Endothelial vasoactive factors are closely involved in the development of systemic sclerosis and may be used as predictors of treatment efficiency. (authors)

  1. Progressive systemic sclerosis: high-resolution computed tomography findings; Esclerose sistemica progressiva: aspectos na tomografia computadorizada de alta resolucao

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    Gasparetto, Emerson L.; Pimenta, Rodrigo; Ono, Sergio E.; Escuissato, Dante L. [Parana Univ., Curitiba, PR (Brazil). Hospital de Clinicas. Servico de Radiologia Medica]. E-mail: dante.luiz@onda.com.br; Inoue, Cesar [Parana Univ., Curitiba, PR (Brazil). Faculdade de Medicina

    2005-09-15

    Objective: To describe the high-resolution computed tomography findings in the lung of patients with systemic sclerosis, independently of the respiratory symptoms. Materials and methods: Seventy-three high-resolution computed tomography scans of 44 patients with clinical diagnosis of systemic sclerosis were reviewed and defined by the consensus of two radiologists. Results: Abnormalities were seen in 91.8% (n = 67) of the scans. The most frequent findings were reticular pattern (90.4%), ground-glass opacities (63%), traction bronchiectasis and bronchiolectasis (56.2%), esophageal dilatation (46.6%), honeycombing pattern (28.8%) and signs of pulmonary hypertension (15.6%). In most cases the lesions were bilateral (89%) and symmetrical (58.5%). The lesions were predominantly located in the basal (91.2%) and peripheral (92.2%) regions. Conclusion: In the majority of the patients, progressive systemic sclerosis can cause pulmonary fibrosis mainly characterized by reticular pattern with basal and peripheral distribution on high-resolution computed tomography. (author)

  2. 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

  3. Serum amyloid A is a marker for pulmonary involvement in systemic sclerosis.

    Directory of Open Access Journals (Sweden)

    Katja Lakota

    Full Text Available Inflammation in systemic sclerosis (SSc is a prominent, but incompletely characterized feature in early stages of the disease. The goal of these studies was to determine the circulating levels, clinical correlates and biological effects of the acute phase protein serum amyloid A (SAA, a marker of inflammation, in patients with SSc. Circulating levels of SAA were determined by multiplex assays in serum from 129 SSc patients and 98 healthy controls. Correlations between SAA levels and clinical and laboratory features of disease were analyzed. The effects of SAA on human pulmonary fibroblasts were studied ex vivo. Elevated levels of SAA were found in 25% of SSc patients, with the highest levels in those with early-stage disease and diffuse cutaneous involvement. Significant negative correlations of SAA were found with forced vital capacity and diffusion capacity for carbon monoxide. Patients with elevated SAA had greater dyspnea and more frequent interstitial lung disease, and had worse scores on patient-reported outcome measures. Incubation with recombinant SAA induced dose-dependent stimulation of IL-6 and IL-8 in normal lung fibroblasts in culture. Serum levels of the inflammatory marker SAA are elevated in patients with early diffuse cutaneous SSc, and correlate with pulmonary involvement. In lung fibroblasts, SAA acts as a direct stimulus for increased cytokine production. These findings suggest that systemic inflammation in SSc may be linked to lung involvement and SAA could serve as a potential biomarker for this complication.

  4. Does dysfunction of the mirror neuron system contribute to symptoms in amyotrophic lateral sclerosis?

    Science.gov (United States)

    Eisen, Andrew; Lemon, Roger; Kiernan, Matthew C; Hornberger, Michael; Turner, Martin R

    2015-07-01

    There is growing evidence that mirror neurons, initially discovered over two decades ago in the monkey, are present in the human brain. In the monkey, mirror neurons characteristically fire not only when it is performing an action, such as grasping an object, but also when observing a similar action performed by another agent (human or monkey). In this review we discuss the origin, cortical distribution and possible functions of mirror neurons as a background to exploring their potential relevance in amyotrophic lateral sclerosis (ALS). We have recently proposed that ALS (and the related condition of frontotemporal dementia) may be viewed as a failure of interlinked functional complexes having their origins in key evolutionary adaptations. This can include loss of the direct projections from the corticospinal tract, and this is at least part of the explanation for impaired motor control in ALS. Since, in the monkey, corticospinal neurons also show mirror properties, ALS in humans might also affect the mirror neuron system. We speculate that a defective mirror neuron system might contribute to other ALS deficits affecting motor imagery, gesture, language and empathy. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  5. 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.

  6. Prospective evaluation of frequency of signs of systemic sclerosis in 76 patients with morphea.

    Science.gov (United States)

    Lipsker, Dan; Bessis, Didier; Cosnes, Anne; Kluger, Nicolas; Lutz, Virginie; Sauleau, Erik; Francès, Camille

    2015-01-01

    Some authors consider that morphoea and systemic sclerosis (SSc) could be part of the same disease spectrum. The aim of this study was to analyse the prevalence of signs indicative of SSc in a cohort of patients with morphoea. This is a prospective multi-centre study performed in four French academic dermatology departments: 76 patients with morphoea and 101 age- and sex-matched controls, who underwent complete clinical examination, were enrolled. A systemic search for signs indicative of SSc (e.g. Raynaud's phenomenon, reflux) was performed with the help of a standardised questionnaire. There were 58 women and 18 men (ration=3/1) with a median age of 59 years. Mean age at diagnosis was 54 years (extremes, 13-87). 49 subjects had plaque morphoea, 9 had generalised morphoea and 18 had linear morphoea. Mean duration of morphoea was 7.9 years. Signs possibly indicative of SSc were noted in four patients of the control group and in 8 patients with morphoea. This difference was not statistically significant (p=0.129). Further investigations ruled out SSc in all patients. Signs indicative of SSc are statistically not more frequently present in patients with morphoea than in controls and this study does not support the view that those 2 entities are part of a common disease spectrum.

  7. Posterior Reversible Encephalopathy Syndrome as Presenting Form of Very Early Systemic Sclerosis

    Directory of Open Access Journals (Sweden)

    María Isabel Pedraza

    2015-01-01

    Full Text Available Introduction. Posterior Reversible Encephalopathy Syndrome (PRES is an increasingly recognized clinical and radiological entity with a wide spectrum of symptoms. Its mechanism depends on failure of the blood-brain barrier due to high systemic blood pressure (BP and loss of integrity of vascular endothelium related with different triggers. Methods. We aim to report a case of PRES induced by arterial hypertension and very early systemic sclerosis (SSc not previously known. Results. A 64-year-old female was admitted due to 1-week pulsating headache more prominent on frontal scalp, accompanied by phonophobia, photophobia, and facial flushing. Neurological exam revealed brisk deep tendon reflex. Brain magnetic resonance imaging (MRI showed subcortical lesions mainly located in posterior regions. BP was monitored and episodic arterial hypertension was detected. In laboratory tests positive anti-topoisomerase I antibodies were detected. BP was controlled with angiotensin-converting-enzyme inhibitors and headache improved. In a new MRI a month later improvement of white matter lesions was observed. Capillaroscopy showed “active pattern,” considered typical of SSc. Conclusion. In SSc anti-endothelial cell antibodies impair vascular endothelium and liberation of vasoconstrictors leads to BP increasing and disruption of blood-brain barrier autoregulation mechanisms. PRES can be the first manifestation of very early SSc and this entity should be considered even in absence of skin lesions or Raynaud phenomenon.

  8. Detection of multiple sclerosis with visual evoked potentials--an unsupervised computational intelligence system.

    Science.gov (United States)

    Dasey, T J; Micheli-Tzanakou, E

    2000-09-01

    This paper describes the application of a novel unsupervised pattern recognition system to the classification of the Visual Evoked Potentials (VEP's) of normal and multiple sclerosis (MS) patients. The method combines a traditional statistical feature extractor with a fuzzy clustering method, all implemented in a parallel neural network architecture. The optimization routine, ALOPEX, is used to train the network while decreasing the likelihood of local solutions. The unsupervised system includes a feature extraction and clustering module, trained by the optimization routine ALOPEX. Through maximization of the output variance of each node, and an architecture which excludes redundancy, the feature extraction network retains the most significant Karhunen-Loeve expansion vectors. The clustering module uses a modification to the Fuzzy c-Means (FCM) clustering algorithms, where ALOPEX adjusts a set of cluster centers to minimize an objective error function. The result combines the power of the FCM algorithms with the advantage of a more global solution from ALOPEX. The new pattern recognition system is used to cluster the VEP's of 13 normal and 12 MS subjects. The classification with this technique can, without supervision, separate the patient population into two groups which largely correspond to the MS and control subject groups. A suitable threshold can be chosen so that the recognizer chooses no false negatives. The use of multiple stimulation patterns appears to improve the reliability of the decision. The reasoning of most neural networks in their decision making cannot easily be extracted upon the completion of training. However, due to the linearity of the network nodes, the cluster prototypes of this unsupervised system can be reconstructed to illustrate the reasoning of the system. In this application, this analysis hints at the usefulness of previously unused portions of the VEP in detecting MS. It also indicates a possible use of the system as a training

  9. NASA Engineering Network Lessons Learned

    Data.gov (United States)

    National Aeronautics and Space Administration — The NASA Lessons Learned system provides access to official, reviewed lessons learned from NASA programs and projects. These lessons have been made available to the...

  10. Genetic predictors of systemic sclerosis-associated interstitial lung disease: a review of recent literature.

    Science.gov (United States)

    Stock, Carmel J W; Renzoni, Elisabetta A

    2018-02-23

    The interplay between genetic and environmental factors is likely involved in the pathogenesis of systemic sclerosis (SSc). Interstitial lung disease associated in the context of SSc (SSc-ILD) is associated with significant morbidity, and is the leading cause of death in SSc. The spectrum of SSc-ILD severity is wide, ranging from patients with only limited and inherently stable pulmonary involvement, to those with extensive and progressive pulmonary fibrosis. In order to provide accurate prognostic information for patients, and to initiate appropriate monitoring and treatment regimens, the ability to identify patients at risk of developing severe ILD early in the disease course is crucial. Identification of genetic variants involved in disease pathogenesis can not only potentially provide diagnostic/prognostic markers, but can also highlight dysregulated molecular pathways for therapeutic targeting. A number of genetic associations have been established for susceptibility to SSc, but far fewer studies have investigated genetic susceptibility to SSc-ILD specifically. In this review we present a summary of the studies assessing genetic associations with SSc-ILD.

  11. Relationship of endothelial dysfunction and kidney functional state in patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    A M Basova

    2009-01-01

    Full Text Available Objective. To study vasoregulatory function of vascular wall in pts with systemic sclerosis (SS and chronic scleroderma-related renal disease (SRD and determine relationship with main measures of kidney functional state. Material and methods. 25 pts with SS (24 female with mean age 46,4±10,7 years and mean disease duration 7,5±4,7 years were included. 24 pts (96% had diffuse form and 17 pts (68% – generalized stage of SS. 22 pts (88% had chronic course of the disease with typical damage of vessels, heart, lungs and skin. SRD was revealed in 17 pts (68%. Sonographic method of Celermejer D. et al. (1992 was used for assessment of vascular endothelial function. 15 healthy persons without SS were included in control group. Results. Most prominent changes of brachial artery reactivity with insufficient vasodilatation and paradoxical vasoconstriction to reactive hyperemia were revealed in most pts with moderate and severe SRD. Conclusion. These changes of endothelium dependent and endothelium independent parameters in pts with SRD pointed to irreversible probably scleroderma-related vascular wall damage.

  12. Plasma urotensin II levels in primary Raynaud's phenomenon and systemic sclerosis

    Science.gov (United States)

    Gözel, Nevzat; Karataş, Ahmet; Yardım, Meltem; Kınacı, Mesude Seda; Ulu, Ramazan; Demircan, Fatih; Kılınç, Faruk; Öz, Burak; Dönder, Emir; Aydın, Süleyman; Koca, Süleyman Serdar

    2017-12-19

    Background/aim: The pathogenesis of Raynaud's phenomenon (RP) has not yet been fully elucidated. RP is characterized by exaggerated cold-induced vasoconstriction. Urotensin II (UII) is a potent vasoconstrictor. The aim of the present study was to evaluate plasma UII levels in both primary RP and secondary RP associated with systemic sclerosis (SSc).Materials and methods: Fifteen patients with primary RP, 30 patients with RP secondary to SSc, and 30 healthy controls (HC) were included in the study. Raynaud condition scores (RCS) were determined in the primary RP and SSc groups. Modified Rodnan skin score (MRSS) was determined for the SSc patients. Plasma UII level was analyzed by the ELISA method. Results: When compared to the HC group, plasma UII level was lower in the secondary RP group, but not in the primary RP group. Plasma UII level was not directly related to RCS in either the primary or secondary RP group. Moreover, it was not correlated with MRSS in the secondary RP group.Conclusion: The results of the present study suggest that UII is not associated with primary RP. Its level was lower in the secondary RP (SSc) patients. Therefore, it can be concluded that decreased UII level is related to SSc instead of RP.

  13. 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

  14. Aerobic and resistance exercise in systemic sclerosis: State of the art.

    Science.gov (United States)

    de Oliveira, Natália Cristina; Portes, Leslie Andrews; Pettersson, Henrik; Alexanderson, Helene; Boström, Carina

    2017-12-01

    Patients with systemic sclerosis (SSc) experience reduced exercise capacity and muscle strength compared with healthy subjects. There are also indications of reduced levels of physical activity. To present the current knowledge of physical exercise in SSc. Most studies presently available [three case studies, one single subject experimental design, one study comparing patients with healthy controls, one quasi experimental design (pre-post), two clinical trials and two random controlled trials] have included small samples of patients, mostly composed of patients with and without pulmonary involvement. It seems that patients with SSc without pulmonary involvement are able to perform and benefit from aerobic exercises of at least moderate intensity. Exercise tolerance, aerobic capacity, walking distance, muscle strength and muscle function as well as health-related quality of life (HRQL) have been found to be improved after participation in programmes including aerobic exercise and aerobic exercise combined with resistance exercises. Improvements seem to be only partially retained at follow up. Patients with pulmonary involvement may also experience improved muscle strength, physical and aerobic capacity, as well as HRQL following exercise. Patients with SSc without pulmonary involvement can be recommended to be as physically active as the general population. Patients with mild pulmonary involvement can be recommended to be physically active by engaging in exercises of moderate intensity and to participate in moderate-load resistance exercises. Health professionals should inform patients with SSc about the importance of physical activity and avoidance of a sedentary lifestyle. Copyright © 2017 John Wiley & Sons, Ltd.

  15. [Hashimoto thyroiditis may be associated with a subset of patients with systemic sclerosis with pulmonary hypertension].

    Science.gov (United States)

    Costa, Ciliana Cardoso B; Medeiros, Morgana; Watanabe, Karen; Martin, Patricia; Skare, Thelma L

    2014-01-01

    Recent studies show an association between autoimmune thyroiditis and systemic sclerosis (SSc) and suggest that this condition may interfere with the ES phenotype. However these studies evaluate the autoimmune thyroiditis as a whole and none of them specifically addresses Hashimoto's thyroiditis (HT) in SSc. To investigate the presence of HT in SSc patients and its possible association with disease manifestations. Clinical manifestations of hypothyroidism, TSH and anti-thyroid auto antibodies (anti-TPO. anti TBG and TRAb) were studied in 56 patients with SSc. SSc patients with HT were compared with SSc patients without thyroiditis. HT was observed in 19.64% of patients with SSc. No association was observed between HT and the different forms of disease or profile of autoantibodies. Likewise, there was no difference between the mean modified Rodnan score and presence of Raynaud's phenomenon, scars, digital necrosis, myositis, arthritis, sicca symptoms, esophageal dysmotility and scleroderma renal crisis when the groups were compared. On the other hand, patients with HT had higher frequency of pulmonary hypertension in relation to patients without HT (66.6% vs 22.5%, p=0.016). In the studied sample patients with ES and HT had higher prevalence of pulmonary hypertension. Long-term follow-up studies with a larger number of TH and SSc patients are needed to confirm these data. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Prevalence and clinical significance of cathepsin G antibodies in systemic sclerosis

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    M. Favaro

    2011-09-01

    Full Text Available Objectives: To evaluate the prevalence and clinical significance of cathepsin G antibodies in patients affected with systemic sclerosis (SSc, scleroderma. Methods: 115 patients affected by SSc, 55 (47,8% with diffuse scleroderma (dSSc and 60 (52,2% with limited scleroderma (lSSc, were tested for cathepsin G antibodies by ELISA method. Moreover these sera were evaluated by indirect immunofluorescence (IIF on ethanol and formalin fixed human neutrophils. Results: By means of the ELISA method 16 (13,9% patients were found to be sera positive for anti-cathepsin G, 2 (12.5% of which showed a perinuclear fluorescence pattern (P-ANCA and 4 (25% an atypical ANCA staining, while 10 (62,5% were negative on IIF. The IIF on scleroderma sera revealed 5 (4,3% P-ANCA and 18 (15,7% atypical ANCA patterns. The anti-cathepsin G antibodies significantly prevailed in scleroderma sera (p=0.02 when their frequency was compared with that of healthy controls; while they were not significantly associated to any clinical or serological features of SSc patients. Conclusions: The anti-cathepsin G antibodies were significantly frequent in scleroderma sera; however, no clinical correlations were found. Thus, the significance of their presence in SSc still needs to be clarified.

  18. 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.

  19. Very early and early systemic sclerosis in the Spanish scleroderma Registry (RESCLE) cohort.

    Science.gov (United States)

    Trapiella-Martínez, Luis; Díaz-López, José Bernardino; Caminal-Montero, Luis; Tolosa-Vilella, Carles; Guillén-Del Castillo, Alfredo; Colunga-Argüelles, Dolores; Rubio-Rivas, Manuel; Iniesta-Arandia, Nerea; Castillo-Palma, María Jesús; Sáez-Comet, Luis; Egurbide-Arberas, María Victoria; Ortego-Centeno, Norberto; Freire, Mayka; Vargas-Hitos, Jose Antonio; Ríos-Blanco, Juan José; Todolí-Parra, Jose Antonio; Rodríguez-Carballeira, Mónica; Marín-Ballvé, Adela; Chamorro-Fernández, Antonio Javier; Pla-Salas, Xavier; Madroñero-Vuelta, Ana Belén; Ruiz-Muñóz, Manuel; Fonollosa-Pla, Vicent; Simeón-Aznar, Carmen Pilar

    2017-08-01

    According to the existence of subclinical organ involvement pre-scleroderma should be divided into two subsets: very early and early disease. Pre-scleroderma patients included in the Spanish Scleroderma Registry (RESCLE) Cohort were reclassified into subsets. Differences were evaluated and the risk of progression to definite systemic sclerosis was estimated. The characteristics of very early and early SSc patients were compared. A logistic regression model was used to determine the risk factors of progression. 1632 patients were included, 36 (2.2%) in the very early subset and 111 (6.8%) in the early subset. There were no differences in sex, age at disease onset, duration of Raynaud's phenomenon, antinuclear antibodies or capillaroscopic findings. Three (8.3%) very early SSc patients evolved to definite SSc, 2 (5.6%) of them meeting the ACR/EULAR 2013 criteria, unlike 31 (28%) early SSc patients, 20 (24%) of them meeting the criteria (p=0.034). Digestive involvement was an independent risk factor of progression (OR 17; 95% CI, 6.1-47.2). The classification of early forms of scleroderma identifies patients with different prognostic risk of progression. The evolution to definite SSc is more frequent in early than in very early SSc patients. Digestive involvement is a risk factor of progression. An active assessment of organ damage in preclinical stages allows a correct classification and risk stratification, with implications for monitoring and treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Phenotyping Exercise Limitation in Systemic Sclerosis: The Use of Cardiopulmonary Exercise Testing.

    Science.gov (United States)

    Boutou, Afroditi K; Pitsiou, Georgia G; Siakka, Panagiota; Dimitroulas, Theodoros; Paspala, Asimina; Sourla, Evdokia; Chavouzis, Nikolaos; Garyfallos, Alexandros; Argyropoulou, Paraskevi; Stanopoulos, Ioannis

    2016-01-01

    Exercise impairment is a common symptom of systemic sclerosis (SSc), a disorder which is frequently complicated by cardiopulmonary involvement. This study's aims were: (a) to define the prevalence and the potential causes of limited exercise capacity and (b) to study potential differences in clinical, radiological and functional characteristics and blood serology among SSc patients with exercise limitation of different etiology. Prospectively collected data on SSc patients who had conducted full lung function testing, blood serology, thorax high-resolution computed tomography, Doppler echocardiogram and a maximal cardiopulmonary exercise testing (CPET) were retrospectively analyzed. Using a CPET algorithm, patients were characterized as having normal or subnormal exercise capacity (N), respiratory limitation (RL), left ventricular dysfunction (LVD) or pulmonary vasculopathy (PV). Group comparisons were conducted using either one-way ANOVA or the Kruskal-Wallis test. A p value present in 32.1%, LVD in 25.6% and RL in 10.2%, while 32.1% of the patients constituted the N group. The presence of antisclero-70 antibodies, low anaerobic threshold and low peak exercise capacity measures could discriminate LVD from the other groups. Low end-tidal carbon dioxide pressure and its change from rest to anaerobic threshold could discriminate between the PV, LVD and N groups, while respiratory restriction along with ventilatory inefficiency indices could differentiate the RL group from the rest. The combined evaluation of CPET gas exchange patterns with baseline measurements could discriminate the causes of exercise limitation among SSc patients. © 2016 S. Karger AG, Basel.

  1. Absolute count of T and B lymphocyte subsets is decreased in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Gambichler T

    2010-01-01

    Full Text Available Abstract Background Previous reports on lymphocyte subpopulations in systemic sclerosis (SSc are conflicting. Therefore, we aimed to investigate the lymphocyte subsets in SSc patients who were not on immunosuppressive therapy. Methods Lymphocyte subsets were assessed in the peripheral blood of SSc patients (n = 29 and healthy controls (n = 29 using the four colour flow cytometry method. Correlation studies were also performed in order to assess the relationship between lymphocyte subsets and clinical parameters. Results The absolute count of lymphocytes (P = 0.0042, CD3+ (P = 0.0014, CD4+ (P = 0.0070, CD8+ (P = 0.021, and CD19+ cells (P = 0.024 was significantly decreased in SSc patients when compared to healthy controls. CD4+/CD8+ ratio and the absolute count of CD56+ cells observed in SSc patients did not significantly differ from controls (P = 0.165; P = 0.632, respectively. There was no substantial relationship between the lymphocyte subset levels and clinical features (i.e., SSc subtype, autoantibody profiles, organ involvement, except for a significant inverse correlation of CD19+ cells and the modified Rodnan skin score (r = -0.43, P = 0.020. Conclusion Our data support previous reports indicating that subsets of T lymphocytes as well as B lymphocytes play a role in the pathogenesis of SSc.

  2. Perceived functioning has ethnic-specific associations in systemic sclerosis: another dimension of personalized medicine.

    Science.gov (United States)

    McNearney, Terry A; Hunnicutt, Sonya E; Fischbach, Michael; Friedman, Alan W; Aguilar, Martha; Ahn, Chul W; Reveille, John D; Lisse, Jeffrey R; Baethge, Bruce A; Goel, Niti; Mayes, Maureen D

    2009-12-01

    To measure self-reported physical and mental functioning and associated clinical features at study entry in 3 ethnic groups with systemic sclerosis (SSc). Sixty Hispanic, 39 African American, and 104 Caucasian patients with recent-onset SSc ( fatigue scores > IBQ > clinical variables (hypertension, skin score, and percentage predicted DLCO). Scleroderma-HAQ scores had ethnic-specific associations with IBQ > AHI scores > most clinical and laboratory variables. Decreased mental component summary (MCS) scores associated with AHI > ISEL. Ethnic-specific immunogenetic variables HLA-DQB1*0202 (Caucasian) and HLA-DRB 1*11 (African American), and HLA-DQA1*0501 (Hispanic) also associated with MCS. Antinuclear autoantibodies, anti-topoisomerase I, and RNA polymerases I and III also demonstrated associations with functioning in African American and Hispanic groups. Clinical, psychosocial, and immunogenetic variables had ethnic-specific associations with perceived physical and mental functioning. Consideration of ethnic-specific psychological and behavioral support in designing more personalized, relevant therapeutic interventions for the patient may improve therapeutic efficacy in SSc.

  3. Effects of cisapride on colonic transit in patients with progressive systemic sclerosis

    International Nuclear Information System (INIS)

    Wang, S.J.; Lin, W.Y.; Lan, J.L.; Chen, D.Y.; Chen, Y.H.; Hsieh, T.Y.

    2002-01-01

    Progressive systemic sclerosis (PSS) may involve any portion of the gastrointestinal tract including the colon. Constipation is common in patients with PSS. Cisapride, a benzamide derivative, is a potentially useful agent in the treatment if chronic idiopathic constipation. The effect of cisapride on colonic transit was evaluated in 16 PSS patients by radionuclide colonic transit method. Static images were acquired at regular times, then the geometric center (GC) values were calculated. Each patient received cisapride orally three times a day for a week. The median GC at 4 hours was 0.351 in patients before treatment and 0.775 after treatment. The difference is significant with a p value of 0.026. The median GC at 24 hours was 1.957 in patients before treatment and significantly increased to 2.509 after treatment. The p value was 0.038. Clinically, twelve patients had symptoms of constipation and 8 of them showed improvement of the symptoms after administration of cisapride. The result showed acceleration in colonic transit in response to cisapride. We conclude that cisapride is effective in the treatment of constipation in patients with PSS

  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. Clinical and laboratory features of systemic sclerosis complicated with localized scleroderma.

    Science.gov (United States)

    Toki, Sayaka; Motegi, Sei-ichiro; Yamada, Kazuya; Uchiyama, Akihiko; Kanai, Sahori; Yamanaka, Masayoshi; Ishikawa, Osamu

    2015-03-01

    Localized scleroderma (LSc) primarily affects skin, whereas systemic sclerosis (SSc) affects skin and various internal organs. LSc and SSc are considered to be basically different diseases, and there is no transition between them. However, LSc and SSc have several common characteristics, including endothelial cell dysfunction, immune activation, and excess fibrosis of the skin, and there exist several SSc cases complicated with LSc during the course of SSc. Clinical and laboratory characteristics of SSc patients with LSc remain unclear. We investigated the clinical and laboratory features of 8 SSc patients with LSc among 220 SSc patients (3.6%). The types of LSc included plaque (5/8), guttate (2/8), and linear type (1/8). All cases were diagnosed as having SSc within 5 years before or after the appearance of LSc. In three cases of SSc with LSc (37.5%), LSc skin lesions preceded clinical symptoms of SSc. Young age, negative antinuclear antibody, and positive anti-RNA polymerase III antibody were significantly prevalent in SSc patients with LSc. The positivity of anticentromere antibody tended to be prevalent in SSc patients without LSc. No significant difference in the frequency of complications, such as interstitial lung disease, reflux esophagitis, and pulmonary artery hypertension, was observed. The awareness of these characteristic of SSc with LSc are essential to establish an early diagnosis and treatment. © 2015 Japanese Dermatological Association.

  6. Factors influencing the occupational trajectory of patients with systemic sclerosis: a qualitative study.

    Science.gov (United States)

    Decuman, Saskia; Smith, Vanessa; Grypdonck, Maria; De Keyser, Filip; Verhaeghe, Sofie

    2015-01-01

    To describe, from the patient's point of view, the factors influencing the occupational trajectory of patients with systemic sclerosis (SSc). This was a qualitative study designed using grounded theory with constant comparison. Data were collected through semi-structured interviews with 14 patients who fulfilled the American College of Rheumatology or Leroy-Medsger criteria for SSc. Based on our interviews, we found that the occupational trajectory of patients with SSc is influenced by the continuous interplay between four groups of factors. The first group concerns the values patients attribute to work, including identity, normality, financial value, social contact, and structure. The meaning of these values and how they relate to each other underlies the desire to work. A second group of factors is those influencing the balance between daily life, work participation, and medical condition (e.g. job content, flexibility in organising work, and the willingness to ask for accommodations at work). The occupational trajectory is also influenced by external factors, including availability of support, know-ledge of the disease, pressure to work, contact with medical professionals, and existing regulations and the patient's knowledge about them. Finally, the occupational trajectory is influenced by personal factors, including socio-demographics, psychological assets, and disease- and work-related personal factors. The decisions patients with SSc take concerning work depend on an interplay between many factors and, especially, on the patients' personal interpretation of these factors. These need to be taken into account when helping patients with SSc determine their occupational trajectory.

  7. An Evaluation of Geographic Information Systems in Social Studies Lessons: Teachers' Views

    Science.gov (United States)

    Aladag, Elif

    2014-01-01

    The aim of this study is to evaluate the applicability of Geographic Information Systems (GIS), used increasingly in primary and secondary education across the world, in social studies lessons in Turkey. In line with this aim, 14 social studies teachers working in the province of Aydin, Turkey received a 6-hour training course about GIS during the…

  8. Lessons learned from implementation of postdischarge telephone calls at Baylor Health Care System.

    Science.gov (United States)

    Cochran, Veronica Y; Blair, Brenda; Wissinger, Laurie; Nuss, Terri D

    2012-01-01

    Postdischarge telephone calls can enhance patient satisfaction, outcomes, and care continuity. The authors describe the Dallas-Fort Worth-based Baylor Health Care System standardized process for placing emergency department discharge telephone calls to patients. The metrics and guidelines related to the process as well as lessons learned, models of care, the future state of the postdischarge telephone calls, and findings are discussed.

