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

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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.

Environmental Mycobiome Modifiers of Inflammation and Fibrosis in Systemic Sclerosis

Science.gov (United States)

2016-09-01

autoimmune systemic sclerosis and cancer: disease stratification, co-expression networks and genetic polymorphisms” Cancer Mechanisms Program, Norris ...NOTES 14. ABSTRACT This project is focused on Systemic Sclerosis (SSc), a progressive fibrotic disease characterized by skin fibrosis and damage to...quantitative manner. Our studies suggest that disease pathogenesis includes a common environmental fungal trigger, Rhodotorula glutinis, which we

Eosinophilic Esophagitis in Two Patients with Systemic Sclerosis

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Tracy M. Frech

2016-01-01

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

The role of platelets in the pathogenesis of systemic sclerosis

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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.

Is there an association between glaucoma and capillaroscopy in patients with systemic sclerosis?

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Gomes, Beatriz Fiuza; Souza, Rebeca; Valadão, Thiago; Kara-Junior, Newton; Moraes, Haroldo Vieira; Santhiago, Marcony R

2018-02-01

To evaluate the relationship between glaucoma diagnosis and the nailfold capillaroscopy pattern in patients with systemic sclerosis. An observational study in a cohort of patients with SSc was conducted. Patients with at least one nailfold videocapillaroscopy and one ophthalmology examination at the same year were included. Data collected were: age, sex; type of systemic sclerosis according to the degree of skin impairment, self-reported ethnicity, disease duration, current use and dosage of systemic corticosteroid, current use and dosage of bosentan ® , intraocular pressure, central corneal thickness, diagnosis of glaucoma and capillaroscopy pattern. Thirty-one patients with systemic sclerosis were enrolled, 23% had glaucoma. There was no statistically significant association between glaucoma diagnosis and the capillaroscopic pattern (p = 0.86). There was also no significant difference (p = 0.66) regarding intraocular pressure between patients with mild (13.9 ± 3.8 mmHg) and severe capillaroscopic pattern (14.4 ± 2.8 mmHg). The odds ratio of glaucoma for severe capillaroscopic pattern compared to mild was 1.6 (95% confidence interval: 0.3-9.5). Up to 23% of patients with SSc have glaucoma. The high prevalence of glaucoma in SSc suggests a possible systemic vascular disturbance as the cause. However, there seems to be no significant association between the capillaroscopy pattern and glaucoma in systemic sclerosis. Further research is required to improve the understanding of glaucoma in the context of systemic sclerosis.

Association of systemic sclerosis and psoriatic arthritis: a case report

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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.

From Localized Scleroderma to Systemic Sclerosis: Coexistence or Possible Evolution.

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Dilia, Giuggioli; Michele, Colaci; Emanuele, Cocchiara; Amelia, Spinella; Federica, Lumetti; Clodoveo, Ferri

2018-01-01

Systemic sclerosis (SSc) and localized scleroderma (LoS) are two different diseases that may share some features. We evaluated the relationship between SSc and LoS in our case series of SSc patients. We analysed the clinical records of 330 SSc patients, in order to find the eventual occurrence of both the two diseases. Eight (2.4%) female patients presented both the two diagnoses in their clinical histories. Six developed LoS prior to SSc; in 4/6 cases, the presence of autoantibodies was observed before SSc diagnosis. Overall, the median time interval between LoS and SSc diagnosis was 18 (range 0-156) months. LoS and SSc are two distinct clinical entities that may coexist. Moreover, as anecdotally reported in pediatric populations, we suggested the possible development of SSc in adult patients with LoS, particularly in presence of Raynaud's phenomenon or antinuclear antibodies before the SSc onset.

The association of illness perceptions with physical and mental health in systemic sclerosis patients: an exploratory study.

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Arat, Seher; Verschueren, Patrick; De Langhe, Ellen; Smith, Vanessa; Vanthuyne, Marie; Diya, Luwis; Van den Heede, Koen; Blockmans, Daniel; De Keyser, Filip; Houssiau, Frédéric A; Westhovens, René

2012-03-01

The aim of the present study was to evaluate the association between illness perceptions and the ability to cope with physical and mental health problems in a large cohort of systemic sclerosis (SSc) patients. This was a cross-sectional study in 217 systemic sclerosis patients from the Belgian Systemic Sclerosis Cohort. Illness perception and coping were measured by the Revised Illness Perception Questionnaire and a coping questionnaire--the Coping Orientation of Problem Experience inventory (COPE). Physical and mental health-related quality of life was measured by the 36-item short-form health survey (SF-36), as were disease activity and several severity parameters. The relationship between illness perceptions and the ability to cope with physical/mental health problems was examined using multiple linear regression analysis. According to LeRoy's classification, 49 patients had limited SSc (lSSc), 129 had limited cutaneous SSc (lcSSc) and 39 had diffuse cutaneous SSc (dcSSc). Median disease duration was five years and the modified Rodnan skin score was 4. Good physical health was significantly associated with the lcSSc subtype and low disease activity (p consequences' and strong 'illness identity' correlated with poor physical health (p mental health was associated with low illness identity scores and low 'emotional response' scores (p mental health compared with the illness perception items. Illness representations contribute more than classical disease characteristics to physical and mental health. Copyright © 2011 John Wiley & Sons, Ltd.

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

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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...... on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. RESULTS: 30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy...... 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...

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

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

2014-12-01

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. 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. 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). 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. Copyright © 2014 Elsevier Inc. All rights reserved.

Small intestinal bacterial overgrowth in patients with systemic sclerosis

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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.

MDCT imaging of calcinosis in systemic sclerosis

International Nuclear Information System (INIS)

Freire, V.; Becce, F.; Feydy, A.; Guérini, H.; Campagna, R.; Allanore, Y.; Drapé, J.-L.

2013-01-01

Calcinosis is a typical feature of systemic sclerosis (SSc) and can be found in many different tissues including the superficial soft tissues, periarticular structures, muscles, and tendons. It can also provoke erosive changes on bones. Investigation is conducted most often with plain radiographs. However, when a more detailed assessment is necessary, multidetector computed tomography (MDCT) is helpful owing to its multiplanar reformat (MPR) ability. The purpose of this review is to provide an overview of the various appearances of calcinosis in SSc patients as visualized at MDCT

Validation of potential classification criteria for systemic sclerosis.

NARCIS (Netherlands)

Johnson, S.R.; Fransen, J.; Khanna, D.; Baron, M.; Hoogen, F. van den; Medsger TA, J.r.; Peschken, C.A.; Carreira, P.E.; Riemekasten, G.; Tyndall, A.; Matucci-Cerinic, M.; Pope, J.E.

2012-01-01

OBJECTIVE: Classification criteria for systemic sclerosis (SSc; scleroderma) are being updated jointly by the American College of Rheumatology and European League Against Rheumatism. Potential items for classification were reduced to 23 using Delphi and nominal group techniques. We evaluated the

Treatment outcome in early diffuse cutaneous systemic sclerosis

DEFF Research Database (Denmark)

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

2017-01-01

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

Molecular subtypes of systemic sclerosis in association with anti-centromere antibodies and digital ulcers

NARCIS (Netherlands)

Bos, C. L.; van Baarsen, L. G. M.; Timmer, T. C. G.; Overbeek, M. J.; Basoski, N. M.; Rustenburg, F.; Baggen, J. M. C.; Thiesen, H. J.; Dijkmans, B. A. C.; van der Pouw Kraan, T. C. T. M.; Voskuyl, A. E.; Verweij, C. L.

2009-01-01

The objective of this study was to identify molecular profiles that may distinguish clinical subtypes in systemic sclerosis (SSc). Large-scale gene expression profiling was performed on peripheral blood (PB) from 12 SSc patients and 6 healthy individuals. Significance analysis of microarrays,

Pulmonary function tests as outcomes for systemic sclerosis interstitial lung disease.

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Caron, Melissa; Hoa, Sabrina; Hudson, Marie; Schwartzman, Kevin; Steele, Russell

2018-06-30

Interstitial lung disease (ILD) is the leading cause of morbidity and mortality in systemic sclerosis (SSc). We performed a systematic review to characterise the use and validation of pulmonary function tests (PFTs) as surrogate markers for systemic sclerosis-associated interstitial lung disease (SSc-ILD) progression.Five electronic databases were searched to identify all relevant studies. Included studies either used at least one PFT measure as a longitudinal outcome for SSc-ILD progression ( i.e. outcome studies) and/or reported at least one classical measure of validity for the PFTs in SSc-ILD ( i.e. validation studies).This systematic review included 169 outcome studies and 50 validation studies. Diffusing capacity of the lung for carbon monoxide ( D LCO ) was cumulatively the most commonly used outcome until 2010 when it was surpassed by forced vital capacity (FVC). FVC (% predicted) was the primary endpoint in 70.4% of studies, compared to 11.3% for % predicted D LCO Only five studies specifically aimed to validate the PFTs: two concluded that D LCO was the best measure of SSc-ILD extent, while the others did not favour any PFT. These studies also showed respectable validity measures for total lung capacity (TLC).Despite the current preference for FVC, available evidence suggests that D LCO and TLC should not yet be discounted as potential surrogate markers for SSc-ILD progression. Copyright ©ERS 2018.

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

OpenAIRE

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

2014-01-01

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

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. METHODS...

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

Gastrointestinal transit in patients with systemic sclerosis.

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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.

Environmental Mycobiome Modifiers of Inflammation and Fibrosis in Systemic Sclerosis

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2016-09-01

shown that PBMCs and macrophages from SSc patients (monocytes isolated from peripheral blood of SSc patients that are differentiated in autologous...systemic sclerosis, pulmonary fibrosis and pulmonary arterial hypertension ” Scleroderma Research Foundation Annual Workshop, San Francisco, CA 2/16...Cruz), and patient sera for 1 h at room temperature. Secondary antibodies (anti-goat-Cy3, anti-mouse-Cy2, and anti-human-Cy5) were purchased from

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.

The Role of PPAR Gamma in Systemic Sclerosis

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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.

Limited Mouth Opening Secondary to Diffuse Systemic Sclerosis

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Tomoko Wada

2013-01-01

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

Serum osteopontin and vitronectin levels in systemic sclerosis.

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Gundogdu, Baris; Yolbas, Servet; Yilmaz, Musa; Aydin, Suleyman; Koca, Sulayman Serdar

2017-11-01

Osteopontin a matricellular protein has pro-fibrotic effects and binds integrin such as αvβ1 and αvβ3. Vitronectin is one of the integrin αvβ3 ligands and is a multifunctional glycoprotein. The aim of the present study was to evaluate serum osteopontin and vitronectin levels in a cohort of patients with systemic sclerosis (SSc). Eighty-six patients with SSc, 46 patients with systemic lupus erythematosus (SLE), and 38 healthy controls (HC) were enrolled in the study. Serum osteopontin, vitronectin, IL-6, and TGF-β levels were analyzed. Serum osteopontin levels were higher in the SSc and SLE groups compared to the HC group (p < 0.01 and p < 0.001, respectively). However, it was not correlated with disease activity and severity scores in the SSc group. On the other hand, serum vitronectin levels were lower in the SSc group than in the SLE and HC groups (p < 0.001 for both). These results may suggest that osteopontin levels may be increased due to the inflammatory process and osteopontin has not a specific role on fibrosis in SSc. On the other hand, serum vitronectin levels decrease in SSc in contrast to SLE. It may be concluded that the one cause of decreased serum vitronectin levels in SSc may be its accumulation in fibrotic area.

Systemic sclerosis complicated with localized scleroderma-like lesions induced by Köbner phenomenon.

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Saigusa, Ryosuke; Asano, Yoshihide; Yamashita, Takashi; Takahashi, Takehiro; Nakamura, Kouki; Miura, Shunsuke; Ichimura, Yohei; Toyama, Tetsuo; Taniguchi, Takashi; Sumida, Hayakazu; Tamaki, Zenshiro; Miyazaki, Miki; Yoshizaki, Ayumi; Sato, Shinichi

2018-03-01

Scleroderma is a chronic disease of unknown etiology characterized by skin fibrosis and is divided into two clinical entities: systemic sclerosis (SSc) and localized scleroderma (LSc). In general, LSc is rarely complicated with SSc, but a certain portion of SSc patients manifests bilateral symmetric LSc-like lesions on the trunk and extremities. We investigated SSc patients with LSc-like lesions to clarify the underlying pathophysiology. Nine SSc cases complicated with LSc-like lesions were clinically and histologically characterized. SSc patients with LSc-like lesions exhibited multiple progressive hyper- and/or hypo-pigmented plaques with mild sclerosis symmetrically distributed on the trunk and extremities, especially abdominal region. In histological assessment, epidermal IL-1α expression was elevated in both forearms and LSc-like lesions of these patients to a greater extent than in forearms of control patients (SSc patients without LSc-like lesions). Of note, the infiltration and degranulation of mast cells were evident throughout the dermis of LSc-like lesions, while detectable to a lesser extent in forearms of SSc patients with LSc-like lesions and control patients. The epidermis of SSc patients with LSc-like lesions seems to possess an inflammatory phenotype, leading to the activation of mast cells in the dermis of mechanically stressed skin. Köbner phenomenon may be involved in the induction of LSc-like lesions in a certain subset of SSc. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

Circulating angiostatin serum level in patients with systemic sclerosis

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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.

Erasmus syndrome: Association of silicosis and systemic sclerosis

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Reena K Sharma

2018-01-01

Full Text Available Silicosis is an inflammatory disease of the lung characterized by irreversible lung fibrosis which develops from prolonged pulmonary inhalation and retention of crystalline silica and immune reaction. It mainly appears as an occupational hazard in persons involved in stone-quarrying, mining, and sand blasting. Crystalline silica is not only known to be responsible for silicosis but also for other autoimmune diseases including systemic lupus erythematosus (SLE, rheumatoid arthritis (RA-Caplan syndrome, systemic sclerosis (SSc, and antineutrophil cytoplasmic antibody (ANCA-related vasculitis. Erasmus syndrome is the association of silica exposure and subsequent development of SSc. The limited numbers of cases reported in the literature were miners and only sporadically involved in other professionals. Here, we report a case of a 52 -year-old stone cutter who developed silicosis and SSc after 25 years of exposure.

Work Disability in Early Systemic Sclerosis

DEFF Research Database (Denmark)

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

2015-01-01

OBJECTIVE: To study work disability (WD) with reference to levels of sick leave and disability pension in early systemic sclerosis (SSc). METHODS: Patients with SSc living in the southern part of Sweden with onset of their first non-Raynaud symptom between 2003 and 2009 and with a followup of 36...... months were included in a longitudinal study. Thirty-two patients (26 women, 24 with limited SSc) with a median age of 47.5 years (interquartile range 43-53) were identified. WD was calculated in 30-day intervals from 12 months prior to disease onset until 36 months after, presented as the prevalence...... of WD per year (0-3) and as the period prevalence of mean net days per month (± SD). Comparisons were made between patients with different disease severity and sociodemographic characteristics, and between patients and a reference group (RG) from the general population. RESULTS: Seventy-eight percent...

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.

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

Influence of clinical features, serum antinuclear antibodies, and lung function on survival of patients with systemic sclerosis

DEFF Research Database (Denmark)

Jacobsen, Søren; Ullman, S; Shen, G Q

2001-01-01

OBJECTIVE: To evaluate the independent contribution of several clinical and laboratory variables to the mortality of a cohort of Danish patients with systemic sclerosis (SSc). METHODS: A cohort of 174 patients with incident SSc was retrospectively identified using clinical charts and study record...

EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR)

NARCIS (Netherlands)

Kowal-Bielecka, O.; Landewé, R.; Avouac, J.; Chwiesko, S.; Miniati, I.; Czirjak, L.; Clements, P.; Denton, C.; Farge, D.; Fligelstone, K.; Földvari, I.; Furst, D. E.; Müller-Ladner, U.; Seibold, J.; Silver, R. M.; Takehara, K.; Toth, B. Garay; Tyndall, A.; Valentini, G.; van den Hoogen, F.; Wigley, F.; Zulian, F.; Matucci-Cerinic, Marco

2009-01-01

The optimal treatment of systemic sclerosis (SSc) is a challenge because the pathogenesis of SSc is unclear and it is an uncommon and clinically heterogeneous disease affecting multiple organ systems. The aim of the European League Against Rheumatism (EULAR) Scleroderma Trials and Research group

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

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

NARCIS (Netherlands)

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

2017-01-01

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

Systemic sclerosis, birth order and parity.

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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.

Plasma exchange in progressive systemic sclerosis

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Mohammad Bagher Owlia

2015-10-01

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

Systemic Sclerosis and the Gastrointestinal Tract-Clinical Approach.

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Braun-Moscovici, Yolanda; Brun, Rita; Braun, Marius

2016-10-31

Systemic sclerosis (SSc) is a multisystem disease characterized by functional and structural abnormalities of small blood vessels, fibrosis of the skin and internal organs, immune system activation, and autoimmunity. The gastrointestinal tract is involved in nearly all patients and is a source of significant morbidity and even mortality. The aim of this review is to summarize the pathogenesis and to provide a clinical approach to these patients.

A System Out of Breath: How Hypoxia Possibly Contributes to the Pathogenesis of Systemic Sclerosis

OpenAIRE

van Hal, T. W.; van Bon, L.; Radstake, T. R. D. J.

2011-01-01

Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular alterations and immunological disturbances and fibrosis, the order of which remains to be fully determined. Clinically, patients show clear signs of hypoxia in skin and internal organs. The low oxygen tension is potentially caused by a yet to be indentified circuitry involving the three features that typify SSc. In addition, once present, the hypoxia creates a vicious circle of ongoing pathology. In this paper, we pro...

[The diagnostic significance of nailfold video-capillaroscopy in systemic sclerosis].

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Li, Lin-Guang; Zhang, Jiang-Lin; Liu, Xiu-Hua; Huang, Feng

2012-05-01

To observe nailfold capillary changes in a cohort of connective tissue disease (CTD) with Raynaud's phenomenon (RP) and to explore the diagnostic value of nailfold video-capillaroscopy (NVC) in systemic sclerosis (SSc). Sixty CTD patients with RP divided into SSc group (n = 36) and non-SSc group (n = 24) were referred to an experienced operator for NVC. The patients had decreased capillary loops in SSc group with the capillary diameter more enlarged in SSc group than non-SSc group. The number of patients in SSc group with giant capillaries was 14, while 3 in non-SSc group. There were 23 patients with haemorrhages in SSc group and 9 in non-SSc group. The number of patients with severe effusion was 15 in SSc group, while 2 in non-SSc group. By using the ROC curves, indexes with AUC at least 0.7 of the input capillary diameter, the output capillary diameter, the middle capillary diameter, blood color and effusion for the diagnostic cutoff points were 18.5 µm, 24.5 µm, 19.5µm, deep red and severe effusion. With at least 2 out of the top 3 indexes, the diagnostic sensitivity and specificity of SSc were higher. CTD Patients with RP of SSc have less capillary loops, more enlarged capillaries, more giant capillaries, more severe effusion and more haemorrhages than non-SSc patients. The characteristics of nailfold capillary changes in SSc patients with RP can be helpful for the diagnosis and the differential diagnosis of SSc.

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+

Plasma D-dimer concentration in patients with systemic sclerosis

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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.

Gastric involvement in systemic sclerosis: a prospective study.

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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.

A system out of breath: how hypoxia possibly contributes to the pathogenesis of systemic sclerosis.

NARCIS (Netherlands)

Hal, T.W. van; Bon, L. van; Radstake, T.R.D.J.

2011-01-01

Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular alterations and immunological disturbances and fibrosis, the order of which remains to be fully determined. Clinically, patients show clear signs of hypoxia in skin and internal organs. The low oxygen tension is potentially

Fructose Malabsorption in Systemic Sclerosis

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

Preliminary analysis of the very early diagnosis of systemic sclerosis (VEDOSS) EUSTAR multicentre study: evidence for puffy fingers as a pivotal sign for suspicion of systemic sclerosis.

NARCIS (Netherlands)

Minier, T.; Guiducci, S.; Bellando-Randone, S.; Bruni, C.; Lepri, G.; Czirjak, L.; Distler, O.; Walker, U.A.; Fransen, J.; Allanore, Y.; Denton, C.; Cutolo, M.; Tyndall, A.; Muller-Ladner, U.; Matucci-Cerinic, M.

2014-01-01

OBJECTIVES: The EULAR (European League Against Rheumatism) Scleroderma Trials and Research Group (EUSTAR) has identified preliminary criteria for very early diagnosis of systemic sclerosis (SSc). Our aim was to assess the prevalence of each proposed diagnostic item in a large observational patient

HLA typing in systemic sclerosis

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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.

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

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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.

A system out of breath: how hypoxia possibly contributes to the pathogenesis of systemic sclerosis.

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van Hal, T W; van Bon, L; Radstake, T R D J

2011-01-01

Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular alterations and immunological disturbances and fibrosis, the order of which remains to be fully determined. Clinically, patients show clear signs of hypoxia in skin and internal organs. The low oxygen tension is potentially caused by a yet to be indentified circuitry involving the three features that typify SSc. In addition, once present, the hypoxia creates a vicious circle of ongoing pathology. In this paper, we provide an overview of the evidence that points towards the mechanisms causing hypoxia in SSc. In addition, data that suggest how hypoxia itself may orchestrate worsening of symptoms is presented. Altogether, it is clear that hypoxia is an important hallmark in SSc patients. By providing an overview of the mechanisms at play and the possible therapeutic avenues that have emerged, we hope to stimulate researchers to provide novel clues into the conundrum in SSc patients.

Gastrointestinal mucosal abnormalities using videocapsule endoscopy in systemic sclerosis.

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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.

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

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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.

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...... of B19 infection in SSc, skin biopsies and bone marrow samples from patients and controls were analysed for B19V DNA detection, genotyping and viral expression. RESULTS: B19V DNA was detected in skin biopsies from 39/49 SSc patients and from 20/28 controls. Bone marrow showed positive in 17/29 SSc...... in the skin of genotype 1-positive patients and not in control skins. CONCLUSION: The results outline some differences in the rate of persistence of B19V DNA, in the simultaneous persistence of 2 genotypes and in the pattern of viral expression among SSc patients and controls Udgivelsesdato: 2009...

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

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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%, p<0.001). Mean Modified Rodnan Skin Score was independently associated with the presence of NP (p<0.05, OR 1.90). Peripheral nervous system involvement in SSc is not well studied and, as far as the authors are aware, this is the first study published evaluating NP 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.

Workplace barriers encountered by employed persons with systemic sclerosis.

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Poole, Janet L; Anwar, Sahar; Mendelson, Cindy; Allaire, Saralynn

2016-01-01

Systemic sclerosis (SSc) is an auto-immune connective tissue disease characterized by fibrosis of skin, blood vessels, and internal organs that results in significant disability. To identify the work barriers faced by people with systemic sclerosis (SSc) in maintaining employment. Thirty-six people with SSc who were working more than 8 hours per week completed the Work Experience Survey, which contains lists of potential work barriers, including the ability to travel to and from work; get around at work; perform essential job functions, including physical, cognitive, and task-related activities; work with others; and manage work conditions. Thirty-three participants completed and returned the questionnaires, most of whom were female, and working full time and in professional careers. Principal disease symptoms included fatigue, Raynaud's phenomenon, esophageal involvement, and leg or hand/wrist pain. All participants reported some barriers with a mean of 18 barriers per participant. At least three quarters of participants cited outside temperature (82%), cold temperatures inside the workplace (76%), and household work (76%), as barriers. The next most common barriers were using both hands (64%), arranging and taking part in social activities (64%), being able to provide self-care (61%) and working 8 hours (58%). Participants reported a wide range of barriers, from cold temperatures, to physical job, fatigue related, and non-workplace demands, in maintaining the worker role. The barriers reflect the disease symptoms they reported. Identifying workplace barriers facilitates the creation of job accommodations or adaptations that will allow people with SSc to continue working.

Matrix metalloproteinases: a review of their structure and role in systemic sclerosis.

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Peng, Wen-jia; Yan, Jun-wei; Wan, Ya-nan; Wang, Bing-xiang; Tao, Jin-hui; Yang, Guo-jun; Pan, Hai-feng; Wang, Jing

2012-12-01

Matrix metalloproteinases (MMPs) are the main enzymes involved in arterial wall extracellular matrix (ECM) degradation and remodeling, whose activity has been involved in various normal and pathologic processes, such as inflammation, fibrosis. As a result, the MMPs have come to consider as both therapeutic targets and diagnostic tools for the treatment and diagnosis of autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. Systemic sclerosis (SSc) is a rare autoimmune disease of unknown etiology characterized by an excessive over-production of collagen and other ECM, resulting in skin thickening and fibrosis of internal organs. In recent years, abnormal expression of MMPs has been demonstrated with the pathogenesis of SSc, and the association of different polymorphisms on MMPs genes with SSc has been extensively studied. This review describes the structure, function and regulation of MMPs and shortly summarizes current understanding on experimental findings, genetic associations of MMPs in SSc.

A System Out of Breath: How Hypoxia Possibly Contributes to the Pathogenesis of Systemic Sclerosis

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T. W. van Hal

2011-01-01

Full Text Available Systemic sclerosis (SSc is an autoimmune disease characterized by vascular alterations and immunological disturbances and fibrosis, the order of which remains to be fully determined. Clinically, patients show clear signs of hypoxia in skin and internal organs. The low oxygen tension is potentially caused by a yet to be indentified circuitry involving the three features that typify SSc. In addition, once present, the hypoxia creates a vicious circle of ongoing pathology. In this paper, we provide an overview of the evidence that points towards the mechanisms causing hypoxia in SSc. In addition, data that suggest how hypoxia itself may orchestrate worsening of symptoms is presented. Altogether, it is clear that hypoxia is an important hallmark in SSc patients. By providing an overview of the mechanisms at play and the possible therapeutic avenues that have emerged, we hope to stimulate researchers to provide novel clues into the conundrum in SSc patients.

A gender gap in primary and secondary heart dysfunctions in systemic sclerosis

DEFF Research Database (Denmark)

Elhai, Muriel; Avouac, Jérôme; Walker, Ulrich A

2016-01-01

OBJECTIVES: In agreement with other autoimmune diseases, systemic sclerosis (SSc) is associated with a strong sex bias. However, unlike lupus, the effects of sex on disease phenotype and prognosis are poorly known. Therefore, we aimed to determine sex effects on outcomes. METHOD: We performed...

The role of klotho in systemic sclerosis

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R. Talotta

2017-12-01

Full Text Available The aim was to evaluate the role of klotho in the pathogenesis of systemic sclerosis (SSc, through the measurement of its serum concentration in SSc patients compared to healthy controls, and to assess the association with cutaneous and visceral involvement. Blood samples obtained from both SSc patients and healthy controls were analysed by an ELISA assay for the detection of human klotho. SSc patients were globally evaluated for disease activity and assessed through the modified Rodnan’s Skin Score, Medsger’s scale, pulmonary function tests, 2D-echocardiography, nailfold capillaroscopy and laboratory tests. Our cohort consisted of 69 SSc patients (61 females, mean age 64.5±12.5 years, median disease duration 9.0 (IQR 8 years and 77 healthy controls (28 females, mean age 49.7±10.2 years. In the group of SSc patients, 19 (27.5% suffered from a diffuse form of SSc. All patients were receiving IV prostanoids, and some of them were concomitantly treated with immunosuppressive drugs (prednisone, hydroxychloroquine, mofetil mycophenolate, methotrexate, cyclosporin A and azathioprine. The median serum concentration of klotho was significantly lower in patients compared to controls (0.23 ng/mL vs 0.60 ng/mL; p<0.001. However, Spearman’s test showed no significant association between klotho serum levels and disease activity, concerning either clinical, laboratory or instrumental findings. Our data show a significant deficit of klotho in SSc patients although any significant association was detected between klotho serum concentration and the clinical, laboratory or instrumental features of the disease. However, due to the limits of the study, further investigations are required.

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

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

2014-09-02

Systemic sclerosis (SSc) is a rare and potentially life threatening autoimmune disorder. The burden of disease compared to other dermatoses is unknown. The purpose of this study was to assess both the quality of life in patients with SSc and the variables that are associated with poor quality of life. Forty-one patients with systemic sclerosis (29 limited, 2 diffuse, 10 undifferentiated forms) were assessed with respect to their health status and compared to published data for the normal population, SSc patients from other studies, and patients with chronic skin diseases. For the most part, our SSc patients had better outcomes in all 8 dimensions of the SF-36 than SSc patients from other studies, and poorer scores than the healthy population and those with occupational contact dermatitis, ichthyosis, non-melanoma skin cancer, contact dermatitis, atopic eczema, chronic nail disease, vitiligo, health care workers with work-related disease, and those with other chronic skin diseases, but significantly better scores for mental health than those with nail disease, vitiligo, and health-care workers. Patients with atopic dermatitis, psoriasis and pemphigus had significantly poorer mean scores in social function and mental health than SSc patients. Patients with pemphigus were also significantly impaired in their physical and emotional roles. Patients with systemic lupus erythematosus (SLE) had the significantly poorest mean scores for QoL in all 8 domains except bodily pain and emotional role. Besides SLE, SSc is one of the most severe chronic dermatologic diseases in terms of reduced QoL. Since SSc cannot be cured, treatment strategies should include therapeutic interventions such as psychotherapy, social support, physiotherapy, and spiritual care. Their beneficial effects could be studied in future.

Evaluation and management of esophageal manifestations in systemic sclerosis.

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Denaxas, Konstantinos; Ladas, Spyros D; Karamanolis, George P

2018-01-01

Systemic sclerosis (SSc) is a multisystemic autoimmune connective tissue disorder; in the gastrointestinal tract, the esophagus is the most commonly affected organ. Symptoms of esophageal disease are due to gastroesophageal reflux disease (GERD) and esophageal motor dysfunction. Since the development of high-resolution manometry (HRM), this method has been preferred for the study of SSc patients with esophageal involvement. Using HRM, classic scleroderma esophagus, defined as absent or ineffective peristalsis of the distal esophagus in combination with a hypotensive lower esophageal sphincter, was found in as many as 55% of SSc patients. Endoscopy is the appropriate test for evaluating dysphagia and identifying evidence and possible complications of GERD. In the therapeutic area, treatment ranges from general supportive measures to the administration of drugs such as proton pump inhibitors and/or prokinetics. However, as many SSc patients do not respond to existing therapies, there is an urgent need for new therapeutic modalities. Buspirone, a 5-hydroxytryptamine 1A receptor agonist, could be a putative therapeutic option, as it was found to exert a significant beneficial effect in SSc patients with esophageal involvement. This review summarizes our knowledge concerning the evaluation and management of esophageal manifestations in SSc patients, including emerging therapeutic modalities.

The circulating cell-free microrna profile in systemic sclerosis is distinct from both healthy controls and Systemic Lupus Erythematosus

DEFF Research Database (Denmark)

Steen, S. O.; Iversen, L. V.; Carlsen, A. L.

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...

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)

Correlations between skin blood perfusion values and nailfold capillaroscopy scores in systemic sclerosis patients.

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Ruaro, B; Sulli, A; Pizzorni, C; Paolino, S; Smith, V; Cutolo, M

2016-05-01

To correlate blood perfusion (BP) values assessed by laser speckle contrast analysis (LASCA) in selected skin areas of hands and face with nailfold capillary damage scores in systemic sclerosis (SSc) patients. Seventy SSc patients (mean SSc duration 6 ± 5 years) and 70 volunteer healthy subjects were enrolled after informed consent. LASCA was performed at different areas of the face (forehead, tip of nose, zygomas and perioral region) and at dorsal and volar regions of hands. Microvascular damage was assessed and scored by nailfold videocapillaroscopy (NVC) and the microangiopathy evolution score (MES) was calculated. SSc patients showed a significantly lower BP than healthy subjects at fingertips, periungual areas and palm of hands (pnailfold capillaroscopy scores of microangiopathy. Copyright © 2016. Published by Elsevier Inc.

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.

A proposal of criteria for the classification of systemic sclerosis.

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Nadashkevich, Oleg; Davis, Paul; Fritzler, Marvin J

2004-11-01

Sensitive and specific criteria for the classification of systemic sclerosis are required by clinicians and investigators to achieve higher quality clinical studies and approaches to therapy. A clinical study of systemic sclerosis patients in Europe and Canada led to a set of criteria that achieve high sensitivity and specificity. Both clinical and laboratory investigations of patients with systemic sclerosis, related conditions and diseases with clinical features that can be mistaken as part of the systemic sclerosis spectrum were undertaken. Laboratory investigations included the detection of autoantibodies to centromere proteins, Scl-70 (topoisomerase I), and fibrillarin (U3-RNP). Based on the investigation of 269 systemic sclerosis patients and 720 patients presenting with related and confounding conditions, the following set of criteria for the classification of systemic sclerosis was proposed: 1) autoantibodies to: centromere proteins, Scl-70 (topo I), fibrillarin; 2) bibasilar pulmonary fibrosis; 3) contractures of the digital joints or prayer sign; 4) dermal thickening proximal to the wrists; 5) calcinosis cutis; 6) Raynaud's phenomenon; 7) esophageal distal hypomotility or reflux-esophagitis; 8) sclerodactyly or non-pitting digital edema; 9) teleangiectasias. The classification of definite SSc requires at least three of the above criteria. Criteria for the classification of systemic sclerosis have been proposed. Preliminary testing has defined the sensitivity and specificity of these criteria as high as 99% and 100%, respectively. Testing and validation of the proposed criteria by other clinical centers is required.

Abscisic acid ameliorates the systemic sclerosis fibroblast phenotype in vitro

International Nuclear Information System (INIS)

Bruzzone, Santina; Battaglia, Florinda; Mannino, Elena; Parodi, Alessia; Fruscione, Floriana; Basile, Giovanna; Salis, Annalisa; Sturla, Laura; Negrini, Simone; Kalli, Francesca; Stringara, Silvia; Filaci, Gilberto

2012-01-01

Highlights: ► ABA is an endogenous hormone in humans, regulating different cell responses. ► ABA reverts some of the functions altered in SSc fibroblasts to a normal phenotype. ► UV-B irradiation increases ABA content in SSc cultures. ► 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-β (TGF-β). Conversely, migration toward ABA, but not toward TGF-β, 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.

Survival and causes of death in systemic sclerosis patients: a single center registry report from Iran.

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Poormoghim, Hadi; Andalib, Elham; Jalali, Arash; Ghaderi, Afshin; Ghorbannia, Ali; Mojtabavi, Nazanin

2016-07-01

The aims of the study were to determine prognostic factors for survival and causes of death in a cohort of patients with systemic sclerosis (SSc). This was a cohort study of SSc patients in single rheumatologic center from January 1998 to August 2012. They fulfilled the American College of Rheumatology classification criteria for SSc or had calcinosis Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia or sine sclerosis. Causes of death were classified as SSc related and non-SSc related. Kaplan-Meier and Cox proportional hazard regression models were used in univariate and multivariate analysis to analyse survival in subgroups and determine prognostic factors of survival. The study includes 220 patients (192 female, 28 male). Out of thirty-two (14.5 %) who died, seventeen (53.1 %) deaths were SSc related and in nine (28.1 %) non-SSc-related causes, and in six (18.8 %) of patients causes of death were not defined. Overall survival rate was 92.6 % (95 % CI 87.5-95.7 %) after 5 years and 82.3 % (95 % CI 73.4-88.4 %) after 10 years. Pulmonary involvement was a major SSc-related cause of death, occurred in seven (41.1 %) patients. Cardiovascular events were leading cause of in overall death (11) 34.3 % and 6 in non-SSc-related death. Independent risk factors for mortality were age >50 at diagnosis (HR 5.10) advance pulmonary fibrosis (HR 11.5), tendon friction rub at entry (HR 6.39), arthritis (HR 3.56). In this first Middle Eastern series of SSc registry, pulmonary and cardiac involvements were the leading cause of SSc-related death.

STAT4 is a genetic risk factor for systemic sclerosis in a Chinese population.

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Yi, L; Wang, J C; Guo, X J; Gu, Y H; Tu, W Z; Guo, G; Yang, L; Xiao, R; Yu, L; Mayes, M D; Assassi, S; Jin, L; Zou, H J; Zhou, X D

2013-01-01

Systemic sclerosis (SSc) is an immune-mediated and complex genetic disease. An association of single-nucleotide polymorphisms (SNPs) in the STAT4 gene with SSc has been reported in European Caucasians, North Americans and Japanese. We undertook the current study to examine whether the STAT4 SNPs are also associated with susceptibility to SSc and SSc subsets in a Han Chinese population. A total of 453 Han Chinese patients with SSc and 534 healthy controls were examined in the study. The SNPs rs7574865, rs10168266 and rs3821236 of the STAT4 gene were examined with SNP TaqMan assays. The T-allele carriers of rs7574865 and rs10168266 were strongly associated with the presence of anti-topoisomerase I (ATA) and pulmonary fibrosis in SSc patients, as well as with diffuse cutaneous SSc (dcSSc). The presence of anti-centromere (ACA) and limited cutaneous SSc (lcSSc) did not show significant association with any of the examined SNPs. The results were consistent with previous reports in other ethnic populations in supporting the notion that polymorphisms of STAT4 may play an important role in susceptibility to SSc. It also revealed different genetic aspects of SSc subsets in a Han Chinese population.

Early- versus Late-Onset Systemic Sclerosis

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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

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...

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.

Penile involvement in Systemic Sclerosis: New Diagnostic and Therapeutic Aspects

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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.

Abscisic acid ameliorates the systemic sclerosis fibroblast phenotype in vitro

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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.

Molecular stratification and precision medicine in systemic sclerosis from genomic and proteomic data.