  9. From cannabis to endocannabinoids in multiple sclerosis: a paradigm of central nervous system autoimmune diseases.

    Science.gov (United States)

    Malfitano, Anna Maria; Matarese, Giuseppe; Bifulco, Maurizio

    2005-12-01

    An increasing body of evidence suggests that cannabinoids have beneficial effects on the symptoms of multiple sclerosis, including spasticity and pain. Endogenous molecules with cannabinoid-like activity, such as the "endocannabinoids", have been shown to mimic the anti-inflammatory properties of cannabinoids through the cannabinoid receptors. Several studies suggest that cannabinoids and endocannabinoids may have a key role in the pathogenesis and therapy of multiple sclerosis. Indeed, they can down regulate the production of pathogenic T helper 1-associated cytokines enhancing the production of T helper 2-associated protective cytokines. A shift towards T helper 2 has been associated with therapeutic benefit in multiple sclerosis. In addition, cannabinoids exert a neuromodulatory effect on neurotransmitters and hormones involved in the neurodegenerative phase of the disease. In vivo studies using mice with experimental allergic encephalomyelitis, an animal model of multiple sclerosis, suggest that the increase of the circulating levels of endocannabinoids might have a therapeutic effect, and that agonists of endocannabinoids with low psychoactive effects could open new strategies for the treatment of multiple sclerosis.

  10. 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.

  11. Lessons learned from nuclear power plant posttrip monitoring systems

    International Nuclear Information System (INIS)

    Barasa, W.A.

    1989-01-01

    This paper discusses a program to identify common causes of unit trips and cost-effective evaluation of the options for addressing the causes. The core of the program is a living historical data base of events, based on root-cause analysis of station-specific events, that provides a means of segregating common-cause failures from random failures. Once common-cause failures at a specific plant are identified, the payback periods of the options to address a specific unit trip cause - modification, procedural changes, or status quo - can be calculated by comparing the cost of the modifications with the cost of the lost electrical production, which is also determined from the historical data base. This paper describes how the information is developed and gives examples of how the lessons learned from previous trips can be applied to the elimination of the causes

  12. 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.

  13. 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

  14. Separate influences of birth order and gravidity/parity on the development of systemic sclerosis.

    Science.gov (United States)

    Cockrill, Tonya; del Junco, Deborah J; Arnett, Frank C; Assassi, Shervin; Tan, Filemon K; McNearney, Terry; Fischbach, Michael; Perry, Marilyn; Mayes, Maureen D

    2010-03-01

    Birth order has been valuable in revealing the role of environmental influences on the risk of developing certain diseases such as allergy and atopy. In addition, pregnancy has profound effects on the immune system such as short-term effects that permit fetal survival as well as longer-term effects that could influence late-onset diseases. In order to better evaluate these influences, we studied the association of birth order and gravidity/parity as risk factors for systemic sclerosis (SSc; scleroderma). Data regarding SSc cases and their unaffected sibling controls were obtained from the Scleroderma Family Registry and DNA Repository. The case-sibling design was used to minimize confounding due to differences in age, race, ethnicity, or calendar time. The gravidity/parity analysis was based on sibships with at least one SSc-affected and one unaffected sister. Birth order was examined in 974 sibships, comparing SSc cases (n = 987) with their unaffected siblings (n = 3,088). The risk of scleroderma increased with increasing birth order (odds ratio [OR] 1.25, 95% confidence interval [95% CI] 1.06-1.50 for birth order 2-5; OR 2.22, 95% CI 1.57-3.15 for birth order 6-9; and OR 3.53, 95% CI 1.68-7.45 for birth order 10-15). Gravidity/parity was analyzed in 168 sibships (256 unaffected sisters, 172 SSc cases). We found an association between a history of one or more pregnancies and SSc (OR 2.8). Birth order and pregnancy were independently associated with a higher risk of developing SSc. These findings suggest that immune development in early childhood and/or pregnancy-associated events, including but not limited to microchimerism, plays a role in SSc susceptibility.

  15. Vasoactive Therapy in Systemic Sclerosis: Real-life Therapeutic Practice in More Than 3000 Patients.

    Science.gov (United States)

    Moinzadeh, Pia; Riemekasten, Gabriela; Siegert, Elise; Fierlbeck, Gerhard; Henes, Joerg; Blank, Norbert; Melchers, Inga; Mueller-Ladner, Ulf; Frerix, Marc; Kreuter, Alexander; Tigges, Christian; Lahner, Nina; Susok, Laura; Guenther, Claudia; Zeidler, Gabriele; Pfeiffer, Christiane; Worm, Margitta; Karrer, Sigrid; Aberer, Elisabeth; Bretterklieber, Agnes; Genth, Ekkehard; Simon, Jan C; Distler, Joerg H W; Hein, Ruediger; Schneider, Matthias; Seitz, Cornelia S; Herink, Claudia; Steinbrink, Kerstin; Sárdy, Miklos; Varga, Rita; Mensing, Hartwig; Mensing, Christian; Lehmann, Percy; Neeck, Gunther; Fiehn, Christoph; Weber, Manfred; Goebeler, Matthias; Burkhardt, Harald; Buslau, Michael; Ahmadi-Simab, Keihan; Himsel, Andrea; Juche, Aaron; Koetter, Ina; Kuhn, Annegret; Sticherling, Michael; Hellmich, Martin; Kuhr, Kathrin; Krieg, Thomas; Ehrchen, Jan; Sunderkoetter, Cord; Hunzelmann, Nicolas

    2016-01-01

    Vasculopathy is a key factor in the pathophysiology of systemic sclerosis (SSc) and the main cause for Raynaud phenomenon (RP), digital ulcers (DU), and/or pulmonary arterial hypertension (PAH). It is so far unknown how patients with SSc are treated with vasoactive agents in daily practice. To determine to which extent patients with SSc were treated with different vasoactive agents, we used data from the German Network for Systemic Scleroderma registry. The data of 3248 patients with SSc were analyzed. Patients were treated with vasoactive drugs in 61.1% of cases (1984/3248). Of these, 47.6% received calcium channel inhibitors, followed by 34.2% treated with angiotensin-converting enzyme (ACE) inhibitors, 21.1% treated with intravenous (IV) prostanoids, 10.1% with pentoxifylline, 8.8% with angiotensin 1 receptor antagonists (AT1RA), 8.7% with endothelin 1 receptor antagonists (ET1RA), 4.1% with phosphodiesterase type 5 (PDE5) inhibitors, and 5.3% with others. Patients with RP received vasoactive therapy in 63.3% of cases, with DU in 70.1%, and with PAH in 78.2% of cases. Logistic regression analysis revealed that patients with PAH were significantly more often treated with PDE5 inhibitors and ET1RA, and those with DU with ET1RA and IV prostanoids. In addition, 41.8% of patients were treated with ACE inhibitors and/or AT1RA. Patients registered after 2009 received significantly more often ET1RA, AT1RA, and IV prostanoids compared with patients registered prior to 2005. These data clearly indicate that many patients with SSc do not yet receive sufficient vasoactive therapy. Further, in recent years, a marked change of treatment regimens can be observed.

  16. Familial risk of systemic sclerosis and co-aggregation of autoimmune diseases in affected families.

    Science.gov (United States)

    Kuo, Chang-Fu; Luo, Shue-Fen; Yu, Kuang-Hui; See, Lai-Chu; Zhang, Weiya; Doherty, Michael

    2016-10-12

    Systemic sclerosis (SSc) is a rare and devastating disease affecting skin and internal organs. Familial aggregation of SSc and co-aggregation with other autoimmune diseases is rarely reported. We identified 23,658,577 beneficiaries registered with the National Health Insurance database in 2010, 1891 of whom had SSc. We identified 21,009,551 parent-child relationships and 17,168,340 full sibling pairs. The familial risks of SSc and other autoimmune diseases and familial transmission were estimated. The prevalence of SSc in the general population was 0.008 %. There are 3801 individuals had at least one first-degree relative with SSc, among them 3 people had SSc which was equivalent to a prevalence of 0.08 %. The adjusted relative risk (RR) (95 % CI) for SSc was 81.21 (11.40-579.72) for siblings of SSc patients. The familial transmission (genetic plus shared environmental contribution to total phenotypic variance of SSc) was 0.72. However, 84.1 % of patients were expected to be sporadic cases. The RR (95 % CI) in first-degree relatives of SSc patients was 2.64 (1.46-4.75) for rheumatoid arthritis, 6.51 (4.05-10.46) for systemic lupus erythematosus, 2.77 (1.04-7.35) for Sjögren's syndrome, 8.05 (2.03-31.92) for idiopathic inflammatory myositis, and 1.52 (1.15-2.01) for psoriasis. The risks of SSc and other autoimmune diseases are increased in relatives of people with SSc, and family factors explain over two-thirds of the phenotypic variance of the disease. These findings may be useful in counselling families of patients with SSc and for further genetic studies.

  17. Algorithm for the Diagnosis of Scleroderma. Early Systemic Sclerosis: Definitions and diagnostic criteria

    Directory of Open Access Journals (Sweden)

    Domenico Galasso

    2013-04-01

    Full Text Available Introduction: The term scleroderma derives from the Greek words skleros, which means hard, and derma, which means skin. It refers to an acquired systemic inflammatory disease of the connective tissue –also known as systemic sclerosis (SSc– characterized by excessive collagen deposition in the skin and the internal organs that results in fibrosis. The typical vascular lesion in SSc leads to narrowing of the vessel lumen, intimal thickening, medial hypotrophy, and adventitial fibrosis of small muscular vessels, collagen deposition in the other matrix components of interstice, and the Raynaud phenomenon secondary to these widespread microvascular abnormalities. All these characteristics lead to a connective tissue re-modeling. Discussion: Several clinical studies utilize the American Rheumatology Association’s 1980 classification. However, these diagnostic criteria are unsatisfactory because they fail to take into consideration part of the disease spectrum. Early-phase SSc is characterized by the Raynaud phenomenon (in 90% of all patients, sclerodactyly, and positivity for SSc-specific autoantibodies (antinuclear antibodies, anti-topoisomerase I antibodies, anti-RNA polymerase I and III antibodies, anti-centromere antibodies, anti-fibrillarin antibodies, anti-PM-SCL antibodies.. It is necessary to reduce delays in the diagnosis of SSc. Conclusions: Patients with red-flag positivity (Raynaud phenomenon and digital edema require Phase I SSc screening, which consists in capillaroscopic assessment of possible microvascular abnormalities. The work-up will then focus on inflammatory indices, renal function tests, and internal organ involvement (echocardiography, high-resolution computed tomography of the chest, diffusing capacity of the lungs for carbon monoxide.

  18. CURRENT VIEWS ON THE HETEROGENEITY OF RENAL INVOLVEMENTS IN PATIENTS WITH SYSTEMIC SCLEROSIS

    Directory of Open Access Journals (Sweden)

    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.

  19. 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.

  20. Autonomic Dysfunction Predicts Early Cardiac Affection in Patients with Systemic Sclerosis

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    Khaled M. Othman

    2010-01-01

    Full Text Available Objective To detect the early preclinical alterations in cardiac autonomic control as well as altered cardiac function in systemic sclerosis (SSc patients and their relevance to the clinical features of the disease using noninvasive methods. Methods 30 SSc patients and 15 healthy controls matched for age and sex underwent clinical examination, serological analysis, and echocardiographic assessment including Doppler flow imaging to evaluate cardiac function, and 24-hour Holter monitoring analyzed for arrhythmia and heart rate variability (HRV in the time and frequency domains. Results The trans-mitral Doppler of early to atrial wave (E/A ratio was reversed in five patients (16.6% and the tricuspid E/A ratio was reversed in 10 patients (33.3%. Holter analysis for SSc patients revealed an increased prevalence of premature ventricular contractions (PVC ≥ 10/h ( P = 0.02, supra-ventricular tachycardias (SVTs ( P = 0.2, and total PVC count ( P = 0.0000. Highly significant ( P = 0.000 impairment in all HRV parameters was demonstrated in the SSc patients. Total skin thickness score (TSS, Raynaud's phenomenon and anti-scleroderma 70 (anti-SCL70 showed significant positive correlations with all arrhythmia parameters, while showing a significant negative correlation with the impaired ventricular diastolic function and various HRV parameters. No correlation was found between arrhythmia and HRV parameters and disease duration, disease type, or presence of anti-centromere antibodies. Conclusion Low heart rate variability, increased TSS and the presence of anti-SCL70 are correlated with preclinical cardiac involvement in SSc patients and may predict the likelihood of malignant arrhythmia and sudden cardiac death. Therefore, noninvasive HRV evaluation before clinical cardiac involvement in these patients might be beneficial when added to the clinical and laboratory assessments in detecting high-risk patients, and may allow for implementation of preventive

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

    Science.gov (United States)

    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.

  2. 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

  3. Determinants of unemployment amongst Australian systemic sclerosis patients: results from a multicentre cohort study.

    Science.gov (United States)

    Morrisroe, Kathleen; Huq, Molla; Stevens, Wendy; Rabusa, Candice; Proudman, Susanna M; Nikpour, Mandana

    2016-01-01

    We sought to assess employment status, risk factors for unemployment and the associations of unemployment with patients' health related quality of life (HRQoL). All patients enrolled in a systemic sclerosis (SSc) longitudinal cohort study, completed an employment questionnaire on enrolment. Clinical manifestations were defined based on presence at the time of enrolment. Summary statistics, chi-square tests, univariate and multivariable logistic regression were used to determine the associations of various risk factors with employment. Among 1587 SSc patients, 160 (20%) were unemployed at the time of cohort enrolment excluding retired patients. Of these, 63% had limited disease subtype. Mean (±SD) age at enrollment was 51.9 (±10.4) years; 13 years below the average retirement age in Australia. Mean (±SD) disease duration at recruitment was 11.1 (±10.9) years. Multivariable regression analysis revealed the presence of digital amputation (OR 3.9, 95%CI 1.7-9.1, p=0.002), diffuse disease subtype (OR 2.2, 95%CI 1.3-3.5, p-value=0.002), sicca symptoms (OR 2.7, 95%CI 1.6-4.4, punemployment. Unemployed patients had consistently poorer HRQoL scores in all domains (physical, emotional and mental health) of the SF-36 form than those who were employed. SSc is associated with substantial work disability and unemployment, which is in turn associated with poor quality of life. Raising awareness, identifying modifiable risk factors and implementing employment strategies and work place modifications are possible ways of reducing this burden.

  4. Prediction of improvement in skin fibrosis in diffuse cutaneous systemic sclerosis: a EUSTAR analysis.

    Science.gov (United States)

    Dobrota, Rucsandra; Maurer, Britta; Graf, Nicole; Jordan, Suzana; Mihai, Carina; Kowal-Bielecka, Otylia; Allanore, Yannick; Distler, Oliver

    2016-10-01

    Improvement of skin fibrosis is part of the natural course of diffuse cutaneous systemic sclerosis (dcSSc). Recognising those patients most likely to improve could help tailoring clinical management and cohort enrichment for clinical trials. In this study, we aimed to identify predictors for improvement of skin fibrosis in patients with dcSSc. We performed a longitudinal analysis of the European Scleroderma Trials And Research (EUSTAR) registry including patients with dcSSc, fulfilling American College of Rheumatology criteria, baseline modified Rodnan skin score (mRSS) ≥7 and follow-up mRSS at 12±2 months. The primary outcome was skin improvement (decrease in mRSS of >5 points and ≥25%) at 1 year follow-up. A respective increase in mRSS was considered progression. Candidate predictors for skin improvement were selected by expert opinion and logistic regression with bootstrap validation was applied. From the 919 patients included, 218 (24%) improved and 95 (10%) progressed. Eleven candidate predictors for skin improvement were analysed. The final model identified high baseline mRSS and absence of tendon friction rubs as independent predictors of skin improvement. The baseline mRSS was the strongest predictor of skin improvement, independent of disease duration. An upper threshold between 18 and 25 performed best in enriching for progressors over regressors. Patients with advanced skin fibrosis at baseline and absence of tendon friction rubs are more likely to regress in the next year than patients with milder skin fibrosis. These evidence-based data can be implemented in clinical trial design to minimise the inclusion of patients who would regress under standard of care. 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/

  5. Specific central nervous system recruitment of HLA-G(+) regulatory T cells in multiple sclerosis.

    Science.gov (United States)

    Huang, Yu-Hwa; Zozulya, Alla L; Weidenfeller, Christian; Metz, Imke; Buck, Dorothea; Toyka, Klaus V; Brück, Wolfgang; Wiendl, Heinz

    2009-08-01

    We have recently described a novel population of natural regulatory T cells (T(reg)) that are characterized by the expression of HLA-G and may be found at sites of tissue inflammation (HLA-G(pos) T(reg)). Here we studied the role of these cells in multiple sclerosis (MS), a prototypic autoimmune inflammatory disorder of the central nervous system (CNS). Sixty-four patients with different types of MS, 9 patients with other neurological diseases, and 20 healthy donors were included in this study. Inflamed brain lesions from 5 additional untreated MS patients were examined. HLA-G(pos) T(reg) were analyzed in the cerebrospinal fluid (CSF) by flow cytometry and in inflammatory demyelinating lesions of MS brain specimens by immunohistochemistry. Functional capacity was accessed and transmigration was determined using an in vitro model of the human blood-brain barrier (BBB). HLA-G(pos) T(reg) were found enriched in the inflamed CSF of MS patients and in inflammatory demyelinating lesions of MS brain specimens. HLA-G(pos) T(reg) showed a strong propensity to transmigrate across BBB, which was vigorously driven by inflammatory chemokines, and associated with a gain of suppressive capacity upon transmigration. CSF-derived HLA-G(pos) T(reg) of MS patients represented a population of activated central memory activated T cells with an upregulated expression of inflammatory chemokine receptors and exhibiting full suppressive capacity. Unlike natural FoxP3-expressing T(reg), HLA-G(pos) T(reg) derived from peripheral blood were functionally unimpaired in MS. In MS, HLA-G(pos) T(reg) may serve to control potentially destructive immune responses directly at the sites of CNS inflammation and to counterbalance inflammation once specifically recruited to the CNS.

  6. Angiogenic T cell expansion correlates with severity of peripheral vascular damage in systemic sclerosis.

    Directory of Open Access Journals (Sweden)

    Mirko Manetti

    Full Text Available The mechanisms underlying endothelial cell injury and defective vascular repair in systemic sclerosis (SSc remain unclear. Since the recently discovered angiogenic T cells (Tang may have an important role in the repair of damaged endothelium, this study aimed to analyze the Tang population in relation to disease-related peripheral vascular features in SSc patients. Tang (CD3+CD31+CXCR4+ were quantified by flow cytometry in peripheral blood samples from 39 SSc patients and 18 healthy controls (HC. Circulating levels of the CXCR4 ligand stromal cell-derived factor (SDF-1α and proangiogenic factors were assessed in paired serum samples by immunoassay. Serial skin sections from SSc patients and HC were subjected to CD3/CD31 and CD3/CXCR4 double immunofluorescence. Circulating Tang were significantly increased in SSc patients with digital ulcers (DU compared either with SSc patients without DU or with HC. Tang levels were significantly higher in SSc patients with late nailfold videocapillaroscopy (NVC pattern than in those with early/active NVC patterns and in HC. No difference in circulating Tang was found when comparing either SSc patients without DU or patients with early/active NVC patterns and HC. In SSc peripheral blood, Tang percentage was inversely correlated to levels of SDF-1α and CD34+CD133+VEGFR-2+ endothelial progenitor cells (EPC, and positively correlated to levels of vascular endothelial growth factor and matrix metalloproteinase-9. Tang were frequently detected in SSc dermal perivascular inflammatory infiltrates. In summary, our findings demonstrate for the first time that Tang cells are selectively expanded in the circulation of SSc patients displaying severe peripheral vascular complications like DU. In SSc, Tang may represent a potentially useful biomarker reflecting peripheral vascular damage severity. Tang expansion may be an ineffective attempt to compensate the need for increased angiogenesis and EPC function. Further

  7. Reliability of widefield capillary microscopy to measure nailfold capillary density in systemic sclerosis.

    Science.gov (United States)

    Hudson, M; Masetto, A; Steele, R; Arthurs, E; Baron, M

    2010-01-01

    To determine intra- and inter-observer reliability of widefield microscopy to measure nailfold capillary density in patients with systemic sclerosis (SSc). Five SSc patients were examined with a STEMV-8 Zeiss biomicroscope with 50x magnification. The nailfold of the second, third, fourth and fifth fingers of both hands of each patient were photographed twice by each of two observers, once in the morning and again in the afternoon (total of 32 pictures). Two raters reviewed the photographs to produce capillary density readings. Intra- and inter-rater reliability of the readings were computed using intra-class correlations (ICC). Additional analyses were undertaken to determine the impact of other sources of variability in the data, namely patient, finger, technician and time. Intra-and inter-rater reliability were substantial (ICC 0.72-0.84) when raters were reading the same photographs or photographs taken at the same time of day. Agreement was only fair between morning and afternoon density readings (ICC 0.30-0.37). Patients, individual fingers and technician accounted for a large part of the variability in the data (combined variance component of 7.69 out of the total 12.23). The coefficient of variation of widefield microscopy was 24%. Although intra- and inter-rater reliability of nailfold capillary density measurements using widefield microscopy are good, proper standardisation of the conditions under which capillaroscopy is done and better imaging of nailfold capillary abnormalities should be considered if nailfold capillary density is to be used as an outcome measure in multi-centre clinical trials in SSc.

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

    Science.gov (United States)

    Yuen, H K; Hant, F N; Hatfield, C; Summerlin, L M; Smith, E A; Silver, R M

    2014-08-01

    To identify factors associated with oral hygiene practices in adults with systemic sclerosis (SSc). 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. Multivariable logistic regression modelling 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. 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. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. A New Way of Thinking about Systemic Sclerosis: The Opportunity for a Very Early Diagnosis.

    Science.gov (United States)

    Guiducci, Serena; Bellando-Randone, Silvia; Matucci-Cerinic, Marco

    2016-01-01

    Systemic sclerosis (SSc) is a heterogeneous chronic autoimmune disease that it is extremely difficult to diagnose in the early phase, resulting in a critical delay in therapy which is often begun when internal organ involvement is already irreversible. The ACR or LeRoy criteria have a low sensitivity for the early phases; these criteria were replaced by the ACR/EULAR 2013 criteria which improved the disease classification. Therefore, the SSc diagnosis may be delayed for several years after the onset of Raynaud's phenomenon (RP) and even after the onset of the first non-RP symptom. RP, antinuclear antibodies (ANA) positivity, and puffy fingers were recently indicated as "red flags" (by the VEDOSS project)--that is, the main elements for suspicion of SSc in the very early phase of the disease. Confirming the diagnosis requires further tests, particularly nailfold videocapillaroscopy and evaluation of specific disease antibodies (anti-centromere and anti-topoisomerase I). In this way, the VEDOSS project identified patients in the very early phase of disease enabling a "window of opportunity" whereby the physician can act with effective drugs to block or at least slow the progression of the disease. The principal challenge in the fight against SSc is to detect valid predictors of disease evolution in order to treat patients in the early stage of disease. While waiting to find valid predictors, a close follow-up of the patients with the VEDOSS red flags is essential, as is a close collaboration between rheumatologists and general practitioners in order to identify all potential SSc patients as soon as possible.

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

    Science.gov (United States)

    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.

  11. Nailfold Videocapillaroscopy Alterations in Dermatomyositis and Systemic Sclerosis: Toward Identification of a Specific Pattern.

    Science.gov (United States)

    Manfredi, Andreina; Sebastiani, Marco; Campomori, Federica; Pipitone, Nicolò; Giuggioli, Dilia; Colaci, Michele; Praino, Emanuela; Ferri, Clodoveo

    2016-08-01

    The term scleroderma pattern typically defines capillary abnormalities of scleroderma spectrum disorders, mainly systemic sclerosis (SSc) and dermatomyositis (DM). Our study aimed to investigate differences in nailfold videocapillaroscopy (NVC) between DM and SSc, with a cross-sectional and longitudinal evaluation. NVC features of 29 consecutive patients with DM were compared with 90 patients with SSc categorized into the 3 subsets of scleroderma pattern: early, active, and late. Twenty patients with DM and all with SSc were also longitudinally reevaluated after 30 months of followup. At baseline, all SSc groups showed giant capillaries, with significant differences with DM only for early and active pattern. Ramified capillaries were significantly more frequent and severe in DM than in early and active patterns, while DM showed an opposite trend compared with late pattern. Capillary loss was lower in early pattern and higher in active and late, compared with DM. Finally, giant-ramified capillaries were almost exclusive of DM. During followup, NVC showed a different evolution in DM and SSc. In DM we recorded a reduction of giant capillaries, while ramified capillaries increased both in DM and in early and active SSc pattern. The number of capillaries recovered in DM; conversely, capillary loss slightly worsened in all SSc patterns. Giant-ramified capillaries significantly decreased in patients with DM, remaining rare in patients with SSc. Our study strengthens the specificity of DM and SSc microangiopathy and points out the need for large prospective studies to confirm our results and possibly to revise current terminology by distinguishing between "scleroderma" and "dermatomyositis" patterns.

  12. 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.

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

    Science.gov (United States)

    2010-01-01

    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 < 0.001) compared to the control group (244 ± 96 μg/ml). In contrast, there was no statistically significant difference between blood DBP concentrations in patients with MS (310 ± 68 μg/ml) and the control group (314 ± 82 μg/ml). GSN and DBP concentrations in CSF also did not significantly differ between those two groups. 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. PMID:21040581

  14. Imatinib Mesylate Causes Genome-wide Transcriptional Changes in Systemic Sclerosis Fibroblasts in vitro

    Science.gov (United States)

    Hinchcliff, Monique; Huang, Chiang-Ching; Ishida, Wataru; Fang, Feng; Lee, Jungwha; Jafari, Nadereh; Wilkes, Mark; Bhattacharyya, Swati; Leof, Edward; Varga, John

    2013-01-01

    Objective Systemic sclerosis (SSc) is a heterogeneous multifactorial disease dominated by progressive skin and internal organ fibrosis that is driven in part by Transforming Growth Factor-beta (TGF-β). An important downstream target of TGF-β is the Abelson (c-Abl) tyrosine kinase, and its inhibition by imatinib mesylate (Gleevec)attenuates fibrosis in mice. Here we examined the effect of c-Abl activation and blockade in explanted healthy control and SSc fibroblasts. Methods Skin biopsies and explanted fibroblasts from healthy subjects and patients with SSc were studied. Changes in genome-wide expression patterns in imatinib-treated control and SSc fibroblasts were analyzed by DNA microarray. Results Treatment of control fibroblasts with TGF-β resulted in activation of c-Abl and stimulation of fibrotic gene expression that was prevented by imatinib. Moreover, imatinib reduced basal collagen gene expression in SSc but not control fibroblasts. No significant differences in tissue levels of c-Abl and phospho-c-Abl were detected between SSc and control skin biopsies. In vitroimatinib induced dramatic changes in the expression of genes involved in fibrosis, cardiovascular disease, inflammation, and lipid and cholesterol metabolism. Remarkably, of the 587-imatinib-responsive genes, 91% showed significant change in SSc fibroblasts, but only 12% in control fibroblasts. Conclusion c-Abl plays a key role in fibrotic responses. Imatinib treatment results in dramatic changes in gene expression in SSc fibroblasts but has only modest effects in control fibroblasts. These data provide novel insights into the mechanisms underlying the antifibrotic effect of imatinib in SSc. PMID:22691216

  15. Increased risk for bone loss in women with systemic sclerosis: a comparative study with rheumatoid arthritis.

    Science.gov (United States)

    Kilic, Gamze; Kilic, Erkan; Akgul, Ozgur; Ozgocmen, Salih

    2016-04-01

    To assess bone mass in women with systemic sclerosis (SSc) in comparison to age and sex-matched patients with rheumatoid arthritis (RA), and to evaluate factors influencing bone mineral density (BMD). Patients were consecutively recruited and assessed for BMD at the lumbar spine and hip by dual-energy X-ray absorptiometry (DEXA) using a densitometer. In SSc, the extent of skin involvement, modified Rodnan skin thickness score (mRSS) and Medsger disease severity index were assessed. Forty-three patients with SSc and 38 age-matched patients with RA were included. There was no difference in BMD measurements between patients with diffuse or limited SSc. Patients with SSc had similar risk factors associated with osteoporosis (OP) or low bone mass except for low body mass index (BMI) and low vitamin D levels compared to patients with RA. Lumbar spinal BMD and T score were similar between groups. Total hip and femoral neck BMD and T score at femoral neck and total hip were significantly lower in patient with SSc versus RA. There was significant association between mRSS, Medsger severity score (peripheral vascular involvement and skin) and femoral BMD. There is an increased risk for bone loss in patients with SSc and the risk of OP is associated with disease severity, prolonged menopause and disease duration. The complex pathophysiology of bone metabolism as well as complex pathogenesis of the SSc pose some difficulty reaching clear-cut conclusions on the causal relationship between SSc and bone loss. © 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  16. Tuberous sclerosis

    Science.gov (United States)

    ... symptoms. Depending on the severity of the mental disability, the child may need special education. Some seizures are controlled ... often do well. However, children with severe mental disability or ... when a child is born with severe tuberous sclerosis, one of ...

  17. Multiple Sclerosis

    Science.gov (United States)

    ... read or download the National Academies/Institute of Medicine report, go to: " Multiple Sclerosis: Current Status and Strategies for the Future ." Information from the National Library of Medicine’s MedlinePlus ...