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Martyanov, Viktor; Whitfield, Michael L

2016-01-01

The goal of this review is to summarize recent advances into the pathogenesis and treatment of systemic sclerosis (SSc) from genomic and proteomic studies. Intrinsic gene expression-driven molecular subtypes of SSc are reproducible across three independent datasets. These subsets are a consistent feature of SSc and are found in multiple end-target tissues, such as skin and esophagus. Intrinsic subsets as well as baseline levels of molecular target pathways are potentially predictive of clinical response to specific therapeutics, based on three recent clinical trials. A gene expression-based biomarker of modified Rodnan skin score, a measure of SSc skin severity, can be used as a surrogate outcome metric and has been validated in a recent trial. Proteome analyses have identified novel biomarkers of SSc that correlate with SSc clinical phenotypes. Integrating intrinsic gene expression subset data, baseline molecular pathway information, and serum biomarkers along with surrogate measures of modified Rodnan skin score provides molecular context in SSc clinical trials. With validation, these approaches could be used to match patients with the therapies from which they are most likely to benefit and thus increase the likelihood of clinical improvement.

Relationship between Body Mass Composition, Bone Mineral Density, Skin Fibrosis and 25(OH Vitamin D Serum Levels in Systemic Sclerosis.

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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.

Nailfold capillaroscopy by digital microscope in an Indian population with systemic sclerosis.

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Bhakuni, Darshan S; Vasdev, Vivek; Garg, M K; Narayanan, Krishanan; Jain, Rahul; Mullick, Gautam

2012-02-01

Nailfold capillaroscopy (NFC) is a simple, non-invasive method with exceptional predictive value for the analysis of microvascular abnormalities, especially in systemic sclerosis (SSc) but remains underutilized due to cost factors of the nailfold videocapillaroscope, lack of expertise and availability issues. The aim of this study was to establish the utility of an inexpensive digital microscope to study NFC changes in SSc in correlation with disease subsets and extent of skin involvement. Twenty-two diffuse cutaneous SSc (DSS), 20 limited cutaneous SSc (LSS) patients and 42 controls were evaluated with NFC using a digital microscope at 30× and 100× magnification. Digital micrographs were used to study qualitative and quantitative changes in microvasculature. The capillary density was significantly less in all cases of SSc as compared to controls (5.3 ± 1.4 vs. 8.7 ± 1.2; P Nailfold capillaroscopy changes in SSc are related to disease subset and MRSS. NFC with digital microscope is a simplified, inexpensive, outpatient procedure with results comparable to previous studies. © 2011 The Authors. International Journal of Rheumatic Diseases © 2011 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.

Transcriptional Activity of Nuclear Factor κB Family Genes in Patients with Systemic Sclerosis.

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Lis-Święty, Anna; Gola, Joanna; Mazurek, Urszula; Brzezińska-Wcisło, Ligia

2017-05-01

Systemic sclerosis (SSc) is a connective tissue disease of unknown etiology and unclear pathogenesis. Evaluation of the activation of nuclear factor κB (NF-κB) family genes IκBα, p50, p52, p65, and c-Rel, potentially involved in the regulation of immunity, inflammation, angiogenesis, and tissue remodeling in SSc, was carried out. The study included 19 patients with limited SSc, 11 patients with early SSc, and 10 healthy persons constituting the control group. Real-time QRT-PCR was used to evaluate the mRNAs in peripheral blood samples. The patients with early SSc showed a decrease in transcriptional activity of IκBα inhibitor and c-Rel subunit. Transcriptional activity decrease in the other patients with limited SSc included genes encoding c-Rel and p50, subunits of NF-κB factor. Deregulation of intracellular signal transduction by NF-κB takes place at the beginning of SSc and in its fibrosis stage. Associations between clinical variables and NF-κB related gene expression as well as the activation of NF-κB family members in SSc patients should be addressed in future studies. © 2017 by the Association of Clinical Scientists, Inc.

Systemic sclerosis and localized scleroderma--current concepts and novel targets for therapy.

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Distler, Oliver; Cozzio, Antonio

2016-01-01

Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Skin and organ fibrosis are key manifestations of SSc, for which no generally accepted therapy is available. Thus, there is a high unmet need for novel anti-fibrotic therapeutic strategies in SSc. At the same time, important progress has been made in the identification and characterization of potential molecular targets in fibrotic diseases over the recent years. In this review, we have selected four targeted therapies, which are tested in clinical trials in SSc, for in depths discussion of their preclinical characterization. Soluble guanylate cyclase (sGC) stimulators such as riociguat might target both vascular remodeling and tissue fibrosis. Blockade of interleukin-6 might be particularly promising for early inflammatory stages of SSc. Inhibition of serotonin receptor 2b signaling links platelet activation to tissue fibrosis. Targeting simultaneously multiple key molecules with the multityrosine kinase-inhibitor nintedanib might be a promising approach in complex fibrotic diseases such as SSc, in which many partially independent pathways are activated. Herein, we also give a state of the art overview of the current classification, clinical presentation, diagnostic approach, and treatment options of localized scleroderma. Finally, we discuss whether the novel targeted therapies currently tested in SSc could be used for localized scleroderma.

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

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Zarir F Udwadia

2015-01-01

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

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.

Solvent oriented hobbies and the risk of systemic sclerosis.

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Nietert, P J; Sutherland, S E; Silver, R M; Pandey, J P; Dosemeci, M

1999-11-01

To examine whether those participating in solvent oriented hobbies (SOH) are at greater risk of developing systemic sclerosis (SSc), and if the association is modified by the presence of the anti-Scl70 antibody. Patients with SSc and controls were recruited from a university hospital rheumatology clinic. Recreational hobby and occupational histories were obtained along with blood samples. Cumulative scores were created for participation in SOH. Logistic regression was used to calculate odds ratios associated with SOH exposure after adjustment for sex, age at diagnosis, and occupational solvent exposure, and to examine the association between SOH exposure and the presence of anti-Scl70. Solvent exposure based on hobbies and occupations was determined for 178 cases (141 women, 37 men) and 200 controls (138 women, 62 men). Overall participation in SOH was not associated with SSc. However, odds of high cumulative SOH exposure was 3 times greater in those patients with SSc testing positive for the anti-Scl70 antibody compared to patients testing negative (OR 2.9, 95% CI 1.1, 7.9), and twice as great as controls (OR 2.5, 95% CI 1.1, 5.9). While patients with SSc did not participate more often in SOH than controls over all, odds of high cumulative SOH exposure was greater among patients with SSc testing positive for anti-Scl70 compared to those testing negative and compared to controls. These results provide further evidence that environmental agents may play a role in the development of Ssc.

Common measure of quality of life for people with systemic sclerosis across seven European countries: a cross-sectional study.

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Ndosi, Mwidimi; Alcacer-Pitarch, Begonya; Allanore, Yannick; Del Galdo, Francesco; Frerix, Marc; García-Díaz, Sílvia; Hesselstrand, Roger; Kendall, Christine; Matucci-Cerinic, Marco; Mueller-Ladner, Ulf; Sandqvist, Gunnel; Torrente-Segarra, Vicenç; Schmeiser, Tim; Sierakowska, Matylda; Sierakowska, Justyna; Sierakowski, Stanslaw; Redmond, Anthony

2018-02-20

The aim of this study was to adapt the Systemic Sclerosis Quality of Life Questionnaire (SScQoL) into six European cultures and validate it as a common measure of quality of life in systemic sclerosis (SSc). This was a seven-country (Germany, France, Italy, Poland, Spain, Sweden and UK) cross-sectional study. A forward-backward translation process was used to adapt the English SScQoL into target languages. SScQoL was completed by patients with SSc, then data were validated against the Rasch model. To correct local response dependency, items were grouped into the following subscales: function, emotion, sleep, social and pain and reanalysed for fit to the model, unidimensionality and cross-cultural equivalence. The adaptation of the SScQoL was seamless in all countries except Germany. Cross-cultural validation included 1080 patients with a mean age 58.0 years (SD 13.9) and 87% were women. Local dependency was evident in individual country data. Grouping items into testlets corrected the local dependency in most country specific data. Fit to the model, reliability and unidimensionality was achieved in six-country data after cross-cultural adjustment for Italy in the social subscale. The SScQoL was then calibrated into an interval level scale. The individual SScQoL items have translated well into five languages and overall, the scale maintained its construct validity, working well as a five-subscale questionnaire. Measures of quality of life in SSc can be directly compared across five countries (France, Poland Spain, Sweden and UK). Data from Italy are also comparable with the other five countries although require an adjustment. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

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

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Teruel, María; Simeón Aznar, Carmen Pilar; Broen, Jasper C.; Vonk, Madelon C.; Carreira, Patricia; Camps García, María Teresa; García-Portales, Rosa; Delgado-Frías, Esmeralda; Gallego, Maria; Espinosa Garriga, Gerard; Spanish Scleroderma Group; Beretta, Lorenzo; Airó, Paolo; Lunardi, Claudio; Riemekasten, Gabriela

2012-01-01

Introduction: The aim of the present study was to investigate the possible role of CD40 and CD40 ligand (CD40LG) genes in the susceptibility and phenotype expression of systemic sclerosis (SSc). Methods: In total, 2,670 SSc patients and 3,245 healthy individuals from four European populations (Spain, Germany, The Netherlands, and Italy) were included in the study. Five single-nucleotide polymorphisms (SNPs) of CD40 (rs1883832, rs4810485, rs1535045) and CD40LG (rs3092952, rs3092920) were genot...

SSC Cryogenic System

International Nuclear Information System (INIS)

Brown, D.P.; Louttit, R.I.; Rode, C.; VanderArend, P.C.

1985-01-01

The design of the 4.5 K primary cooling system and higher temperature shield cooling systems for the SSC are described. Typical flow diagrams for the magnet piping systems are presented. Estimated heat loads are given. The systems have been designed to accomodate the great distances, 90 km and up, over which the load will be distributed. Provision has been made for cooldown, warmup, quench recovery and magnet replacement, as well as for steady-state operation

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

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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.

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

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

2009-06-01

The aim of this study was to investigate the possible role of STAT4 gene in the genetic predisposition to systemic sclerosis (SSc) susceptibility or clinical phenotype. A total of 1317 SSc patients [896 with limited cutaneous SSc (lcSSc) and 421 with diffuse cutaneous SSc (dcSSc)] and 3113 healthy controls, from an initial case-control set of Spanish Caucasian ancestry and five independent cohorts of European ancestry (The Netherlands, Germany, Sweden, Italy and USA), were included in the study. The rs7574865 polymorphism was selected as STAT4 genetic marker. We observed that the rs7574865 T allele was significantly associated with susceptibility to lcSSc in the Spanish population [P = 1.9 x 10(-5) odds ratio (OR) 1.61 95% confidence intervals (CI) 1.29-1.99], but not with dcSSc (P = 0.41 OR 0.84 95% CI 0.59-1.21). Additionally, a dosage effect was observed showing individuals with rs7574865 TT genotype higher risk for lcSSc (OR 3.34, P = 1.02 x 10(-7) 95% CI 2.11-5.31). The association of the rs7574865 T allele with lcSSc was confirmed in all the replication cohorts with different effect sizes (OR ranging between 1.15 and 1.86), as well as the lack of association of STAT4 with dcSSc. A meta-analysis to test the overall effect of the rs7574865 polymorphism showed a strong risk effect of the T allele for lcSSc susceptibility (pooled OR 1.54 95% CI 1.36-1.74; P < 0.0001). Our data show a strong and reproducible association of the STAT4 gene with the genetic predisposition to lcSSc suggesting that this gene seems to be one of the genetic markers influencing SSc phenotype.

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

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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.

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

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

2014-08-01

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

Screening for pulmonary arterial hypertension in systemic sclerosis

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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.

Comprehensive approach to systemic sclerosis patients during pregnancy.

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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.

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

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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...

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

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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

New insight on the Xq28 association with systemic sclerosis

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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

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

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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.

Environmental Pollution by Benzene and PM10 and Clinical Manifestations of Systemic Sclerosis: A Correlation Study.

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Borghini, Alice; Poscia, Andrea; Bosello, Silvia; Teleman, Adele Anna; Bocci, Mario; Iodice, Lanfranco; Ferraccioli, Gianfranco; La Milìa, Daniele Ignazio; Moscato, Umberto

2017-10-26

Atmospheric air pollution has been associated with a range of adverse health effects. The environment plays a causative role in the development of Systemic Sclerosis (SSc). The aim of the present study is to explore the association between particulate (PM 10 ) and benzene (B) exposure in Italian patients with systemic sclerosis and their clinical characteristics of the disease. A correlation study was conducted by enrolling 88 patients who suffer from SSc at the Fondazione Policlinico "A. Gemelli" in Rome (Italy) in the period from January 2013 to January 2014. The average mean concentrations of B (in 11 monitoring sites) and PM 10 (in 14 sites) were calculated using data from the Regional Environmental Protection Agency's monitoring stations located throughout the Lazio region (Italy) and then correlated with the clinical characteristics of the SSc patients. Of the study sample, 92.5% were female. The mean age was 55 ± 12.9 years old and the mean disease duration from the onset of Raynaud's phenomenon was 13.0 ± 9.4 years. The Spearman's correlation showed that concentrations of B correlate directly with the skin score (R = 0.3; p ≤ 0.05) and inversely with Diffusing Lung Carbon Monoxide (DLCO) results (R = -0.36; p = 0.04). This study suggests a possible role of B in the development of diffuse skin disease and in a worse progression of the lung manifestations of SSc.

Central Hemodynamics and Arterial Stiffness in Systemic Sclerosis.

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Bartoloni, Elena; Pucci, Giacomo; Cannarile, Francesca; Battista, Francesca; Alunno, Alessia; Giuliani, Marco; Cafaro, Giacomo; Gerli, Roberto; Schillaci, Giuseppe

2016-12-01

Although microvascular disease is a hallmark of systemic sclerosis (SSc), a higher prevalence of macrovascular disease and a poorer related prognosis have been reported in SSc than in the general population. The simultaneous assessment of prognostically relevant functional properties of larger and smaller arteries, and their effects on central hemodynamics, has never been performed in SSc using the state-of-the-art techniques. Thirty-four women with SSc (aged 61±15 years, disease duration 17±12 years, and blood pressure 123/70±18/11 mm Hg) and 34 healthy women individually matched by age and mean arterial pressure underwent the determination of carotid-femoral (aortic) and carotid-radial (upper limb) pulse wave velocity (a direct measure of arterial stiffness), aortic augmentation (a measure of the contribution of reflected wave to central pulse pressure), and aortobrachial pulse pressure amplification (brachial/aortic pulse pressure) through applanation tonometry (SphygmoCor). Patients and controls did not differ by carotid-femoral or carotid-radial pulse wave velocity. Aortic augmentation index corrected for a heart rate of 75 bpm (AIx@75) was higher in women with SSc (30.9±16% versus 22.2±12%; P=0.012). Patients also had a lower aortobrachial amplification of pulse pressure (1.22±0.18 versus 1.33±0.25; P=0.041). SSc was an independent predictor of AIx@75 (direct) and pulse pressure amplification (inverse). Among patients, age, mean arterial pressure, and C-reactive protein independently predicted carotid-femoral pulse wave velocity. Age and mean arterial pressure were the only predictors of AIx@75. Women with SSc have increased aortic augmentation and decreased pulse pressure amplification (both measures of the contribution of reflected wave to central waveform) but no changes in aortic or upper limb arterial stiffness. Microvascular involvement occurs earlier than large artery stiffening in SSc. © 2016 American Heart Association, Inc.

Nailfold Capillaroscopy - Its Role in Diagnosis and Differential Diagnosis of Microvascular Damage in Systemic Sclerosis.

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Lambova, Sevdalina; Hermann, W; Muller-Ladner, Ulf

2013-01-01

In the nailfold area, specific diagnostic microvascular abnormalities are easily recognized via capillaroscopic examination in systemic sclerosis (SSc). They are termed "scleroderma" type capillaroscopic pattern, which includes presence of dilated, giant capillaries, haemorrhages, avascular areas, and neoangiogenic capillaries and are observed in the majority of SSc patients (in more than 90%). LeRoy and Medsger (2001) proposed criteria for early diagnosis of SSc with inclusion of the abnormal capillaroscopic changes and suggested to prediagnose SSc prior to the development of other manifestations of the disease. It is a new era in the diagnosis of SSc. At present, an international multicenter project is performed. It aims validation of criteria for very early diagnosis of SSc (project VEDOSS (Very Early Diagnosis of Systemic Sclerosis) and is organized by European League Against Rheumatism (EULAR) Scleroderma Trials and Reasearch. Very recently the first results of the VEDOSS project were processed and new EULAR/ACR (American College of Rheumatology) classification criteria have been validated and published (2013), in which the characteristic capillaroscopic changes have been included. Our observations confirm the high frequency of the specific capillaroscopic changes of the fingers in SSc, which have been found in 97.2% of the cases from the studied patient population. We have performed for the first time capillaroscopic examinations of the toes in SSc. Interestingly,"scleroderma type" capillaroscopic pattern was also found at the toes in a high proportion of patients - 66.7%, but it is significantly less frequent as compared with fingers (97.2%, p<0.05). In our opinion, the examination of the toes of SSc patients should be considered as it suggests an additional opportunity for evaluation of the microvascular changes in these patients although the observed changes are in a lower proportion of cases. Thus, capillaroscopic examination is a cornerstone for the very

Endothelin-1 in systemic sclerosis

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C. Pizzorni

2011-09-01

Full Text Available We evaluated endothelin-1 (ET-1 plasma levels in patients affected by primary Raynaud’s phenomenon (PRP, as well as in patients with systemic sclerosis (SSc and secondary Raynaud’s phenomenon (SRP. Furthermore, ET-1 levels were investigated in SSc patients with different patterns of peripheral microvascular damage, as evaluated by nailfold videocapillaroscopy (NVC. Methods: 23 PRP patients, 67 SSc patients according to ACR criteria, and 23 healthy subjects were enrolled. SSc microvascular involvement was classified in three different patterns (Early, Active, and Late by NVC, as previously described. Results: ET-1 was found significantly higher in both PRP and SRP, when compared with controls (median ±IQR: 3.3±2.8, 2.7±2.2, 2.0±2.2, respectively (p=0.05. No statistically significant difference of ET-1 levels was observed between PRP and SRP patients. ET-1 was found higher in patients with Late NVC pattern, when compared with both Active and Early NVC patterns (median±IQR: 3.4±2.5, 2.4±2.2, 2.5±2.1, respectively, but without statistical significance. Patients with Late NVC pattern showed significantly higher ET-1 plasma levels than controls (p=0.03. No correlation was found between ET-1 levels and disease duration in both groups, as well as between ET-1 levels and age of patients. Conclusions: These data support previous studies, reporting increased ET-1 plasma levels in both PRP and SRP patients. Interestingly, patients with the Late NVC pattern of microangiopathy showed higher ET-1 plasma levels than controls. The high levels of ET-1 detected in the Late NVC pattern of microangiopathy might be related to the larger fibrotic involvement typical of the advanced stages of disease.

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

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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...

Modulation of Fibrosis in Systemic Sclerosis by Nitric Oxide and Antioxidants

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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.

Progranulin Overproduction Due to Fli-1 Deficiency Contributes to the Resistance of Dermal Fibroblasts to Tumor Necrosis Factor in Systemic Sclerosis.