  18. Usage of Multimodal Evoked Potentials in Diagnosis of Changes in Central Nervous System in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Bahar Özbek

    2011-03-01

    Full Text Available OBJECTIVE: Evoked potentials are used in the functional assessment of sensory and motor pathways. Conflicting results have been reported in different studies about the value of evoked potentials in demyelinating diseases. Over 80% of patients with multiple sclerosis present with a relapsing–remitting form of the disease. In this study we aimed to examine the value of each evoked potential to demonstrate the demyelinating lesions in a homogenous group of patients with relapsing remitting multiple sclerosis. We also aimed to examine the correlation between clinical status and evoked potential abnormalities. METHODS: Twenty patients with relapsing remitting multiple sclerosis and ten healthy volunteers were included in the study to evaluate the value of evoked potentials in a homogenous group. Visual, somatosensory and motor evoked potentials were measured and EDSS scores of the patients were calculated. RESULTS: Of 20 patients, 15 patients(75% had VEP abnormality, 14 patients (70% had MEP abnormality and 12 patients (60% had tibial SEP abnormality. All patients had at least one abnormal evoked potential measurement. The abnormality of evoked potentials also had a correlation with high EDSS scores. CONCLUSION: We concluded that evoked potentials, especially used in combination, are good markers to show the nervous damage in patients with multiple sclerosis

  19. 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

  20. 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

  1. Pressure and pain In Systemic sclerosis/Scleroderma - an evaluation of a simple intervention (PISCES: randomised controlled trial protocol

    Directory of Open Access Journals (Sweden)

    Alcacer-Pitarch Begonya

    2012-02-01

    Full Text Available Abstract Background Foot problems associated with Systemic Sclerosis (SSc/Scleroderma have been reported to be both common and disabling. There are only limited data describing specifically, the mechanical changes occurring in the foot in SSc. A pilot project conducted in preparation for this trial confirmed the previous reports of foot related impairment and reduced foot function in people with SSc and demonstrated a link to mechanical etiologies. To-date there have been no formal studies of interventions directed at the foot problems experienced by people with Systemic Sclerosis. The primary aim of this trial is to evaluate whether foot pain and foot-related health status in people with Systemic Sclerosis can be improved through the provision of a simple pressure-relieving insole. Methods The proposed trial is a pragmatic, multicenter, randomised controlled clinical trial following a completed pilot study. In four participating centres, 140 consenting patients with SSc and plantar foot pain will be randomised to receive either a commercially available pressure relieving and thermally insulating insole, or a sham insole with no cushioning or thermal properties. The primary end point is a reduction in pain measured using the Foot Function Index Pain subscale, 12 weeks after the start of intervention. Participants will complete the primary outcome measure (Foot Function Index pain sub-scale prior to randomisation and at 12 weeks post randomisation. Secondary outcomes include participant reported pain and disability as derived from the Manchester Foot Pain and Disability Questionnaire and plantar pressures with and without the insoles in situ. Discussion This trial protocol proposes a rigorous and potentially significant evaluation of a simple and readily provided therapeutic approach which, if effective, could be of a great benefit for this group of patients. Trial registration number ISRCTN: ISRCTN02824122

  2. 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.

  3. Designing to Sample the Unknown: Lessons from OSIRIS-REx Project Systems Engineering

    Science.gov (United States)

    Everett, David; Mink, Ronald; Linn, Timothy; Wood, Joshua

    2017-01-01

    On September 8, 2016, the third NASA New Frontiers mission launched on an Atlas V 411. The Origins, Spectral Interpretation, Resource Identification, Security-Regolith Explorer (OSIRIS-REx) will rendezvous with asteroid Bennu in 2018, collect a sample in 2020, and return that sample to Earth in September 2023. The development team has overcome a number of challenges in order to design and build a system that will make contact with an unexplored, airless, low-gravity body. This paper will provide an overview of the mission, then focus in on the system-level challenges and some of the key system-level processes. Some of the lessons here are unique to the type of mission, like discussion of operating at a largely-unknown, low-gravity object. Other lessons, particularly from the build phase, have broad implications. The OSIRIS-REx risk management process was particularly effective in achieving an on-time and under-budget development effort. The systematic requirements management and verification and the system validation also helped identify numerous potential problems. The final assessment of the OSIRIS-REx performance will need to wait until the sample is returned in 2023, but this post-launch assessment will capture some of the key systems-engineering lessons from the development team.

  4. Reply: Pauling, et al., Efficacy and Safety of Selexipag in Adults With Raynaud's Phenomenon Secondary to Systemic Sclerosis.

    Science.gov (United States)

    Denton, Christopher P; Herrick, Ariane L

    2018-03-07

    Pauling et al highlight some of the limitations of using the Raynaud's Condition Score (RCS) in clinical trials of Raynaud's phenomenon and the need for better patient reported outcome measures. They have explored this in a survey of patients with systemic sclerosis who completed the RCS and although the number of cases in the survey is small, and possibly not representative of a clinical trial population, the points raised are interesting.We acknowledge the difficulties of undertaking clinical trials in Raynaud's phenomenon. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. 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.)

  6. 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.

  7. Lessons learned from a whole hospital PACS installation. Picture Archiving and Communication System.

    Science.gov (United States)

    Pilling, J R

    2002-09-01

    The Norfolk and Norwich University Hospital has incorporated a fully filmless Picture Archiving and Communication System (PACS) as part of a new hospital provision using PFI funding. The PACS project has been very successful and has met with unanimous acclaim from radiologists and clinicians. A project of this size cannot be achieved without learning some lessons from mistakes and recognising areas where attention to detail resulted in a successful implementation. This paper considers the successes and problems encountered in a large PACS installation.

  8. Lessons Learned from the Space Shuttle Engine Cutoff System (ECO) Anomalies

    Science.gov (United States)

    Martinez, Hugo E.; Welzyn, Ken

    2011-01-01

    The Space Shuttle Orbiter's main engine cutoff (ECO) system first failed ground checkout in April, 2005 during a first tanking test prior to Return-to-Flight. Despite significant troubleshooting and investigative efforts that followed, the root cause could not be found and intermittent anomalies continued to plague the Program. By implementing hardware upgrades, enhancing monitoring capability, and relaxing the launch rules, the Shuttle fleet was allowed to continue flying in spite of these unexplained failures. Root cause was finally determined following the launch attempts of STS-122 in December, 2007 when the anomalies repeated, which allowed drag-on instrumentation to pinpoint the fault (the ET feedthrough connector). The suspect hardware was removed and provided additional evidence towards root cause determination. Corrective action was implemented and the system has performed successfully since then. This white paper presents the lessons learned from the entire experience, beginning with the anomalies since Return-to-Flight through discovery and correction of the problem. To put these lessons in better perspective for the reader, an overview of the ECO system is presented first. Next, a chronological account of the failures and associated investigation activities is discussed. Root cause and corrective action are summarized, followed by the lessons learned.

  9. Evaluation of membrane-bound and soluble forms of HLA-G in Systemic Sclerosis.

    Science.gov (United States)

    Contini, Paola; Negrini, Simone; Murdaca, Giuseppe; Borro, Matteo; Puppo, Francesco

    2018-04-16

    Systemic sclerosis (SSc) is a complex disease characterized by immune dysregulation, extensive vascular damage and wide-spread fibrosis. Human leukocyte antigen-G (HLA-G) is a non-classic class I major histocompatibility complex (MHC) molecule characterized by complex immuno-modulating properties. HLA-G is expressed on the membrane of different cell lineages in both physiological and pathological conditions. HLA-G is also detectable in soluble form (sHLA-G) deriving from the shedding of surface isoforms (sHLA-G1) or the secretion of soluble isoforms (HLA-G5). Several immunosuppressive functions have been attributed to both membrane-bound and soluble HLA-G molecules. The plasma levels of sHLA-G were higher in SSc patients (444.27 ± 304.84 U/ml) as compared to controls (16.74 ± 20.58 U/ml) (p G (r: 0.65; p G1 (r: 0.60; p = 0.003) and HLA-G5 (r: 0.47; p = 0.02). The percentage of HLA-G-positive monocytes (0.98 ± 1.72), CD4+ (0.37 ± 0.68), CD8+ (2.05 ± 3.74) and CD4+CD8+ double positive cells (14.53 ± 16.88) was higher in SSc patients than in controls (0.11 ± 0.08, 0.01 ± 0.01, 0.01 ± 0.01 and 0.39 ± 0.40, respectively) (p G molecules and the membrane expression of HLA-G by PBMC is clearly elevated suggesting an involvement of HLA-G molecules in the immune dysregulation of SSc. This article is protected by copyright. All rights reserved. © 2018 British Society for Immunology.

  10. 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

  11. 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

    2017-01-01

    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 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. Results 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. Conclusions 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. Trial registration number NCT02339441. PMID:28188239

  12. Clinical differences between Thai systemic sclerosis patients with positive versus negative anti-topoisomerase I.

    Science.gov (United States)

    Foocharoen, Chingching; Suwannachat, Prangsuporn; Netwijitpan, Sittichai; Mahakkanukrauh, Ajanee; Suwannaroj, Siraphop; Nanagara, Ratanavadee

    2016-03-01

    Anti-topoisomerase I antibody (ATA) carries an increased risk of systemic sclerosis (SSc) internal organ involvement. There have been no published comparisons of the clinical characteristics of patients positive and negative for ATA in Thailand, where the positive rate for ATA is higher than among Caucasians. To define the clinical differences between SSc, positive versus negative, for ATA. A retrospective cohort study was performed among SSc patients over 18 at Srinagarind Hospital, Khon Kaen University, Thailand, during January 2006-December 2013. SSc-overlap syndrome was excluded. Two hundred and ninety-four SSc patients were included (female : male 2.5 : 1). The majority (68.6%) were the diffuse cutaneous SSc subset (dcSSc). ATA was positive in 252 patients (85.7%), among whom 71.7% had dcSSc and 28.2% limited cutaneous SSc (lcSSc). Using a multivariate analysis, hand deformity had a significantly positive association with ATA (odds ratio [OR] 7.01; 95% CI 1.02-48.69), whereas being anti-centromere (ACA) positive had a negative association (OR 0.17; 95% CI 0.03-0.92). After doing a subgroup analysis of the SSc subset, the median duration of disease at time of pulmonary fibrosis detection among ATA positive dcSSc was significantly shorter than the ATA negative group (1.05 vs. 6.77 years, P = 0.01). Raynaud's phenomenon (RP) at onset was significantly more frequent in lcSSc sufferers who were ATA negative than those who were ATA positive (90.5% vs. 56.9%, P = 0.005). A high prevalence of ATA positivity was found among Thai SSc patients and this was associated with a high frequency of hand deformity, ACA negativity, a short duration of pulmonary fibrosis in dcSSc and a lower frequency of RP in lcSSc. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  13. NASA's Earth Science Data Systems - Lessons Learned and Future Directions

    Science.gov (United States)

    Ramapriyan, Hampapuram K.

    2010-01-01

    In order to meet the increasing demand for Earth Science data, NASA has significantly improved the Earth Science Data Systems over the last two decades. This improvement is reviewed in this slide presentation. Many Earth Science disciplines have been able to access the data that is held in the Earth Observing System (EOS) Data and Information System (EOSDIS) at the Distributed Active Archive Centers (DAACs) that forms the core of the data system.

  14. Efficacy of Botulinum Toxin B Injection for Raynaud's Phenomenon and Digital Ulcers in Patients with Systemic Sclerosis.

    Science.gov (United States)

    Motegi, Sei-Ichiro; Uehara, Akihito; Yamada, Kazuya; Sekiguchi, Akiko; Fujiwara, Chisako; Toki, Sayaka; Date, Yuki; Nakamura, Tetsuya; Ishikawa, Osamu

    2017-07-06

    The efficacy and safety of botulinum toxin B (BTX-B) for treatment of Raynaud's phenomenon and digital ulcers in patients with systemic sclerosis was assessed. A total of 45 patients with systemic sclerosis who had Raynaud's phenomenon were blinded and divided randomly into 4 groups: a no-treatment control group, and 3 treatment groups, using 250, 1,000 or 2,000 international units (U) of BTX-B injections in the hand with more severe symptoms. Four weeks after injection, pain/numbness visual analogue scale scores and Raynaud's score in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group and the group treated with 250 U BTX-B. These beneficial effects were sustained until 16 weeks after the single injection. At 4 weeks after injection skin temperature recovery in the group treated with 2,000 U BTX-B was significantly improved. The numbers of digital ulcers in the groups treated with 1,000 and 2,000 U BTX-B were significantly lower than in the control group. In conclusion, 1,000 and 2,000 U BTX-B injections significantly suppressed the activity of Raynaud's phenomenon and digital ulcers in patients with SSc without serious adverse events.

  15. Depressive symptoms in patients with systemic sclerosis: Association between clinical variables, functional status and the quality of life

    Directory of Open Access Journals (Sweden)

    Mustafa Akif Sarıyıldız

    2013-03-01

    Full Text Available Objective: The aim of this study is to evaluate the relationshipbetween the depressive symptoms with diseaserelatedvariables, functional status and quality of life inpatients with systemic sclerosis (SSc.Material and methods: Forty patients diagnosed withSSc and 36 healthy control subjects were enrolled in thestudy. The demographic and clinical characteristics of thepatients such as the Raynaud’s phenomenon, SSc subtype,digital ulcers, gastrointestinal and lung involvementand disease activity were recorded. All patients were assessedusing the Short Form-36 Quality of Life (SF-36QoL scale, the Health Assessment Questionnaire (HAQand the Beck Depression Inventory (BDI. Generalizedpain and fatigue was assessed with the Visual AnalogueScale.Results: The patients with SSc had significantly higherscores in the depressive symptoms in terms of the BDIscore compared to the healthy control group. Accordingto the results of Spearman’s analysis, there was a significantlycorrelation between the depressive symptomswith education level, generalized pain, dyspnea, diseaseactivity score, gastroesophageal reflux, dysphagia, functionalstatus, mental and physical score of the SF-36.Conclusion: Depressive symptoms is enhanced in patientswith SSc. Depressive symptoms is especially associatedwith the generalised pain, disease activity, dysphagia,functional status, mental and quality of life in patientswith SSc.Key words: Systemic sclerosis, depressive symptom,pain, functional status, quality of life

  16. Correlation of Endostatin and Tissue Inhibitor of Metalloproteinases 2 (TIMP2 Serum Levels With Cardiovascular Involvement in Systemic Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Bozena Dziankowska-Bartkowiak

    2005-01-01

    pathogenesis of SSc. Heart fibrosis is one of the most important prognostic factors in SSc patients. So, the aim of our study was to examine cardiovascular dysfunction in SSc patients and its correlation with serum levels of vascular endothelial growth factor (VEGF, endostatin, and tissue inhibitor of metalloproteinase 2 (TIMP2. The study group comprised 34 patients (19 with limited scleroderma (lSSc and 15 with diffuse scleroderma (dSSc. The control group consisted of 20 healthy persons, age and sex matched. Internal organ involvement was assessed on the basis of specialist procedures. Serum VEGF, endostatin, and TIMP2 levels were evaluated by ELISA. We found cardiovascular changes in 15 patients with SSc (8 with lSSc and 7 with dSSc. The observed symptoms were of different characters and also coexisted with each other. Higher endostatin serum levels in all systemic sclerosis patients in comparison to the control group were demonstrated (P<.05. Also higher serum levels of endostatin and TIMP2 were observed in patients with cardiovascular changes in comparison to the patients without such changes (P<.05. The obtained results support the notion that angiogenesis and fibrosis disturbances may play an important role in SSc. Evaluation of endostatin and TIMP2 serum levels seems to be one of the noninvasive, helpful examinations of heart involvement in the course of systemic sclerosis.

  17. Paradoxical reaction of raynaud phenomenon following the repeated administration of iloprost in a patient with diffuse cutaneous systemic sclerosis.

    Science.gov (United States)

    Barreira, Rebeca Iglesias; García, Belén Bardán; López, Mónica Granero; Legazpi, Iria Rodríguez; Díaz, Hortensia Álvarez; Penín, Isaura Rodríguez

    2012-10-01

    To report a paradoxical reaction of Raynaud phenomenon following the repeated administration of iloprost in a patient with diffuse cutaneous systemic sclerosis with vascular involvement. In January 2006, a 40-year-old male was diagnosed with diffuse cutaneous systemic sclerosis with pulmonary, esophageal, cutaneous, and vascular involvement (Raynaud phenomenon, with digital ulcers on his hands). In December 2008, treatment with iloprost was started due to worsening disease. Nine cycles of iloprost were administered at a rate of 0.5-1 ng/kg/min (6 hours per day, for 5 days every 6-8 weeks); the patient tolerated this treatment well. However, on the fourth day of cycles 10 and 11, the patient developed paradoxical Raynaud phenomenon in the hand with perfusion when the infusion was increased to 1 ng/kg/min, requiring treatment to be stopped. Treatment was continued during cycles 12 and 13 at 0.5 ng/kg/min; the patient tolerated the treatment well, although paradoxical Raynaud phenomenon occurred when the rate of infusion was increased. Raynaud phenomenon is extremely common in patients with scleroderma, and often is severe. Iloprost has vasodilating, antiplatelet, cytoprotective, and immunomodulating properties, and has been found to be an efficacious alternative to nifedipine for the treatment of Raynaud phenomenon in patients with scleroderma. The Naranjo probability scale indicated that iloprost was the probable cause of the paradoxical Raynaud phenomenon in this patient. This case demonstrates a probable relationship between the rate of infusion of iloprost and the paradoxical reaction of Raynaud phenomenon.

  18. Wound healing after hand surgery in patients with systemic sclerosis--a retrospective analysis of 41 operations in 19 patients.

    Science.gov (United States)

    Tägil, M; Dieterich, J; Kopylov, P

    2007-06-01

    This retrospective study evaluates the results of 41 consecutive hand and forearm operations in 19 patients with systemic sclerosis performed between 1985 and 2000. The mean age of the patients was 50 (14-84) years. Twenty-seven operations were elective and 14 were acute, carried out for skin breakdown and/or skin necrosis. One minor wound healing problem occurred in the elective group. In the acute group, seven of 14 operations healed uneventfully. Four patients had necrosis/infections after surgery, which required further surgery. Two patients had repeated wound infections. Another patient only healed after he stopped smoking. In systemic sclerosis, surgery performed electively does not seem to have increased difficulty with wound healing. Even larger operations, such as wrist arthrodesis or wrist replacement, can be performed safely. In acute cases with spontaneous skin breakdown and/or necrosis and/or critically ischaemic fingers, wound healing is more precarious and several procedures may be necessary to achieve skin healing.

  19. High-resolution computed tomography versus chest radiography in the diagnosis of interstitial lung disease in systemic sclerosis

    International Nuclear Information System (INIS)

    Azevedo, Ana Beatriz Cordeiro de; Calderaro, Debora; Moreira, Caio; Guimaraes, Silvana Mangeon Meirelles; Tavares Junior, Wilson Campos; Leao Filho, Hilton Muniz; Andrade, Diego Correa de; Ferreira, Cid Sergio; Vieira, Jose Nelson Mendes

    2005-01-01

    Objective: To compare the accuracy of high-resolution computed tomography (HRCT) with chest radiography in the diagnosis of interstitial lung disease in systemic sclerosis (SSc). Materials And Methods: HRCT scans and chest radiographs in postero-anterior and lateral views were performed in 34 patients with systemic sclerosis, according to the American College of Rheumatology preliminary criteria for the diagnosis of SSc. The prevalence of radiological findings suggestive of interstitial lung disease in SSc seen on both imaging methods was compared. Results: Interstitial disease was observed on HRCT images of 31 patients (91%) and in the chest radiographs of 16 patients (47%). The most frequent findings observed on HRCT were septal lines (74%), honeycombing (56%) and parenchymal bands (26%). Chest radiographs showed reticular areas of attenuation in 11 patients (32%) and parenchymal distortion in 12% of the patients. In 18 patients (53%) with normal chest radiographs HRCT showed septal lines in 55%, ground glass in 44%, honeycombing in 38.5% and cysts in 33%. Conclusion: HRCT is more sensitive than chest radiography in the evaluation of incipient interstitial lung involvement in patients with SSc and can provide a justification for immunosuppressive therapy in patients with early disease. (author)

  20. 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 psychological concerns. Thus it should be included in patient evaluations and assessed in daily clinical practice.

  1. Lessons learned in systems change initiatives: benchmarks and indicators.

    Science.gov (United States)

    Kreger, Mary; Brindis, Claire D; Manuel, Diane M; Sassoubre, Lauren

    2007-06-01

    Measuring progress toward systems change, sustainable efforts that address root causes of an issue by changing policies and practices, is a difficult task for communities, evaluators, and foundations. Tracking and documenting changes in resources, power, policy, sustainable funding, structured relationships and roles, and underlying values require multi-level analyses. Systems change analysts must consider at least four "strata" at once: (1) events and trends, (2) patterns of interaction, (3) context and cultural or social models, and (4) the systems themselves. In this paper we provide a brief overview of systems change; a discussion of collaboratives as one "engine" of social change; a discussion of benchmarks and indicators of collaboratives focused on systems change; and suggestions for further research. The analysis draws upon several analytic frameworks described in the literature. We illustrate these concepts with examples from six systems change initiatives funded by The California Endowment. The need for further research is outlined.

  2. Managing a major security system installation: Practical lessons learned

    International Nuclear Information System (INIS)

    Roehrig, S.C.

    1986-01-01

    Sandia National Laboratories has been heavily involved for over a decade in aiding a number of DOE facilities in defining and implementing upgraded security safeguards systems. Because security system definition, design, and installation is still a relatively new field to the commercial world, effective project management must pay special attention to first understanding and then interpreting the unique aspects of a security system for all concerned parties. Experiences from an actual security system installation are used to illustrate some project management approaches which have been found to be effective

  3. Embedding research in health systems: lessons from complexity theory.

    Science.gov (United States)

    Caffrey, Louise; Wolfe, Charles; McKevitt, Christopher

    2016-07-22

    Internationally, there has been increasing focus on creating health research systems. This article aims to investigate the challenges of implementing apparently simple strategies to support the development of a health research system. We focus on a case study of an English National Health Service Hospital Trust that sought to implement the national recommendation that health organisations should introduce a statement about research on all patient admission letters. We apply core concepts from complexity theory to the case study and undertake a documentary analysis of the email dialogue between staff involved in implementing this initiative. The process of implementing a research statement in patient admission letters in one clinical service took 1 year and 21 days. The length of time needed was influenced firstly by adaptive self-organisation, underpinned by competing interests. Secondly, it was influenced by the relationship between systems, rather than simply being a product of issues within those systems. The relationship between the health system and the research system was weaker than might have been expected. Responsibilities were unclear, leading to confusion and delayed action. Conventional ways of thinking about organisations suggest that change happens when leaders and managers change the strategic vision, structure or procedures in an organisation and then persuade others to rationally implement the strategy. However, health research systems are complex adaptive systems characterised by high levels of unpredictability due to self-organisation and systemic interactions, which give rise to 'emergent' properties. We argue for the need to study how micro-processes of organisational dynamics may give rise to macro patterns of behaviour and strategic organisational direction and for the use of systems approaches to investigate the emergent properties of health research systems.

  4. Envolvimento macrovascular e esclerose sistêmica Macrovascular involvement and systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Emmanuelle Tenório Albuquerque Madruga Godoi

    2009-03-01

    .The objectives of this article are to review aspects described in the literature on macrovasculature onset in systemic sclerosis and to assess occurrence and distribution of macrovascular alterations in patients with systemic sclerosis using Doppler ultrasound and ankle-brachial index. In addition, the article evaluates the association of these findings with demographic characteristics, clinical form, clinical course of the disease, Raynauds phenomenon, digital changes, limb ulcers, reabsorption of phalanges, amputation, and risk factors and antecedents of atheromatous disease. A prospective, case series study of 20 patients was performed. The sample was comprised of 19 women, with a mean age of 46.30 years. All patients had objective Raynauds phenomenon, 85% were diffuse, 55% had digital pulp changes, 15% current limb ulcer, 25% reabsorption of phalange, no amputations, and 70% presented one to four risk factors. Studies were performed by color Doppler ultrasound of the aortic and carotid arteries and lower and upper limb arteries to assess thickening of the intima-media complex, presence of plaques and aneurysms. Ankle-brachial index was also performed in lower limb arteries. Ankle-brachial index was normal in all patients, but 12 (60% had macrovascular disease assessed by Doppler ultrasound, nine (45% of these in the aorta, six (30% in the carotid arteries, one (5% in the upper limb arteries, and seven (35% in lower limb arteries. There was an association between macrovascular disease and digital pulp changes (p = 0.0045. Macrovascular disease was identified in 60% of the patients via Doppler ultrasound, but not via ankle-brachial index, which resulted normal in all patients. There was a significant association between macrovascular disease and current digital pulp changes, which did not occur with the other variables.

  5. Illness representations of systemic lupus erythematosus and systemic sclerosis: a comparison of patients, their rheumatologists and their general practitioners.

    Science.gov (United States)

    Arat, Seher; Lenaerts, Jan L; De Langhe, Ellen; Verschueren, Patrick; Moons, Philip; Vandenberghe, Joris; Taelman, Veerle; Westhovens, Rene

    2017-01-01

    Discrepancies in illness representations between patients and physicians result in treatment difficulties, decreased well-being of patients and misunderstandings and disrupted communication. Hence, the objective of this study was to compare illness perceptions of individual patients with systemic lupus erythematosus (SLE) and systemic sclerosis (SSc), their rheumatologists and their general practitioners (GPs) and explore potential differences. This study has a cross-sectional design. Patients with SLE and SSc, who were followed at the rheumatology department of the University Hospitals Leuven (Belgium), completed the revised Illness Perception Questionnaire which measures patients' perceptions of their condition and captures nine dimensions. Physicians completed the Revised Illness Perception Questionnaire for Healthcare Professionals which consists of seven dimensions and measures perceptions of the healthcare professional regarding the disease of their patients. Intraclass correlation was performed to examine relationships between pairs of respondents; Cohen's d was used for estimating the magnitude of the difference. Questionnaires were sent to 284 patients of whom 241 (113 SSc and 128 SLE patients) were included. Five rheumatologists and 160 GPs participated. For both diseases, positive correlations were found for 'consequences', 'illness coherence' and 'emotional representations' among patients, rheumatologists and GPs. GPs scored higher on the 'consequences' of these diseases for the patient (d=0.71 for SLE; d=0.80 for SSc). Differences between rheumatologists and GPs were small for SSc and moderate to large for 'consequences' (d=0.56) and 'timeline acute/chronic' (d=0.95) in SLE with higher scores for GPs. For both diseases and among the three groups, significant correlations are detected for the dimensions 'consequences', 'illness coherence' and 'emotional representations'. Differences between rheumatologists and GPs were mainly detected in the case of SLE

  6. 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...

  7. A sustainable primary care system: lessons from the Netherlands.

    NARCIS (Netherlands)

    Faber, M.J.; Burgers, J.S.; Westert, G.P.

    2012-01-01

    The Dutch primary care system has drawn international attention, because of its high performance at low cost. Primary care practices are easily accessible during office hours and collaborate in a unique out-of-hours system. After the reforms in 2006, there are no copayments for patients receiving

  8. Space Moves: Adding Movement to Solar System Lessons

    Science.gov (United States)

    Jenkins, Deborah Bainer; Heidorn, Brent

    2009-01-01

    Earth and space science figure prominently in the National Science Education Standards for levels 5-8 (NRC 1996). The Earth in the Solar System standard focuses on students' ability to understand (1) the composition of the solar system (Earth, Moon, Sun, planets with their moons, and smaller objects like asteroids and comets) and (2) that…

  9. A sustainable primary care system: lessons from the Netherlands.

    Science.gov (United States)

    Faber, Marjan J; Burgers, Jako S; Westert, Gert P

    2012-01-01

    The Dutch primary care system has drawn international attention, because of its high performance at low cost. Primary care practices are easily accessible during office hours and collaborate in a unique out-of-hours system. After the reforms in 2006, there are no copayments for patients receiving care in the primary care practice in which they are registered. Financial incentives support the transfer of care from hospital specialists to primary care physicians, and task delegation from primary care physicians to practice nurses. Regional collaborative care groups of primary care practices offer disease management programs. The quality assessment system and the electronic medical record system are predominantly driven by health care professionals. Bottom-up and top-down activities contributed to a successful Dutch primary care system.

  10. [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.

  11. Administrative compensation for medical injuries: lessons from three foreign systems.

    Science.gov (United States)

    Mello, Michelle M; Kachalia, Allen; Studdert, David M

    2011-07-01

    The United States requires patients injured by medical negligence to seek compensation through lawsuits, an approach that has drawbacks related to fairness, cost, and impact on medical care. Several countries, including New Zealand, Sweden, and Denmark, have replaced litigation with administrative compensation systems for patients who experience an avoidable medical injury. Sometimes called "no-fault" systems, such schemes enable patients to file claims for compensation without using an attorney. A governmental or private adjudicating organization uses neutral medical experts to evaluate claims of injury and does not require patients to prove that health care providers were negligent in order to receive compensation. Information from claims is used to analyze opportunities for patient safety improvement. The systems have successfully limited liability costs while improving injured patients' access to compensation. American policymakers may find many of the elements of these countries' systems to be transferable to demonstration projects in the U.S.

  12. Lessons from the domestic Ebola response: Improving health care system resilience to high consequence infectious diseases.