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Ichimura, Yohei; Asano, Yoshihide; Akamata, Kaname; Noda, Shinji; Taniguchi, Takashi; Takahashi, Takehiro; Toyama, Tetsuo; Tada, Yayoi; Sugaya, Makoto; Sato, Shinichi; Kadono, Takafumi

2015-12-01

Progranulin is a growth factor that is active in wound repair and is an antagonist of tumor necrosis factor (TNF) receptors, regulating fibroblast activation, angiogenesis, and inflammation. Because long-standing activation of gene programs related to wound healing is a hallmark of systemic sclerosis (SSc), we sought to investigate the role of progranulin in SSc. Progranulin expression levels in human and murine skin samples were determined by immunohistochemical analysis and quantitative reverse transcription-polymerase chain reaction. The role of progranulin in fibroblast activation was examined using a gene-silencing technique. Progranulin levels in serum obtained from 60 patients with SSc and 16 healthy control subjects were determined by enzyme-linked immunosorbent assay. Progranulin expression was increased in SSc dermal fibroblasts compared with normal dermal fibroblasts, both in vivo and in vitro. Transcription factor Fli-1, a deficiency of which is involved in the activation of SSc dermal fibroblasts, served as a potent repressor of the progranulin gene, and Fli-1(+/-) mice and bleomycin-treated wild-type mice exhibited up-regulated expression of progranulin in dermal fibroblasts. SSc dermal fibroblasts were resistant to the antifibrotic effect of TNF, but this resistance was reversed by gene silencing of progranulin. Serum progranulin levels were elevated in patients with early diffuse cutaneous SSc (dcSSc), especially in those with inflammatory skin symptoms, and were positively correlated with the C-reactive protein level. Progranulin overproduction due to Fli-1 deficiency may contribute to the constitutive activation of SSc dermal fibroblasts by antagonizing the antifibrotic effect of TNF. Progranulin may also be involved in the inflammatory process associated with progressive skin sclerosis in early dcSSc. © 2015, American College of Rheumatology.

There is a need for new systemic sclerosis subset criteria. A content analytic approach.

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Johnson, S R; Soowamber, M L; Fransen, J; Khanna, D; Van Den Hoogen, F; Baron, M; Matucci-Cerinic, M; Denton, C P; Medsger, T A; Carreira, P E; Riemekasten, G; Distler, J; Gabrielli, A; Steen, V; Chung, L; Silver, R; Varga, J; Müller-Ladner, U; Vonk, M C; Walker, U A; Wollheim, F A; Herrick, A; Furst, D E; Czirjak, L; Kowal-Bielecka, O; Del Galdo, F; Cutolo, M; Hunzelmann, N; Murray, C D; Foeldvari, I; Mouthon, L; Damjanov, N; Kahaleh, B; Frech, T; Assassi, S; Saketkoo, L A; Pope, J E

2018-01-01

Systemic sclerosis (SSc) is heterogenous. The objectives of this study were to evaluate the purpose, strengths and limitations of existing SSc subset criteria, and identify ideas among experts about subsets. We conducted semi-structured interviews with randomly sampled international SSc experts. The interview transcripts underwent an iterative process with text deconstructed to single thought units until a saturated conceptual framework with coding was achieved and respondent occurrence tabulated. Serial cross-referential analyses of clusters were developed. Thirty experts from 13 countries were included; 67% were male, 63% were from Europe and 37% from North America; median experience of 22.5 years, with a median of 55 new SSc patients annually. Three thematic clusters regarding subsetting were identified: research and communication; management; and prognosis (prediction of internal organ involvement, survival). The strength of the limited/diffuse system was its ease of use, however 10% stated this system had marginal value. Shortcomings of the diffuse/limited classification were the risk of misclassification, predictions/generalizations did not always hold true, and that the elbow or knee threshold was arbitrary. Eighty-seven percent use more than 2 subsets including: SSc sine scleroderma, overlap conditions, antibody-determined subsets, speed of progression, and age of onset (juvenile, elderly). We have synthesized an international view of the construct of SSc subsets in the modern era. We found a number of factors underlying the construct of SSc subsets. Considerations for the next phase include rate of change and hierarchal clustering (e.g. limited/diffuse, then by antibodies).

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

NARCIS (Netherlands)

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

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

Association of the FAM167A-BLK region with systemic sclerosis.

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Ito, Ikue; Kawaguchi, Yasushi; Kawasaki, Aya; Hasegawa, Minoru; Ohashi, Jun; Kawamoto, Manabu; Fujimoto, Manabu; Takehara, Kazuhiko; Sato, Shinichi; Hara, Masako; Tsuchiya, Naoyuki

2010-03-01

An association of single-nucleotide polymorphisms (SNPs) in the FAM167A (previously referred to as C8orf13)-BLK region with systemic lupus erythematosus (SLE) has been demonstrated in Caucasians and in Asians. Recent studies have shown that many genes, including IRF5, STAT4, and PTPN22, are shared susceptibility genes in multiple autoimmune diseases. We undertook the current study to examine whether the FAM167A-BLK region is also associated with susceptibility to systemic sclerosis (SSc). Japanese patients with SSc (n = 309) and healthy controls (n = 769) were enrolled in a 2-tiered case-control association study. In tier 1, 124 patients and 412 controls were tested to determine association of 16 tag SNPs encompassing the FAM167A-BLK region with SSc. In tier 2, an additional 185 patients and 357 controls were analyzed for SNP rs13277113. Two haplotype blocks that correspond approximately to FAM167A and BLK were observed. In tier 1 of the study, the rs13277113A allele in the BLK block exhibited the most significant association with SSc after correction for multiple testing (permutated P = 0.024). Two SNP haplotypes formed by rs13277113 and the most significant SNP in the FAM167A block did not exhibit stronger association. When samples from tier 1 and tier 2 were combined, the rs13277113A allele was significantly associated with SSc (odds ratio 1.45 [95% confidence interval 1.17-1.79], P = 6.1 x 10(-4)). Association or a tendency toward association of rs13277113A with SSc was observed regardless of a patient's autoantibody profile or whether a patient had diffuse cutaneous or limited cutaneous SSc. Our findings indicate that the rs13277113A allele is associated not only with SLE but also with SSc and that the FAM167A-BLK region is a common genetic risk factor for both SLE and SSc.

Effectiveness and safety of oxycodone/naloxone in the management of chronic pain in patients with systemic sclerosis with recurrent digital ulcers: two case reports

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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

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

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Krasimirova E.

2017-05-01

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

Polymorphisms in STAT4 and IRF5 increase the risk of systemic sclerosis: a meta-analysis.

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Xu, Yang; Wang, Wenling; Tian, Yanli; Liu, Jingyang; Yang, Rongya

2016-04-01

Systemic sclerosis (SSc) is the most severe connective tissue disorder. Recent studies have demonstrated that genetic factors may play a role in the development of SSc. The aim of this study was to investigate the association of signal transducer and activator of transcription 4 (STAT4) rs7574865 and interferon regulatory factor 5 (IRF5) rs2004640 polymorphisms with risk of SSc. Case-control studies were obtained from the electronic database of PubMed, Medline, Embase, and CNKI (China National Knowledge Infrastructure) up to December 2013. The association between STAT4 and IRF5 polymorphisms and SSc susceptibility was assessed by pooled odds ratios (ORs) and 95% confidence intervals (CI). Six related studies, including 4746 SSc cases and 7399 healthy controls, were pooled in this meta-analysis. For STAT4 polymorphism, we observed a statistically significant positive association between risk factor T allele carriers and SSc susceptibility (OR = 1.37, 95% CI = 1.27-1.48, P rs7574865 and IRF5 rs2004640G/T substitution are associated with a susceptibility to SSc, and they may serve as the SSc genetic susceptibility factor. These data confirmed that genetic polymorphisms may play a role in the development of SSc and have provided new insight into the pathogenesis of SSc. © 2015 The International Society of Dermatology.

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

Systems engineering and integrated for the SSC

International Nuclear Information System (INIS)

Laintz, D.J.; Crosby, B.; Davis, M.; Eben, D.; Gliozzi, J.; Kientz, E.; Knafelc, J.; Phelps, J.; Rider, M.; Shearer, K.

1989-01-01

Experience in high technology projects of scale and scope similar to the SSC, leads the authors to propose utilization of a Systems Engineering and Integration (SE and I) process tailored specifically to the SSC project. They begin by giving an overview of SE and I. This overview includes the purpose, history, definition, and a discussion of when to use it. They then proceeded to give a description of a formalized SE and I process. They discuss tailoring the process to a project and close by recommending an early commitment to an SE and I methodology for the SSC. 2 refs., 2 figs

Esophageal transit scintigraphy and structured questionnaire in patients with systemic sclerosis with endoscopically proven reflux esophagitis

International Nuclear Information System (INIS)

Nakajima, Kenichi; Inaki, Anri; Hiramatsu, Takashi; Hasegawa, Minoru; Fujimoto, Manabu; Takehara, Kazuhiko; Kinuya, Seigo

2009-01-01

Esophageal complications are common in patients with systemic sclerosis (SSc). The relationship between gastroesophageal reflux (GER) symptoms and dysmotility was examined in endoscopically confirmed patients suspected of having reflux esophagitis. A total of 32 patients with limited and diffuse type SSc (lSSc, dSSc) were examined based on a structured questionnaire score (QS) of GER symptoms, retention fraction of esophageal scintigraphy at 90 s (R 90 ) and gastric emptying time. The QS was significantly higher in the reflux esophagitis group than in the non-esophagitis group (5.4±3.5, 1.4±2.9, P=0.003). When the non-esophagitis group was further divided into lSSc and dSSc groups, R 90 was higher in the reflux esophagitis group (31±18%) and the non-esophagitis group with dSSc (34±32%) than in the non-esophagitis group with lSSc (8±3%, P=0.02). Both high R 90 ≥15% and QS≥4 indicated reflux esophagitis. Conversely, both normal R 90 and QS indicated no reflux esophagitis. A combination of esophageal scintigraphy and structured questionnaire demonstrated different aspects of esophageal dysfunction, namely dysmotility and GER. Patients with high QS and dysmotility may be indicated for further evaluation including endoscopic examination and medical treatment.(author)

Aortic pulse wave velocity measurement in systemic sclerosis patients

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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.

Systems level analysis of systemic sclerosis shows a network of immune and profibrotic pathways connected with genetic polymorphisms.

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J Matthew Mahoney

2015-01-01

Full Text Available Systemic sclerosis (SSc is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6-12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes using a gene-gene interaction network, and place the genetic risk loci in the context of the intrinsic subsets. To identify gene expression modules common to three independent datasets from three different clinical centers, we developed a consensus clustering procedure based on mutual information of partitions, an information theory concept, and performed a meta-analysis of these genome-wide gene expression datasets. We created a gene-gene interaction network of the conserved molecular features across the intrinsic subsets and analyzed their connections with SSc-associated genetic polymorphisms. The network is composed of distinct, but interconnected, components related to interferon activation, M2 macrophages, adaptive immunity, extracellular matrix remodeling, and cell proliferation. The network shows extensive connections between the inflammatory- and fibroproliferative-specific genes. The network also shows connections between these subset-specific genes and 30 SSc-associated polymorphic genes including STAT4, BLK, IRF7, NOTCH4, PLAUR, CSK, IRAK1, and several human leukocyte antigen (HLA genes. Our analyses suggest that the gene expression changes underlying the SSc subsets may be long-lived, but mechanistically interconnected

Association between nailfold capillaroscopy findings and pulmonary function tests in patients with systemic sclerosis.

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Castellví, Ivan; Simeón-Aznar, Carmen Pilar; Sarmiento, Mónica; Fortuna, Ana; Mayos, Mercedes; Geli, Carme; Diaz-Torné, César; Moya, Patricia; De Llobet, Josep Maria; Casademont, Jordi

2015-02-01

To determine whether there is an association between different capillaroscopic findings and pulmonary function tests in systemic sclerosis (SSc). We did a retrospective observational study in a cohort of patients with SSc and early SSc. Patients with at least 1 nailfold videocapillaroscopy (NVC) magnified 120× were included. Pathological findings were giant capillaries, angiogenesis, and density loss. Findings were compared with lung function values: percent expected value of forced vital capacity (FVC), DLCO, and FVC/DLCO ratio. Other variables collected were sex and SSc type, and the presence of digital ulcers (DU), interstitial lung disease (ILD), scleroderma renal crisis, and/or pulmonary hypertension (PH). Of 136 patients with SSc, 85 had undergone an NVC. The frequency of ILD, DU, and PH was 24.1%, 28.7%, and 17.2%, respectively. Data analysis showed that patients with density loss had worse FVC% (86.91 ± 19.42 vs 101.13 ± 16.06, p < 0.01) and DLCO% (71.43 ± 21.19 vs 85.9 ± 19.81, p < 0.01) compared to those without. Patients with loss of density present worse FVC and DLCO values. Prospective studies are warranted to determine whether NVC is useful for studying pulmonary function in SSc.

Severe Hypothyroidism due to the Loss of Therapeutic Efficacy of l-Thyroxine in a Patient with Esophageal Complication Associated with Systemic Sclerosis.

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Lobasso, Antonio; Nappi, Liliana; Barbieri, Letizia; Peirce, Carmela; Ippolito, Serena; Arpaia, Debora; Rossi, Francesca Wanda; de Paulis, Amato; Biondi, Bernadette

2017-01-01

Thyroid function abnormalities and thyroid autoantibodies have been frequently described in patients with systemic autoimmune diseases as systemic sclerosis (SSc). Serum TSH levels are higher in SSc patients with more severe skin diseases and a worse modified Rodnan skin score. Asymptomatic esophageal involvement due to SSc has never been described as a cause of severe hypothyroidism due to l-thyroxine (l-T4) malabsorption in patients with Hashimoto's thyroiditis (HT) and SSc. Here, we report a case of a 56-year-old female affected by both SSc and HT who developed severe hypothyroidism due to the loss of therapeutic efficacy of l-T4. Therapeutic failure resulted from the altered l-T4 absorption because of SSc esophageal complications. Clinical findings improved after the administration of oral liquid l-T4. Thyroid function completely normalized with a full clinical recovery, the disappearance of the pericardial effusion and the improvement of the pulmonary pressure. A recognition of a poor absorption is crucial in patients with hypothyroidism and SSc to reduce the risk of the subsequent adverse events. This case suggests the importance of clinical and laboratory surveillance in patients with SSc and HT because the systemic complications of these dysfunctions may worsen the prognosis of hypothyroid SSc/HT patients.

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

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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

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

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

2016-01-01

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

Elevated expression of type VII collagen in the skin of patients with systemic sclerosis. Regulation by transforming growth factor-beta.

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Rudnicka, L; Varga, J; Christiano, A M; Iozzo, R V; Jimenez, S A; Uitto, J

1994-01-01

A hallmark of systemic sclerosis (SSc) is the development of tissue fibrosis. Excessive production of several connective tissue components normally present in the dermis, including type I, III, V, and VI collagens as well as fibronectin and proteoglycans, is a consistent finding in the skin of SSc patients. Type VII collagen is a major constituent of anchoring fibrils, present in the skin at the dermal-epidermal basement membrane zone. TGF-beta has been shown to upregulate the expression of t...

The challenge of establishing treatment efficacy for cutaneous vascular manifestations of systemic sclerosis.

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Pauling, John D

2018-05-01

The cutaneous vascular manifestations of systemic sclerosis (SSc) comprise Raynaud's phenomenon, cutaneous ulceration, telangiectasia formation and critical digital ischaemia; each of which are associated with significant disease-related morbidity. Despite the availability of multiple classes of vasodilator therapy, many of which have been the subject of RCTs, a limited number of pharmacological interventions are currently approved for the management of cutaneous vascular manifestations of SSc. Areas covered: A major challenge has been demonstrating treatment efficacy with examples of promising therapies yielding contrasting results in controlled trial settings. Differences between consensus best-practice guidelines, evidence-based recommendations and marketing approvals in different jurisdictions has resulted in geographic variation in clinical practice concerning the management of cutaneous vascular manifestations of SSc. Difficulty demonstrating treatment efficacy risks waning industry engagement for drug development programmes in this field. This article highlights the key challenges in establishing treatment efficacy and barriers that must be overcome to support successful clinical trial programmes across the spectrum of cutaneous vascular manifestations of SSc. Expert commentary: The paucity of approved treatments for cutaneous vascular manifestations of SSc relates as much to challenges in clinical trial design and the need for reliable clinical trial endpoints, as to lack of therapeutic options.

A meta-analysis of the association between cytokine gene polymorphisms and systemic sclerosis.

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Peng, Wen-jia; Pan, Hai-feng; Tao, Jin-hui; Wang, Bing-xiang; Lu, Man-man; Wang, Song; He, Qian; Wang, Jing

2012-09-01

We conducted a comprehensive meta-analysis to quantitatively evaluate the association of cytokine gene polymorphisms with systemic sclerosis (SSc) susceptibility. Electronic databases were used to identify published studies before July 2011. In total, 23 case-control studies including 3524 SSc cases and 6086 healthy controls were included in the meta-analysis. We examined the relationship between five gene polymorphisms [cytotoxic T lymphocyte associated antigen 4 (CTLA-4) -1722T/C, CTLA-4 -318C/T, CTLA-4 +49A/G, angiotensin-converting enzyme I/D, STAT-4 rs7574865] and susceptibility to SSc. The combined odds ratio (OR) with 95% confidence interval (95% CI) was calculated to estimate the strength of the association in a fixed or random effect model. Heterogeneity and publication bias were also assessed. We found a significant association between SSc and STAT rs7574865 (TT vs. GG: OR 0.44, 95% CI 0.36-0.54; TT vs. TG + GG: OR 0.48, 95% CI 0.39-0.59; TT + TG vs. GG: OR 0.74, 95% CI 0.66-0.83; T vs. G: OR 0.72, 95% CI 0.66-0.79), but there were no other statistically significant associations with other gene polymorphisms. Our study suggested that SSc is associated with STAT gene rs7574865 polymorphism.

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

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

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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

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

International Nuclear Information System (INIS)

Ninaber, Maarten K.; Stolk, Jan; Smit, Jasper; Le Roy, Ernest J.; Kroft, Lucia J.M.; Els Bakker, M.; Vries Bouwstra, Jeska K. de; Schouffoer, Anne A.; Staring, Marius; Stoel, Berend C.

2015-01-01

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

Esophageal hypomotility in systemic sclerosis. Close relationship with pulmonary involvement

International Nuclear Information System (INIS)

Kinuya, Keiko; Nakajima, Kenichi; Kinuya, Seigo; Michigishi, Takatoshi; Tonami, Norihisa; Takehara, Kazuhiko

2001-01-01

Esophageal motility was assessed in patients with systemic sclerosis (SSc) by scintigraphy and compared with extent of scleroderma, duration of disease, index of anti-topoisomerase I antibody (topo I), and pulmonary involvement. A multiple-swallow test was performed in 47 patients with SSc in the supine position with 99m Tc-DTPA. A region of interest on the entire esophagus was defined and the retention ratio (RR) was calculated from a time-activity curve. Patients with diffuse scleroderma had higher RRs than those with limited scleroderma (48.8% vs. 30.0%; p CO ) had higher RRs than those with normal %DL CO (40.5% vs. 19.6%; p=0.03). Patients with reduced % vital capacity (%VC) had higher RRs than those with normal %VC (54.6% vs. 25.0%; p<0.005). Patients with pulmonary fibrosis had higher RRs than those who were negative (58.5% vs. 20.3%; p<0.00005). Esophageal dysfunction in patients with SSc showed a correlation with the extent of scleroderma, positive topo I, and pulmonary involvement. The RR can be an objective clinical marker for the severity of organ fibrosis. (author)

Survival, causes of death, and prognostic factors in systemic sclerosis: analysis of 947 Brazilian patients.

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Sampaio-Barros, Percival D; Bortoluzzo, Adriana B; Marangoni, Roberta G; Rocha, Luiza F; Del Rio, Ana Paula T; Samara, Adil M; Yoshinari, Natalino H; Marques-Neto, João Francisco

2012-10-01

To analyze survival, prognostic factors, and causes of death in a large cohort of patients with systemic sclerosis (SSc). From 1991 to 2010, 947 patients with SSc were treated at 2 referral university centers in Brazil. Causes of death were considered SSc-related and non-SSc-related. Multiple logistic regression analysis was used to identify prognostic factors. Survival at 5 and 10 years was estimated using the Kaplan-Meier method. One hundred sixty-eight patients died during the followup. Among the 110 deaths considered related to SSc, there was predominance of lung (48.1%) and heart (24.5%) involvement. Most of the 58 deaths not related to SSc were caused by infection, cardiovascular or cerebrovascular disease, and cancer. Male sex, modified Rodnan skin score (mRSS) > 20, osteoarticular involvement, lung involvement, and renal crisis were the main prognostic factors associated to death. Overall survival rate was 90% for 5 years and 84% for 10 years. Patients presented worse prognosis if they had diffuse SSc (85% vs 92% at 5 yrs, respectively, and 77% vs 87% at 10 yrs, compared to limited SSc), male sex (77% vs 90% at 5 yrs and 64% vs 86% at 10 yrs, compared to female sex), and mRSS > 20 (83% vs 90% at 5 yrs and 66% vs 86% at 10 yrs, compared to mRSS < 20). Survival was worse in male patients with diffuse SSc, and lung and heart involvement represented the main causes of death in this South American series of patients with SSc.

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

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

2013-01-01

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

[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.

Fertility and pregnancy outcome in women with systemic sclerosis.

Science.gov (United States)

Steen, V D; Medsger, T A

1999-04-01

To determine fertility and pregnancy outcome in women with systemic sclerosis (SSc; scleroderma) who had disease onset before age 45 years. All living women with scleroderma who had first been evaluated at the University of Pittsburgh Scleroderma Clinic after January 1, 1972 were sent a detailed self-administered questionnaire in 1986 specifically concerning pregnancy outcomes and infertility. This group was compared with 2 race- and age-matched control groups, one comprising women with rheumatoid arthritis (RA) and one comprising healthy neighborhood women identified by random-digit dialing. We determined the number, history, treatment, and outcome of women who either had never been pregnant or had attempted to become pregnant unsuccessfully for more than 1 year. We also obtained data regarding pregnancy outcomes, including the frequency of miscarriage, premature births, small full-term infants, perinatal deaths, and births of live healthy infants. The study group comprised 214 women with SSc, 167 with RA, and 105 neighborhood controls. There were no significant differences in the overall rates of miscarriage, premature births, small full-term births, or neonatal deaths between the 3 groups. Women with SSc were more likely than those without SSc to have adverse outcomes of pregnancy after the onset of their rheumatic disease, particularly premature births (also seen in RA women after disease onset) and small full-term infants. Although a significantly greater number of women with SSc had never been pregnant, there were no significant differences in the frequency of never having been pregnant or of infertility in the 3 groups after adjustment for contributing factors. This study indicates that women with SSc have acceptable pregnancy outcomes compared with those of women with other rheumatic disease and healthy neighborhood controls. Infertility was not a frequent problem. We believe that there are no excessive pregnancy risks to women with SSc or their infants

System engineering in the SSC Linac

International Nuclear Information System (INIS)

Tooker, J.F.; Chang, C.R.; Cutler, R.I.; Funk, L.W.; Guy, F.W.; Hale, R.; Leifeste, G.T.; Nonte, J.; Prichard, B.; Raparia, D.; Saadatmand, K.; Sethi, R.C.; Yao, C.G.

1992-01-01

The design and construction of the SSC Linac involves various departments within the SSCL and many outside vendors. The adaptive incorporation of system engineering principles into the SSC Linac is described. This involves the development of specification trees with the breakdown and flow of functional and physical requirements from the top level system specifications to the lower level component specifications. Interfaces are defined, which specify and control the interconnections between the various components. Review cycles are presented during which the requirements, evolution of the design, and test plans are reviewed, monitored, and finalized. The Linac specification tree, interface definition, and reviews of the Linac are presented, including typical examples. (Author) 2 refs., 3 tabs

Cross-sectional study of soluble selectins, fractions of circulating microparticles and their relationship to lung and skin involvement in systemic sclerosis

DEFF Research Database (Denmark)

Iversen, Line V; Ullman, Susanne; Østergaard, Ole

2015-01-01

BACKGROUND: Endothelial damage and activation may play central roles in the pathogenesis of systemic sclerosis (SSc) and are reflected by microparticles (MPs) and soluble selectins. The objective of this study was to determine if these potential biomarkers are associated with specific organ invol...

Esophageal transit study using a sliding sum image. Application to patients with probable and definite systemic sclerosis

International Nuclear Information System (INIS)

Nakajima, Kenichi; Hasegawa, Minoru; Inaki, Anri; Wakabayashi, Hiroshi; Takehara, Kazuhiko; Kinuya, Seigo; Hosoya, Tetsuo

2011-01-01

Esophageal complication is common in systemic sclerosis (SSc), but scintigraphic transit patterns based on each subtype have not been understood well. The aim of this study was to develop a new algorithm for integrating a dynamic esophageal transit study and to apply the method to patients with SSc. A total of 40 patients suspected of having SSc were examined by a dynamic esophageal transit study. The subtypes included 32 with definite SSc (15 limited cutaneous type and 17 diffuse cutaneous type) and 8 with probable SSc. The serial esophageal images were shifted and summed to a functional image (sliding sum image) and compared to a conventional condensed image analysis. Esophageal retention fraction at 90 s (R 90 ) and half-time (T 1/2 ) of transit were also measured. The four patterns of the sliding sum image and condensed image agreed in all patients. Abnormal retention patterns were observed in none of the 8 (0%) patients with the probable SSc and in 15 of 32 (47%) patients with definite SSc (p=0.014). The severity of scleroderma assessed by modified Rodnan skin thickness score correlated with that of esophageal retention R 90 (p=0.04). The sliding sum image is a simple and effective method for integrating esophageal transit. Patients with definite SSc and severe scleroderma had significantly higher retention patterns, while probable SSc patients showed no esophageal dysmotility. (author)

Epidemiology of systemic sclerosis: incidence, prevalence, survival, risk factors, malignancy, and environmental triggers.

Science.gov (United States)

Barnes, Jammie; Mayes, Maureen D

2012-03-01

To identify the recent data regarding prevalence, incidence, survival, and risk factors for systemic sclerosis (SSc) and to compare these data to previously published findings. SSc disease occurrence data are now available for Argentina, Taiwan, and India and continue to show wide variation across geographic regions. The survival rate is negatively impacted by older age of onset, male sex, scleroderma renal crisis, pulmonary fibrosis, pulmonary arterial hypertension, cancer, and antitopoisomerase and anti-U1 antibodies. It appears that silica exposure confers an increased risk for developing scleroderma, but this exposure accounts for a very small proportion of male patients. Smoking is not associated with increased SSc susceptibility. Malignancies are reported in scleroderma at an increased rate, but the magnitude of this risk and the type of cancer vary among reports. Prevalence and incidence of SSc appears to be greater in populations of European ancestry and lower in Asian groups. Exposure to silica dust appears to be an environmental trigger, but this only accounts for a small proportion of male cases. Evidence for increased risk of neoplasia is suggestive, but the magnitude of the risk and the types of malignancies vary among reports.

Specific oxidative stress parameters differently correlate with nailfold capillaroscopy changes and organ involvement in systemic sclerosis.

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Riccieri, Valeria; Spadaro, Antonio; Fuksa, Leos; Firuzi, Omidreza; Saso, Luciano; Valesini, Guido

2008-02-01

Oxidative stress is suggested to be involved in the pathogenesis of systemic sclerosis (SSc). The aim of the present study was to clarify such a hypothesis by determination of four different plasmatic parameters of oxidative stress, and to define its role in the microvascular damage, assessed by nailfold capillaroscopy (NC). Plasma samples of 18 patients with SSc were analyzed. The biomarkers measured were: total antioxidant capacity, hydroperoxides (ROOHs), and sulfhydryl (SH) and carbonyl (CO) groups. Each patient had a detailed clinical assessment and underwent an NC. The results showed significantly increased ROOHs in SSc patients compared to control group (5.02 +/- 0.24 vs 3.28 +/- 0.19 micromol/l; p capillaroscopy semiquantitative rating scale score (p < 0.05) and with the rating system for avascular areas (p < 0.03). The levels of CO groups inversely correlated with modified Rodnan's skin score (p < 0.039) and were lower in patients with pulmonary fibrosis (p < 0.045), while the levels of SH groups were lower in those presenting gastrointestinal involvement (p < 0.029). The obtained data indicate augmented free radical-mediated injury in SSc and also show correlations among oxidative abnormalities, some clinical findings, and signs of a more severe microvascular involvement. These results give more evidence to the connection between oxidative impairment and SSc.

Severe Hypothyroidism due to the Loss of Therapeutic Efficacy of l-Thyroxine in a Patient with Esophageal Complication Associated with Systemic Sclerosis

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Antonio Lobasso

2017-09-01

Full Text Available BackgroundThyroid function abnormalities and thyroid autoantibodies have been frequently described in patients with systemic autoimmune diseases as systemic sclerosis (SSc. Serum TSH levels are higher in SSc patients with more severe skin diseases and a worse modified Rodnan skin score. Asymptomatic esophageal involvement due to SSc has never been described as a cause of severe hypothyroidism due to l-thyroxine (l-T4 malabsorption in patients with Hashimoto’s thyroiditis (HT and SSc.Case reportHere, we report a case of a 56-year-old female affected by both SSc and HT who developed severe hypothyroidism due to the loss of therapeutic efficacy of l-T4. Therapeutic failure resulted from the altered l-T4 absorption because of SSc esophageal complications. Clinical findings improved after the administration of oral liquid l-T4. Thyroid function completely normalized with a full clinical recovery, the disappearance of the pericardial effusion and the improvement of the pulmonary pressure.ConclusionA recognition of a poor absorption is crucial in patients with hypothyroidism and SSc to reduce the risk of the subsequent adverse events. This case suggests the importance of clinical and laboratory surveillance in patients with SSc and HT because the systemic complications of these dysfunctions may worsen the prognosis of hypothyroid SSc/HT patients.

Serum Endoglin Levels in Patients Suffering from Systemic Sclerosis and Elevated Systolic Pulmonary Arterial Pressure

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Paola Ximena Coral-Alvarado

2010-01-01

Full Text Available Background. Pulmonary arterial hypertension (PAH is the main cause of morbimortality in systemic sclerosis (SSc. Increased Eng expression has been demonstrated in SSc patients. Objective. Ascertaining serum levels of Eng in SSc patients with and without elevated systolic pulmonary arterial pressure (sPAP and comparing them with that of healthy volunteers. Methods. A cross-sectional study was carried out. A commercial ELISA kit was used for measuring serum concentrations of Eng in 60 subjects: 40 patients with SSc with and without elevated sPAP, compared to 20 healthy control subjects. Elevated sPAP was detected by echocardiogram. Results. No association between positive Eng and elevated sPAP was found when compared to the SSc without elevated sPAP group (OR=2.85; 0.65–12.88 95% CI; P=.11; however, an association was found between positive Eng and elevated sPAP compared to healthy controls (OR=23.22; 2.46–1050.33 95% CI; P=.001, and weak association was found between the positive Eng with SSc without elevated sPAP group compared to healthy controls (OR=8.14, 0.8–393.74 95% CI; P=.046. Conclusion. Raised serum levels of Eng in SSc patients compared to healthy controls were found, suggesting a role for Eng in SSc vasculopathy and not just in elevated sPAP. However, prospective studies are needed to verify such observations.

Separate Influences of Birth Order and Gravidity/Parity on the Development of Systemic Sclerosis

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COCKRILL, TONYA; del JUNCO, DEBORAH J.; ARNETT, FRANK C.; ASSASSI, SHERVIN; TAN, FILEMON K.; McNEARNEY, TERRY; FISCHBACH, MICHAEL; PERRY, MARILYN; MAYES, MAUREEN D.

2010-01-01

Objective 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). Methods 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. Results 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). Conclusion 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. PMID:20391489

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

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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.

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

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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.

High IL-17E and Low IL-17C Dermal Expression Identifies a Fibrosis-Specific Motif Common to Morphea and Systemic Sclerosis

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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...

KCNA5 gene is not confirmed as a systemic sclerosis-related pulmonary arterial hypertension genetic susceptibility factor

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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

The role of nailfold capillary dropout on mortality in systemic sclerosis.

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Tieu, Joanna; Hakendorf, Paul; Woodman, Richard J; Patterson, Karen; Walker, Jenny; Roberts-Thomson, Peter

2018-05-01

Semi-quantitative wide-field nailfold capillaroscopy (NFC) is a simple technique with proven utility in the early diagnosis of systemic sclerosis (SSc). Its role in prognosis, however, remains uncertain. To investigate the possible utility of NFC in predicting survival. Patients with SSc listed on the South Australian Scleroderma Register (SASR) with prior NFC performed at Flinders Medical Centre from 1991 to 2015 were included in this study. Baseline demographic data, diagnosis, scleroderma antibody status and mortality status were also collected for each patient. The cohort consisted of 99 patients with limited cutaneous SSc, 30 patients with diffuse cutaneous SSc and 23 with an overlap scleroderma syndrome. Fifty-six patients died during the period of study (censured end June 2015). Patients with diffuse scleroderma had significantly greater capillary dropout compared with limited and overlap scleroderma (P dropout scores (log-rank χ 2 = 8.75, P = 0.003) and antibody status (log-rank χ 2 = 13.94, P = 0.003) were associated with mortality. ANOVA showed a significant association between antibody status and capillary dropout (P dropout attenuated the impact of autoantibody group on survival. Nailfold capillary dropout was significantly associated with mortality and the severity of dropout attenuates survival dictated by antibody status. Together these observations support the hypothesis that capillary dropout is on the causal pathway between induction of scleroderma associated autoantibodies and mortality. © 2018 Royal Australasian College of Physicians.

A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis: A EUSTAR exploratory study.

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Ingegnoli, Francesca; Boracchi, Patrizia; Gualtierotti, Roberta; Smith, Vanessa; Cutolo, Maurizio; Foeldvari, Ivan

2015-11-01

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. Data collected between June 2004 and April 2013 were examined with focus on capillaroscopy. In this retrospective exploratory study, series of patients with juvenile-onset SSc were matched with series of adult-onset SSc having the same gender and autoantibody profile. 30 of 123 patients with juvenile-onset and 2108 of 7133 with adult-onset SSc had data on capillaroscopy. 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. 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, but a similar distribution of the three patterns was suggested. Further studies are needed to define this issue. Copyright © 2015 Elsevier Inc. All rights reserved.

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

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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

Gene Profiling in Patients with Systemic Sclerosis Reveals the Presence of Oncogenic Gene Signatures

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Marzia Dolcino

2018-03-01

Full Text Available Systemic sclerosis (SSc is a rare connective tissue disease characterized by three pathogenetic hallmarks: vasculopathy, dysregulation of the immune system, and fibrosis. A particular feature of SSc is the increased frequency of some types of malignancies, namely breast, lung, and hematological malignancies. Moreover, SSc may also be a paraneoplastic disease, again indicating a strong link between cancer and scleroderma. The reason of this association is still unknown; therefore, we aimed at investigating whether particular genetic or epigenetic factors may play a role in promoting cancer development in patients with SSc and whether some features are shared by the two conditions. We therefore performed a gene expression profiling of peripheral blood mononuclear cells (PBMCs derived from patients with limited and diffuse SSc, showing that the various classes of genes potentially linked to the pathogenesis of SSc (such as apoptosis, endothelial cell activation, extracellular matrix remodeling, immune response, and inflammation include genes that directly participate in the development of malignancies or that are involved in pathways known to be associated with carcinogenesis. The transcriptional analysis was then complemented by a complex network analysis of modulated genes which further confirmed the presence of signaling pathways associated with carcinogenesis. Since epigenetic mechanisms, such as microRNAs (miRNAs, are believed to play a central role in the pathogenesis of SSc, we also evaluated whether specific cancer-related miRNAs could be deregulated in the serum of SSc patients. We focused our attention on miRNAs already found upregulated in SSc such as miR-21-5p, miR-92a-3p, and on miR-155-5p, miR 126-3p and miR-16-5p known to be deregulated in malignancies associated to SSc, i.e., breast, lung, and hematological malignancies. miR-21-5p, miR-92a-3p, miR-155-5p, and miR-16-5p expression was significantly higher in SSc sera compared to

Skin Autofluorescence, as Marker of Accumulation of Advanced Glycation Endproducts and of Cumulative Metabolic Stress, Is Not Increased in Patients with Systemic Sclerosis

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M. E. Hettema

2011-01-01

Full Text Available 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 accumulation of AGEs, was assessed by measuring UV-A light excitation-emission matrices (AF-EEMS in 41 SSc patients and 41 age- and sex-matched controls. Traditional cardiovascular risk factors and disease-related risk factors were recorded. Results. Skin AF-EEMS did not differ between SSc patients and controls (1.68±0.58 a.u. versus 1.63±0.41 a.u., P=0.684. Skin AF-EEMS in SSc patients was associated with levels of CRP (r=0.44, P=0.004, Medsger's severity scale (r=0.45, P=0.006, and use of agents intervening in the renin-angiotensin system (r=0.33, P=0.027. When analysing SSc patients and controls together, in multivariate analysis, only age and use of agents intervening in the renin-angiotensin system were independently associated with AF-EEMS. Conclusion. These data demonstrate that skin AGEs are not increased in SSc patients.

Computer use problems and accommodation strategies at work and home for people with systemic sclerosis: a needs assessment.

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Baker, Nancy A; Aufman, Elyse L; Poole, Janet L

2012-01-01

We identified the extent of the need for interventions and assistive technology to prevent computer use problems in people with systemic sclerosis (SSc) and the accommodation strategies they use to alleviate such problems. Respondents were recruited through the Scleroderma Foundation. Twenty-seven people with SSc who used a computer and reported difficulty in working completed the Computer Problems Survey. All but 1 of the respondents reported one problem with at least one equipment type. The highest number of respondents reported problems with keyboards (88%) and chairs (85%). More than half reported discomfort in the past month associated with the chair, keyboard, and mouse. Respondents used a variety of accommodation strategies. Many respondents experienced problems and discomfort related to computer use. The characteristic symptoms of SSc may contribute to these problems. Occupational therapy interventions for computer use problems in clients with SSc need to be tested. Copyright © 2012 by the American Occupational Therapy Association, Inc.