    Science.gov (United States)

    Meyer, Diane; Kirk Sell, Tara; Schoch-Spana, Monica; Shearer, Matthew P; Chandler, Hannah; Thomas, Erin; Rose, Dale A; Carbone, Eric G; Toner, Eric

    2017-12-15

    The domestic response to the West Africa Ebola virus disease (EVD) epidemic from 2014-2016 provides a unique opportunity to distill lessons learned about health sector planning and operations from those individuals directly involved. This research project aimed to identify and integrate these lessons into an actionable checklist that can improve health sector resilience to future high-consequence infectious disease (HCID) events. Interviews (N = 73) were completed with individuals involved in the domestic EVD response in 4 cities (Atlanta, Dallas, New York, and Omaha), and included individuals who worked in academia, emergency management, government, health care, law, media, and public health during the response. Interviews were transcribed and analyzed qualitatively. Two focus groups were then conducted to expand on themes identified in the interviews. Using these themes, an evidence-informed checklist was developed and vetted for completeness and feasibility by an expert advisory group. Salient themes identified included health care facility issues-specifically identifying assessment and treatment hospitals, isolation and treatment unit layout, waste management, community relations, patient identification, patient isolation, limitations on treatment, laboratories, and research considerations-and health care workforce issues-specifically psychosocial impact, unit staffing, staff training, and proper personal protective equipment. The experiences of those involved in the domestic Ebola response provide critical lessons that can help strengthen resilience of health care systems and improve future responses to HCID events. Copyright © 2017 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

  13. 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

  14. 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

  15. 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.

  16. Skin autofluorescence, as marker of accumulation of advanced glycation endproducts and of cumulative metabolic stress, is not increased in patients with systemic sclerosis

    NARCIS (Netherlands)

    Hettema, M. E.; Bootsma, H; Graaff, R; de Vries, R; Kallenberg, C G M; Smit, A J

    2011-01-01

    Objective. To investigate whether advanced glycation endproducts (AGEs) in the skin are increased in patients with systemic sclerosis (SSc) and are related to the presence of disease-related and traditional cardiovascular risk factors. Methods. Skin autofluorescence, as a measure for the

  17. The DECam DAQ System: lessons learned after one year of operations

    Science.gov (United States)

    Honscheid, K.; Elliott, A.; Bonati, M.; Buckley-Geer, E.; Castander, F.; da Costa, L.; Diehl, H. T.; Eiting, J.; Estay, O.; Fausti, A.; Flaugher, B.; Karliner, I.; Kuhlmann, S.; Mandrichenko, I.; Neilsen, E.; Patton, K.; Reil, K.; Roodman, A.; Thaler, J.; Schumacher, G.; Serrano, S.; Suchyta, E.; Vittone, M.; Walker, A.

    2014-07-01

    The Dark Energy Camera (DECam) is a new 520 Mega Pixel CCD camera with a 3 square degree field of view built for the Dark Energy Survey (DES). DECam is mounted at the prime focus of the Blanco 4-m telescope at the Cerro-Tololo International Observatory (CTIO). DES is a 5-year, high precision, multi-bandpass, photometric survey of 5000 square degrees of the southern sky that started August 2013. In this paper we briefly review SISPI, the data acquisition and control system of the Dark Energy Camera and follow with a discussion of our experience with the system and the lessons learned after one year of survey operations.

  18. High Gain Antenna System Deployment Mechanism Integration, Characterization, and Lessons Learned

    Science.gov (United States)

    Parong, Fil; Russell, Blair; Garcen, Walter; Rose, Chris; Johnson, Chris; Huber, Craig

    2014-01-01

    The integration and deployment testing of the High Gain Antenna System for the Global Precipitation Measurement mission is summarized. The HGAS deployment mechanism is described. The gravity negation system configuration and its influence on vertical, ground-based, deployment tests are presented with test data and model predictions. A focus is made on the late discovery and resolution of a potentially mission degrading deployment interference condition. The interaction of the flight deployment mechanism, gravity negation mechanism, and use of dynamic modeling is described and lessons learned presented.

  19. Enterprise Digital Asset Management System Pilot: Lessons Learned

    Directory of Open Access Journals (Sweden)

    Yong-Mi Kim

    2007-12-01

    Full Text Available Enterprise digital asset management (DAM systems are beginning to be explored in higher education, but little information about their implementation issues is available. This article describes the University of Michigan’s investigation of managing and retrieving rich media assets in an enterprise DAM system. It includes the background of the pilot project and descriptions of its infrastructure and metadata schema. Two case studies are summarized—one in healthcare education, and one in teacher education and research. Experiences with five significant issues are summarized: privacy, intellectual ownership, digital rights management, uncataloged materials backlog, and user interface and integration with other systems.

  20. STRUCTURAL AND FUNCTIONAL CHANGES EVALUATED BY ECHOCARDIOGRAPHY IN PATIENTS WITH SYSTEMIC SCLEROSIS AND HEART RATE VARIABILITY

    Directory of Open Access Journals (Sweden)

    E. O. Saad

    2017-01-01

    Full Text Available Objective: to estimate heart rate variability (HRV in patients with systemic sclerosis (SS and to investigate their relationship to echocardiographic structural and functional changes in the heart.Subjects and methods. The investigation enrolled 125 patients with SS and 50 gender- and age-matched apparently healthy individuals who made up a control group. In addition to clinical examinations, 73 patients underwent HRV assessment from 24-hour Holter electrocardiogram (ECG monitoring results and 121 patients had echocardiography (EchoCG. 24-hour Holter ECG monitoring was carried out in all control individuals.Results and discussion. Examination of the main parameters of time-domain HRV in patients with SS revealed a significant decline in all temporal and spectral indices, except for the mean R–R interval duration (meanNN, as compared with the control group. EchoCG detected a variety of changes, primarily the induration and calcification of aortic and mitral valves in most patients. Left ventricular diastolic dysfunction was encountered in almost half of the patients with SS. Eight patients had a lower left ventricular ejection fraction (LVEF, which was <55%. Studying the association of HRV values with separate EchoCG parameters revealed significant inverse correlations of the mean standard deviation of R–R intervals in 5-minute recording segments during 24 hours with the thickness of the interventricular septum (r = -0.18; p < 0.05 and with the induration of the aortic valve (r = -0.18; p < 0.05; the square root mean squared of successive differences (RMSSD, ms for R–R intervals and the percentage of adjacent R–R intervals that varied by more than 50 ms (pNN50 correlated with the induration of the aortic valve (r = -0.23; p<0.05 and r = -0.25; p < 0.05, respectively, with the presence of pericarditis (r = -0.24; p < 0.05 and r = -0,27; p < 0.05, respectively, and with the level of pulmonary artery systolic pressure (r = -0

  1. 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...

  2. 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…

  3. 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 correlati...

  4. 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...

  5. Risk of coronary artery disease in patients with systemic sclerosis: a systematic review and meta-analysis.

    Science.gov (United States)

    Ungprasert, Patompong; Charoenpong, Prangthip; Ratanasrimetha, Praveen; Thongprayoon, Charat; Cheungpasitporn, Wisit; Suksaranjit, Promporn

    2014-08-01

    Several chronic inflammatory disorders, such as rheumatoid arthritis and systemic lupus erythematosus, have been shown to increase coronary artery disease (CAD) risk but the data on systemic sclerosis (SSc) is unclear. We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing CAD risk in patients with SSc versus non-SSc participants. Pooled risk ratio and 95 % confidence intervals were calculated using a random effect, generic inverse variance method. Four studies were identified and included in our data analysis. The pooled risk ratio of CAD in patients with SSc was 1.82 (95 % CI, 1.40 to 2.36). The statistical heterogeneity of this meta-analysis was moderate with an I (2) of 73 %. Our study demonstrated a statistically significant increased CAD risk among patients with SSc.

  6. Understanding complex systems: lessons from Auzoux's and von ...

    Indian Academy of Sciences (India)

    2009-12-09

    Dec 9, 2009 ... Animal and human anatomy is among the most complex systems known, and suitable teaching methods have been of great importance in the progress of knowledge. Examining the human body is part of the process by which medical students come to understand living forms. However, the need to ...

  7. Okaholo: Contract labour system and lessons for post colonial ...

    African Journals Online (AJOL)

    These aspects are relevant when exploring the exploitation and attempts at totalitarian control by the colonial administration that nurtured class consciousness and political militancy. The exploitative and repressive conditions entrenched in the contract labour system persisted since the inception of Kavango and Ovambo ...

  8. Lessons learned from small space systems development using magnesium alloys

    Energy Technology Data Exchange (ETDEWEB)

    Matunaga, S.; Sawada, H. [Dept. of Mechanical and Aerospace Engineering, Tokyo Inst. of Tech. (Japan); Furuya, H. [Dept. of Built Environment, Tokyo Inst. of Tech., Kanagawa (Japan); Kogiso, N. [Dept. of Aerospace Engineering, Osaka Prefecture Univ. (Japan)

    2003-07-01

    In this paper, we discuss the effectiveness of magnesium alloys through practical space applications in which we have developed a few small-sized space systems and have used magnesium alloys in order to reduce the total mass of the systems. We introduce three examples of our developed systems. The first one is a CanSat whose is a pico-satellite sized of 350 ml can, less than 350 g in mass, and the second one is a small docking mechanism in order to grasp and guide a micro satellite for a small mothership-daughtership satellites formation flying in orbit. The last one is a CubeSat whose is a pico-satellite sized of 10 cm{sup *}10 cm{sup *}10 cm, less than 1 kg in mass and is planned to launch into a Low Earth orbit. Outline description of the systems is given, and design restrictions against magnesium alloys and the mass reduction effect compared with aluminum alloys are discussed. Also, issues of manufacturing, processing and surface treatment for the elaborate magnesium parts are explored. (orig.)

  9. Lessons learned in digital upgrade projects digital control system implementation at US nuclear power stations

    International Nuclear Information System (INIS)

    Kelley, S.; Bolian, T. W.

    2006-01-01

    AREVA NP has gained significant experience during the past five years in digital upgrades at operating nuclear power stations in the US. Plants are seeking modernization with digital technology to address obsolescence, spare parts availability, vendor support, increasing age-related failures and diminished reliability. New systems offer improved reliability and functionality, and decreased maintenance requirements. Significant lessons learned have been identified relating to the areas of licensing, equipment qualification, software quality assurance and other topics specific to digital controls. Digital control systems have been installed in non safety-related control applications at many utilities within the last 15 years. There have also been a few replacements of small safety-related systems with digital technology. Digital control systems are proving to be reliable, accurate, and easy to maintain. Digital technology is gaining acceptance and momentum with both utilities and regulatory agencies based upon the successes of these installations. Also, new plants are being designed with integrated digital control systems. To support plant life extension and address obsolescence of critical components, utilities are beginning to install digital technology for primary safety-system replacement. AREVA NP analyzed operating experience and lessons learned from its own digital upgrade projects as well as industry-wide experience to identify key issues that should be considered when implementing digital controls in nuclear power stations

  10. 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

  11. Polio Endgame: Lessons Learned From the Immunization Systems Management Group.

    Science.gov (United States)

    Zipursky, Simona; Vandelaer, Jos; Brooks, Alan; Dietz, Vance; Kachra, Tasleem; Farrell, Margaret; Ottosen, Ann; Sever, John L; Zaffran, Michel J

    2017-07-01

    The Immunization Systems Management Group (IMG) was established to coordinate and oversee objective 2 of the Polio Eradication and Endgame Strategic Plan 2013-2018, namely, (1) introduction of ≥1 dose of inactivated poliovirus vaccine in all 126 countries using oral poliovirus vaccine (OPV) only as of 2012, (2) full withdrawal of OPV, starting with the withdrawal of its type 2 component, and (3) using polio assets to strengthen immunization systems in 10 priority countries. The IMG's inclusive, transparent, and partnership-focused approach proved an effective means of leveraging the comparative and complementary strengths of each IMG member agency. This article outlines 10 key factors behind the IMG's success, providing a potential set of guiding principles for the establishment and implementation of other interagency collaborations and initiatives beyond the polio sphere. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  12. Building inclusive health innovation systems: lessons from India.

    Science.gov (United States)

    Abrol, Dinesh; Sundararaman, T; Madhavan, Harilal; Joseph, K J

    2016-11-03

    This article presents an overview of the changes that are taking place within the public and private health innovation systems in India including delivery of medical care, pharmaceutical products, medical devices, and Indian traditional medicine. The nature of the flaws that exist in the health innovation system is pinpointed. The response by the government, the health, technology and medical institutions, and the evolving industry is addressed on a national level. The article also discusses how the alignment of policies and institutions was developed within the scope of national health innovation systems, and how the government and the industry are dealing with the challenges to integrate health system, industry, and social policy development processes. Resumo: O artigo apresenta um panorama das mudanças atualmente em curso dentro dos sistemas público e privado de inovação em saúde na Índia, incluindo a prestação de serviços médicos, produtos farmacêuticos, dispositivos médicos e medicina tradicional indiana. É destacada a natureza das falhas que existem nos sistemas de inovação em saúde. As respostas do governo, das instituições médicas, de saúde e tecnologia e indústrias envolvidas, são abordadas em nível nacional. O artigo também discute como foi desenvolvido o alinhamento de políticas e instituições no escopo dos sistemas nacionais de inovação em saúde, e como governo e indústria estão lidando com os desafios para integrar o sistema de saúde, a indústria e o desenvolvimento de políticas sociais.

  13. Fielding Army Weapon Systems: Experiences and Lessons Learned

    Science.gov (United States)

    1980-06-01

    at the highest rate we can, and the l1wer priority systems at the minimum economic rate.• I 3 Sj3 Inmortance of the Fielding Process However strong and...C OM.i1erdtJ.on neceds to be given to establishing the of- fio undiri.. the DCSLOG raithemr th’.n DCSOPS. El ffici,!-nt. fie].ding n:eq1u.1r4:,s

  14. EUnetHTA information management system: development and lessons learned.

    Science.gov (United States)

    Chalon, Patrice X; Kraemer, Peter

    2014-11-01

    The aim of this study was to describe the techniques used in achieving consensus on common standards to be implemented in the EUnetHTA Information Management System (IMS); and to describe how interoperability between tools was explored. Three face to face meetings were organized to identify and agree on common standards to the development of online tools. Two tools were created to demonstrate the added value of implementing interoperability standards at local levels. Developers of tools outside EUnetHTA were identified and contacted. Four common standards have been agreed on by consensus; and consequently all EUnetHTA tools have been modified or designed accordingly. RDF Site Summary (RSS) has demonstrated a good potential to support rapid dissemination of HTA information. Contacts outside EUnetHTA resulted in direct collaboration (HTA glossary, HTAi Vortal), evaluation of options for interoperability between tools (CRD HTA database) or a formal framework to prepare cooperation on concrete projects (INAHTA projects database). While being entitled a project on IT infrastructure, the work program was also about people. When having to agree on complex topics, fostering a cohesive group dynamic and hosting face to face meetings brings added value and enhances understanding between partners. The adoption of widespread standards enhanced the homogeneity of the EUnetHTA tools and should thus contribute to their wider use, therefore, to the general objective of EUnetHTA. The initiatives on interoperability of systems need to be developed further to support a general interoperable information system that could benefit the whole HTA community.

  15. 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.

  16. 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...

  17. Lessons Learnt from the Monetary System of Guernsey

    Directory of Open Access Journals (Sweden)

    Gábor Sárdi

    2017-10-01

    Full Text Available Bailiwick of Guernsey, situated in the English Channel off the coast of Normandy, just like Jersey and the Isle of Man, is an UK Crown dependency and an autonomous jurisdiction. These Crown dependencies are not members of the Commonwealth of Nations nor of the European Union. Furthermore, Guernsey is not part of France nor of the United Kingdom. This atypical status of Guernsey runs back several hundred years: from 1204 the island takes advantage of its special legal status and in general, it has not been managed badly. Despite all this, it cannot be considered as a totally independent, sovereign state. In addition to its special legal status, Guernsey is considered to be special in regard to its money system. According to a very popular story spread across the economic literature, the issuance of Guernsey pound prospered the island as some kind of a magic cure. While it is a considerable part, the current paper emphasize that it was not the only factor. The issuance happened in an economically declining period of Guernsey: after the Napoleonic wars the previous successful economic situation became worse mainly because of the actions of the British authorities that suppressed smuggling, a formerly thriving economic sector of the island. People established their living on this activity were hit hard, but as before, looked for opportunities where their unique status could be used efficiently, and thus, could stabilize their conditions (shipbuilding, vegetable production, tourism, etc.. Guernsey’s money system, however, remains an important topic as its way of operation is indeed unusual in the global economy. Whereas money supply in most countries consists primarily of privately issued bank-debt money (about 95%, Guernsey (States of Guernsey finance its public spending via quasi state issued money since 1817. This type of money system is usually termed as ‘public money system’ and receives a growing attention nowadays.

  18. Lessons from the Army’s Future Combat Systems Program

    Science.gov (United States)

    2012-01-01

    University DCMA Defense Contracting Management Agency DDR &E Director of Defense Research and Engineering DFARS Defense Federal Acquisition Regulations...th e A rm y Fu tu re C o m b at System s Pro g ram Figure 6.1 Integrated Program Summary for FCS Increment 1 RAND MG1206-6.1 Fiscal year Calendar...Integration Dep PM Operations Dep PM Bus Integration FC S Pro g ram M an ag em en t 145 Figure 6.5 FCS LSI Organization, March 2005 Seattle site lead

  19. 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-associated au......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......-associated autoantibodies. Objective: To investigate whether BAFF levels are associated with disease severity/activity in untreated MS patients, and to assess the effect of IFN-beta therapy on circulating BAFF and anti-myelin basic protein (MBP) autoantibody levels. Results: Twenty-three patients with relapsing......-remitting MS (RRMS) were followed longitudinally from initiation of IFN-beta therapy. Their blood levels of BAFF correlated positively at baseline with the expanded disability status scale (p

  20. Turbine Control System Replacement at NPP NEK; System Specifics, Project Experience and Lessons Learned

    International Nuclear Information System (INIS)

    Mandic, D.; Zilavy, M. J.

    2010-01-01

    constitutes only of soft panels or monitor graphics (all MCB - Main Control Board and its controls are available as graphic images on workstations), while the HMI for FG KFSS includes full scope replica of NEK MCR and MCB. The new PDEH system was installed on two KFSS platforms (BG and FG) in October-November, 2008; pre-outage or on-line field installation work was performed in the January-March 2009 time frame; while the old DEH Mod II was decommissioned and the new plant PDEH system was installed during the outage in April, 2009 and tested with the plant on line in May, 2009. PDEH system improvements and specifics compared to the old DEH system and compared to other similar references will be presented and the most interesting project experience and lessons learned will also be discussed in the paper.(author).

  1. The rise and fall of a risk-based priority system: Lessons from DOE's Environmental Restoration Priority System

    International Nuclear Information System (INIS)

    Jenni, K.E.; Merkhofer, M.W.; Williams, C.

    1995-01-01

    This paper presents the history of the Environmental Restoration Priority System (ERPS), a decision aid developed by the U.S. Department of Energy (DOE) to help determine how to allocate funds for cleaning up hazardous waste sites. Although praised in technical peer review, the system was strongly criticized by stakeholders external to DOE. Ultimately, and in the midst of a National Academy of Sciences review, DOE shelved the system. The rise and fall of ERPS provides useful lessons for analysts hoping to improve risk management in the public sector. 49 refs., 3 figs., 3 tabs

  2. Lessons learned from the Fukushima accident to improve the performance of the national nuclear preparedness system

    International Nuclear Information System (INIS)

    Dewi Apriliani

    2013-01-01

    A study of emergency response failure in the early phase of a nuclear accident in Fukushima, Japan has conducted. This study aimed to obtain lesson learned from the problems and constraints that exist at the time of the Fukushima emergency response. This lesson learned will be adjusted to the situation, conditions and problems in nuclear preparedness systems in Indonesia, so that it can obtain the necessary recommendations to improve the performance of SKNN (National Nuclear Emergency Preparedness System). Recommendations include: improvements in coordination and information systems, including early warning systems and dissemination of information; improvements in the preparation of emergency plans/contingency plan, which includes an integrated disaster management; improvement in the development of disaster management practice/field exercise, by extending the scenario and integrate it with nuclear disaster, chemical, biological, and acts of terrorism; and improvement in public education of nuclear emergency preparedness and also improvement in management for dissemination of information to the public and the mass media. These improvements need to be done as part of efforts in preparing a reliable nuclear emergency preparedness in order to support nuclear power plant development plan. (author)

  3. Estudo da densidade óssea na esclerodermia sistêmica Bone density in systemic sclerosis (scleroderma patients

    Directory of Open Access Journals (Sweden)

    H.C. da Silva

    1997-03-01

    Full Text Available OBJETIVO. A osteopenia em pacientes com esclerodermia sistêmica foi descrita, radiologicamente, em mãos e, por densidade óssea, no terço proximal e distal do rádio. A redução da massa óssea, nesses pacientes, tem sido atribuída à isquemia, imobilização e à menopausa precoce. O objetivo deste estudo é analisar a densidade óssea na coluna, região proximal do fêmur e corpo todo de pacientes com esclerodermia sistêmica. PACIENTES E MÉTODO. Foram examinadas 25 pacientes caucasóides, sem outras condições que pudessem afetar o metabolismo ósseo. A média de idade das pacientes foi de 48 ± 12 anos, e o tempo de doença, de 7 ± 7 anos; 13 estavam na pós-menopausa há 8 ± 8 anos. A medida de massa óssea foi realizada na coluna, região proximal do fêmur e corpo todo, utilizando-se densitômetro de dupla emissão com fonte de raios X (Lunar - modelo DPX. RESULTADOS. Não houve diferença estatisticamente significante na densidade óssea das regiões avaliadas nas pacientes com esclerodermia sistêmica e as mulheres-controle pareadas para a idade, peso, altura e anos de menopausa. A densidade óssea das pacientes com forma limitada não foi diferente daquelas com a forma difusa. Pacientes com calcinose apresentaram menor densidade óssea na região proximal do fêmur que aquelas sem calcinose. CONCLUSÕES. Os autores concluíram que pacientes com esclerodermia sistêmica não apresentam perda de massa óssea. Portanto, a esclerodermia não é um fator de risco para o desenvolvimento de osteoporose generalizada.BACKGROUND - Osteopenia in systemic sclerosis (scleroderma patients was reported in X-ray studies of hands and by proximal and distal forearm bone mass measurement. It has been suggested that bone loss in these patients might be due to chronic ischemia, immobilization and early menopause. Nevertheless it is not established if these patients present generalized osteopenia. To shed light into this point we studied bone

  4. Relapsing Remitting Multiple Sclerosis in X-Linked Charcot-Marie-Tooth Disease with Central Nervous System Involvement

    Directory of Open Access Journals (Sweden)

    Georgios Koutsis

    2015-01-01

    Full Text Available We report a patient with relapsing remitting multiple sclerosis (MS and X-linked Charcot-Marie-Tooth disease (CMTX, carrying a GJB1 mutation affecting connexin-32 (c.191G>A, p. Cys64Tyr which was recently reported by our group. This is the third case report of a patient with CMTX developing MS, but it is unique in the fact that other family members carrying the same mutation were found to have asymptomatic central nervous system (CNS involvement (diffuse white matter hyperintensity on brain MRI and extensor plantars. Although this may be a chance association, the increasing number of cases with CMTX and MS, especially with mutations involving the CNS, may imply some causative effect and provide insights into MS pathogenesis.

  5. 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.

  6. 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...

  7. A technology ecosystem perspective on hospital management information systems: lessons from the health literature.

    Science.gov (United States)

    Bain, Christopher A; Standing, Craig

    2009-01-01

    Hospital managers have a large range of information needs including quality metrics, financial reports, access information needs, educational, resourcing and decision support needs. Currently these needs involve interactions by managers with numerous disparate systems, both electronic such as SAP, Oracle Financials, PAS' (patient administration systems) like HOMER, and relevant websites; and paper-based systems. Hospital management information systems (HMIS) can be thought of sitting within a Technology Ecosystem (TE). In addition, Hospital Management Information Systems (HMIS) could benefit from a broader and deeper TE model, and the HMIS environment may in fact represents its own TE (the HMTE). This research will examine lessons from the health literature in relation to some of these issues, and propose an extension to the base model of a TE.

  8. Lessons from a European study[Financing Renewable Energy Systems

    Energy Technology Data Exchange (ETDEWEB)

    Langniss, Ole [German Aerospace Center, Stuttgart (Germany); Helby, Peter [Lund Univ. (Sweden). Dept. of Environmental and Energy System Studies

    2000-10-01

    A large number of proven technical solutions exists for the use of renewable energies (RE). However, their dissemination is still too slow to meet the political goal of substituting 12 % of the primary energy demand in the European Union by the year 2010. Even renewable energy systems (RES) with economic potential are only partly exploited. There is a long literature concerning the barriers to RE use. In particular it has become clear that the availability of finance and the forms and conditions upon which it is lent have a major impact on RE deployment. An area of importance is the deficiency of appropriate ownership forms and properly adapted financing instruments in certain countries. Moreover, different regulations and institutional barriers in the European countries hinder the free flow of capital for RES within the European common market. On the other hand, solutions have been developed very successfully in individual countries. Differences in cultures and institutions have promoted growth of several approaches to RE investment. These differences can be understood as a European source of experience that constitutes a rich basis for transnational emulation. The research project FIRE analysed and compared the means of financing RES in Austria, Denmark, Germany, Italy, the Netherlands, Spain, Sweden and the United Kingdom to put forward best practise recommendations so that RE deployments will occur at a faster rate. Main tasks of this study were to analyse the means of financing RES in a number of countries; to provide an analysis of best practise; and to provide an analysis of the barriers to the implementation in the investigated countries. Different means of financing RES were analysed in relation to the country-specific environment. This included exogenous conditions such as tax aspects, legal restrictions and subsidies, as well as individually defined risk management strategies and collateral requirements. Eight in-depth-case studies were undertaken for

  9. Using the CLEAN educational resource collection for building three-dimensional lessons to teach the climate system

    Science.gov (United States)

    Gold, A. U.; Sullivan, S. M.; Manning, C. L. B.; Ledley, T. S.; Youngman, E.; Taylor, J.; Niepold, F., III; Kirk, K.; Lockwood, J.; Bruckner, M. Z.; Fox, S.

    2017-12-01

    The impacts of climate change are a critical societal challenge of the 21st century. Educating students about the globally connected climate system is key in supporting the development of mitigation and adaptation strategies. Systems thinking is required for students to understand the complex, dynamic climate systems and the role that humans play within them. The interdisciplinary nature of climate science challenges educators, who often don't have formal training in climate science, to identify resources that are scientifically accurate before weaving them together into units that teach about the climate system. The Climate Literacy and Energy Awareness Network (CLEAN) supports this work by providing over 700 peer-reviewed, classroom-ready resources on climate and energy topics. The resource collection itself provide only limited instructional guidance, so educators need to weave the resources together to build multi-dimensional lessons that develop systems thinking skills. The Next Generation Science Standards (NGSS) science standards encourage educators to teach science in a 3-dimensional approach that trains students in systems thinking. The CLEAN project strives to help educators design NGSS-style, three-dimensional lessons about the climate system. Two approaches are currently being modeled on the CLEAN web portal. The first is described in the CLEAN NGSS "Get Started Guide" which follows a step-by-step process starting with the Disciplinary Core Idea and then interweaves the Cross-Cutting Concepts (CCC) and the Science and Engineering Practices (SEP) based on the teaching strategy chosen for the lesson or unit topic. The second model uses a climate topic as a starting place and the SEP as the guide through a four-step lesson sequence called "Earth Systems Investigations". Both models use CLEAN reviewed lessons as the core activity but provide the necessary framework for classroom implementation. Sample lessons that were developed following these two

  10. Clearance of inhaled technetium-99m-DTPA as a clinical index of pulmonary vascular disease in systemic sclerosis

    Energy Technology Data Exchange (ETDEWEB)

    Kon, O.M.; Daniil, Z.; Bois, R.M. du [Royal Brompton Hospital, Interstitial Lung Disease Unit, London (United Kingdom); Black, C.M. [Royal Free Hospital, Dept. of Rheumatology, London (United Kingdom)

    1999-01-01

    This study evaluated the utility of the clearance time of inhaled diethylenetriamine pentaacetate (DTPA) to distinguish pulmonary vascular disease from early fibrosing alveolitis (FA) in patients with systemic sclerosis (SSc) It was hypothesized that this would be preserved in patients with vascular disease compared with FA, despite similar gas-transfer deficits and matching lung volumes, because of the preservation of alveolar epithelial integrity. All patients had SSc and were categorized into a control group (C; n=9), pulmonary vascular group (VAS; n=14) or FA group (n=14) dependent on the appearance on a computed tomography (CT) scan and the transfer factor of the lung for carbon monoxide (TL,CO) (VAS and FA {<=}70%, C {>=}80%). All patients had a forced vital capacity (FVC) of >80%. The TL,CO (median) was similar in the VAS (57.5%) and FA (60%) groups. There was a significant difference in median DTPA clearance half-times between FA (21.25 min) and VAS (46.5 min) (p=0.014) and between FA and C (84.5 min) (p=0.0004). No difference was found between VAS and C (p=0.0778). Follow-up data from the VAS group showed no subsequent development of FA on the CT scan and no decrease in FVC (n=13, mean 42 months). These results suggest that clearance of diethylenetriamine pentaacetate is preserved in patients likely to have pulmonary vascular disease and may be useful in distinguishing fibrosing alveolitis from vascular disease in systemic sclerosis. (au) 22 refs.

  11. Bone mineral density, bone turnover markers and fractures in patients with systemic sclerosis: a case control study.

    Directory of Open Access Journals (Sweden)

    Marco Atteritano

    Full Text Available OBJECTIVE: The aim of our study was to elucidate the pathophysiology of systemic sclerosis-related osteoporosis and the prevalence of vertebral fragility fracture in postmenopausal women with systemic sclerosis (SSc. METHODOLOGY: Fifty-four postmenopausal women with scleroderma and 54 postmenopausal controls matched for age, BMI, and smoking habits were studied. BMD was measured by dual energy-x-ray absorptiometry at spine and femur, and by ultrasonography at calcaneus The markers of bone turnover included serum osteocalcin and urinary deoxypyridinoline. All subjects had a spine X-ray to ascertain the presence of vertebral fractures. RESULTS: bone mineral density at lumbar spine (BMD 0.78±0.08 vs 0.88±0.07; p<0,001, femoral neck (BMD: 0.56±0.04 vs 0.72±0.07; p<0,001 and total femur (BMD: 0.57±0.04 vs 0.71±0.06; p<0,001 and ultrasound parameter at calcaneus (SI: 80.10±5.10 vs 94.80±6.10 p<0,001 were significantly lower in scleroderma compared with controls; bone turnover markers and parathyroid hormone level were significantly higher in scleroderma compared with controls, while serum of 25(OHD3 was significantly lower. In scleroderma group the serum levels of 25(OHD3 significantly correlated with PTH levels, BMD, stiffness index and bone turnover markers. One or more moderate or severe vertebral fractures were found in 13 patients with scleroderma, wherease in control group only one patient had a mild vertebral fracture. CONCLUSION: Our data shows, for the first time, that vertebral fractures are frequent in subjects with scleroderma, and suggest that lower levels of 25(OHD3 may play a role in the risk of osteoporosis and vertebral fractures.

  12. 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.

  13. Multiple sclerosis.

    Science.gov (United States)

    Thompson, Alan J; Baranzini, Sergio E; Geurts, Jeroen; Hemmer, Bernhard; Ciccarelli, Olga

    2018-03-22

    Multiple sclerosis continues to be a challenging and disabling condition but there is now greater understanding of the underlying genetic and environmental factors that drive the condition, including low vitamin D levels, cigarette smoking, and obesity. Early and accurate diagnosis is crucial and is supported by diagnostic criteria, incorporating imaging and spinal fluid abnormalities for those presenting with a clinically isolated syndrome. Importantly, there is an extensive therapeutic armamentarium, both oral and by infusion, for those with the relapsing remitting form of the disease. Careful consideration is required when choosing the correct treatment, balancing the side-effect profile with efficacy and escalating as clinically appropriate. This move towards more personalised medicine is supported by a clinical guideline published in 2018. Finally, a comprehensive management programme is strongly recommended for all patients with multiple sclerosis, enhancing health-related quality of life through advocating wellness, addressing aggravating factors, and managing comorbidities. The greatest remaining challenge for multiple sclerosis is the development of treatments incorporating neuroprotection and remyelination to treat and ultimately prevent the disabling, progressive forms of the condition. Copyright © 2018 Elsevier Ltd. All rights reserved.

  14. Multiple sclerosis

    International Nuclear Information System (INIS)

    Sadashima, Hiromichi; Kusaka, Hirofumi; Imai, Terukuni; Takahashi, Ryosuke; Matsumoto, Sadayuki; Yamamoto, Toru; Yamasaki, Masahiro; Maya, Kiyomi

    1986-01-01

    Eleven patients with a definite diagnosis of multiple sclerosis were examined in terms of correlations between the clinical features and the results of cranial computed tomography (CT), and magnetic resonance imaging (MRI). Results: In 5 of the 11 patients, both CT and MRI demonstrated lesions consistent with a finding of multiple sclerosis. In 3 patients, only MRI demonstrated lesions. In the remaining 3 patients, neither CT nor MRI revealed any lesion in the brain. All 5 patients who showed abnormal findings on both CT and MRI had clinical signs either of cerebral or brainstem - cerebellar lesions. On the other hand, two of the 3 patients with normal CT and MRI findings had optic-nerve and spinal-cord signs. Therefore, our results suggested relatively good correlations between the clinical features, CT, and MRI. MRI revealed cerebral lesions in two of the four patients with clinical signs of only optic-nerve and spinal-cord lesions. MRI demonstrated sclerotic lesions in 3 of the 6 patients whose plaques were not detected by CT. In conclusion, MRI proved to be more helpful in the demonstration of lesions attributable to chronic multiple sclerosis. (author)

  15. Clinical characteristics of children with Juvenile Systemic Sclerosis: follow-up of 23 patients in a single tertiary center

    Directory of Open Access Journals (Sweden)

    Katsicas María M

    2007-05-01

    Full Text Available Abstract Background Juvenile systemic sclerosis (JSS is a multisystem connective tissue disease characterized by skin fibrosis and internal organ involvement. It has a low prevalence, even in a tertiary facility setting. The purpose of the present study is to describe and analyze the clinical and laboratory characteristics of a group of children with JSS followed in a single center. Methods Clinical charts of children with a diagnosis of JSS who were seen at a tertiary referral center between 1995 and 2005 were reviewed. Clinical features were recorded and analysed. Results Twenty-three patients who met preliminary classification criteria for JSS were included. Age at first symptom attributable to JSS was 6 (1–14 years, The first symptom attributable to JSS was Raynaud's phenomenon in 14 cases. Proximal sclerosis (23 patients, 100%, sclerodactyly (21, 91%, Raynaud's phenomenon (19, 83%, and periungual capillaropathy (17, 74% were the most consistent clinical findings during follow-up. Respiratory involvement occurred in two thirds of our patients, and it manifested as dyspnea as well as abnormal imaging and/or pulmonary function tests; pulmonary hypertension was an infrequent finding. Dysphagia was the commonest gastrointestinal symptom (9 patients, 39%. The most frequent musculoskeletal symptom was arthralgia (14 children, 6%; symmetrical arthritis was found in 8 (35% patients. Periungual capillary abnormalities were evident during physical examination in 17 children; capillaroscopy revealed abnormalities in all 19 examined patients. ANA were present in 17 (74% children: homogeneous pattern was the most frequent (8 patients, nucleolar (5 and speckled (4 were less common. Conclusion Raynaud's phenomenon heralds the beginning of the disease. Capilaroscopy is a major adjuvant in the diagnosis, since autoantibody determination may not offer sensitive and specific markers. Skin and vascular manifestations are the most common clinical features

  16. 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.

  17. 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.

  18. Lessons Learned about Perceived Purposes of the Head Start National Reporting System at the Local Program Level

    Science.gov (United States)

    Kallemeyn, Leanne M.; DeStefano, Lizanne

    2010-01-01

    Two purposes for early childhood assessment systems are informing program development and providing accountability. Based on findings from a case study of a local Head Start program implementing the National Reporting System (NRS) in 2004-2005, we provide 5 lessons learned from experiences with the NRS that may have implications for other…

  19. Multi-unit Operations in Non-Nuclear Systems: Lessons Learned for Small Modular Reactors

    Energy Technology Data Exchange (ETDEWEB)

    OHara J. M.; Higgins, J.; DAgostino, A.

    2012-01-17

    The nuclear-power community has reached the stage of proposing advanced reactor designs to support power generation for decades to come. Small modular reactors (SMRs) are one approach to meet these energy needs. While the power output of individual reactor modules is relatively small, they can be grouped to produce reactor sites with different outputs. Also, they can be designed to generate hydrogen, or to process heat. Many characteristics of SMRs are quite different from those of current plants and may be operated quite differently. One difference is that multiple units may be operated by a single crew (or a single operator) from one control room. The U.S. Nuclear Regulatory Commission (NRC) is examining the human factors engineering (HFE) aspects of SMRs to support licensing reviews. While we reviewed information on SMR designs to obtain information, the designs are not completed and all of the design and operational information is not yet available. Nor is there information on multi-unit operations as envisioned for SMRs available in operating experience. Thus, to gain a better understanding of multi-unit operations we sought the lesson learned from non-nuclear systems that have experience in multi-unit operations, specifically refineries, unmanned aerial vehicles and tele-intensive care units. In this paper we report the lessons learned from these systems and the implications for SMRs.

  20. Compromiso pulmonar en esclerosis sistémica Lung involvement in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Silvia Quadrelli

    2007-10-01

    Full Text Available El objetivo del estudio fue determinar las características clínicas de los pacientes con esclerodermia y compromiso pulmonar y evaluar si existen factores clínicos predictores de mayor riesgo de enfermedad intersticial. Se estudiaron en forma retrospectiva 40 pacientes con esclerodermia. Fueron divididos en 2 grupos: capacidad de difusión del monóxido de carbono (DLCO normal (n = 22 y DLCO disminuida (n = 18, 45%. Los pacientes con DLCO disminuida no fueron diferentes en edad (51.1 ± 13.5 vs. 53.5 ± 9.3 años, p = 0.5182, sexo (varones 13.6%, p = 0.6088 , presencia de Raynaud (86.6% vs. 85%, p = 0.6272, síndrome de ojo seco (6.2% vs. 10.5%, p = 1.0000 prevalencia de enfermedad difusa (94.1% vs. 83.3%, p = 0.6026 o de dilatación esofágica. El tiempo de evolución de la enfermedad no fue diferente. La sensibilidad de la disnea para detectar una DLCO alterada fue 46.6% con una especificidad del 90% y la de la caída de la saturación de O2 (SaO2 del 71.4% y 80% respectivamente. Los pacientes con DLCO baja tuvieron mayor prevalencia de anticuerpos anti-Scl 70 positivos (5/9 vs. 0/11, p = 0.0081 y de incapacidad ventilatoria restrictiva aunque en 56.7% de los pacientes con DLCO disminuida la capacidad pulmonar total (CPT era normal. La presencia de hipertensión pulmonar medida por ecocardiograma Doppler fue idéntica (11/13 vs. 10/11, p = 1.0000. Los pacientes con DLCO disminuida tuvieron una prevalencia muy superior de tomografía computada de tórax con evidencias de compromiso intersticial (82.3% vs. 5.8%, p ≤ 0.0001. En conclusión, nuestros datos sugieren que la disminución de la DLCO es un hallazgo, muy frecuentemente asociado a TAC de tórax con compromiso intersticial y que no hay variables clínicas que permitan predecir su anormalidad.The objective of this study was to determine clinical predictors of interstitial lung disease in patients with systemic sclerosis (SSc and pulmonary involvement as defined by presence of a

  1. Design lessons from using programmable controllers in the MFTF-BETA Personnel Safety and Interlocks System

    International Nuclear Information System (INIS)

    Branum, J.D.

    1983-01-01

    Applying programmable controllers in critical applications such as personnel safety and interlocks systems requires special considerations in the design of both hardware and software. All modern programmable controller systems feature extensive internal diagnostic capabilities to protect against problems such as program memory errors; however most, if not all present designs lack an intrinsic capability for detecting and countering failures on the ''field-side'' of their I/O modules. Many of the most common styles of I/O modules can also introduce potentially dangerous sneak circuits, even without component failure. This paper presents the most significant lessons learned to date in the design of the MFTF-BETA Personnel Safety and Interlocks System, which utilizes two non-redundant programmable controllers with over 800 I/O points each. Specific problems recognized during the design process as well as those discovered during initial testing and operation are discussed along with their specific solutions in hardware and software

  2. Design lessons from using programmable controllers in the MFTF-B personnel safety and interlocks system

    International Nuclear Information System (INIS)

    Branum, J.D.

    1983-01-01

    Applying programmable controllers in critical applications such as personnel safety and interlocks systems requires special considerations in the design of both hardware and software. All modern programmable controller systems feature extensive internal diagnostic capabilities to protect against problems such as program memory errors; however most, if not all present designs lack an intrinsic capability for detecting and countering failures on the field-side of their I/O modules. Many of the most common styles of I/O modules can also introduce potentially dangerous sneak circuits, even without component failure. This paper presents the most significant lessons learned to date in the design of the MFTF-B Personnel Safety and Interlocks System, which utilizes two non-redundant programmable controllers with over 800 I/O points each. Specific problems recognized during the design process as well as those discovered during initial testing and operation are discussed along with their specific solutions in hardware and software

  3. ALS (Amyotrophic Lateral Sclerosis)

    Science.gov (United States)

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

  4. Review of LCA studies of solid waste management systems – Part I: Lessons learned and perspectives

    DEFF Research Database (Denmark)

    Laurent, Alexis; Bakas, Ioannis; Clavreul, Julie

    2014-01-01

    , e.g. construction and demolition waste. Waste management practitioners are thus encouraged to abridge these gaps in future applications of LCA. In addition to this contextual analysis, we also evaluated the findings of selected studies of good quality and found that there is little agreement......The continuously increasing solid waste generation worldwide calls for management strategies that integrate concerns for environmental sustainability. By quantifying environmental impacts of systems, life cycle assessment (LCA) is a tool, which can contribute to answer that call. But how, where...... and to which extent has it been applied to solid waste management systems (SWMSs) until now, and which lessons can be learnt from the findings of these LCA applications? To address these questions, we performed a critical review of 222 published LCA studies of SWMS. We first analysed the geographic...

  5. Lessons Learned for Cx PRACA. Constellation Program Problem Reporting, Analysis and Corrective Action Process and System

    Science.gov (United States)

    Kelle, Pido I.; Ratterman, Christian; Gibbs, Cecil

    2009-01-01

    This slide presentation reviews the Constellation Program Problem Reporting, Analysis and Corrective Action Process and System (Cx PRACA). The goal of the Cx PRACA is to incorporate Lessons learned from the Shuttle, ISS, and Orbiter programs by creating a single tool for managing the PRACA process, that clearly defines the scope of PRACA applicability and what must be reported, and defines the ownership and responsibility for managing the PRACA process including disposition approval authority. CxP PRACA is a process, supported by a single information gathering data module which will be integrated with a single CxP Information System, providing interoperability, import and export capability making the CxP PRACA a more effective and user friendly technical and management tool.

  6. Lessons Learned From Developing Three Generations of Remote Sensing Science Data Processing Systems

    Science.gov (United States)

    Tilmes, Curt; Fleig, Albert J.

    2005-01-01

    The Biospheric Information Systems Branch at NASA s Goddard Space Flight Center has developed three generations of Science Investigator-led Processing Systems for use with various remote sensing instruments. The first system is used for data from the MODIS instruments flown on NASA s Earth Observing Systems @OS) Terra and Aqua Spacecraft launched in 1999 and 2002 respectively. The second generation is for the Ozone Measuring Instrument flying on the EOS Aura spacecraft launched in 2004. We are now developing a third generation of the system for evaluation science data processing for the Ozone Mapping and Profiler Suite (OMPS) to be flown by the NPOESS Preparatory Project (NPP) in 2006. The initial system was based on large scale proprietary hardware, operating and database systems. The current OMI system and the OMPS system being developed are based on commodity hardware, the LINUX Operating System and on PostgreSQL, an Open Source RDBMS. The new system distributes its data archive across multiple server hosts and processes jobs on multiple processor boxes. We have created several instances of this system, including one for operational processing, one for testing and reprocessing and one for applications development and scientific analysis. Prior to receiving the first data from OMI we applied the system to reprocessing information from the Solar Backscatter Ultraviolet (SBUV) and Total Ozone Mapping Spectrometer (TOMS) instruments flown from 1978 until now. The system was able to process 25 years (108,000 orbits) of data and produce 800,000 files (400 GiB) of level 2 and level 3 products in less than a week. We will describe the lessons we have learned and tradeoffs between system design, hardware, operating systems, operational staffing, user support and operational procedures. During each generational phase, the system has become more generic and reusable. While the system is not currently shrink wrapped we believe it is to the point where it could be readily

  7. 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....... Ninety-five percent lived in own house or flat and 70 percent received disablement pension. More than half of the patients (56.4 percent) were dependent on help from close relatives, most frequently spouse. The need for help, the risk of divorce, loss of contact with relatives, difficulty in going out...

  8. 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.

  9. Systemic pharmacokinetics and cerebrospinal fluid uptake of intravenous ceftriaxone in patients with amyotrophic lateral sclerosis.

    Science.gov (United States)

    Zhao, Yanli; Cudkowicz, Merit E; Shefner, Jeremy M; Krivickas, Lisa; David, William S; Vriesendorp, Francine; Pestronk, Alan; Caress, James B; Katz, Jonathan; Simpson, Ericka; Rosenfeld, Jeffrey; Pascuzzi, Robert; Glass, Jonathan; Rezania, Kourosh; Harmatz, Jerold S; Schoenfeld, David; Greenblatt, David J

    2014-10-01

    The cephalosporin antibiotic ceftriaxone was evaluated as a potential therapeutic agent for the treatment of amyotrophic lateral sclerosis (ALS). The pharmacokinetics (PK) of ceftriaxone in plasma and cerebrospinal fluid (CSF) were investigated in 66 participants in a previously reported clinical trial. Their mean age was 51 years, and 65% were male. Participants were randomly assigned to 1 of 3 treatment groups receiving intravenous infusions (mean duration: 25 minutes) every 12 hours of either: placebo and placebo; 2 g ceftriaxone and placebo; or 2 g ceftriaxone twice. Mean steady-state plasma PK variables were: volume of distribution, 14 L (0.17 L/kg); elimination half-life, 8-9 h; total clearance, 17-21 mL/min (0.22-0.25 mL/min/kg). Values were not different between dosage groups. CSF PK analysis, determined through sparse CSF sampling, indicated apparent entry and elimination half-life values of 1.0 and 34 hours, respectively. With both dosage regimens, CSF concentrations were maintained above the target threshold of 1.0 µM (0.55 µg/mL) as determined from in vitro models. The plasma and CSF PK profiles of ceftriaxone were used as a basis for planning the Phase 3 clinical trial of ceftriaxone in ALS. © 2014, The American College of Clinical Pharmacology.

  10. Unusual association of amyotrophic lateral sclerosis and myasthenia gravis: A dysregulation of the adaptive immune system?

    Science.gov (United States)

    Del Mar Amador, Maria; Vandenberghe, Nadia; Berhoune, Nawel; Camdessanché, Jean-Philippe; Gronier, Sophie; Delmont, Emilien; Desnuelle, Claude; Cintas, Pascal; Pittion, Sophie; Louis, Sarah; Demeret, Sophie; Lenglet, Timothée; Meininger, Vincent; Salachas, François; Pradat, Pierre-François; Bruneteau, Gaëlle

    2016-06-01

    Myasthenia gravis is an autoimmune disorder affecting neuromuscular junctions that has been associated with a small increased risk of amyotrophic lateral sclerosis (ALS). Here, we describe a retrospective series of seven cases with a concomitant diagnosis of ALS and myasthenia gravis, collected among the 18 French reference centers for ALS in a twelve year period. After careful review, only six patients strictly met the diagnostic criteria for both ALS and myasthenia gravis. In these patients, limb onset of ALS was reported in five (83%) cases. Localization of myasthenia gravis initial symptoms was ocular in three (50%) cases, generalized in two (33%) and bulbar in one (17%). Median delay between onset of the two conditions was 19 months (6-319 months). Anti-acetylcholine receptor antibodies testing was positive in all cases. All patients were treated with riluzole and one had an associated immune-mediated disease. In the one last ALS case, the final diagnosis was false-positivity for anti-acetylcholine receptor antibodies. The co-occurrence of ALS and myasthenia gravis is rare and requires strict diagnostic criteria. Its demonstration needs thoughtful interpretation of electrophysiological results and exclusion of false positivity for myasthenia gravis antibody testing in some ALS cases. This association may be triggered by a dysfunction of adaptive immunity. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. 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

  12. Development of a data mining and imaging informatics display tool for a multiple sclerosis e-folder system

    Science.gov (United States)

    Liu, Margaret; Loo, Jerry; Ma, Kevin; Liu, Brent

    2011-03-01

    Multiple sclerosis (MS) is a debilitating autoimmune disease of the central nervous system that damages axonal pathways through inflammation and demyelination. In order to address the need for a centralized application to manage and study MS patients, the MS e-Folder - a web-based, disease-specific electronic medical record system - was developed. The e-Folder has a PHP and MySQL based graphical user interface (GUI) that can serve as both a tool for clinician decision support and a data mining tool for researchers. This web-based GUI gives the e-Folder a user friendly interface that can be securely accessed through the internet and requires minimal software installation on the client side. The e-Folder GUI displays and queries patient medical records--including demographic data, social history, past medical history, and past MS history. In addition, DICOM format imaging data, and computer aided detection (CAD) results from a lesion load algorithm are also displayed. The GUI interface is dynamic and allows manipulation of the DICOM images, such as zoom, pan, and scrolling, and the ability to rotate 3D images. Given the complexity of clinical management and the need to bolster research in MS, the MS e-Folder system will improve patient care and provide MS researchers with a function-rich patient data hub.

  13. Nailfold videocapillaroscopy micro-haemorrhage and giant capillary counting as an accurate approach for a steady state definition of disease activity in systemic sclerosis

    OpenAIRE

    Sambataro, Domenico; Sambataro, Gianluca; Zaccara, Eleonora; Maglione, Wanda; Polosa, Riccardo; Afeltra, Antonella MV; Vitali, Claudio; Del Papa, Nicoletta

    2014-01-01

    Introduction Nailfold videocapillaroscopy (NVC) in systemic sclerosis (SSc) is a procedure commonly used for patient classification and subsetting, but not to define disease activity (DA). This study aimed to evaluate whether the number of micro-haemorrhages (MHE), micro-thrombosis (MT), giant capillaries (GC), and normal/dilated capillaries (Cs) in NVC could predict DA in SSc. Methods Eight-finger NVC was performed in 107 patients with SSc, and the total number of MHE/MT, GC, and the mean nu...

  14. Development of the National Health Information Systems in Botswana: Pitfalls, prospects and lessons.

    Science.gov (United States)

    Seitio-Kgokgwe, Onalenna; Gauld, Robin D C; Hill, Philip C; Barnett, Pauline

    2015-01-01

    Studies evaluating development of health information systems in developing countries are limited. Most of the available studies are based on pilot projects or cross-sectional studies. We took a longitudinal approach to analysing the development of Botswana's health information systems. We aimed to: (i) trace the development of the national health information systems in Botswana (ii) identify pitfalls during development and prospects that could be maximized to strengthen the system; and (iii) draw lessons for Botswana and other countries working on establishing or improving their health information systems. This article is based on data collected through document analysis and key informant interviews with policy makers, senior managers and staff of the Ministry of Health and senior officers from various stakeholder organizations. Lack of central coordination, weak leadership, weak policy and regulatory frameworks, and inadequate resources limited development of the national health information systems in Botswana. Lack of attention to issues of organizational structure is one of the major pitfalls. The ongoing reorganization of the Ministry of Health provides opportunity to reposition the health information system function. The current efforts including development of the health information management policy and plan could enhance the health information management system.

  15. Physiotherapy in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Anna Łuszczyńska

    2015-10-01

    Full Text Available Introduction: Multiple sclerosis (MS is a chronic, progressive, demyelinating disease of the central nervous system. 2.5 million people are affected by MS worldwide; in Poland, the number of patients is approximately 40,000. Patients with multiple sclerosis suffer from a number of symptoms associated with this disease. Aim of the research: To assess the effectiveness of physiotherapy in MS. Material and methods : The study enrolled 25 MS patients aged 27–72 years (including 16 females and 9 males, undergoing 6-week rehabilitation. They were examined twice: before and after rehabilitation. The study used two questionnaires created by the author. Evaluation of the clinical status and disease severity was based on the Kurtzke Expanded Disability Status Scales (EDSS, the Lawton Instrumental Activities of Daily Living (IADL Scale, and the Multiple Sclerosis Impact Scale (MSIS-29. The results were analysed with Student’s t-test and the chi-square (χ 2 test. Results : Statistical analysis showed significant (the level of significance was 0.05 progress in the functional status of the patients after physiotherapy, as evidenced by improved results with respect to the motor efficiency in the Kurtzke Expanded Disability Status Scale (EDSS, the functional assessment in the Lawton Instrumental Activities of Daily Living (IADL Scale, and the influence of MS on patients’ daily life in the Multiple Sclerosis Impact Scale (MSIS-29 seen in the majority of the patients, which confirms a positive impact of the therapy. Conclusions: In the study group, comprehensive rehabilitation had a beneficial influence on the improvement of functional status and the level of motor ability. Physiotherapy turned out to be an extremely effective form of symptomatic treatment of MS patients.

  16. A methodology for exploring biomarker--phenotype associations: application to flow cytometry data and systemic sclerosis clinical manifestations.

    Science.gov (United States)

    Huang, Hongtai; Fava, Andrea; Guhr, Tara; Cimbro, Raffaello; Rosen, Antony; Boin, Francesco; Ellis, Hugh

    2015-09-15

    This work seeks to develop a methodology for identifying reliable biomarkers of disease activity, progression and outcome through the identification of significant associations between high-throughput flow cytometry (FC) data and interstitial lung disease (ILD) - a systemic sclerosis (SSc, or scleroderma) clinical phenotype which is the leading cause of morbidity and mortality in SSc. A specific aim of the work involves developing a clinically useful screening tool that could yield accurate assessments of disease state such as the risk or presence of SSc-ILD, the activity of lung involvement and the likelihood to respond to therapeutic intervention. Ultimately this instrument could facilitate a refined stratification of SSc patients into clinically relevant subsets at the time of diagnosis and subsequently during the course of the disease and thus help in preventing bad outcomes from disease progression or unnecessary treatment side effects. The methods utilized in the work involve: (1) clinical and peripheral blood flow cytometry data (Immune Response In Scleroderma, IRIS) from consented patients followed at the Johns Hopkins Scleroderma Center. (2) machine learning (Conditional Random Forests - CRF) coupled with Gene Set Enrichment Analysis (GSEA) to identify subsets of FC variables that are highly effective in classifying ILD patients; and (3) stochastic simulation to design, train and validate ILD risk screening tools. Our hybrid analysis approach (CRF-GSEA) proved successful in predicting SSc patient ILD status with a high degree of success (>82% correct classification in validation; 79 patients in the training data set, 40 patients in the validation data set). IRIS flow cytometry data provides useful information in assessing the ILD status of SSc patients. Our new approach combining Conditional Random Forests and Gene Set Enrichment Analysis was successful in identifying a subset of flow cytometry variables to create a screening tool that proved effective in

  17. 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

  18. Polymorphism of the Fractalkine Receptor CX3CR1 and Systemic Sclerosis-associated Pulmonary Arterial Hypertension

    Directory of Open Access Journals (Sweden)

    Bianca Marasini

    2005-01-01

    Full Text Available Fractalkine (FKN and its receptor CX3CR1 are critical mediators in the vascular and tissue damage of several chronic diseases, including systemic sclerosis (SSc and pulmonary arterial hypertension (PAH. Interestingly, the V249I and T280M genetic polymorphisms influence CX3CR1 expression and function. We investigated whether these polymorphisms are associated with PAH secondary to SSc. CX3CR1 genotypes were analyzed by PCR and sequencing in 76 patients with limited SSc and 204 healthy controls. PAH was defined by colorDoppler echocardiography. Homozygosity for 249II as well as the combined presence of 249II and 280MM were significantly more frequent in patients with SSc compared to controls (17 vs 6%, p = 0.0034 and 5 vs 1%, p = 0.0027, respectively. The 249I and 280M alleles were associated with PAH (odd ratio [OR] 2.2, 95% confidence interval [CI] 1.01-4.75, p = 0.028 and OR 7.37, 95%CI: 2.45-24.60, p = 0.0001, respectively. In conclusion, the increased frequencies of 249I and 280M CX3CR1 alleles in a subgroup of patients with SSc-associated PAH suggest a role for the fractalkine system in the pathogenesis of this condition. Further, the 249I allele might be associated with susceptibility to SSc.

  19. Intrinsic functional plasticity of the thalamocortical system in minimally disabled patients with relapsing-remitting multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Fuqing eZhou

    2016-01-01

    Full Text Available The thalamus plays a crucial role in sensorimotor, cognitive and attentional circuit functions. Disruptions in thalamic connectivity are believed to underlie the symptoms of multiple sclerosis (MS. Therefore, assessing thalamocortical structural connectivity (SC and functional connectivity (FC may provide new insights into the mechanism of intrinsic functional plasticity in a large-scale neural network. We used resting-state FC measurement and diffusion tensor imaging probabilistic tractography to study the functional and structural integrity of the thalamocortical system in patients with relapsing-remitting MS (RRMS and matched healthy controls. In the thalamocortical connections of RRMS patients, we found lesion load-related regional FC in the right temporal pole, which reflected compensatory hyperconnectivity related to lesion-related demyelination. We also found significant correlations between increased diffusivity and slowed cognitive processing (PASAT or the impact of fatigue (MFIS-5, as well as between connective fiber loss and disease duration. Taken together, the evidence from SC and FC analysis of the thalamocortical system suggests that minimally disabled RRMS patients exhibit a dissociated SC-FC pattern and limited regional functional plasticity to compensate for the chronic demyelination-related loss of long-distance SC. These results also provide further evidence supporting the notion that MS is a disorder of anatomical disconnection.

  20. Deploying quantum light sources on nanosatellites I: lessons and perspectives on the optical system

    Science.gov (United States)

    Chandrasekara, R.; Tang, Z.; Tan, Y. C.; Cheng, C.; Septriani, B.; Durak, K.; Grieve, J. A.; Ling, A.

    2015-09-01

    The Small Photon Entangling Quantum System is an integrated instrument where the pump, photon pair source and detectors are combined within a single optical tray and electronics package that is no larger than 10cm×10cm×3cm. This footprint enables the instrument to be placed onboard nanosatellites or the CubeLab facility within the International Space Station. The first mission is to understand the different environmental conditions that may affect the operation of an entangled photon source in low Earth orbit. This understanding is crucial for the construction of cost-effective entanglement based experiments that utilize nanosatellite architecture. We will discuss the challenges and lessons we have learned over three years of development and testing of the integrated optical platform and review the perspectives for future advanced experiments.