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

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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.

Nailfold capillaroscopy in systemic sclerosis: is there any difference between videocapillaroscopy and dermatoscopy?

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Dogan, Sibel; Akdogan, Ali; Atakan, Nilgün

2013-11-01

Vasculopathy is known to destroy nailfold capillary pattern (NCP) in systemic sclerosis (SSc). There are several methods for the evaluation of NCP of which the most common are dermatoscopy and videocapillaroscopy (VCAP). No study has been reported in the literature comparing these two techniques for their diagnostic value. To compare the diagnostic value of dermatoscopy and VCAP which are widely used to determine changes in the NCP in SSc patients. A total of 382 nailfolds were visualized. NCP was evaluated in 39 SSc patients using dermatoscopy and VCAP. Defined dermatoscopic groups were matched with early, active and late phase NCP groups determined by VCAP for comparisons. Both dermatoscopy and VCAP demonstrated distinct NCP of SSc efficiently. According to dermatoscopic NCP, capillary dilatation, giant capillaries and disrupted vascular configuration were able to be visualized. VCAP revealed early phase NCP in N = 8 (20,5%), active phase in N = 18 (46,2%) and late phase NCP in N = 13 (33.3%) of the patients. Statistical evaluation of grouped data resulted a Cohen kappa value (K) = 0,527. Although VCAP was able to facilitate a more detailed evaluation of NCP, there was no difference between dermatoscopy and VCAP for the identification of distinct NCP in SSc. We suggest that dermatoscopy is efficient enough to identify pathognomonic changes in NCP in SSc as well as VCAP and find dermatoscopy as a very easy applicable and convenient method than VCAP although VCAP facilitates a more detailed evaluation of NCP. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

GERD questionnaire for diagnosis of gastroesophageal reflux disease in systemic sclerosis.

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Chunlertrith, K; Noiprasit, A; Foocharoen, C; Mairiang, P; Sukeepaisarnjaroen, W; Sangchan, A; Sawadpanitch, K

2014-01-01

Gastroesophageal reflux disease (GERD) is clinically-identified in patients with systemic sclerosis (SSc). The GERD-questionnaire (GERD-Q) score is a sensitive, non-invasive, diagnostic screening tool for diagnosis of GERD in general patients, but it has been not investigated for use in SSc. Our aim was to evaluate the proper cut-off GERD-Q score, sensitivity and specificity for a diagnosis of GERD in SSc patients. A cross-sectional study using the GERD-Q was performed during May 2012-January 2013 on patients over 18 with the diffuse SSc subset. Both esophago-gastro-duodenoscopy (EGD) and 24-hr pH-monitoring (24hr-pH) were performed as the gold standard tests for both symptomatic and asymptomatic GERD. A total of 75 SSc patients completed the GERD-Q, EGD and 24hr-pH. We identified 22 males (29.3%), 53 females (70.7%) with a mean age of 54.2 years. The respective number of symptomatic and asymptomatic GERD was 69 and 6 cases. For a GERD diagnosis, a cut-off GERD-Q score of 4 provided the best balance between sensitivity and specificity (96.9% and 50%, respectively). Of 48 participants (69.6%) with symptomatic GERD (i.e. positive for both EGD and 24hr-pH), 65 (94.2%) were positive for either EGD or 24hr-pH, and 4 (5.8%) were negative for both EGD and 24hr-pH. A respective majority (83%) vs. one-third of the asymptomatic group had reflux as detected by 24hr-pH vs. A GERD-Q score of 4 or higher indicates a high sensitivity for a diagnosis of GERD in SSc. It can thus be used as a non-invasive screening tool for diagnosing GERD in cases where EGD and 24hr-pH are unavailable.

Systemic sclerosis in Argentina: evaluation of a large cohort from a single centre and comparison with other international series.

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Scolnik, M; Lancioni, E; Saucedo, C; Marin, J; Sabelli, M; Bedran, Z; Soriano, E R; Catoggio, L J

2014-01-01

Prevalence of systemic sclerosis (SSc) and different clinical subsets varies across the world. Few data have been published on SSc patients in Latin America. Our objective was to describe a SSc cohort in Argentina and to compare clinical findings, disease subsets and antibodies with other international SSc populations. Patients with SSc (n=234) seen at the Rheumatology section of the Hospital Italiano de Buenos Aires between 2000-2011 were retrospectively analysed. Data on clinical manifestations, disease subsets and antibodies were obtained. Patients were classified into diffuse cutaneous (dc) and limited cutaneous (lc) subsets. Comparison with other cohorts (France, United States, Germany, Italy, Mexico, EUSTAR and Brazil) was made based on published information. A higher female:male ratio (12:1) and a higher limited subset prevalence (76.1%) was found in this Argentine cohort comparing with others. We also found a lower prevalence of diffuse disease, anti Scl-70 (antitopoisomerase) and nucleolar pattern antinuclear antibodies. Within each subset, clinical findings were similar with other SSc populations except for a very low prevalence in renal crisis (0.02% of dc SS). With slight variations perhaps due to genetic, environmental or referral factors, SSc in this cohort appears to be similar to that described in other parts of the world.

Prospective, open-label, uncontrolled pilot study to study safety and efficacy of sildenafil in systemic sclerosis-related pulmonary artery hypertension and cutaneous vascular complications.

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Kumar, Uma; Sankalp, Gokhale; Gokhle, Sankalp S; Sreenivas, V; Kaur, Satbir; Misra, Durgaprasanna

2013-04-01

Pulmonary artery hypertension (PAH) remains the leading cause of morbidity and mortality in systemic sclerosis, while Raynaud's phenomenon and digital ulcers significantly add to the morbidity in systemic sclerosis (SSc). This study was undertaken to evaluate the role of sildenafil in PAH, Raynaud's phenomenon, and digital ulcers in systemic sclerosis patients. A prospective, open-label, uncontrolled pilot study was done at a tertiary care centre in India to study the safety and efficacy of oral sildenafil in PAH, Raynaud's phenomenon, digital infarcts, and ulcers in SSc. Seventeen patients fulfilling ACR classification criteria for scleroderma and having PAH were recruited. Six-minute walk test, WHO class of dyspnoea, severity of Raynaud's phenomenon, and 2D ECHO were performed in all the study subjects at baseline and at 3 months post-treatment. All patients were treated with oral sildenafil 25 mg three times a day for a period of 3 months. The pre- and post-treatment values of mean pulmonary artery pressure (PAP), 6-min walk test, WHO class of dyspnoea, and severity of Raynaud's phenomenon were compared to look for any significant change. Sixteen patients who completed 3-month follow-up had shown statistically significant improvement in 6-min walk test, WHO class of dyspnoea, severity of Raynaud's phenomenon, and mPAP. Also, there was no occurrence of new digital infarcts or ulcers, and existing ulcers showed signs of healing. Sildenafil is highly efficacious cheaper and safe alternative to other available therapies for SSc-associated PAH, Raynaud's phenomenon, and digital infarcts/ulcers.

Incidence of childhood linear scleroderma and systemic sclerosis in the UK and Ireland.

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Herrick, Ariane L; Ennis, Holly; Bhushan, Monica; Silman, Alan J; Baildam, Eileen M

2010-02-01

Childhood scleroderma encompasses a rare, poorly understood spectrum of conditions. Our aim was to ascertain the incidence of childhood scleroderma in its different forms in the UK and Ireland, and to describe the age, sex, and ethnicity of the cases. The members of 5 specialist medical associations including pediatricians, dermatologists, and rheumatologists were asked to report all cases of abnormal skin thickening suspected to be localized (including linear) scleroderma or systemic sclerosis (SSc) in children scleroderma and 7 (7%) with SSc. This gave an incidence rate per million children per year of 3.4 (95% confidence interval [95% CI] 2.7-4.1) for localized scleroderma, including an incidence rate of 2.5 (95% CI 1.8-3.1) for linear scleroderma, and 0.27 (95% CI 0.1-0.5) for SSc. Of the 87 localized cases, 62 (71%) had linear disease. Of localized disease cases, 55 (63%) were female, 71 (82%) were classified as white British, and the patients' mean age when first seen in secondary care was 10.4 years. Of the 7 SSc cases, all were female, 6 (86%) were white British, and the mean age when first seen was 12.1 years. The median delay between onset and being first seen was 13.1 months for localized scleroderma and 7.2 months for SSc. These data provide additional estimates of the incidence of this rare disorder and its subforms.

Influence of antibody profile in clinical features and prognosis in a cohort of Spanish patients with systemic sclerosis.

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Iniesta Arandia, Nerea; Simeón-Aznar, Carmen Pilar; Guillén Del Castillo, Alfredo; Colunga Argüelles, Dolores; Rubio-Rivas, Manuel; Trapiella Martínez, Luis; García Hernández, Francisco José; Sáez Comet, Luis; Egurbide Arberas, María Victoria; Ortego-Centeno, Norberto; Freire, Mayka; Marí Alfonso, Begoña; Vargas Hitos, José Antonio; Ríos Blanco, Juan José; Todolí Parra, José Antonio; Rodríguez-Carballeira, Monica; Marín Ballvé, Adela; Chamorro Fernández, Antonio Javier; Pla Salas, Xavier; Madroñero Vuelta, Ana Belen; Ruiz Muñoz, Manuel; Fonollosa Pla, Vicent; Espinosa, Gerard

2017-01-01

To assess the clinical manifestations and prognosis of Spanish patients with systemic sclerosis (SSc) according to their immunological profile. From the Spanish Scleroderma Study Group or RESCLE (Registro de ESCLErodermia as Spanish nomenclature) Registry we selected those patients in which anti-centromere (ACA), anti-topoisomerase I (ATA), and anti-RNA polymerase III (ARA) antibodies had been determined, and a single positivity for each SSc specific antibody was detected. Demographic, clinical, laboratory, and survival data were compared according to the serologic status of these antibodies. Overall, 209 SSc patients were included. In 128 (61%) patients ACA was the only positive antibody, 46 (22%) were only positive for ATA, and 35 (17%) for ARA. Of note, the three groups were mutually exclusive. In univariate analysis, patients with ACA presented more frequently limited cutaneous SSc (lcSSc) (p<0.001), whereas diffuse cutaneous SSc (dcSSc) was the most frequent subtype in patients with ATA (54%) and ARA (62%) (both p<0.001). Positive patients for ARA showed the highest prevalence of joint involvement (p<0.001) and those from ATA group had a higher prevalence of interstitial lung disease (ILD) (p<0.001). Scleroderma renal crisis was more frequent in the ARA group (p<0.001). In multivariate analysis, ACA were associated with female gender and were protective for dcSSc and ILD. ATA were found to be protective for lcSSc and they were independently associated with interstitial reticular pattern. ARA positivity was independently associated with dcSSc. We did not find differences in mortality between the three groups. In Spanish SSc patients, the presence of SSc specific antibodies conferred a distinctive clinical profile.

Patients' views and needs about systemic sclerosis and its management: a qualitative interview study.

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Mouthon, Luc; Alami, Sophie; Boisard, Anne-Sophie; Chaigne, Benjamin; Hachulla, Eric; Poiraudeau, Serge

2017-05-30

Systemic sclerosis (SSc) is a chronic connective-tissue disease responsible for reduced life expectancy, disability and a decreased quality of life. In order to optimize patients-physicians relationship and care strategy we aimed to survey views of patients on SSc and its management to reveal potential hurdles and improve health care strategies. A qualitative study combined semi-structured interviews, focus groups, and a direct observation of an information session was performed between November 2008 and January 2009. Twenty-five patients with SSc were included. They encounter difficulties to have a clear representation of their disease. Physical, psychological, and social repercussions of SSc may lead to a psychological distress and different coping strategies, which widely differ among interviewed patients. Patients' views on their therapeutic journey and the management of their disease highlighted strong expectations about patient-physician relationship. These expectations were numerous, complex and sometimes ambivalent. Patients expected physicians to be human and attentive but also involved in research in the field and to provide psychological and affective support to help them to accept the uncertainty of disease evolution and lack of curative treatment. They also expected more individualized management, improvements in diagnosis and follow-up organization, more efforts in education and information, comprehensive behaviors and support from working colleagues and relatives, and increased funding from the health care system. Our results suggest that SSc management could be optimized, particularly with more attention to the patient-practitioner relationship. Patient profiles should be more precisely defined in terms of coping strategies and treatment preferences to propose more individualized options.

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

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Secchi, M E; Sulli, A; Pizzorni, C; Cutolo, M

2009-01-01

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. Twenty-seven 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 degrees C. Statistical evaluation was carried out by non-parametric procedures. Blood flow was found significantly lower in SSc patients when compared with healthy subjects (p<0.05). The heating of the probe to 36 degrees 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). 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.

Membrane diffusion- and capillary blood volume measurements are not useful as screening tools for pulmonary arterial hypertension in systemic sclerosis: a case control study

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Spreeuwenberg Marieke D

2008-10-01

Full Text Available Abstract Background There is no optimal screening tool for the assessment of pulmonary arterial hypertension (PAH in patients with systemic sclerosis (SSc. A decreasing transfer factor of the lung for CO (TLCO is associated with the development of PAH in SSc. TLCO can be partitioned into the diffusion of the alveolar capillary membrane (Dm and the capillary blood volume (Vc. The use of the partitioned diffusion to detect PAH in SSc is not well established yet. This study evaluates whether Dm and Vc could be candidates for further study of the use for screening for PAH in SSc. Methods Eleven SSc patients with PAH (SScPAH+, 13 SSc patients without PAH (SScPAH- and 10 healthy control subjects were included. Pulmonary function testing took place at diagnosis of PAH. TLCO was partitioned according to Roughton and Forster. As pulmonary fibrosis in SSc influences values of the (partitioned TLCO, these were adjusted for fibrosis score as assessed on HRCT. Results TLCO as percentage of predicted (% was lower in SScPAH+ than in SScPAH- (41 ± 7% vs. 63 ± 12%, p vs. 39 ± 12%, p Conclusion SScPAH+ patients have lower Dm% than SScPAH- patients. There are no correlations between Dm% and hemodynamic parameters of PAH in SScPAH+. These findings do not support further study of the role of partitioning TLCO in the diagnostic work- up for PAH in SSc.

A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis.

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Taroni, Jaclyn N; Greene, Casey S; Martyanov, Viktor; Wood, Tammara A; Christmann, Romy B; Farber, Harrison W; Lafyatis, Robert A; Denton, Christopher P; Hinchcliff, Monique E; Pioli, Patricia A; Mahoney, J Matthew; Whitfield, Michael L

2017-03-23

Systemic sclerosis (SSc) is a multi-organ autoimmune disease characterized by skin fibrosis. Internal organ involvement is heterogeneous. It is unknown whether disease mechanisms are common across all involved affected tissues or if each manifestation has a distinct underlying pathology. We used consensus clustering to compare gene expression profiles of biopsies from four SSc-affected tissues (skin, lung, esophagus, and peripheral blood) from patients with SSc, and the related conditions pulmonary fibrosis (PF) and pulmonary arterial hypertension, and derived a consensus disease-associate signature across all tissues. We used this signature to query tissue-specific functional genomic networks. We performed novel network analyses to contrast the skin and lung microenvironments and to assess the functional role of the inflammatory and fibrotic genes in each organ. Lastly, we tested the expression of macrophage activation state-associated gene sets for enrichment in skin and lung using a Wilcoxon rank sum test. We identified a common pathogenic gene expression signature-an immune-fibrotic axis-indicative of pro-fibrotic macrophages (MØs) in multiple tissues (skin, lung, esophagus, and peripheral blood mononuclear cells) affected by SSc. While the co-expression of these genes is common to all tissues, the functional consequences of this upregulation differ by organ. We used this disease-associated signature to query tissue-specific functional genomic networks to identify common and tissue-specific pathologies of SSc and related conditions. In contrast to skin, in the lung-specific functional network we identify a distinct lung-resident MØ signature associated with lipid stimulation and alternative activation. In keeping with our network results, we find distinct MØ alternative activation transcriptional programs in SSc-associated PF lung and in the skin of patients with an "inflammatory" SSc gene expression signature. Our results suggest that the innate immune

Vitamin D, parathyroid hormone, and acroosteolysis in systemic sclerosis.

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Braun-Moscovici, Yolanda; Furst, Daniel E; Markovits, Doron; Rozin, Alexander; Clements, Philip J; Nahir, Abraham Menahem; Balbir-Gurman, Alexandra

2008-11-01

.Sclerodactyly with acroosteolysis (AO) and calcinosis are prominent features of systemic sclerosis (SSc), but the pathogenesis of these findings is poorly understood. Vitamin D and parathyroid hormone (PTH) have a crucial role in bone metabolism and resorption and may affect AO and calcinosis. We assessed vitamin D and PTH in patients with SSc. Medical records of 134 consecutive patients with SSc (American College of Rheumatology criteria) followed at the rheumatology department during the years 2003-2006 were reviewed for clinical assessment, laboratory evaluation [including 25(OH) vitamin D, calcium, phosphorus, alkaline phosphatase, PTH, creatinine, and albumin]; imaging data confirming AO and/or calcinosis. Patients followed routinely at least once a year were included (81 patients). Of these, 60 patients' medical records were found to have complete, relevant clinical, laboratory, and radiographic imaging. Thirteen patients had diffuse disease and 47 limited disease - 51 women and 9 men, 44 Jews and 16 Arabs; mean age 55 +/- 14 years; disease duration 8 +/- 6 years. AO with or without calcinosis was observed in 42 patients (70%). Vitamin D deficiency was found in 46% of patients (16 out of 44 Jewish patients, 10 out of 16 Arab patients). PTH was elevated in 21.7% of patients. Significant correlations were observed between acroosteolysis and PTH (p = 0.015), calcinosis (p = 0.009), and disease duration (p = 0.008), and between PTH and vitamin D levels (p = 0.01). All patients had normal serum concentrations of calcium, phosphorus, magnesium, and albumin, and liver and kidney functions. In this group of Mediterranean patients with SSc, the incidence of vitamin D deficiency and secondary hyperparathyroidism was surprisingly high. This finding correlated with the occurrence of AO and calcinosis. Low levels of vitamin D may reflect silent malabsorption and might be a risk factor for secondary hyperparathyroidism and bone resorption. Traditional dress habits and low

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

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Bagnato, Gianluca; Roberts, William Neal; Roman, Jesse; Gangemi, Sebastiano

2017-06-30

Lung fibrosis can be observed in systemic sclerosis and in idiopathic pulmonary fibrosis, two disorders where lung involvement carries a poor prognosis. Although much has been learned about the pathogenesis of these conditions, interventions capable of reversing or, at the very least, halting disease progression are not available. Recent studies point to the potential role of micro messenger RNAs (microRNAs) in cancer and tissue fibrogenesis. MicroRNAs are short non-coding RNA sequences (20-23 nucleotides) that are endogenous, evolutionarily conserved and encoded in the genome. By acting on several genes, microRNAs control protein expression. Considering the above, we engaged in a systematic review of the literature in search of overlapping observations implicating microRNAs in the pathogenesis of both idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc). Our objective was to uncover top microRNA candidates for further investigation based on their mechanisms of action and their potential for serving as targets for intervention against lung fibrosis. Our review points to microRNAs of the -29 family, -21-5p and -92a-3p, -26a-5p and let-7d-5p as having distinct and counter-balancing actions related to lung fibrosis. Based on this, we speculate that readjusting the disrupted balance between these microRNAs in lung fibrosis related to SSc and IPF may have therapeutic potential. Copyright ©ERS 2017.