  1. Integrated radwaste treatment system lessons learned from 2 1/2 years of operation

    International Nuclear Information System (INIS)

    Baker, M.N.; Fussner, R.J.

    1997-05-01

    The Integrated Radwaste Treatment System (IRTS) at the West Valley Demonstration Project (WVDP) is a pretreatment scheme to reduce the amount of salts in the high-level radioactive waste (vitrification) stream. Following removal of cesium-137 (Cs-137) by ion-exchange in the Supernatant Treatment System (STS), the radioactive waste liquid is volume-reduced by evaporation. Trace amounts of Cs-137 in the resulting distillate are removed by ion-exchange, then the distillate is discharged to the existing plant water treatment system. The concentrated product, 37 to 41 percent solids by weight, is encapsulated in cement producing a stable, low-level waste form. The Integrated Radwaste Treatment System (IRTS) operated in this mode from May 1988 through November 1990, decontaminating 450,000 gallons of high-level waste liquid; evaporating and encapsulating the resulting concentrates into 10,393 71-gallon square drums. A number of process changes and variations from the original operating plan were required to increase the system flow rate and minimize waste volumes. This report provides a summary of work performed to operate the IRTS, including system descriptions, process highlights, and lessons learned

  2. Probabilistic Analysis of Passive Safety System Reliability in Advanced Small Modular Reactors: Methodologies and Lessons Learned

    Energy Technology Data Exchange (ETDEWEB)

    Grabaskas, David; Bucknor, Matthew; Brunett, Acacia; Grelle, Austin

    2015-06-28

    Many advanced small modular reactor designs rely on passive systems to fulfill safety functions during accident sequences. These systems depend heavily on boundary conditions to induce a motive force, meaning the system can fail to operate as intended due to deviations in boundary conditions, rather than as the result of physical failures. Furthermore, passive systems may operate in intermediate or degraded modes. These factors make passive system operation difficult to characterize with a traditional probabilistic framework that only recognizes discrete operating modes and does not allow for the explicit consideration of time-dependent boundary conditions. Argonne National Laboratory has been examining various methodologies for assessing passive system reliability within a probabilistic risk assessment for a station blackout event at an advanced small modular reactor. This paper describes the most promising options: mechanistic techniques, which share qualities with conventional probabilistic methods, and simulation-based techniques, which explicitly account for time-dependent processes. The primary intention of this paper is to describe the strengths and weaknesses of each methodology and highlight the lessons learned while applying the two techniques while providing high-level results. This includes the global benefits and deficiencies of the methods and practical problems encountered during the implementation of each technique.

  3. Carbon Monitoring System Applications Framework: Lessons Learned from Stakeholder Engagement Activities

    Science.gov (United States)

    Sepulveda Carlo, E.; Escobar, V. M.; Delgado Arias, S.; Forgotson, C.

    2017-12-01

    The NASA Carbon Monitoring System initiated by U.S. Congress in 2010 is developing products that characterize and quantify carbon sources and sinks in the United States and the global tropics. In 2013, an applications effort was selected to engage potential end users and gather feedback about their data needs. For the past four years the CMS applications efforts has expanded and implemented a number of strategies to connect carbon scientists to decision-makers, contributing to the societal benefits of CMS data products. The applications efforts use crowd sourcing to collects feedback from stakeholders on challenges and lessons learned in the use of CMS data products. Some of the most common data needs from engaged organizations include above and below-ground biomass and fluxes in forestlands and wetlands, and greenhouse gas (GHG) emissions across all land use/cover and land use changes. Stakeholder organizations' needs for CMS data products support national GHG inventories following the Paris Agreement, carbon markets, and sub-national natural resources management and policies. The lessons learned report presents stakeholder specific applications, challenges, and successes from using CMS data products. To date, the most common uses of CMS products include: conservation efforts, emissions inventory, forestry and land cover applications, and carbon offset projects. The most common challenges include: the need for familiar and consistent products over time, budget constraints, and concern with uncertainty of modeled results. Recurrent recommendations from stakeholder indicate that CMS should provide high resolution (30m) and frequent data products updates (annually). The applications efforts have also helped identified success stories from different CMS projects, including the development of the GHG emissions inventory from Providence, RI, the improvement of the U.S. GHG Inventory though the use of satellite data, and the use of high resolution canopy cover maps for

  4. Remote Systems Experience at the Oak Ridge National Laboratory--A Summary of Lessons Learned

    Energy Technology Data Exchange (ETDEWEB)

    Noakes, Mark W [ORNL; Burgess, Thomas W [ORNL; Rowe, John C [ORNL

    2011-01-01

    Oak Ridge National Laboratory (ORNL) has a long history in the development of remote systems to support the nuclear environment. ORNL, working in conjunction with Central Research Laboratories, created what is believed to be the first microcomputer-based implementation of dual-arm master-slave remote manipulation. As part of the Consolidated Fuel Reprocessing Program, ORNL developed the dual-arm advanced servomanipulator focusing on remote maintainability for systems exposed to high radiation fields. ORNL also participated in almost all of the various technical areas of the U.S. Department of Energy s Robotics Technology Development Program, while leading the Decontamination and Decommissioning and Tank Waste Retrieval categories. Over the course of this involvement, ORNL has developed a substantial base of working knowledge as to what works when and under what circumstances for many types of remote systems tasks as well as operator interface modes, control bandwidth, and sensing requirements to name a few. By using a select list of manipulator systems that is not meant to be exhaustive, this paper will discuss history and outcome of development, field-testing, deployment, and operations from a lessons learned perspective. The final outcome is a summary paper outlining ORNL experiences and guidelines for transition of developmental remote systems to real-world hazardous environments.

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

    Science.gov (United States)

    Jewett, Lisa R; Kwakkenbos, Linda; Hudson, Marie; Baron, Murray; Thombs, Brett D

    2017-09-01

    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 the SWAP among 856 Canadian English- or French-speaking SSc patients. Confirmatory factor analysis was used to evaluate the SWAP two-factor structure (Dissatisfaction with Appearance and Social Discomfort). The Multiple-Indicator Multiple-Cause model was utilized to assess differential item functioning. Results revealed that the established two-factor model of the SWAP demonstrated relatively good fit. Statistically significant, but small-magnitude differential item functioning was found for three SWAP items based on language; however, the cumulative effect on SWAP scores was negligible. Findings provided empirical evidence that SWAP scores from Canadian English- and French-speaking patients can be compared and pooled without concern that measurement differences may substantially influence results. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Pulmonary magnetic resonance imaging is similar to chest tomography in detecting inflammation in patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Carolina de Souza Müller

    Full Text Available Abstract 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.

  7. Efficacy of bosentan in the treatment of Raynaud's phenomenon in patients with systemic sclerosis never treated with prostanoids.

    Science.gov (United States)

    Parisi, S; Bruzzone, M; Centanaro Di Vittorio, C; Laganà, A; Peroni, C L; Fusaro, E

    2014-03-17

    The objective of this study was to evaluate the efficacy of the endothelin receptor antagonist, bosentan, in patients with Raynaud's phenomenon secondary to systemic sclerosis never treated with prostanoids and without digital ulcers. The study design is a preliminary, prospective open label trial. The patients recruited took one 62.5 mg dose of bosentan twice daily for 4 weeks, followed by 125 mg twice daily for 24 weeks. Of the 10 patients recruited, all completed the study. The reduction in Raynaud's phenomenon attacks at week 24 from the baseline was statistically significant (Δ-1.3, P=0.0126). The Raynaud's condition score showed a statistically significant improvement (Δ-1.4, P=0.0279), as did the visual analog pain scale (Δ-1.5, P=0.0016) at the 24th week. Bosentan appears to be effective and may be a valid alternative for the treatment of severe secondary Raynaud's phenomenon for patients where prostanoids therapy is contraindicated or refused.

  8. Diminished production of TWEAK by the peripheral blood mononuclear cells is associated with vascular involvement in patients with systemic sclerosis.

    Directory of Open Access Journals (Sweden)

    Otylia Kowal-Bielecka

    2010-02-01

    Full Text Available Widespread vasculopathy and profound fibrosis are key features of the pathogenesis of systemic sclerosis (SSc. We hypothesized that the TNF-like weak inducer of apoptosis (TWEAK, a recently recognized multifunctional cytokine which regulates angiogenesis and tissue remodeling, may play a role in the development of SSc. The production of TWEAK by the peripheral blood mononuclear cells (PBMC was investigated, by means of ELISA, in 24 SSc patients and 14 healthy subjects. Moreover, production of TWEAK was correlated with clinical features of SSc. PBMC were isolated using density gradient centrifugation on Histopaque and were cultured in FCS supplemented RPMI medium at 37 degrees C under 5% CO2. Production of TWEAK by PBMC was significantly diminished in patients with more severe microvascular damage, as indicated by the presence of "active" capillaroscopic pattern, compared with SSc patients with less pronounced microangiopathy ("slow" pattern, and healthy subjects. Moreover production of TWEAK correlated inversely with duration of Raynaud's phenomenon. PBMC from patients with scleroderma-related interstitial lung disease tended to produce lower amounts of TWEAK compared with SSc patients without lung involvement but the difference was not significant. The results of our study suggest that diminished production of TWEAK might play a role in the pathogenesis of vascular injury in SSc patients. Whether TWEAK may represent a new therapeutic target in SSc requires further studies.

  9. Evidence of cell-mediated cardiac myocyte injury involved in the heart failure of a patient with progressive systemic sclerosis.

    Science.gov (United States)

    Takahashi, N; Seko, Y; Azuma, M; Yagita, H; Okumura, K; Yazaki, Y

    1999-01-01

    A 54-year-old woman with progressive systemic sclerosis (PSS) was admitted to hospital because of dyspnea and chest pain. Echocardiogram revealed diffuse hypokinesis of the left ventricle (ejection fraction 24%). Methylprednisolone, heparin, and diuretics were administered, without benefit. Anemia, thrombocytopenia, and renal dysfunction rapidly progressed, and she died of heart failure on the 14th hospital day. Immunohistochemical study of the myocardial tissue showed mild to moderate cell infiltration, mainly consisting of natural killer (NK) cells, macrophages, cytotoxic T lymphocytes (CTLs), and T helper cells. Perforin, a cytolytic factor, was expressed in the infiltrating CTLs and NK cells, indicating that these cells were activated killer cells. Furthermore, human leukocyte antigen classes I and II, intercellular adhesion molecule-1, as well as costimulatory molecules B7-1, B7-2, and CD40, all of which are known not to be expressed in cardiac myocytes under normal conditions, were moderately to strongly expressed in cardiac myocytes. There was no detectable level of enterovirus genomes in the polymerase chain reaction products from the myocardial tissue of this patient. These findings strongly suggest that the infiltrating killer cells recognized cardiac myocytes as target cells and directly damaged them by releasing perforin. Enhanced expression of these antigens may have played an important role in the activation and cytotoxicity of the infiltrating killer cells. Absence of enterovirus genomes in the myocardial tissue may suggest that this autoimmune process is primarily induced by PSS.

  10. Genetic variation near IRF8 is associated with serologic and cytokine profiles in systemic lupus erythematosus and multiple sclerosis.

    Science.gov (United States)

    Chrabot, B S; Kariuki, S N; Zervou, M I; Feng, X; Arrington, J; Jolly, M; Boumpas, D T; Reder, A T; Goulielmos, G N; Niewold, T B

    2013-12-01

    Alleles of interferon (IFN) regulatory factor 8 (IRF8) are associated with susceptibility to both systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Although high-type I IFN is thought to be causal in SLE, type I IFN is used as a therapy in MS. We investigated whether IRF8 alleles were associated with type I IFN levels or serologic profiles in SLE and MS. Alleles that have been previously associated with SLE or MS were genotyped in SLE and MS patients. The MS-associated rs17445836G allele was associated with anti-double-stranded DNA (dsDNA) autoantibodies in SLE patients (meta-analysis odds ratio=1.92). The same allele was associated with decreased serum IFN activity in SLE patients with anti-dsDNA antibodies, and with decreased type I IFN-induced gene expression in peripheral blood mononuclear cell from anti-dsDNA-negative SLE patients. In secondary progressive MS patients, rs17445836G was associated with decreased serum type I IFN. Rs17445836G was associated with increased IRF8 expression in SLE patient B cells. In summary, IRF8 rs17445836G is associated with human autoimmune disease characterized by low-type I IFN levels, and this may have pharmacogenetic relevance as type I IFN is modulated in SLE and MS. The association with autoantibodies and increased IRF8 expression in B cells supports a role for rs17445836G in humoral tolerance.

  11. Expressions of p53 and PUMA in fibroblasts of systemic sclerosis patients are normal at transcription level.

    Science.gov (United States)

    Mahmoudi, Mohammad Bagher; Abed Khojasteh, Majid; Alsahebfosoul, Fereshteh; Gharibdoost, Farhad; Mostafaei, Shayan; Ganjalikhani-Hakemi, Mazdak; Mahmoudi, Mahdi

    2017-09-14

    Systemic sclerosis (SSc) fibroblasts show resistance apoptosis mechanisms, which enhances the fibrosis stage of the disease. Impaired function of p53 upregulated modulator of apoptosis (PUMA) has been related to deficits in p53-dependant apoptosis pathway. This study aimed to evaluate the transcriptional levels of p53 and PUMA mRNAs in fibroblasts from SSc patients and compare it with healthy individuals. In this case-control study, skin biopsy samples were obtained from 19 patients with diffuse cutaneous SSc (DcSSc) and 16 healthy controls. Afterward, dermal fibroblasts were isolated and cultured. After extraction of total RNA from cultured fibroblasts, complementary DNA (cDNA) was synthesized. mRNA quantification was carried out using real-time PCR, SYBR Green PCR master mix, and specific primers for p53 and PUMA. No significant alteration was observed in mRNA expression levels of p53 and PUMA (P = .99 and .23, respectively) in fibroblasts from SSc patients compared with controls. Apoptosis pathways are impaired in fibroblasts from patients with SSc, leading to chronic fibrosis. Nonetheless, PUMA/p53 pathway may not be involved in dysfunction of apoptosis mechanisms in fibroblasts of patients with SSc. © 2017 Wiley Periodicals, Inc.

  12. Differential diagnosis of critical digital ischemia in systemic sclerosis: Report of five cases and review of the literature.

    Science.gov (United States)

    Sharp, Charlotte A; Akram, Qasim; Hughes, Michael; Muir, Lindsay; Herrick, Ariane L

    2016-10-01

    Critical digital ischemia is a rare, but serious complication of systemic sclerosis (SSc) and is not always due solely to the non-inflammatory angiopathy that characterizes the SSc disease process. Our objective was to illustrate the range of presentations and causes of critical digital ischemia in patients with SSc in order to highlight how optimal management is dependent upon establishing the correct diagnosis. Five cases exemplifying differential diagnoses were identified and their case notes reviewed in order to extract clinically relevant data and images. A review of the literature was performed in PubMed in English. Causes of critical digital ischemia included typical micro-angiopathic changes and proximal (large vessel) disease. One case highlighted the difficulty of ascertaining whether an inflammatory cause is also present in SSc/SLE overlap syndrome. Two cases demonstrated embolic causes (thromboembolism due to atrial fibrillation and septic emboli). Critical digital ischemia in patients with SSc requires thorough investigation in order to avoid missing additional potentially modifiable causes including large vessel disease, inflammation, embolism, infection, and paraneoplastic syndromes. A firm evidence base for current medical and surgical interventions is lacking, highlighting the need for further research into the optimum management of this rare, but painful, debilitating, and limb-threatening complication of SSc. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. In Systemic Sclerosis, Anxiety and Depression Assessed by Hospital Anxiety Depression Scale Are Independently Associated with Disability and Psychological Factors

    Directory of Open Access Journals (Sweden)

    Angela Del Rosso

    2013-01-01

    Full Text Available Background. 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. Methods. 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. Results. Both depression and anxiety in SSc are 36%. Depressive patients with comorbid anxiety have higher HADS-D score than patients with depression only (. 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 (. By multiple regression, HADS-D is independently associated with FACIT-F (, RSES (, and MHISS total score (, together explaining 50% of variance. HADS-A is independently associated with RSES (, COPE-NIV SA (, COPE-NIV SS (, FACIT-F (, and MHISS mouth opening (, explaining 41% of variance. Conclusions. In SSc depression and anxiety correlate to local and global disabilities and psychological characteristics. Depressive patients with comorbid anxiety have higher level of depressive symptoms.

  14. Growth Differentiation Factor-15 (GDF-15) Level and Relation to Clinical Manifestations in Egyptian Systemic Sclerosis patients: Preliminary Data.

    Science.gov (United States)

    Gamal, Sherif M; Elgengehy, Fatema T; Kamal, Asmaa; El Bakry, Samah A; Shabaan, Elham; Elgendy, Aliaa; Bassyouni, Iman H

    2017-10-01

    This study aims to assess Growth differentiation factor-15 (GDF-15) level in Scleroderma patients and its relation to disease manifestations. This study included 55 scleroderma patients and 40 age and sex matched healthy volunteers. All patients were subjected to full history taking, thorough clinical examination, and laboratory investigations. GDF-15 serum levels were analyzed in patients and controls using human GDF-15 immunoassay Quantikine ELISA kit. The GDF-15 serum level was significantly higher in Systemic sclerosis (SSc) patients in comparison to healthy control individuals, p-value = 0.004. In addition, the GDF-15 serum levels increased in a significant way in patients with diffuse SSc than those with limited SSc, p = 0.026. Also, we had discovered a significant positive correlation between serum GDF-15 levels and the modified Rodnan score of the SSc patients, r = 0.442, p = 0.001 and a significant association was found between high GDF-15 level and SSc patients with interstitial pulmonary fibrosis (IPF) as compared to healthy controls (p = 0.002). However, no significant difference was found between SSc patients without IPF and healthy subjects regarding GDF-15 level (p = 0.106). GDF-15 serum levels were elevated in patients with SSc and correlated with the extent of skin fibrosis, and it was found to be higher in SSc patients with IPF. Such results may suggest a pivotal role of GDF-15 in fibrotic changes in SSc, and GDF-15 could be a treatment target in SSc patients in future.

  15. Quality of life in patients with systemic sclerosis compared to the general population and patients with other chronic conditions.

    Science.gov (United States)

    Hudson, Marie; Thombs, Brett D; Steele, Russell; Panopalis, Pantelis; Newton, Evan; Baron, Murray

    2009-04-01

    Systemic sclerosis (SSc) affects multiple physical, psychological, and social domains and is associated with impaired health-related quality of life (HRQOL).We compared the HRQOL of SSc patients with individuals in the general population and patients with other common chronic diseases. HRQOL of SSc patients in the Canadian Scleroderma Research Group registry was measured using version 2 of the Medical Outcomes Trust Short Form-36 (SF-36). Results were compared to US general population norms and scores reported for patients with other common chronic diseases, namely heart disease, lung disease, hypertension, diabetes, and depression. SF-36 scores were available for 504 SSc patients (86% women, mean age 56 yrs, mean disease duration since onset of first non-Raynaud's manifestation of SSc 11 yrs). The greatest impairment in SF-36 subscale scores appeared to be in the physical functioning, general health, and role physical domains. SF-36 subscale and summary scores in SSc were significantly worse compared to US general population norms for women of similar ages, except for mental health and mental component summary score, which were not significantly different, and were generally comparable to or worse than the scores of patients with other common chronic conditions. HRQOL of patients with SSc is significantly impaired compared to that of the general population and is comparable to or worse than that of patients with other common chronic conditions.

  16. 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

  17. Longitudinal patterns of pain in patients with diffuse and limited systemic sclerosis: integrating medical, psychological, and social characteristics.

    Science.gov (United States)

    Merz, Erin L; Malcarne, Vanessa L; Roesch, Scott C; Nair, Deepthi K; Salazar, Gloria; Assassi, Shervin; Mayes, Maureen D

    2017-01-01

    Pain is a common but understudied quality of life concern in systemic sclerosis (SSc). This investigation sought to describe patient-reported pain during the early phase of the disease and to examine potential predictors of this over time. A prospective cohort (N = 316) of patients with early-disease SSc from the Genetics versus ENvironment In Scleroderma Outcome Study (GENISOS) were followed for 3 years. Multilevel modeling was used to describe longitudinal changes in pain and the extent to which pain variance was explained by disease type, emotional health, perceived physical health, health worry, and social support. Patient-reported pain remained relatively stable, with slight improvement over time. More severe disease type was associated with worse initial pain, but the association was reduced to nonsignificance after accounting for the psychosocial variables. Better emotional health and perceived physical health were associated with lower initial pain. There were marginal interactive effects for perceived physical health and social support such that initial perceptions of poorer physical health, and higher social support, were predictive of greater improvements in pain over time. These data suggest that emotional health, perceived physical health, and social support are more relevant to longitudinal SSc pain than disease severity and that perceived physical health and social support may impact pain trajectories. Researchers and rheumatology health professionals should consider these factors in comprehensive pain models and pain management protocols.

  18. Patients' Perspectives and Experiences Living with Systemic Sclerosis: A Systematic Review and Thematic Synthesis of Qualitative Studies.

    Science.gov (United States)

    Nakayama, Ayano; Tunnicliffe, David J; Thakkar, Vivek; Singh-Grewal, Davinder; O'Neill, Sean; Craig, Jonathan C; Tong, Allison

    2016-07-01

    Systemic sclerosis (SSc) is a chronic, progressive autoimmune disease with major end-organ involvement. Much attention has been focused on the management of physical and clinical manifestations; however, the effect of the disease and treatment on the patient's identity, relationships, functioning, and mental well-being are less known. We aimed to describe the patients' perspectives and experiences of living with SSc. Electronic databases were searched to October 2014. Thematic synthesis was used to analyze the findings. We included 26 studies involving 463 patients. Six key themes were identified: distressing appearance transformation (disturbing facial changes, stigmatizing sickness, unrecognizable self), palpable physical limitations (bodily restrictions, frustrating mind-body disconnect, pervasive fatigue, disabling pain), social impairment (breaking intimacy, struggling to fulfill family responsibilities, maintaining work, losing independence), navigating uncertainty (diagnostic ambiguity, medically fending for oneself, unpredictable course of illness), alone and misunderstood (fearful avoidance of fellow patients, invisible suffering), and gradual acceptance and relative optimism (adapting to change and accepting limitations, taking a positive spin, cautious hoping, empowering relationships, valuing medical support). SSc is a rare and unpredictable illness that undermines patients' sense of certainty and control and impairs their self-image, identity, and daily functioning. Patient-centered care that encompasses strategies to promote self-esteem, resilience, and self-efficacy may help to improve treatment satisfaction and health and quality of life outcomes for patients with SSc.

  19. Multiple sclerosis

    DEFF Research Database (Denmark)

    Stenager, E; Knudsen, L; Jensen, K

    1994-01-01

    a significant correlation between results of an attention and perceptual motor speed test i.e. Symbol Digit Modalities test and the ability to read TV-subtitles, but no correlation was found with another attention and perceptual motor speed test, or verbal or visual memory. No correlation between the use......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...... of sedatives and results on neuropsychological tests was found. Anxiety was not correlated with the ability to read TV-subtitles. It is concluded that visual deficits but not the use of sedatives may be a confounding factor in neuropsychological testing in MS....

  20. Lack of activation of renal functional reserve predicts the risk of significant renal involvement in systemic sclerosis.

    Science.gov (United States)

    Livi, Riccardo; Guiducci, Serena; Perfetto, Federico; Ciuti, Gabriele; Grifoni, Elisa; Conforti, Letizia; Galluccio, Felice; Moggi Pignone, Alberto; Matucci Cerinic, Marco

    2011-11-01

    To evaluate if defective activation of renal functional reserve (RFR) in systemic sclerosis (SSc) without clinical signs of renal involvement predicts the risk of developing clinically relevant renal damage. Twenty-eight normotensive SSc patients with normal renal function and no urinary abnormalities were submitted to an intravenous amino acid load to activate RFR. Nineteen patients (six with diffuse cutaneous SSc (dcSSc)) had an RFR activation defect, while nine (two with dcSSc) showed normal RFR. All patients were followed up for 5 years, with periodic evaluation of renal function, urinary protein excretion and systemic blood pressure (BP). At admission, patients with normal RFR had lower BP than those with abnormal RFR; no age, disease duration or creatinine clearance (CCr) differences were found. Five years later, patients with abnormal RFR showed, with respect to basal values, a significantly higher CCr reduction than patients with normal RFR (mean percent decrease 15.4 ± 9.5 vs 2.6 ± 3.8, pRFR, 13 (68.4%) showed a CCr reduction of ≥ 2 ml/min/year, with a final CCr of ≤ 70 ml/min in eight cases; two patients developed microalbuminuria and 10 grade 1 or 2 systemic hypertension. Significant CCr reduction rates were found in eight patients with high BP and in five patients who remained normotensive. No patient with normal RFR had proteinuria or high BP during follow-up. Lack of RFR activation is an early sign of renal involvement in SSc, and is a harbinger of an increased risk of developing renal insufficiency and systemic hypertension.

  1. An overview of the EOSDIS V0 information management system: Lessons learned from the implementation of a distributed data system

    Science.gov (United States)

    Ryan, Patrick M.

    1994-01-01

    The EOSDIS Version 0 system, released in July, 1994, is a working prototype of a distributed data system. One of the purposes of the V0 project is to take several existing data systems and coordinate them into one system while maintaining the independent nature of the original systems. The project is a learning experience and the lessons are being passed on to the architects of the system which will distribute the data received from the planned EOS satellites. In the V0 system, the data resides on heterogeneous systems across the globe but users are presented with a single, integrated interface. This interface allows users to query the participating data centers based on a wide set of criteria. Because this system is a prototype, we used many novel approaches in trying to connect a diverse group of users with the huge amount of available data. Some of these methods worked and others did not. Now that V0 has been released to the public, we can look back at the design and implementation of the system and also consider some possible future directions for the next generation of EOSDIS.

  2. Lessons Learned From the Development, Operation, and Review of Mechanical Systems on the Space Shuttle, International Space Station, and Payloads

    Science.gov (United States)

    Dinsel, Alison; Jermstad, Wayne; Robertson, Brandan

    2006-01-01

    The Mechanical Design and Analysis Branch at the Johnson Space Center (JSC) is responsible for the technical oversight of over 30 mechanical systems flying on the Space Shuttle Orbiter and the International Space Station (ISS). The branch also has the responsibility for reviewing all mechanical systems on all Space Shuttle and International Space Station payloads, as part of the payload safety review process, through the Mechanical Systems Working Group (MSWG). These responsibilities give the branch unique insight into a large number of mechanical systems, and problems encountered during their design, testing, and operation. This paper contains narrative descriptions of lessons learned from some of the major problems worked on by the branch during the last two years. The problems are grouped into common categories and lessons learned are stated.

  3. TANK 241-AN-102 MULTI-PROBE CORROSION MONITORING SYSTEM PROJECT LESSONS LEARNED

    International Nuclear Information System (INIS)

    TAYLOR T; HAGENSEN A; KIRCH NW

    2008-01-01

    During 2007 and 2008, a new Multi-Probe Corrosion Monitoring System (MPCMS) was designed and fabricated for use in double-shell tank 241-AN-102. The system was successfully installed in the tank on May 1, 2008. The 241-AN-102 MPCMS consists of one 'fixed' in-tank probe containing primary and secondary reference electrodes, tank material electrodes, Electrical Resistance (ER) sensors, and stressed and unstressed corrosion coupons. In addition to the fixed probe, the 241-AN-102 MPCMS also contains four standalone coupon racks, or 'removable' probes. Each rack contains stressed and unstressed coupons made of American Society of Testing and Materials A537 CL1 steel, heat-treated to closely match the chemical and mechanical characteristics of the 241-AN-102 tank wall. These coupon racks can be removed periodically to facilitate examination of the attached coupons for corrosion damage. Along the way to successful system deployment and operation, the system design, fabrication, and testing activities presented a number of challenges. This document discusses these challenges and lessons learned, which when applied to future efforts, should improve overall project efficiency

  4. Multiple sclerosis - discharge

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000129.htm Multiple sclerosis - discharge To use the sharing features on this ... Your doctor has told you that you have multiple sclerosis (MS). This disease affects the brain and spinal ...

  5. Corrective Action in Low Performing Schools: Lessons for NCLB Implementation from First-generation Accountability Systems. Vol. 13 No. 48

    Directory of Open Access Journals (Sweden)

    Heinrich Mintrop

    2005-12-01

    Full Text Available This paper explores what lessons we can learn from the experiences of states that instituted NCLB-like accountability systems prior to 2001 (here called first-generation accountability systems. We looked at the experiences of three smaller states (Kentucky, Maryland, North Carolina, four larger ones (California, Florida, New York, Texas, and two large districts (Chicago and Philadelphia. We analyzed evaluative reports and policy documents as well as interviews with state officials and researchers. We condensed the material into eight lessons: sanctions are not the fallback solution; no single strategy has been universally successful; staging should be handled with flexibility; intensive capacity building is necessary; a comprehensive set of strategies seems promising; relationship-building needs to complement powerful programs; competence reduces conflict; and strong state commitment is needed to create system capacity.

  6. Organizing Community-Based Data Standards: Lessons from Developing a Successful Open Standard in Systems Biology

    Science.gov (United States)

    Hucka, M.