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.

Hand and wrist involvement in systemic sclerosis: US features.

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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.

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

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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.

Radiological pleuroparenchymal fibroelastosis associated to limited cutaneous systemic sclerosis: a case report.

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Hassoun, D; Dirou, S; Arrigoni, P P; Durant, C; Hamidou, M; Néel, A; Agard, C

2018-05-18

Pleuroparenchymal fibroelastosis (PPFE) is a very rare interstitial lung disease (ILD) characterized by progressive fibrotic lesions of the visceral pleura and the sub-pleural parenchyma, affecting predominantly the upper lobes. PPFE may occur in different contextes like bone marrow or lung transplantations, but also in the context of telomeropathy with mutations of telomerase reverse transcriptase (TERT), telomerase RNA component (TERC) or regulator of telomere elongation helicase 1 (RTEL1) genes. PPFE-like lesions have recently been described in patients with connective tissue disease (CTD)-related ILD. We report here the first detailed case of PPFE associated to systemic sclerosis (SSc) in a woman free of telomeropathy mutations. A caucasian 46 year old woman was followed for SSc in a limited form with anti-centromere Ab since 1998, and seen in 2008 for a routine visit. Her SSc was stable, and she had no respiratory signs. Pulmonary function tests showed an isolated decreased cTLCO at 55.9% (of predicted value). Cardiac ultrasonography was normal. Thoracic CT-scan showed upper lobes predominant mild and focal pleural and subpleural thickenings, suggestive of PPFE, with a slight worsening at 8 years of follow-up. She remained clinically stable. Biology only found a moderate and stable peripheral thrombocytopenia, and sequencing analysis did not find any mutations in TERT and TERC genes. ILD is frequent in SSc but isolated PPFE has never been described so far. In our case, PPFE is not related to telomeropathy, has indolent outcome and seems to have good prognosis. PPFE might be an extremely rare form of SSc-related ILD, although a fortuitous association remains possible.

Nailfold capillaroscopy for prediction of novel future severe organ involvement in systemic sclerosis.

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Smith, Vanessa; Riccieri, Valeria; Pizzorni, Carmen; Decuman, Saskia; Deschepper, Ellen; Bonroy, Carolien; Sulli, Alberto; Piette, Yves; De Keyser, Filip; Cutolo, Maurizio

2013-12-01

Assessment of associations of nailfold videocapillaroscopy (NVC) scleroderma (systemic sclerosis; SSc) ("early," "active," and "late") with novel future severe clinical involvement in 2 independent cohorts. Sixty-six consecutive Belgian and 82 Italian patients with SSc underwent NVC at baseline. Images were blindly assessed and classified into normal, early, active, or late NVC pattern. Clinical evaluation was performed for 9 organ systems (general, peripheral vascular, skin, joint, muscle, gastrointestinal tract, lung, heart, and kidney) according to the Medsger disease severity scale (DSS) at baseline and in the future (18-24 months of followup). Severe clinical involvement was defined as category 2 to 4 per organ of the DSS. Logistic regression analysis (continuous NVC predictor variable) was performed. The OR to develop novel future severe organ involvement was stronger according to more severe NVC patterns and similar in both cohorts. In simple logistic regression analysis the OR in the Belgian/Italian cohort was 2.16 (95% CI 1.19-4.47, p = 0.010)/2.33 (95% CI 1.36-4.22, p = 0.002) for the early NVC SSc pattern, 4.68/5.42 for the active pattern, and 10.14/12.63 for the late pattern versus the normal pattern. In multiple logistic regression analysis, adjusting for disease duration, subset, and vasoactive medication, the OR was 2.99 (95% CI 1.31-8.82, p = 0.007)/1.88 (95% CI 1.00-3.71, p = 0.050) for the early NVC SSc pattern, 8.93/3.54 for the active pattern, and 26.69/6.66 for the late pattern versus the normal pattern. Capillaroscopy may be predictive of novel future severe organ involvement in SSc, as attested by 2 independent cohorts.

Brief Report: IRF4 Newly Identified as a Common Susceptibility Locus for Systemic Sclerosis and Rheumatoid Arthritis in a Cross-Disease Meta-Analysis of Genome-Wide Association Studies

NARCIS (Netherlands)

López-Isac, Elena; Martín, Jose Ezequiel; Assassi, Shervin; Simeón, Carmen P.; Carreira, Patricia; Ortego-Centeno, Norberto; Freire, Mayka; Beltrán, Emma; Narváez, Javier; Alegre-Sancho, Juan J.; Fernández-Gutiérrez, Benjamín; Balsa, Alejandro; Ortiz, Ana M.; González-Gay, Miguel A.; Beretta, Lorenzo; Santaniello, Alessandro; Bellocchi, Chiara; Lunardi, Claudio; Moroncini, Gianluca; Gabrielli, Armando; Witte, Torsten; Hunzelmann, Nicolas; Distler, Jörg H W; Riekemasten, Gabriella; van der Helm-van Mil, Annette H.; de Vries-Bouwstra, Jeska; Magro-Checa, Cesar; Voskuyl, Alexandre E.; Vonk, Madelon C.; Molberg, Øyvind; Merriman, Tony; Hesselstrand, Roger; Nordin, Annika; Padyukov, Leonid; Herrick, Ariane; Eyre, Steve; Koeleman, Bobby P C; Denton, Christopher P.; Fonseca, Carmen; Radstake, Timothy R D J; Worthington, Jane; Mayes, Maureen D.; Martín, Javier; Ríos, Raquel; Callejas, Jose Luis; Hitos, José Antonio Vargas; Portales, Rosa García; Camps, María Teresa; Fernández-Nebro, Antonio; González-Escribano, María F.; García-Hernández, Francisco José; Castillo, Ma Jesús; Ángeles Aguirre, Ma; Gómez-Gracia, Inmaculada; Rodríguez-Rodríguez, Luis; Peña, Paloma García de la; Vicente, Esther; Andreu, José Luis; de Castro, Mónica Fernández; López-Longo, Francisco Javier; Martínez, Lina; Fonollosa, Vicente; Guillén, Alfredo; Castellví, Iván; Espinosa, Gerard; Tolosa, Carlos; Pros, Anna; Carballeira, Mónica Rodríguez; Narváez, Francisco Javier; Rivas, Manel Rubio; Ortiz-Santamaría, Vera; Madroñero, Ana Belén; Díaz, Bernardino; Trapiella, Luis; Sousa, Adrián; Egurbide, María Victoria; Mateo, Patricia Fanlo; Sáez-Comet, Luis; Díaz, Federico; Hernández, Vanesa; Beltrán, Emma; Román-Ivorra, José Andrés; Grau, Elena; Alegre-Sancho, Juan José; Blanco García, Francisco J.; Oreiro, Natividad

2016-01-01

Objective: Systemic sclerosis (SSc) and rheumatoid arthritis (RA) are autoimmune diseases that have similar clinical and immunologic characteristics. To date, several shared SSc–RA genetic loci have been identified independently. The aim of the current study was to systematically search for new

Performance of the MAGCOOL-subcooler cryogenic system after SSC quadrupole quenches

International Nuclear Information System (INIS)

Wu, K.C.

1993-01-01

The subcooler assembly installed in the MAGCOOL magnet test area at Brookhaven National Laboratory has been used for testing SSC dipoles, quadrupoles and a spool piece since 1989. A detailed description of the system, its steady state capacity and the performance after quenches of a 50 mm SSC dipole were given. Subsequent studies on low current quenches of the SSC dipoles and quenches of the RHIC dipoles were also carried out. In this paper, the performance of the subcooler after quenches of the SSC quadrupole QCC404 is presented. Pressures, temperatures and flow rates in the magnet cooling loop after magnet quenches are given as a function of time. The cooling rates and total energy removed by cooling during quench recovery have been calculated for quench currents between 2000 and 7952 amperes. Because the inductance of the quadrupole is about one tenth that of a SSC dipole, the stored energy released is small and the impact on the system is mild. The cooling loop pressure never exceeds 12 atmospheres and the cryogenic system recovers in less than 15 minutes. As in all past studies, the peak pressure and temperature in the magnet cooling loop are linearly proportional to the energy released during a quench and excellent agreement between the total cooling provided and the magnetic stored energy is found

Esophageal hypomotility in systemic sclerosis. Close relationship with pulmonary involvement

Energy Technology Data Exchange (ETDEWEB)

Kinuya, Keiko [Tonami General Hospital, Toyama (Japan); Nakajima, Kenichi; Kinuya, Seigo; Michigishi, Takatoshi; Tonami, Norihisa; Takehara, Kazuhiko

2001-04-01

Esophageal motility was assessed in patients with systemic sclerosis (SSc) by scintigraphy and compared with extent of scleroderma, duration of disease, index of anti-topoisomerase I antibody (topo I), and pulmonary involvement. A multiple-swallow test was performed in 47 patients with SSc in the supine position with {sup 99m}Tc-DTPA. A region of interest on the entire esophagus was defined and the retention ratio (RR) was calculated from a time-activity curve. Patients with diffuse scleroderma had higher RRs than those with limited scleroderma (48.8% vs. 30.0%; p<0.05). There was no correlation between the RRs and the duration of disease. Patients with positive topo I had higher RRs than those who were negative (53.8% vs. 29.7%; p<0.05). Patients with reduced % diffusion capacity for carbon monoxide (%DL{sub CO}) had higher RRs than those with normal %DL{sub CO} (40.5% vs. 19.6%; p=0.03). Patients with reduced % vital capacity (%VC) had higher RRs than those with normal %VC (54.6% vs. 25.0%; p<0.005). Patients with pulmonary fibrosis had higher RRs than those who were negative (58.5% vs. 20.3%; p<0.00005). Esophageal dysfunction in patients with SSc showed a correlation with the extent of scleroderma, positive topo I, and pulmonary involvement. The RR can be an objective clinical marker for the severity of organ fibrosis. (author)

Mucocutaneous and demographic features of systemic sclerosis: A profile of 46 patients from Eastern India

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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

Esophageal and anorectal involvement in systemic sclerosis: a systematic assessment with high resolution manometry.

Science.gov (United States)

Luciano, Laure; Granel, Brigitte; Bernit, Emmanuelle; Harle, Jean-Robert; Baumstarck, Karine; Grimaud, Jean-Charles; Bouvier, Michel; Vitton, Véronique

2016-01-01

In systemic sclerosis (SSc), esophageal and anorectal involvements are frequent and often associated with each other. In clinical practice, esophageal explorations are often prescribed, while anorectal explorations are rarely proposed and therefore, under-recognised. However, it is well documented in the literature that early detection of anorectal dysfunction could delay and/or prevent the onset of symptoms such as fecal incontinence (FI). The main objective was the systematic evaluation and detection of esophageal and anorectal involvements in SSc patients. In this monocentric retrospective study, all patients with SSc addressed in the Department of Functional Digestive Explorations, North Hospital, Marseille for esophageal and anorectal explorations were included. Self-Questionnaires, evaluating the symptoms and quality of life, were filled by patients during their visit. Explorations were performed on the same day: high resolution esophageal manometry (EHRM), 3 Dimensional high resolution anorectal manometry (3DHRARM) and endo anal sonography (EUS). 44 patients (41 women), mean age 59.8±12 years, were included. With regard to the symptoms, 45.5% of patients had gastro-esophageal reflux disease (GERD), 66.9% dysphagia, 65.9% constipation and 77.3% FI. The incidence of esophageal dismotility was 65.9%, anorectal and both upper and lower dysfunction were 43.2%. More than 89% patients with abnormal explorations (EHRM, 3DHRARM or both) were symptomatic. Duration of SSc and altered quality of life was correlated with the severity of digestive involvement. Anorectal dysfunction appears to be closely linked to esophageal involvement in SSc. Their routine screening is undoubtedly essential to limit the occurrence of severe symptoms such as FI.

Deterioration of lung function is associated with presence of IgM rheumatoid factor and smoking in patients with systemic sclerosis

DEFF Research Database (Denmark)

Broholm, B.; Ullman, S.; Halberg, P.

2008-01-01

of patients with systemic sclerosis (SSc) the influence of smoking and IgM RF on the lung function was calculated. One hundred fifty-five persons with SSc had vital capacity (VC) and diffusing capacity (DLco) measured at least twice with at least 1-year interval as percents of predicted values according......Smoking is a known risk factor for the development of several lung diseases, autoimmune diseases, and IgM rheumatoid factor (RF) in nonrheumatic persons. In patients with rheumatoid arthritis and IgM RF the diffusion capacity is decreased in smokers but not in nonsmokers. In the present study......M RF was found only in smokers or previous smokers, P = 0.007 and P = 0.01, respectively. These findings were confirmed by means of multiple regression analyses. The presence of IgM RF in smoking SSc patients is associated with deteriorating lung function. Whether this is a causal association...

Early aggressive intra-venous pulse cyclophosphamide therapy for interstitial lung disease in a patient with systemic sclerosis. A case report.

LENUS (Irish Health Repository)

Peshin, R

2009-06-01

Interstitial lung disease is an important cause of mortality and morbidity in patients with systemic sclerosis (SSc). There are currently no recommended guidelines for management of these patients. This is probably due to the rarity of this condition, as well as clinical trials with only a small number of cases. There are published case report and case series along with the two main trials, viz. Scleroderma Lung Study and the Fibrosing Alveolitis Study, but again, there is no consensus on treatment protocols. In this report, we present a case of aggressive interstitial lung disease in a patient with SSc, which improved dramatically on treatment with intra-venous cyclophosphamide and high dose prednisolone therapy.

Nailfold capillaroscopy abnormalities correlate with cutaneous and visceral involvement in systemic sclerosis patients.

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Sato, Lucy T; Kayser, Cristiane; Andrade, Luís E C

2009-01-01

The aim of this study was to correlate quantitative and semiquantitative nailfold capillaroscopy (NFC) parameters with the extent of cutaneous and visceral involvement in systemic sclerosis (SSc) patients. The presence of clinical and serological alterations was evaluated retrospectively and correlated with NFC findings (number of capillary loops/mm, vascular deletion score and number of enlarged and giant capillary loops). For evaluation of disease extension five manifestations were analyzed: finger pad lesions, skin involvement, esophageal involvement, interstitial lung disease, and pulmonary hypertension. There were 105 NFC examinations in 92 patients, 13 of whom were evaluated at two different time points. Patients with diffuse cutaneous SSc had a higher vascular deletion score than patients with limited cutaneous SSc, sine scleroderma SSc, and overlap syndrome (1.67+/-0.91 vs 0.99+/-0.82; p=0.0005). Modified Rodnan's skin score correlated positively with capillary deletion, evaluated by the vascular deletion score and the number of capillary loops/mm (p<0.001 and p=0.012; respectively). Patients with three or more involved tracts presented lower number of capillary loops/mm (8.00+/-1.69 vs 9.23+/-1.31 capillary loops/mm; p=0.025) and a higher vascular deletion score (1.41+/-0.95 vs 0.73+/-0.76; p=0.027) when compared to patients with less than three affected tracts. Vascular deletion score was significantly higher in patients with anti-Scl-70 antibodies that in patients without anti-Scl-70 antibodies (p=0.02). NFC abnormalities correlated positively with the diffuse form of SSc, the degree of cutaneous involvement, the number of affected tracts, and the presence of anti-Scl-70 antibodies.

Malnutrition and sarcopenia in a large cohort of patients with systemic sclerosis.

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Caimmi, C; Caramaschi, P; Venturini, A; Bertoldo, E; Vantaggiato, E; Viapiana, O; Ferrari, M; Lippi, G; Frulloni, L; Rossini, M

2018-04-01

Systemic sclerosis (SSc) is an autoimmune disease which may lead to malnutrition. Previous studies have defined it with different criteria. No thorough evaluations of sarcopenia in SSc are available. The aim of the present study was to assess the prevalence and the potential association of malnutrition and sarcopenia in a large cohort of SSc cases. A total of 141 SSc consecutive outpatients were enrolled. Body composition was analyzed by densitometry. Malnutrition was defined according to recently published ESPEN criteria, whereas sarcopenia was diagnosed in patients with reduced skeletal muscle index. Malnutrition was diagnosed in 9.2% of patients (95% CI, 4.4-14.0%). Malnourished patients had worse gastrointestinal symptoms according to UCLA SCTC GIT 2.0 questionnaire (p = 0.007), lower physical activity (p = 0.028), longer disease duration (p = 0.019), worse predicted DLCO/VA and FVC (p = 0.009, respectively), worse disease severity according to Medsger severity score (p < 0.001), lower hemoglobin (p = 0.023), and fat-free mass (p < 0.001) and were more often sarcopenic (p < 0.001). In multivariate analysis, only FVC (p = 0.006) and disease severity (p = 0.003), in particular for the lungs (p = 0.013), were confirmed to be worse in malnourished patients. Sarcopenia was diagnosed in 29\\140 patients (20.7%; 95% CI, 14.0-27.4%); 11\\29 were also malnourished. In multivariate analysis, sarcopenic patients had longer disease duration (p = 0.049), worse DLCO/VA (p = 0.002), and lung (p = 0.006) and skin (p = 0.014) involvement. In SSc, malnutrition defined with ESPEN criteria was found to be lower than previously reported. Sarcopenia was found to be somewhat common. Lung involvement was significantly associated with nutritional status and may not be explained only by muscle weakness.

Autoantibody to Th ribonucleoprotein (nucleolar 7-2 RNA protein particle) in patients with systemic sclerosis

International Nuclear Information System (INIS)

Okano, Y.; Medsger, T.A. Jr.

1990-01-01

We studied sera of 371 consecutive new patients with systemic sclerosis (SSc; scleroderma) who were first evaluated during 1984-1988. All sera were tested for antinuclear antibodies by immunofluorescence staining using HEp-2 cells as substrate. We excluded 219 sera showing dark nucleoli and screened for antibodies to Th in the remaining 152 sera by immunoprecipitation of a 32P-labeled HeLa cell extract. Fifteen (4.0%) of 371 sera were anti-Th+. Anti-Th antibodies were present in 14 (8.4%) of 167 SSc patients with limited cutaneous involvement, in 1 of 167 with diffuse cutaneous involvement, and in 0 of 37 with SSc overlap syndrome. Among 244 controls with other connective tissue diseases, anti-Th was detected in only 3 patients, all having primary Raynaud's phenomenon of less than 2 years duration. In the subgroup with SSc with limited cutaneous involvement, the 14 anti-Th+ patients had a significantly greater frequency of puffy fingers, small bowel involvement, and hypothyroidism, and a significantly lower frequency of arthralgia and/or arthritis. Their cumulative survival rate from the time of onset of symptoms was lower than that for anti-Th- patients (78% versus 91% at 10 years), primarily due to 3 deaths from pulmonary arterial hypertension (2 from primary pulmonary hypertension and 1 from pulmonary hypertension secondary to pulmonary interstitial fibrosis). Serum anti-Th antibodies are present almost exclusively in patients with SSc with limited cutaneous involvement or in those with primary Raynaud's phenomenon whose disease may evolve to SSc with limited cutaneous involvement, and these antibodies may identify those patients who are at greater risk for reduced survival

The status of pulmonary fibrosis in systemic sclerosis is associated with IRF5, STAT4, IRAK1, and CTGF polymorphisms.