    2015-09-01

    In common with many fields, including astronomy, a vast number of software tools for computational modeling and simulation are available today in systems biology. This wealth of resources is a boon to researchers, but it also presents interoperability problems. Despite working with different software tools, researchers want to disseminate their work widely as well as reuse and extend the models of other researchers. This situation led in the year 2000 to an effort to create a tool-independent, machine-readable file format for representing models: SBML, the Systems Biology Markup Language. SBML has since become the de facto standard for its purpose. Its success and general approach has inspired and influenced other community-oriented standardization efforts in systems biology. Open standards are essential for the progress of science in all fields, but it is often difficult for academic researchers to organize successful community-based standards. I draw on personal experiences from the development of SBML and summarize some of the lessons learned, in the hope that this may be useful to other groups seeking to develop open standards in a community-oriented fashion.

  7. Governing large-scale social-ecological systems: Lessons from five cases

    Directory of Open Access Journals (Sweden)

    Forrest D Fleischman

    2014-08-01

    Full Text Available This paper compares lessons drawn from five case studies of large scale governance of common-pool resources: management of forests in Indonesia, the Great Barrier Reef in Australia, the Rhine River in western Europe, the Ozone layer (i.e. the Montreal Protocol, and the Atlantic Bluefin Tuna (i.e. the International Convention on the Conservation of Atlantic Tuna. The goal is to assess the applicability of Ostrom’s design principles for sustainable resource governance to large scale systems, as well as to examine other important variables that may determine success in large scale systems. While we find support for some of Ostrom’s design principles (boundaries, monitoring, sanctions, fit to conditions, and conflict resolution mechanisms are all supported, other principles have only moderate to weak support. In particular, recognition of rights to organize and the accountability of monitors to resource users were not supported. We argue that these differences are the result of differences between small and large scale systems. At large scales, other kinds of political dynamics, including the role of scientists and civil society organizations, appear to play key roles. Other variables emphasized in common-pool resource studies, such as levels of dependence on resources, group size, heterogeneity, disturbances, and resource characteristics also receive mixed support, pointing to the need to reinterpret the meaning of common-pool resource theories in order for them to be applicable at larger scales.

  8. Tuberous sclerosis Anaesthetic considerations

    African Journals Online (AJOL)

    QuickSilver

    SYNDROMIC VIGNETTES IN ANAESTHESIA. Southern African Journal of Anaesthesia & Analgesia - May 2003. 4. 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.

  9. Beneficial effect of botulinum toxin A on Raynaud's phenomenon in Japanese patients with systemic sclerosis: A prospective, case series study.

    Science.gov (United States)

    Motegi, Sei-ichiro; Yamada, Kazuya; Toki, Sayaka; Uchiyama, Akihiko; Kubota, Yuka; Nakamura, Tetsuya; Ishikawa, Osamu

    2016-01-01

    Currently, there is no satisfactory treatment for Raynaud's phenomenon (RP) in systemic sclerosis (SSc). Recently, it has been reported that botulinum toxin A (BTX-A) injection was effective for the treatment of RP in SSc patients. The objective was to assess the efficacy and safety of BTX-A on RP in Japanese SSc patients. In the prospective, case series study, 10 Japanese SSc patients with RP received 10 U of BTX-A injections into the hand. The change in severity of RP, including the frequency of attacks/pain, color changes, duration time of RP and the severity of pain, was assessed by Raynaud's score and pain visual analog scale (VAS) at each visit during 16 weeks. The recovery of skin temperature 20 min after cold water stimulation was examined by thermography at baseline and 4 weeks after injection. The number of digital ulcers (DU) and adverse effects were assessed at each visit. BTX-A injection decreased Raynaud's score and pain VAS from 2 weeks after injection, and the suppressive effect was continued until 16 weeks after injection. Skin temperature recovery after cold water stimulation at 4 weeks after injection was significantly enhanced compared with that before injection. All DU in five patients were healed within 12 weeks after injection. Neither systemic nor local adverse effects were observed in all cases. We conclude that BTX-A injection significantly improved the activity of RP in SSc patients without any adverse events, suggesting that BTX-A may have possible long-term preventive and therapeutic potentials for RP in Japanese SSc patients. © 2015 Japanese Dermatological Association.

  10. Early Endothelial Progenitor Cells (eEPCs) in systemic sclerosis (SSc) - dynamics of cellular regeneration and mesenchymal transdifferentiation.

    Science.gov (United States)

    Patschan, S; Tampe, D; Müller, C; Seitz, C; Herink, C; Müller, G A; Zeisberg, E; Zeisberg, M; Henze, E; Patschan, D

    2016-08-12

    Patients with systemic sclerosis (SSc) are endagered by tissue fibrosis and by microvasculopathy, with the latter caused by endothelial cell expansion/proliferation. SSc-associated fibrosis potentially results from mesenchymal transdifferentiation of endothelial cells. Early Endothelial Progenitor Cells (eEPCs) act proangiogenic under diverse conditions. Aim of the study was to analyze eEPC regeneration and mesenchymal transdifferentiation in patients with limited and diffuse SSs (lSSc and dSSc). Patients with both, lSSc and dSSc were included into the study. The following parameters were evaluated: eEPC numbers and regeneration, concentrations of vasomodulatory mediators, mesenchymal properties of blood-derived eEPC. Serum samples of healthy subjects and SS patients were used for stimulation of cultured human eEPC, subsequently followed by analysis of mesenchymal cell characteristics and mobility. Twenty-nine patients were included into the study. Regenerative activity of blood-derived eEPCs did not differ between Controls and patients. Circulating eEPC were significantly lower in all patients with SSc, and in limited and diffuse SSc (lSSc/dSSc). Serum concentrations of promesenchymal TGF-b was elevated in all patients with SSc. Cultured mononuclear cells from SS patients displayed higher abundances of CD31 and of CD31 and aSMA combined. Finally, serum from SSc patients inhibited migration of cultured eEPCs and the cells showed lower sensitivity towards the endothelin antagonist Bosentan. The eEPC system, which represents an essential element of the endogenous vascular repair machinery is affected in SSc. The increased appearance of mesenchymal properties in eEPC may indicate that alterations of the cells potentially contribute to the accumulation of connective tissue and to vascular malfunction.

  11. 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

  12. 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.

  13. Genome-wide association study for regions of systemic sclerosis susceptibility in a Choctaw Indian population with high disease prevalence.

    Science.gov (United States)

    Zhou, Xiaodong; Tan, Filemon K; Wang, Ning; Xiong, Momiao; Maghidman, Samuel; Reveille, John D; Milewicz, Dianna M; Chakraborty, Ranajit; Arnett, Frank C

    2003-09-01

    Systemic sclerosis (SSc) is a complex, multisystem connective tissue disease in which genetic factors contribute to disease susceptibility. The aim of this study was to localize chromosome regions associated with susceptibility to SSc in a relatively isolated and homogeneous population of Choctaw Indians with a high prevalence of SSc. A genome-wide microsatellite screen at 10 cM resolution (400 markers) was performed in 20 Choctaw patients with SSc and 76 ethically matched controls. Based on the results of the initial screen, fine-scale microsatellite mapping at TOPOI genes, respectively, confirming the results of our previous studies, which used different markers. D1S2800 and D14S63 have been reported to show linkage to systemic lupus erythematosus (SLE) in family-based studies, and D1S206, D6S422, and D6S264 are loci on 1p21.2, 6p22.3, and 6q23-27, respectively, which are in regions reported as showing linkage to SLE and other autoimmune diseases. Other markers showing unique associations with SSc were D7S510 (7p12-11), D7S661 (7q35), D8S514 (8q24.12), D19S221 (19p13.2), D19S220 (19q13.2), D22S423 (22q13.1), DXS1068 (Xp11.4), and DXS8055 (Xq21-23). Further analysis with fine-scale microsatellite mapping revealed at least 14 potential haplotypes associated with SSc. Our findings indicate that a number of genetic loci may contribute to the high prevalence of SSc in the Choctaw and are consistent with the paradigm that some autoimmune rheumatic diseases are likely to share genetic determinants.

  14. Respiratory muscle training for multiple sclerosis

    NARCIS (Netherlands)

    Rietberg, Marc B.; Veerbeek, Janne M.; Gosselink, Rik; Kwakkel, Gert; van Wegen, Erwin E.H.

    2017-01-01

    Background: Multiple sclerosis (MS) is a chronic disease of the central nervous system, affecting approximately 2.5 million people worldwide. People with MS may experience limitations in muscular strength and endurance - including the respiratory muscles, affecting functional performance and

  15. Heritage and Advanced Technology Systems Engineering Lessons Learned from NASA Deep Space Missions

    Science.gov (United States)

    Barley, Bryan; Newhouse, Marilyn; Clardy, Dennon

    2010-01-01

    In the design and development of complex spacecraft missions, project teams frequently assume the use of advanced technology systems or heritage systems to enable a mission or reduce the overall mission risk and cost. As projects proceed through the development life cycle, increasingly detailed knowledge of the advanced and heritage systems within the spacecraft and mission environment identifies unanticipated technical issues. Resolving these issues often results in cost overruns and schedule impacts. The National Aeronautics and Space Administration (NASA) Discovery & New Frontiers (D&NF) Program Office at Marshall Space Flight Center (MSFC) recently studied cost overruns and schedule delays for 5 missions. The goal was to identify the underlying causes for the overruns and delays, and to develop practical mitigations to assist the D&NF projects in identifying potential risks and controlling the associated impacts to proposed mission costs and schedules. The study found that optimistic hardware/software inheritance and technology readiness assumptions caused cost and schedule growth for four of the five missions studied. The cost and schedule growth was not found to result from technical hurdles requiring significant technology development. The projects institutional inheritance and technology readiness processes appear to adequately assess technology viability and prevent technical issues from impacting the final mission success. However, the processes do not appear to identify critical issues early enough in the design cycle to ensure project schedules and estimated costs address the inherent risks. In general, the overruns were traceable to: an inadequate understanding of the heritage system s behavior within the proposed spacecraft design and mission environment; an insufficient level of development experience with the heritage system; or an inadequate scoping of the system-wide impacts necessary to implement an advanced technology for space flight

  16. The Integrative Studies of Genetic and Environmental Factors in Systemic Sclerosis

    National Research Council Canada - National Science Library

    Zhou, Xiaodong

    2008-01-01

    .... To develop a comprehensive statistical analysis in study of dynamic properties of fibroblasts, we employed widely used state-space equations in systems science to model biological systems, and used...

  17. Building institutions for an effective health system: lessons from China's experience with rural health reform.

    Science.gov (United States)

    Bloom, Gerald

    2011-04-01

    This paper is concerned with the management of health system changes aimed at substantially increasing the access to safe and effective health services. It argues that an effective health sector relies on trust-based relationships between users, providers and funders of health services, and that one of the major challenges governments face is to construct institutional arrangements within which these relationships can be embedded. It presents the case of China, which is implementing an ambitious health reform, drawing on a series of visits to rural counties by the author over a 10-year period. It illustrates how the development of reform strategies has been a response both to the challenges arising from the transition to a market economy and the result of actions by different actors, which have led to the gradual creation of increasingly complex institutions. The overall direction of change has been strongly influenced by the efforts made by the political leadership to manage a transition to a modern economy which provides at least some basic benefits to all. The paper concludes that the key lessons for other countries from China's experience with health system reform are less about the detailed design of specific interventions than about its approach to the management of institution-building in a context of complexity and rapid change. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. LESSONS LEARNED IN OPERATING THE HOSE-IN-HOSE SYSTEM FOR TRANSFSERRING SLUDGE AT HANFORD'S K BASINS

    International Nuclear Information System (INIS)

    PERES MW

    2008-01-01

    In May 2007, the Department of Energy and the Fluor Hanford K Basin Closure Project completed transferring sludge from the K East Basin to new containers in the K West Basin using a Hose-in-Hose system. This project presented a number of complex and unique technical, operational, and management challenges that had to be resolved to complete the required transfers and satisfy project milestones. The project team (including DOE; regulators; and Fluor management, operations, maintenance, engineering and all other support organizations) found innovative solutions to each challenge. This paper records lessons learned during the operational phase of the sludge transfer via the Hose-In-Hose system. The subject is limited to the operational phase and does not cover design, development, testing or turnover. A discussion of the situation or problem encountered is provided, along with the lesson learned as applicable to a future program or project

  19. Evolutionary Acquisition of the Global Command and Control System: Lessons Learned

    National Research Council Canada - National Science Library

    Wallis, Johnathan

    1998-01-01

    This paper summarizes a "lessons learned" study that reviews DoD's approach to managing the GCCS program on behalf on the Assistant Secretary of Defense for Command, Control, Communications, and Intelligence (ASD/C3I...

  20. Review of LCA studies of solid waste management systems – Part I: Lessons learned and perspectives

    International Nuclear Information System (INIS)

    Laurent, Alexis; Bakas, Ioannis; Clavreul, Julie; Bernstad, Anna; Niero, Monia; Gentil, Emmanuel; Hauschild, Michael Z.; Christensen, Thomas H.

    2014-01-01

    Highlights: • We perform a critical review of 222 LCA studies of solid waste management systems. • Studies mainly concentrated in Europe with little application in developing countries. • Assessments of relevant waste types apart from household waste have been overlooked. • Local specificities of systems prevent a meaningful generalisation of the LCA results. • LCA should support recommendations representative of the local conditions. - Abstract: The continuously increasing solid waste generation worldwide calls for management strategies that integrate concerns for environmental sustainability. By quantifying environmental impacts of systems, life cycle assessment (LCA) is a tool, which can contribute to answer that call. But how, where and to which extent has it been applied to solid waste management systems (SWMSs) until now, and which lessons can be learnt from the findings of these LCA applications? To address these questions, we performed a critical review of 222 published LCA studies of SWMS. We first analysed the geographic distribution and found that the published studies have primarily been concentrated in Europe with little application in developing countries. In terms of technological coverage, they have largely overlooked application of LCA to waste prevention activities and to relevant waste types apart from household waste, e.g. construction and demolition waste. Waste management practitioners are thus encouraged to abridge these gaps in future applications of LCA. In addition to this contextual analysis, we also evaluated the findings of selected studies of good quality and found that there is little agreement in the conclusions among them. The strong dependence of each SWMS on local conditions, such as waste composition or energy system, prevents a meaningful generalisation of the LCA results as we find it in the waste hierarchy. We therefore recommend stakeholders in solid waste management to regard LCA as a tool, which, by its ability of

  1. Lessons Learned while Exploring Cloud-Native Architectures for NASA EOSDIS Applications and Systems

    Science.gov (United States)

    Pilone, D.

    2016-12-01

    As new, high data rate missions begin collecting data, the NASA's Earth Observing System Data and Information System (EOSDIS) archive is projected to grow roughly 20x to over 300PBs by 2025. To prepare for the dramatic increase in data and enable broad scientific inquiry into larger time series and datasets, NASA has been exploring the impact of applying cloud technologies throughout EOSDIS. In this talk we will provide an overview of NASA's prototyping and lessons learned in applying cloud architectures to: Highly scalable and extensible ingest and archive of EOSDIS data Going "all-in" on cloud based application architectures including "serverless" data processing pipelines and evaluating approaches to vendor-lock in Rethinking data distribution and approaches to analysis in a cloud environment Incorporating and enforcing security controls while minimizing the barrier for research efforts to deploy to NASA compliant, operational environments. NASA's Earth Observing System (EOS) is a coordinated series of satellites for long term global observations. NASA's Earth Observing System Data and Information System (EOSDIS) is a multi-petabyte-scale archive of environmental data that supports global climate change research by providing end-to-end services from EOS instrument data collection to science data processing to full access to EOS and other earth science data. On a daily basis, the EOSDIS ingests, processes, archives and distributes over 3 terabytes of data from NASA's Earth Science missions representing over 6000 data products ranging from various types of science disciplines. EOSDIS has continually evolved to improve the discoverability, accessibility, and usability of high-impact NASA data spanning the multi-petabyte-scale archive of Earth science data products.

  2. A multi-national qualitative research study exploring the patient experience of Raynaud's phenomenon in systemic sclerosis.

    Science.gov (United States)

    Pauling, John D; Domsic, Robyn T; Saketkoo, Lesley A; Almeida, Celia; Withey, Jane; Jay, Hilary; Frech, Tracy M; Ingegnoli, Francesca; Dures, Emma; Robson, Joanna; McHugh, Neil J; Herrick, Ariane L; Matucci-Cerinic, Marco; Khanna, Dinesh; Hewlett, Sarah

    2017-11-21

    Raynaud's phenomenon (RP) is the commonest manifestation of systemic sclerosis (SSc). RP is an episodic phenomenon, not easily assessed in the clinic, leading to reliance on self-report. A thorough understanding of the patient experience of SSc-RP is essential to ensuring patient-reported outcome (PRO) instruments capture domains important to the target patient population. We report the findings of an international qualitative research study investigating the patient experience of SSc-RP. Focus groups (FGs) of SSc patients were conducted across 3 scleroderma centers in the US and UK, using a topic guide and a priori purposive sampling framework devised by qualitative researchers, SSc patients and SSc experts. FGs were audio recorded, transcribed, anonymised and analysed using inductive thematic analysis. FGs were conducted until thematic saturation was achieved. Forty SSc patients participated in 6 focus groups conducted in Bath (UK), New Orleans (US) and Pittsburgh (US). Seven major themes were identified that encapsulate the patient experience of SSc-RP: physical symptoms, emotional impact, triggers & exacerbating factors, constant vigilance & self-management, impact on daily life, uncertainty and adaptation. The inter-relationship of the 7 constituent themes can be arranged within a conceptual map of SSc-RP. We have explored the patient experience of SSc-RP in a diverse and representative SSc cohort and identified a complex interplay of experiences that result in significant impact. Work to develop a novel PRO instrument for assessing the severity and impact of SSc-RP, comprising domains/items grounded in the patient experiences of SSc-RP identified in this study is underway. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  3. Gastric antral vascular ectasia and its clinical correlates in patients with early diffuse systemic sclerosis in the SCOT trial.

    Science.gov (United States)

    Hung, Emily W; Mayes, Maureen D; Sharif, Roozbeh; Assassi, Shervin; Machicao, Victor I; Hosing, Chitra; St Clair, E William; Furst, Daniel E; Khanna, Dinesh; Forman, Stephen; Mineishi, Shin; Phillips, Kristine; Seibold, James R; Bredeson, Christopher; Csuka, Mary Ellen; Nash, Richard A; Wener, Mark H; Simms, Robert; Ballen, Karen; Leclercq, Sharon; Storek, Jan; Goldmuntz, Ellen; Welch, Beverly; Keyes-Elstein, Lynette; Castina, Sharon; Crofford, Leslie J; Mcsweeney, Peter; Sullivan, Keith M

    2013-04-01

    To describe the prevalence and clinical correlates of endoscopic gastric antral vascular ectasia (GAVE; "watermelon stomach") in early diffuse systemic sclerosis (SSc). Subjects with early, diffuse SSc and evidence of specific internal organ involvement were considered for the Scleroderma: Cyclophosphamide Or Transplant (SCOT) trial. In the screening procedures, all patients underwent upper gastrointestinal endoscopy. Patients were then categorized into those with or without endoscopic evidence of GAVE. Demographic data, clinical disease characteristics, and autoantibody data were compared using Pearson chi-square or Student t tests. Twenty-three of 103 (22.3%) individuals were found to have GAVE on endoscopy. Although not statistically significant, anti-topoisomerase I (anti-Scl70) was detected less frequently among those with GAVE (18.8% vs 44.7%; p = 0.071). Similarly, anti-RNP antibodies (anti-U1 RNP) showed a trend to a negative association with GAVE (0 vs 18.4%; p = 0.066). There was no association between anti-RNA polymerase III and GAVE. Patients with GAVE had significantly more erythema or vascular ectasias in other parts of the stomach (26.1% vs 5.0%; p = 0.003). Endoscopic GAVE was present on screening in almost one-fourth of these highly selected patients with early and severe diffuse SSc. While anti-Scl70 and anti-U1 RNP trended toward a negative association with GAVE, there was no correlation between anti-RNA Pol III and GAVE. Patients with GAVE had a higher frequency of other gastric vascular ectasias outside the antrum, suggesting that GAVE may represent part of the spectrum of the vasculopathy in SSc.

  4. MiR-30a-3p negatively regulates BAFF synthesis in systemic sclerosis and rheumatoid arthritis fibroblasts.

    Directory of Open Access Journals (Sweden)

    Ghada Alsaleh

    Full Text Available We evaluated micro (mi RNA-mediated regulation of BAFF expression in fibroblasts using two concomitant models: (i synovial fibroblasts (FLS isolated from healthy controls (N or Rheumatoid Arthritis (RA patients; (ii human dermal fibroblasts (HDF isolated from healthy controls (N or Systemic Sclerosis (SSc patients. Using RT-qPCR and ELISA, we first showed that SScHDF synthesized and released BAFF in response to Poly(I:C or IFN-γ treatment, as previously observed in RAFLS, whereas NHDF released BAFF preferentially in response to IFN-γ. Next, we demonstrated that miR-30a-3p expression was down regulated in RAFLS and SScHDF stimulated with Poly(I:C or IFN-γ. Moreover, we demonstrated that transfecting miR-30a-3p mimic in Poly(I:C- and IFN-γ-activated RAFLS and SScHDF showed a strong decrease on BAFF synthesis and release and thus B cells survival in our model. Interestingly, FLS and HDF isolated from healthy subjects express higher levels of miR-30a-3p and lower levels of BAFF than RAFLS and SScHDF. Transfection of miR-30a-3p antisense in Poly(I:C- and IFN-γ-activated NFLS and NHDF upregulated BAFF secretion, confirming that this microRNA is a basal repressors of BAFF expression in cells from healthy donors. Our data suggest a critical role of miR-30a-3p in the regulation of BAFF expression, which could have a major impact in the regulation of the autoimmune responses occurring in RA and SSc.

  5. Copy Number Variations in Amyotrophic Lateral Sclerosis: Piecing the Mosaic Tiles Together through a Systems Biology Approach.

    Science.gov (United States)

    Morello, Giovanna; Guarnaccia, Maria; Spampinato, Antonio Gianmaria; La Cognata, Valentina; D'Agata, Velia; Cavallaro, Sebastiano

    2018-02-01

    Amyotrophic lateral sclerosis (ALS) is a devastating and still untreatable motor neuron disease. Despite the molecular mechanisms underlying ALS pathogenesis that are still far from being understood, several studies have suggested the importance of a genetic contribution in both familial and sporadic forms of the disease. In addition to single-nucleotide polymorphisms (SNPs), which account for only a limited number of ALS cases, a consistent number of common and rare copy number variations (CNVs) have been associated to ALS. Most of the CNV-based association studies use a traditional candidate-gene approach that is inadequate for uncovering the genetic architectures of complex traits like ALS. The emergent paradigm of "systems biology" may offer a new perspective to better interpret the wide spectrum of CNVs in ALS, enabling the characterization of the complex network of gene products underlying ALS pathogenesis. In this review, we will explore the landscape of CNVs in ALS, putting specific emphasis on the functional impact of common CNV regions and genes consistently associated with increased risk of developing disease. In addition, we will discuss the potential contribution of multiple rare CNVs in ALS pathogenesis, focusing our attention on the complex mechanisms by which these proteins might impact, individually or in combination, the genetic susceptibility of ALS. The comprehensive detection and functional characterization of common and rare candidate risk CNVs in ALS susceptibility may bring new pieces into the intricate mosaic of ALS pathogenesis, providing interesting and important implications for a more precise molecular biomarker-assisted diagnosis and more effective and personalized treatments.

  6. Mapping QTL affecting a systemic sclerosis-like disorder in a cross between UCD-200 and red jungle fowl chickens.

    Science.gov (United States)

    Ek, Weronica; Sahlqvist, Anna-Stina; Crooks, Lucy; Sgonc, Roswitha; Dietrich, Hermann; Wick, Georg; Ekwall, Olov; Andersson, Leif; Carlborg, Örjan; Kämpe, Olle; Kerje, Susanne

    2012-10-01

    Systemic sclerosis (SSc) or scleroderma is a rare, autoimmune, multi-factorial disease characterized by early microvascular alterations, inflammation, and fibrosis. Chickens from the UCD-200 line develop a hereditary SSc-like disease, showing all the hallmarks of the human disorder, which makes this line a promising model to study genetic factors underlying the disease. A backcross was generated between UCD-200 chickens and its wild ancestor - the red jungle fowl and a genome-scan was performed to identify loci affecting early (21 days of age) and late (175 days of age) ischemic lesions of the comb. A significant difference in frequency of disease was observed between sexes in the BC population, where the homogametic males were more affected than females, and there was evidence for a protective W chromosome effect. Three suggestive disease predisposing loci were mapped to chromosomes 2, 12 and 14. Three orthologues of genes implicated in human SSc are located in the QTL region on chromosome 2, TGFRB1, EXOC2-IRF4 and COL1A2, as well as CCR8, which is more generally related to immune function. IGFBP3 is also located within the QTL on chromosome 2 and earlier studies have showed increased IGFBP3 serum levels in SSc patients. To our knowledge, this study is the first to reveal a potential genetic association between IGFBP3 and SSc. Another gene with an immunological function, SOCS1, is located in the QTL region on chromosome 14. These results illustrate the usefulness of the UCD-200 chicken as a model of human SSc and motivate further in-depth functional studies of the implicated candidate genes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Morphometric evaluation of nitric oxide synthase isoforms and their cytokine regulators predict pulmonary dysfunction and survival in systemic sclerosis

    Directory of Open Access Journals (Sweden)

    E.R. Parra

    2013-01-01

    Full Text Available Because histopathological changes in the lungs of patients with systemic sclerosis (SSc are consistent with alveolar and vessel cell damage, we presume that this interaction can be characterized by analyzing the expression of proteins regulating nitric oxide (NO and plasminogen activator inhibitor-1 (PAI-1 synthesis. To validate the importance of alveolar-vascular interactions and to explore the quantitative relationship between these factors and other clinical data, we studied these markers in 23 cases of SSc nonspecific interstitial pneumonia (SSc-NSIP. We used immunohistochemistry and morphometry to evaluate the amount of cells in alveolar septa and vessels staining for NO synthase (NOS and PAI-1, and the outcomes of our study were cellular and fibrotic NSIP, pulmonary function tests, and survival time until death. General linear model analysis demonstrated that staining for septal inducible NOS (iNOS related significantly to staining of septal cells for interleukin (IL-4 and to septal IL-13. In univariate analysis, higher levels of septal and vascular cells staining for iNOS were associated with a smaller percentage of septal and vascular cells expressing fibroblast growth factor and myofibroblast proliferation, respectively. Multivariate Cox model analysis demonstrated that, after controlling for SSc-NSIP histological patterns, just three variables were significantly associated with survival time: septal iNOS (P=0.04, septal IL-13 (P=0.03, and septal basic fibroblast growth factor (bFGF; P=0.02. Augmented NOS, IL-13, and bFGF in SSc-NSIP histological patterns suggest a possible functional role for iNOS in SSc. In addition, the extent of iNOS, PAI-1, and IL-4 staining in alveolar septa and vessels provides a possible independent diagnostic measure for the degree of pulmonary dysfunction and fibrosis with an impact on the survival of patients with SSc.

  8. Comprehensive immune profiling reveals substantial immune system alterations in a subset of patients with amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    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

  9. Relationship Between Disease Characteristics and Oral Radiologic Findings in Systemic Sclerosis: Results From a Canadian Oral Health Study.

    Science.gov (United States)

    Baron, Murray; Hudson, Marie; Dagenais, Marie; Macdonald, David; Gyger, Geneviève; El Sayegh, Tarek; Pope, Janet; Fontaine, Audrey; Masetto, Ariel; Matthews, Debora; Sutton, Evelyn; Thie, Norman; Jones, Niall; Copete, Maria; Kolbinson, Dean; Markland, Janet; Nogueira-Filho, Getulio; Robinson, David; Fritzler, Marvin; Wang, Mianbo; Gornitsky, Mervyn

    2016-05-01

    Systemic sclerosis (SSc; scleroderma) is associated with a wide periodontal ligament (PDL) and mandibular erosions. We investigated the clinical correlates of SSc with these radiologic abnormalities. Subjects from the Canadian Scleroderma Research Group cohort underwent detailed radiologic examinations. Associations between radiologic abnormalities and clinical manifestations of SSc were examined with univariate and multivariate analyses. The study included 159 subjects; 90.6% were women, the mean ± SD age was 56 ± 10 years, diffuse disease was present in 28.3%, and mean ± SD disease duration was 13.7 ± 8.4 years. Widening of the PDL involving at least 1 tooth was present in 38% of subjects, and 14.5% had at least 1 site in the mandible with an erosion. In analyses adjusting for age, disease duration, sex, smoking, and education, we found significant associations between the number of teeth with widening of the PDL and disease severity assessed by the physician global assessment (PGA) (relative risk [RR] 1.19, 95% confidence interval [95% CI] 1.02-1.39, P = 0.028). Analyses replacing the PGA with the skin score, disease subset, or anti-topoisomerase I antibodies confirmed the relationship with indices of disease severity. There was no relationship between either the number of teeth with periodontal disease or the number of missing teeth, and the number of teeth with wide PDL. A smaller interdental distance (RR 0.89, 95% CI 0.82-0.97, P = 0.006), but not disease severity, facial skin score, or ischemia was associated with a larger number of erosions. In SSc, a wide PDL may reflect generalized overproduction of collagen, and mandibular erosions are related to local factors in the oral cavity. © 2016, American College of Rheumatology.

  10. "It's Not Me, It's Not Really Me." Insights From Patients on Living With Systemic Sclerosis: An Interview Study.

    Science.gov (United States)

    Sumpton, Daniel; Thakkar, Vivek; O'Neill, Sean; Singh-Grewal, Davinder; Craig, Jonathan C; Tong, Allison

    2017-11-01

    Patients with systemic sclerosis (SSc) experience severe physical limitations and psychological morbidity, but their lived experience remains underrepresented and is reflected in the scarcity of evidence-based patient-centered interventions. We aimed to describe patients' perspectives of SSc to inform strategies to improve their care. Face-to-face semistructured interviews were conducted with 30 adult patients with limited cutaneous or diffuse cutaneous SSc in Australia. Transcripts were thematically analyzed using HyperRESEARCH software. Six themes were identified: bodily malfunction (restrictive pain, debilitating physical changes, pervasive exhaustion), deprivation of social function (loss of work and career, social isolation, threat to traditional roles, loss of intimacy), disintegration of identity (stigmatizing physical changes, disassociated self-image, extinguished hopes, alone and powerless, invisibility of illness), insecurity of care (unrecognized disease, ambiguity around diagnosis and cause, information insufficiency, resigning to treatment limitations, seeking reassurance, fear of progression), avoiding the sick role (evading thoughts of sickness, protecting family, favorable comparison), and perseverance and hope (positive stoicism, optimism about treatment and monitoring, taking control of own health, pursuing alternative treatments, transcending illness through support). SSc inflicts major bodily and social restrictions that crush patients' identity and self-image. Uncertainties about the cause, diagnosis, and prognosis can undermine confidence in care, leading to anxiety and therapeutic nihilism. Access to psychosocial care to support the patients' role and functioning capacity, as well as communication and education that explicitly address their concerns regarding management may potentially improve treatment satisfaction, self-efficacy, adherence, and outcomes in patients with SSc. © 2017, American College of Rheumatology.

  11. Elevated serum Krebs von den Lungen-6 in systemic sclerosis: a marker of lung fibrosis and severity of the disease.

    Science.gov (United States)

    Benyamine, Audrey; Heim, Xavier; Resseguier, Noémie; Bertin, Daniel; Gomez, Carine; Ebbo, Mikaël; Harlé, Jean-Robert; Kaplanski, Gilles; Rossi, Pascal; Bardin, Nathalie; Granel, Brigitte

    2018-02-17

    We aimed to assess the clinical significance of Krebs von den Lungen-6 (KL-6) in the diagnosis and severity of interstitial lung disease (ILD) in a French cohort of patients with systemic sclerosis (SSc). Serum KL-6 concentrations were measured with chemiluminescent enzyme immunoassay (CLEIA) in 75 SSc patients. Patients were divided into two groups according to the presence of interstitial lung disease (SSc-ILD versus SSc-without ILD) on chest High-Resolution Computed Tomography. Pulmonary function tests, main manifestations and severity of the lung disease (Medsger's severity scale) were collected. KL-6 serum concentrations were significantly higher in SSc-ILD patients than in those without ILD (p < 10 -4 ) and were inversely correlated with forced vital capacity, total lung capacity and diffuse lung capacity of carbon monoxide. Serum KL-6 level superior to 872 U/ml appeared as the optimal cut-off value associated with ILD. Patients with a restrictive pulmonary syndrome and dyspnoea had significant higher KL-6 serum concentrations. SSc patients with anti-topoisomerase 1 antibodies had higher KL-6 serum levels than patients with anti-centromere antibodies (p < 10 - 4 ). ILD and anti-topoisomerase 1 antibodies were independent factors associated with KL-6 in multivariate analysis. Interestingly, KL-6 serum concentrations positively increased with the patient lung severity. Our study confirms that KL-6 is an accurate biomarker for the diagnosis of SSc-ILD in a French cohort of patients. High KL-6 levels should prompt physicians to assess ILD with pulmonary imaging and pulmonary functions tests. Prospective clinical studies are still required to determine whether levels of KL-6 might predict progression of ILD as well as its usefulness in the timing of therapeutic intervention.

  12. Effect of treatment with iloprost with or without bosentan on nailfold videocapillaroscopic alterations in patients with systemic sclerosis.

    Science.gov (United States)

    Cestelli, Valentina; Manfredi, Andreina; Sebastiani, Marco; Praino, Emanuela; Cannarile, Francesca; Giuggioli, Dilia; Ferri, Clodoveo

    2017-01-01

    Vascular involvement plays a decisive role in systemic sclerosis (SSc) pathogenesis; it is responsible for some important clinical manifestations of the disease such as Raynaud's phenomenon and digital ulcers (DU). Bosentan, a dual receptor endothelin antagonist, and iloprost, often in combination therapy, seems to be able to interfere with the scleroderma microangiopathy. Aim of the study was to evaluate the effect of bosentan and iloprost on scleroderma microangiopathy, analyzed by means of capillaroscopic skin ulcer risk index (CSURI), in SSc patients treated for the prevention of DU. Nailfold videocapillaroscopy (NVC) was performed in 95 SSc patients, treated with iloprost alone (group 1) or combination therapy with iloprost and bosentan (group 2), at baseline and after one year. In all patients CSURI was calculated according to the formula "diameter × number of megacapillaries/(total number of capillaries) 2 ": in addition, total number of capillaries, giant capillaries, micro-hemorrhages, disorganization of the vascular array, and ramified capillaries were evaluated by means of a semiquantitative score. After 12 months, we observed a reduction of the number of giant capillaries in both groups, while an increase of ramified capillaries was recorded only in group 2. CSURI improved slightly in group 2 without statistical significance; on the contrary, in group 1 a significant worsening was recorded (p ≤ 0.001). Our study confirms the effectiveness of bosentan, in combination with iloprost, in SSc microangiopathy observed to NVC. Moreover, the observed findings further support the role of CSURI in the evaluation and monitoring of SSc microangiopathy.

  13. A Novel Prothrombotic Pathway in Systemic Sclerosis Patients: Possible Role of Bisphosphonate-Activated γδ T Cells.

    Science.gov (United States)

    Marcu-Malina, Victoria; Balbir-Gurman, Alexandra; Dardik, Rima; Braun-Moscovici, Yolanda; Segel, Michael J; Bank, Ilan

    2014-01-01

    Infusions of aminobisphonates (ABP) activate Vγ9δ2T cells in vivo and induce an acute inflammatory response in 30% of patients treated for osteoporosis. Following the observation of digital thrombosis in a systemic sclerosis (SSc) patient after treatment with an intravenous ABP, zoledronate (Zol), we evaluated whether patient and control peripheral blood (PB) mononuclear cell (MC, PBMC) acquire a prothrombotic phenotype in response to Zol. Vγ9δ2T cells of both patients and healthy donors (HD) upregulated the CD69 activation antigen and secreted tumor necrosis factor (TNF)α in response to Zol in vitro. In addition, exposure to either Zol or lipopolysaccharide (LPS), or to both additively, induced expression of the highly procoagulant, tissue factor (TF)-1 on CD14+ monocytes. Importantly, only Zol-induced TF-1 was blocked by a monoclonal antibody to TNFα. Interestingly, we found that SSc, but not HD, Vδ1+ T cells were concurrently activated by Zol to produce interleukin (IL)-4. Addition of plasma from the blood of the SSc patient who developed critical digital ischemia after infusion of Zol, but neither plasma from a second patient with no adverse clinical response to Zol infusion nor of a HD, strongly enhanced Zol-induced monocyte TF-1, which could still be blocked by anti-TNFα. Aminobisphonates induced secretion of TNFα by Vγ9δ2+ T cells may lead to TNFα-dependent induction of procoagulant TF-1 induction on monocytes. In certain clinical settings, e.g., SSc, TF-1+ monocytes could play a role in triggering clinically relevant thrombosis.

  14. Pilot study assessing pathophysiology and healing of digital ulcers in patients with systemic sclerosis using laser Doppler imaging and thermography.

    Science.gov (United States)

    Murray, Andrea K; Moore, Tonia L; Wragg, Elizabeth; Ennis, Holly; Vail, Andy; Dinsdale, Graham; Muir, Lindsay; Griffiths, Christopher E M; Herrick, Ariane L

    2016-01-01

    Systemic sclerosis (SSc)-related digital ulcers (DU) cause significant pain and disability and are often a primary endpoint in clinical trials. However, their pathophysiology has been little studied. The objectives of this prospective study were to determine whether laser Doppler imaging (LDI) and thermography can identify ischaemic components in both fingertip and extensor surface DU and assess ulcer healing. Patients prospectively reported new DU over a year. Patients' DU underwent imaging until the ulcer had healed. Ischaemia was defined as lower blood flow or skin temperature (and inflammation as higher) within the ulcer, compared to a non-affected site. 53 ulcers (19 fingertip, 18 extensor, 16 'other' sites) in 17 patients were imaged (53 with LDI, 52 with thermography). For LDI data 32 (60%) ulcers were ischaemic; median perfusion ulcer/unaffected area; 0.79 (range 0.11-2.9). For thermography data 35 (66%) were ischaemic; 0.98 (0.89 to 1.1). Inflammation in the surrounding area was identified for all ulcers by LDI but not thermography. In the 36 ulcers with repeat imaging, LDI showed trends (with healing) towards increased ulcer perfusion (p=0.23) and decreased hyperaemia in adjacent areas (p=0.59). Skin temperature at the ulcer site showed no significant change (p=0.13) but adjacent area showed decreased temperature (p=0.04 signifying decreased blood flow). LDI and thermography are sufficiently sensitive to measure ischaemia in both fingertip and extensor ulcers. LDI was better suited to monitoring change in perfusion with healing (due to higher imaging resolution, or vascular changes occurring in more superficial skin layers).

  15. Lower limb muscle strength is associated with functional performance and quality of life in patients with systemic sclerosis

    Directory of Open Access Journals (Sweden)

    Tatiana R. L. Lima

    2015-04-01

    Full Text Available Background: Complaints of peripheral muscle weakness are quite common in patients with systemic sclerosis (SSc. It is likely that the muscle impairments may reduce the patients' exercise performance, which in turn may decrease their functional capacity and exert a direct impact on their quality of life. Objectives: To assess the peripheral and respiratory muscle strength in individuals with SSc and to investigate their correlation with the 6-min walk distance (6MWD and quality of life measurements. Moreover, we aimed to characterize their nutritional status, pulmonary function, functional capacity, and quality of life compared to the controls. Method: The present cross-sectional study included 20 patients with SSc and 20 control subjects. All of the participants were subjected to isometric dynamometry, surface electromyography, bioelectrical impedance analysis, pulmonary function testing, and the 6-min walk test. Patients with SSc also responded to the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36 and the Health Assessment Questionnaire Disability Index (HAQ-DI. Results: The individuals with SSc exhibited a reduction in quadriceps strength (p=0.0001, increased quadriceps fatigability (p=0.034, impaired pulmonary function, and a reduced 6MWD (p=0.0001 compared to the controls. Quadriceps strength was significantly correlated with the 6MWD (Rho=0.719; p=0.0004 and the HAQ-DI (Rho=-0.622; p=0.003. We also found significant correlations between quadriceps fatigability and maximal inspiratory (Rho=0.684; p=0.0009 and maximal expiratory (Rho=0.472; p=0.035 pressure. Conclusions: Patients with SSc exhibited reduced respiratory muscle and quadriceps strength and an increase in its fatigability. In these individuals, there was a relationship between quadriceps strength, functional capacity, and quality of life.

  16. Nailfold capillaroscopy and blood flow laser-doppler analysis of the microvascular damage in systemic sclerosis: preliminary results

    Directory of Open Access Journals (Sweden)

    C. Pizzorni

    2011-06-01

    Full Text Available Objectives: Systemic sclerosis (SSc is characterized by altered microvascular structure and function. Nailfold videocapillaroscopy (NVC is the tool to evaluate capillary morphological structure and laser-Doppler Blood flowmetry (LDF can be used to estimate cutaneous blood flow of microvessels. The aim of this study was to investigate possible relationships between capillary morphology and blood flow in SSc. Methods: 27 SSc patients and 12 healthy subjects were enrolled. SSc microvascular involvement, as evaluated by NVC, was classified in three different patterns (“Early”, “Active”, “Late”. LDF analysis was performed at the II, III, IV, V hand fingers in both hands and both at cutaneous temperature and at 36°C. Statistical evaluation was carried out by non-parametric procedures. Results: Blood flow was found significantly lower in SSc patients when compared with healthy subjects (p<0.05. The heating of the probe to 36°C induced a significant increase in peripheral blood flow in all subjects compared to baseline (p <0.05, however, the amount of variation was significantly lower in patients with SSc, compared with healthy controls (p <0.05. The SSc patients with NVC “Late” pattern, showed lower values of peripheral blood flow than patients with NVC “Active” or “Early” patterns (p<0.05. Moreover, a negative correlation between the tissue perfusion score and the progression of the SSc microangiopathy was observed, as well as between the tissue perfusion and the duration of the Raynaud’s phenomenon (p <0.03. Conclusions: LDF can be employed to evaluate blood perfusion in the microvascular circulation in SSc patients. The blood flow changes observed with the LDF seem to correlate with the severity of microvascular damage in SSc as detected by NVC.

  17. Clinical, autoimmune, and psychiatric parameters correlate with sleep disturbance in patients with systemic sclerosis and rheumatoid arthritis.

    Science.gov (United States)

    Bagnato, Gian Luca; Fiorenza, Alessia; Cordova, Francesca; Roberts, William Neal; Moore, Charles; Greco, Domenica; Monaco, Claudia; Muscatello, Maria Rosaria Anna; Bruno, Antonio; Zoccali, Rocco; Bagnato, Gianfilippo

    2016-01-01

    Sleep disturbance is an important contributor to poor quality of life in rheumatic disorders. This study aims to test whether clinical, autoimmune and psychological factors are associated with sleep disturbance in systemic sclerosis (SSc) compared to rheumatoid arthritis (RA) patients and controls. 101 female subjects (SSc=33, RA=34, healthy controls=34) participated in this observational, cross-sectional, parallel group study. Sleep disturbance was assessed with the Pittsburgh Sleep Quality Index (PSQI). Other assessments included the visual analogue scale (VAS) for pain, 36-item Short-Form Health Survey (SF-36), Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI). Clinical parameters, therapeutic regimen, and serologic status were recorded. In SSc patients, PSQI scores were higher than in RA patients and controls. Linear regression analysis showed that in SSc patients PSQI scores was associated with BDI, disease duration, modified Rodnan skin score and VAS, while DAS28 and BDI were associated with PSQI scores in RA patients. Anti-Scl70 and ANA positive SSc patients showed higher PSQI scores compared to those ANA positive only, while no differences were observed in RA patients classified according to rheumatoid factor positivity. SSc patients treated with immunosuppressants had lower PSQI scores compared to those not on therapy, whereas only corticosteroid treatment was significantly associated with higher PSQI scores in RA patients. RA patients with disease activity higher than moderate (DAS28≥3.2) had higher PSQI scores than those with lower than moderate (DAS28<3.2). Longitudinal studies are needed to identify disease-specific patterns associated with sleep disturbances and the influence on sleep function induced by immunosuppressive therapy among rheumatic patients.

  18. Prototype Applications Of Blended Learning On The Lessons Of Project Management Information System MPSI In College

    Directory of Open Access Journals (Sweden)

    Riswan

    2015-08-01

    Full Text Available This research is further than the initial research has been done on the lessons of project management information system MPSI. Included in the seminar of the International Conference on Technical and Vocation Education and Training High on a hill on the 16th-17th-October 2015 organized by the State University of Padang UNP. As well as on The 2016 Jambi International Seminars on Education JISE in Jambi Indonesia 3-4 April 2016. The results of initial research showed that the quality of the teaching model of face-to-face with MPSI konvensioanal are on enough categories so that needs to be developed a Blended Learning model that is merging model of face-to-face with e-learning model in order to improve the quality of teaching for the better. The results of a pretest data analysis on a class of experiments and classroom control showed results not much different 12.32 for classes experiments and 11.12 for the classroom control. Test of normality that is done for the second class also shows a normal distribution. Where r count for a class experiment 00060 01772 r tables and r count for class control 00572 01772 r tables. Now this research has already come to the stage of prototype application design blended learning will be in validation by an expert of computer design.

  19. Developing novel drugs for systemic lupus erythematosus. Lessons learned from the belimumab trials

    Directory of Open Access Journals (Sweden)

    Cristina Pamfil

    2012-07-01

    Full Text Available Systemic lupus erythematosus is the prototypic autoimmune disease with a broad range of clinical manifestations and a complex pathogenesis. B-cells hold a central role in its pathogenesis, not only as autoantibody producing cells, but also by producing other inflammatory mediators and by presenting autoantigens to autoreactive T cells. BlyS, a soluble ligand of the TNF cytokine family, is a key factor affecting B-cell homeostasis and survival and its blockade ameliorated the disease in animal models and preclinical studies of SLE. Following an unsuccessful phase II trial of belimumab, a monoclonal antibody targeting BlyS, two large phase III studies in patients with mild-to-moderate disease, BLISS-52 and BLISS-76, met their primary endpoints showing better efficacy of the drug over standard of care alone. To this end, development of a novel more sensitive responder index and improvements in study designs were crucial. As a result, belimumab became the first drug to get approval for the treatment of SLE after more than 50 years. In this paper we discuss the rationale, development, indications, lessons learned, pitfalls and challenges for this novel therapy and point-out to additional issues that need to be addressed in the future.http://dx.doi.org/10.7175/rhc.v3i3.206

  20. High IL-17E and Low IL-17C Dermal Expression Identifies a Fibrosis-Specific Motif Common to Morphea and Systemic Sclerosis

    OpenAIRE

    Lonati, Paola Adele; Brembilla, Nicolò Costantino; Montanari, Elisa; Fontao, Lionel; Gabrielli, Armando; Vettori, Serena; Valentini, Gabriele; Laffitte, Emmanuel; Kaya, Gurkan; Meroni, Pier-Luigi; Chizzolini, Carlo

    2014-01-01

    BACKGROUND: High interleukin (IL)-17A levels are characteristically found in the skin of systemic sclerosis (SSc) individuals. Our aim was to investigate whether the dermal expression of IL-17A and related IL-17 family members (i.e. IL-17C, IL-17E and IL-17F) could distinguish fibrotic from healthy skin and could show similarities in SSc and morphea, two disorders with presumed distinct pathogenesis, but characterized by skin fibrosis. METHODS: Biopsies were obtained from the involved skin of...

  1. Bead Game Simulation. Lesson Plan.

    Science.gov (United States)

    Ripp, Ken

    This lesson plan offers students the opportunity to participate in the three basic economic systems (market, command, and tradition). By working in each of the systems, students will internalize the fundamental values present in each system and will gain insights into the basic advantages and disadvantages of each system. The lesson plan provides…

  2. Esclerosis sistémica complicada con síncope y bloqueo AV completo Systemic sclerosis complicated with syncope and complete AV block

    Directory of Open Access Journals (Sweden)

    Francisco Femenía

    2010-10-01

    Full Text Available La esclerosis sistémica es una compleja enfermedad que afecta el tejido conectivo, el sistema vascular y el sistema inmunológico, y se caracteriza por fibrosis cutánea y de órganos viscerales. Los bloqueos de rama y los hemibloqueos se presentan en el 25 a 75% de los casos y constituyen predictores independientes de mortalidad. Los bloqueos auriculoventriculares de segundo o tercer grado son muy raros. Presentamos el caso de una mujer de 47 años de edad, con diagnóstico de esclerosis sistémica, quien presenta episodio sincopal secundario a bloqueo auriculoventricular completo con necesidad de implante de marcapasos definitivo.Systemic sclerosis is a complex disease that affects the connective tissue, the vascular system and the immune system. It typically produces skin and organ fibrosis. Cardiac bundle branch blocks and fascicular blocks occur in 25-75% of the cases and were found to be independent predictors of mortality. Second and third degree atrioventricular block are very rare. We present the case of a 47 year-old female with diagnosis of systemic sclerosis, presented with syncope secondary to complete atrioventricular block requiring permanent pacemaker implantation.

  3. ANTI-HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN B1 (ANTI-RA33 ANTIBODIES IN RHEUMATOID ARTHRITIS AND SYSTEMIC SCLEROSIS

    Directory of Open Access Journals (Sweden)

    P. A. Kuznetsova

    2017-01-01

    Full Text Available Anti-heterogeneous nuclear ribonucleoprotein (RNP autoantibodies (AAbs are encountered in many autoimmune rheumatic diseases (ARDs. The potential diagnostic value of the RA33 AAb complex consisting of RNP A2 and alternative domains of the splicing proteins RNP B1 and RNP B2 is now of interest to rheumatologists. Subjects and methods. The authors studied the frequency of anti-RNP B1 AAbs in 300 patients with systemic ARDs, including those with rheumatoid arthritis (RA, ankylosing spondylitis (AS, systemic lupus erythematosus (SLE, systemic sclerosis (SSc, and Sjö gren's syndrome (SS and in 53 people without ARDs, who constituted a control group. Serum anti-RNP B1 AAbs were assessed by enzyme immunoassay. Results and discussion. The frequency of anti-RNP B1 AAbs in patients with ARDs was much higher than that in the control group: 170/300 (56.6% and 8/53 (13% patients, respectively. Anti-RNP B1 AAbs were detected in 78.5% (113/144 of the patients with RA; 40.3% (23/57 of those with AS, in 67.5% (27/40 of those with SSc, in 36.4% (16/44 of those with SLE, and in 13.3% (2/15 of those with SS. The diagnostic sensitivity of the marker for RA was 78.5%, its diagnostic specificity was 84.9%; the likelihood ratio of positive and negative results was 5.24 and 0.24, respectively. In the patients with RA, the level of anti-RNP B1 AAbs significantly correlated with that of C-reactive protein and erythrocyte sedimentation rate, while in those with SSc the detection of anti-RNP B1 AAbs was related to the rigidity of the vascular wall and the presence of hypertension. The frequency of anti-RNP B1 AAbs among the RA patients seronegative for rheumatoid factor and anti-cyclic citrullinated peptide antibodies was 15.4%. Conclusion. Anti-RNP B1 AAs are a useful laboratory marker (with the upper limit of the normal range being 3.3 U/ml, but are of limited value in the diagnosis of RA. Anti-RNP B1 AAbs may be regarded as an additional diagnostic marker for RA.

  4. Review of LCA studies of solid waste management systems--part I: lessons learned and perspectives.

    Science.gov (United States)

    Laurent, Alexis; Bakas, Ioannis; Clavreul, Julie; Bernstad, Anna; Niero, Monia; Gentil, Emmanuel; Hauschild, Michael Z; Christensen, Thomas H

    2014-03-01

    The continuously increasing solid waste generation worldwide calls for management strategies that integrate concerns for environmental sustainability. By quantifying environmental impacts of systems, life cycle assessment (LCA) is a tool, which can contribute to answer that call. But how, where and to which extent has it been applied to solid waste management systems (SWMSs) until now, and which lessons can be learnt from the findings of these LCA applications? To address these questions, we performed a critical review of 222 published LCA studies of SWMS. We first analysed the geographic distribution and found that the published studies have primarily been concentrated in Europe with little application in developing countries. In terms of technological coverage, they have largely overlooked application of LCA to waste prevention activities and to relevant waste types apart from household waste, e.g. construction and demolition waste. Waste management practitioners are thus encouraged to abridge these gaps in future applications of LCA. In addition to this contextual analysis, we also evaluated the findings of selected studies of good quality and found that there is little agreement in the conclusions among them. The strong dependence of each SWMS on local conditions, such as waste composition or energy system, prevents a meaningful generalisation of the LCA results as we find it in the waste hierarchy. We therefore recommend stakeholders in solid waste management to regard LCA as a tool, which, by its ability of capturing the local specific conditions in the modelling of environmental impacts and benefits of a SWMS, allows identifying critical problems and proposing improvement options adapted to the local specificities. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Avatar Web-Based Self-Report Survey System Technology for Public Health Research: Technical Outcome Results and Lessons Learned.

    Science.gov (United States)

    Savel, Craig; Mierzwa, Stan; Gorbach, Pamina M; Souidi, Samir; Lally, Michelle; Zimet, Gregory; Interventions, Aids

    2016-01-01

    This paper reports on a specific Web-based self-report data collection system that was developed for a public health research study in the United States. Our focus is on technical outcome results and lessons learned that may be useful to other projects requiring such a solution. The system was accessible from any device that had a browser that supported HTML5. Report findings include: which hardware devices, Web browsers, and operating systems were used; the rate of survey completion; and key considerations for employing Web-based surveys in a clinical trial setting.

  6. Learning lessons from accidents with a human and organisational factors perspective: deficiencies and failures of operating experience feedback systems

    International Nuclear Information System (INIS)

    Dechy, N.; Rousseau, J.M.; Jeffroy, F.

    2012-01-01

    This paper aims at reminding the failures of operating experience feedback (OEF) systems through the lessons of accidents and provides a framework for improving the efficiency of OEF processes. The risk is for example to miss lessons from other companies and industrial sectors, or to miss the implementation of adequate corrective actions with the risk to repeat accidents. Most of major accidents have been caused by a learning failure or other organisational factors as a contributing cause among several root causes. Some of the recurring organisational factors are: -) poor recognition of critical components, of critical activities or deficiency in anticipation and detection of errors, -) excessive production pressure, -) deficiency of communication or lack of quality of dialogue, -) Excessive formalism, -) organisational complexity, -) learning deficiencies (OEF, closing feedback loops, lack of listening of whistle-blowers). Some major accidents occurred in the nuclear industry. Although the Three Mile Island accident has multiple causes, in particular, an inappropriate design of the man-machine interface, it is a striking example of the loss of external lessons from incidents. As for Fukushima it is too early to have established evidence on learning failures. The systematic study and organisational analysis of OEF failures in industrial accidents whatever their sector has enabled us to provide a framework for OEF improvements. Five key OEF issues to improve in priority: 1) human and organisational factors analysis of the root causes of the events, 2) listening to the field staff, dissenting voices and whistle-blowers, 3) monitoring of the external events that provide generic lessons, 4) building an alive memory through a culture of accidents with people who become experiences pillars, and 5) the setting of external audit or organisational analysis of the OEF system by independent experts. The paper is followed by the slides of the presentation

  7. Intrinsic Deregulation of Vascular Smooth Muscle and Myofibroblast Differentiation in Mesenchymal Stromal Cells from Patients with Systemic Sclerosis.

    Directory of Open Access Journals (Sweden)

    Björn Hegner

    Full Text Available Obliterative vasculopathy and fibrosis are hallmarks of systemic sclerosis (SSc, a severe systemic autoimmune disease. Bone marrow-derived mesenchymal stromal cells (MSCs from SSc patients may harbor disease-specific abnormalities. We hypothesized disturbed vascular smooth muscle cell (VSMC differentiation with increased propensity towards myofibroblast differentiation in response to SSc-microenvironment defining growth factors and determined responsible mechanisms.We studied responses of multipotent MSCs from SSc-patients (SSc-MSCs and healthy controls (H-MSCs to long-term exposure to CTGF, b-FGF, PDGF-BB or TGF-β1. Differentiation towards VSMC and myofibroblast lineages was analyzed on phenotypic, biochemical, and functional levels. Intracellular signaling studies included analysis of TGF-β receptor regulation, SMAD, AKT, ERK1/2 and autocrine loops.VSMC differentiation towards both, contractile and synthetic VSMC phenotypes in response to CTGF and b-FGF was disturbed in SSc-MSCs. H-MSCs and SSc-MSCs responded equally to PDGF-BB with prototypic fibroblastic differentiation. TGF-β1 initiated myofibroblast differentiation in both cell types, yet with striking phenotypic and functional differences: In relation to H-MSC-derived myofibroblasts induced by TGF-β1, those obtained from SSc-MSCs expressed more contractile proteins, migrated towards TGF-β1, had low proliferative capacity, and secreted higher amounts of collagen paralleled by reduced MMP expression. Higher levels of TGF-β receptor 1 and enhanced canonical and noncanonical TGF-β signaling in SSc-MSCs accompanied aberrant differentiation response of SSc-MSCs in comparison to H-MSCs.Deregulated VSMC differentiation with a shift towards myofibroblast differentiation expands the concept of disturbed endogenous regenerative capacity of MSCs from SSc patients. Disease related intrinsic hyperresponsiveness to TGF-β1 with increased collagen production may represent one responsible mechanism

  8. Design and development of an ethnically-diverse imaging informatics-based eFolder system for multiple sclerosis patients.

    Science.gov (United States)

    Ma, Kevin C; Fernandez, James R; Amezcua, Lilyana; Lerner, Alex; Shiroishi, Mark S; Liu, Brent J

    2015-12-01

    MRI has been used to identify multiple sclerosis (MS) lesions in brain and spinal cord visually. Integrating patient information into an electronic patient record system has become key for modern patient care in medicine in recent years. Clinically, it is also necessary to track patients' progress in longitudinal studies, in order to provide comprehensive understanding of disease progression and response to treatment. As the amount of required data increases, there exists a need for an efficient systematic solution to store and analyze MS patient data, disease profiles, and disease tracking for both clinical and research purposes. An imaging informatics based system, called MS eFolder, has been developed as an integrated patient record system for data storage and analysis of MS patients. The eFolder system, with a DICOM-based database, includes a module for lesion contouring by radiologists, a MS lesion quantification tool to quantify MS lesion volume in 3D, brain parenchyma fraction analysis, and provide quantitative analysis and tracking of volume changes in longitudinal studies. Patient data, including MR images, have been collected retrospectively at University of Southern California Medical Center (USC) and Los Angeles County Hospital (LAC). The MS eFolder utilizes web-based components, such as browser-based graphical user interface (GUI) and web-based database. The eFolder database stores patient clinical data (demographics, MS disease history, family history, etc.), MR imaging-related data found in DICOM headers, and lesion quantification results. Lesion quantification results are derived from radiologists' contours on brain MRI studies and quantified into 3-dimensional volumes and locations. Quantified results of white matter lesions are integrated into a structured report based on DICOM-SR proto