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Zhao, Wenjie; Yue, Xiaoyang; Liu, Kuai; Zheng, Junfeng; Huang, Runda; Zou, Jun; Riemekasten, Gabriela; Petersen, Frank; Yu, Xinhua

2017-08-01

Pulmonary fibrosis (PF) is one of the leading causes of death in systemic sclerosis (SSc) patients. Although all SSc patients are characterized by autoimmunity, only part of them suffer from PF, suggesting that beside autoimmunity, some additional factors are involved in the initiation of PF in SSc. In this study, we aimed to identify genetic polymorphisms associated with the status of PF in SSc. We performed that an exhaustive search of the PubMed database was performed to identify eligible studies. Then, a comprehensive meta-analysis was performed by comparing PF + -SSc and PF - -SSc patients to identify genetic polymorphisms associated with the status of PF in SSc. Among eight SSc-associated susceptibility polymorphisms which were applied for meta-analysis, IRF5 rs2004640 polymorphism (OR 1.12; 95% CI 1.02-1.22, P = 1.39 × 10 -2 ), STAT4 rs7574865 polymorphism (OR 1.25; 95% CI 1.07-1.47, P = 5.3 × 10 -3 ), IRAK1 rs1059702 polymorphism (OR 1.20; 95% CI 1.05-1.37, P = 0.007), and CTGF G-945C polymorphism (OR 1.42; 95% CI 1.18-1.71, P = 0.002) are associated with PF status in SSc, while TNFAIP3 rs5029939, CD226 rs763361, CD247 rs2056626, and IRF5 rs10488631 polymorphisms are not. Since IRF5, STAT4, and IRAK1 are important regulatory factors in the control of innate immune responses and CTGF is involved in the synthesis of extracellular matrix, these results suggest a role of the innate immunity and matrix compounds in the pathogenesis of PF in SSc.

SSC-K code user's manual

Energy Technology Data Exchange (ETDEWEB)

Kwon, Y M; Lee, Y B; Chang, W P; Hahn, D

2000-07-01

The Supper System Code of KAERI (SSC-K) is a best-estimate system code for analyzing a variety of off-normal or accidents in the heat transport system of a pool type LMR design. It is being developed at Korea Atomic Energy Research Inititution (KAERI) on the basis of SSC-L, originally developed at BNL to analyze loop-type LMR transients. SSC-K can handle both designs of loop and pool type LMRs. SSC-K contains detailed mechanistic models of transient thermal, hydraulic, neutronic, and mechanical phenomena to describe the response of the reactor core, coolant, fuel elements, and structures to accident conditions. This report provides an overview of recent model developmentsvfor the SSC-K computer code, focusing on phenomenological model descriptions for new thermal, hydraulic, neutronic, and mechnaical modules. A comprehensive description of the models for pool-type reactor is given in Chapters 2 and 3; the steady-state plant characterization, prior to the initiation of transient is described in Chapter 2 and their transient counterparts are discussed in Chapter 3. In Chapter 4, a discussion on the intermediate heat exchanger (IHX) is presented. The IHX model of SSC-K is similar to that used in the SSC-L, except for some changes required for the pool-type configuration of reactor vessel. In Chapter 5, an electromagnetic (EM) pump is modeled as a component. There are two pump choices available in SSC-K; a centrifugal pump which was originally imbedded into the SSC-L, and an EM pump which was introduced for the KALIMER design. In Chapter 6, a model of passive safety decay heat removal system(PSDRS) is discussed, which removes decay heat through the reactor and containment vessel walls to the ambient air heat sink. In Chapter 7, models for various reactivity feedback effects are discussed. Reactivity effects of importance in fast reactor include the Doppler effect, effects of sodium density changes, effects of dimensional changes in core geometry. Finally in Chapter 8

Clinical algorithms for the diagnosis and prognosis of interstitial lung disease in systemic sclerosis.

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Hax, Vanessa; Bredemeier, Markus; Didonet Moro, Ana Laura; Pavan, Thaís Rohde; Vieira, Marcelo Vasconcellos; Pitrez, Eduardo Hennemann; da Silva Chakr, Rafael Mendonça; Xavier, Ricardo Machado

2017-10-01

Interstitial lung disease (ILD) is currently the primary cause of death in systemic sclerosis (SSc). Thoracic high-resolution computed tomography (HRCT) is considered the gold standard for diagnosis. Recent studies have proposed several clinical algorithms to predict the diagnosis and prognosis of SSc-ILD. To test the clinical algorithms to predict the presence and prognosis of SSc-ILD and to evaluate the association of extent of ILD with mortality in a cohort of SSc patients. Retrospective cohort study, including 177 SSc patients assessed by clinical evaluation, laboratory tests, pulmonary function tests, and HRCT. Three clinical algorithms, combining lung auscultation, chest radiography, and percentage predicted forced vital capacity (FVC), were applied for the diagnosis of different extents of ILD on HRCT. Univariate and multivariate Cox proportional models were used to analyze the association of algorithms and the extent of ILD on HRCT with the risk of death using hazard ratios (HR). The prevalence of ILD on HRCT was 57.1% and 79 patients died (44.6%) in a median follow-up of 11.1 years. For identification of ILD with extent ≥10% and ≥20% on HRCT, all algorithms presented a high sensitivity (>89%) and a very low negative likelihood ratio (algorithms, especially the algorithm C (HR = 3.47, 95% CI: 1.62-7.42), which identified the presence of ILD based on crackles on lung auscultation, findings on chest X-ray, or FVC 20% on HRCT or, in indeterminate cases, FVC algorithms had a good diagnostic performance for extents of SSc-ILD on HRCT with clinical and prognostic relevance (≥10% and ≥20%), and were also strongly related to mortality. Non-HRCT-based algorithms could be useful when HRCT is not available. This is the first study to replicate the prognostic algorithm proposed by Goh et al. in a developing country. Copyright © 2017 Elsevier Inc. All rights reserved.

Esophageal symptoms and their lack of association with high-resolution manometry in systemic sclerosis patients.

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Arana-Guajardo, Ana Cecilia; Barrera-Torres, Gustavo; Villarreal-Alarcón, Miguel Ángel; Vega-Morales, David; Esquivel-Valerio, Jorge Antonio

2017-12-16

The esophageal involvement in systemic sclerosis (SSc) causes impact in the morbidity and mortality. High resolution manometry assesses esophageal involvement. Our aim was to categorize esophageal motor disorder in patients with SSc by HRM. We carried out an observational, descriptive and cross-sectional study. All patients underwent HRM as well as semi-structured interviews to assess frequency and severity of upper GI symptoms. Patients also completed the gastroesophageal reflux questionnaire (Carlsson-Dent). We included 19 patients with SSc, 1 with morphea, and 1 with scleroderma sine scleroderma. Dysphagia and heartburn were the most frequent symptoms (61% each). We found an abnormal HRM in 15 (71.4%) patients. We found no statistically significant association between clinical or demographic variables and an abnormal HRM, or between any upper GI symptom and HRM findings. We observed a high prevalence of esophageal symptoms and of HRM abnormalities. However, there was no clear association between symptomatology and HRM findings. HRM does not seem to accurately predict upper GI symptomatology. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Rituximab for the therapy of systemic sclerosis: a series of 10 cases in a single center.

Science.gov (United States)

Vilela, Verônica Silva; Maretti, Giselle Baptista; Gama, Lívia Marques da Silva; Costa, Claudia Henrique da; Rufino, Rogério Lopes; Levy, Roger A

Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Although cyclophosphamide is effective for severe and refractory cases, there is demand for new treatments. The biological treatment with B-cell depletion with rituximab (RTX) has demonstrated efficacy for this demand in open-label studies. This study was conducted with the aim to retrospectively evaluate all patients who used RTX for the treatment of SSc in our center. We retrospectively evaluated medical records of all patients with SSc who used RTX to treat this disease from January 2009 to January 2015. Systemic, cutaneous, and pulmonary involvement data and laboratory results before and six months after the first infusion of RTX were collected. Ten patients received treatment during the study period and were included in this series. All patients had a diffuse form of the disease. Five patients suffered from an early (duration of disease shorter or equal to four years), rapidly progressive disease, and another five received RTX at late stages of the disease. In both groups of patients, stabilization of the pulmonary picture was observed, with a fall in the skin score in those patients with early forms of the disease. Similar to findings in previous studies, RTX was effective in treating early and rapidly progressive forms of SSc. We also found that patients with long-term illness may benefit from the treatment. Copyright © 2016. Published by Elsevier Editora Ltda.

Orbit correction system for the SSC interaction regions

International Nuclear Information System (INIS)

Nosochkov, Y.; Pilat, F.; Ritson, D.M.

1994-01-01

In this paper we review our design of the orbit correction system for the SSC interaction regions, and discuss the principles of the local orbit correction at the IP. copyright 1994 American Institute of Physics

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

Reassessing the Role of the Active TGF-β1 as a Biomarker in Systemic Sclerosis: Association of Serum Levels with Clinical Manifestations

Directory of Open Access Journals (Sweden)

Andréa Tavares Dantas

2016-01-01

Full Text Available Objective. To determine active TGF-β1 (aTGF-β1 levels in serum, skin, and peripheral blood mononuclear cell (PBMC culture supernatants and to understand their associations with clinical parameters in systemic sclerosis (SSc patients. Methods. We evaluated serum samples from 56 SSc patients and 24 healthy controls (HC. In 20 SSc patients, we quantified spontaneous or anti-CD3/CD28 stimulated production of aTGF-β1 by PBMC. The aTGF-β1 levels were measured by ELISA. Skin biopsies were obtained from 13 SSc patients and six HC, and TGFB1 expression was analyzed by RT-PCR. Results. TGF-β1 serum levels were significantly higher in SSc patients than in HC (p < 0.0001. Patients with increased TGF-β1 serum levels were more likely to have diffuse subset (p = 0.02, digital ulcers (p = 0.02, lung fibrosis (p < 0.0001, positive antitopoisomerase I (p = 0.03, and higher modified Rodnan score (p = 0.046. Most of our culture supernatant samples had undetectable levels of TGF-β1. No significant difference in TGFB1 expression was observed in the SSc skin compared with HC skin. Conclusion. Raised active TGF-β1 serum levels and their association with clinical manifestations in scleroderma patients suggest that this cytokine could be a marker of fibrotic and vascular involvement in SSc.

Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy.

Directory of Open Access Journals (Sweden)

Olga Gorlova

2011-07-01

Full Text Available The aim of this study was to determine, through a genome-wide association study (GWAS, the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc. We considered limited (lcSSc and diffuse (dcSSc cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA, and anti-topoisomerase I (ATA. Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32×10(-12, OR = 0.75. Also, rs12540874 in GRB10 gene (P = 1.27 × 10(-6, OR = 1.15 and rs11047102 in SOX5 gene (P = 1.39×10(-7, OR = 1.36 showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79×10(-61, OR = 2.48, in the HLA-DPA1/B1 loci with ATA (P = 4.57×10(-76, OR = 8.84, and in NOTCH4 with ACA P = 8.84×10(-21, OR = 0.55 and ATA (P = 1.14×10(-8, OR = 0.54. We have identified three new non-HLA genes (IRF8, GRB10, and SOX5 associated with SSc clinical and auto-antibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.

Procollagen Type I and III Aminoterminal Propeptide Levels and Severity of Interstitial Lung Disease in Mexican Women With Progressive Systemic Sclerosis.

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Gonzalez-Lopez, Laura; Rocha-Muñoz, Alberto D; Olivas-Flores, Eva M; Garcia-Gonzalez, Araceli; Peguero-Gómez, Ana R; Flores-Navarro, Juan; Villa-Manzano, Alberto I; Zavaleta-Muñiz, Soraya A; Salazar-Paramo, Mario; Mejía, Mayra; Juárez-Contreras, Pablo; Vazquez-Del Mercado, Monica; Cardona-Muñoz, Ernesto G; Trujillo-Hernández, Benjamin; Nava-Zavala, Arnulfo H; Gamez-Nava, Jorge I

2015-09-01

Interstitial lung disease (ILD) is a frequent complication in progressive systemic sclerosis (SSc), being present in 25% to 90% of cases. To evaluate whether serum levels of procollagen typei and iii aminoterminal propeptide (PINP and PIIINP) correlate with severity and patterns of ILD in Mexican women with SSc. Thirty three SSc patients were assessed for disease characteristics and anti-topoisomerase antibodies (topoi), and also underwent pulmonary function tests and high-resolution computed tomography (HRCT). Nineteen patients had ILD+SSc, and 14 had no lung involvement (no ILD-SSc); data were compared with those from 45 healthy controls. PINP and PIIINP were assessed in all 3 groups. Patients with SSc had higher PINP and PIIINP vs controls (P=.001, P<.001, respectively). Compared to no ILD-SSc patients, those with ILD+SSc had longer disease duration in years (P=.005), higher modified Rodnan skin score (P<.001), higher Health Assessment Questionnaire-Disability-Index scores (P<.001), higher topoi U/mL (P<.001), PINP (49.28±28.63 vs. 32.12±18.58μg/L, P=.05), and PIIINP (4.33±1.03 vs. 2.67±1.26μg/L, P<.001) levels. ILD severity based on total HRCT correlated with PINP (r=.388, P=.03) and PIIINP (P=.594, P<.001). On adjusted analysis, ILD severity was associated with disease duration (P=.037), PIIINP (P=.038), and topoi (P=.045). PINP and PIIINP are useful markers for severe ILD+SSc, suggesting they could play a role in the follow-up of this complication in SSc. Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.

Assessment of T Regulatory Cells and Expanded Profiling of Autoantibodies May Offer Novel Biomarkers for the Clinical Management of Systemic Sclerosis and Undifferentiated Connective Tissue Disease

Directory of Open Access Journals (Sweden)

Paola Cordiali-Fei

2013-01-01

Full Text Available In order to identify disease biomarkers for the clinical and therapeutic management of autoimmune diseases such as systemic sclerosis (SSc and undifferentiated connective tissue disease (UCTD, we have explored the setting of peripheral T regulatory (T reg cells and assessed an expanded profile of autoantibodies in patients with SSc, including either limited (lcSSc or diffuse (dcSSc disease, and in patients presenting with clinical signs and symptoms of UCTD. A large panel of serum antibodies directed towards nuclear, nucleolar, and cytoplasmic antigens, including well-recognized molecules as well as less frequently tested antigens, was assessed in order to determine whether different antibody profiles might be associated with distinct clinical settings. Beside the well-recognized association between lcSSc and anti-centromeric or dcSSC and anti-topoisomerase-I antibodies, we found a significative association between dcSSc and anti-SRP or anti-PL-7/12 antibodies. In addition, two distinct groups emerged on the basis of anti-RNP or anti-PM-Scl 75/100 antibody production among UCTD patients. The levels of T reg cells were significantly lower in patients with SSc as compared to patients with UCTD or to healthy controls; in patients with lcSSc, T reg cells were inversely correlated to disease duration, suggesting that their levels may represent a marker of disease progression.

[The influence of STAT4 rs7574865 (G/T) polymorphism on the risk of clinical and immunological phenotypes of systemic sclerosis in a Russian patient population: Results of a pilot study].

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Krylov, M Yu; Ananyeva, L P; Koneva, О А; Starovoytova, M N; Desinova, O V; Ovsyannikova, O B; Aleksandrova, E N; Novikov, A A; Guseva, I A; Konovalova, N V; Varlamov, D A

To examine the association of signal transducer and activator transcription 4 (STAT4) rs7574865 G/T polymorphism with a predisposition to systemic sclerosis (SSC) and associated clinical and autoimmune phenotypes in a Russian population. A total of 102 patients with SSC and 103 healthy individuals as controls were examined. STAT4 rs7574865 polymorphism was investigated by real-time polymerase chain reaction. The carriers of the T allele showed a statistically significant association with SSC, a diffuse form (DF), the presence of interstitial lung disease (ILD), cardiac injury (CI), and seropositivity for anti-topoisomerase I antibodies (ATA). The findings results confirm the important role of STAT4 gene in the predisposition to SSC and its phenotypes, such as DF, ILD, CI, and ATA in the Russian population.

Assessment of nailfold capillaroscopy in systemic sclerosis by different optical magnification methods.

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Mazzotti, N G; Bredemeier, M; Brenol, C V; Xavier, R M; Cestari, T F

2014-03-01

Systemic sclerosis (SSc) is characterized by target-organ fibrosis and microvascular dysfunction, which can be assessed using nailfold capillaroscopy. Dermoscopy is a useful and easily performed method for diagnosing skin lesions. To compare conventional capillaroscopy, using the gold-standard method (conventional stereomicroscope nailfold capillaroscopy; SNFC), with polarized light noncontact dermoscopy (PNCD) and nonpolarized light contact dermoscopy (NPCD), and to evaluate their accuracy in diagnosing characteristic SSc-related alterations. The study enrolled 45 patients with SSc. Capillaroscopy images and photographs were taken with three devices, SNFC, NPCD and PNCD, and these images were randomly analysed by a blinded observer. The scleroderma pattern was found in 83% of patients. PNCD and NPCD were highly sensitive in identifying the presence of focal capillary loss (96.4% and 100%, respectively), haemorrhage (96.2% and 92%, respectively), and scleroderma (91.9%, 94.6%), and showed high specificity for haemorrhage and enlarged loops. The intra-observer kappa values for detection of the scleroderma pattern by SNFC images, NPCD and PNCD were moderate to good: (κ = 0.71 (95% CI 0.44-0.95), κ = 0.60 (95% CI 0.35-0.83) and κ = 0.60 (95% CI 0.32-0.86), respectively. Evaluation of haemorrhage presence gave high kappa values for all methods: κ = 0.77 (95% CI 0.57-0.95), κ = 0.90 (95% CI 0.76-1.00) and κ = 0.95 (95% CI 0.85-1.00), respectively. Both polarized and nonpolarized dermoscopy are reliable methods for valuation of nailfold capillaroscopy in patients with SSc. They are easy to perform, with good rates of accuracy and results that are comparable with traditional capillaroscopy. © 2013 British Association of Dermatologists.

The role of nailfold capillaroscopy in the assessment of internal organ involvement in systemic sclerosis: A critical review.

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Soulaidopoulos, Stergios; Triantafyllidou, Eva; Garyfallos, Alexandros; Kitas, George D; Dimitroulas, Theodoros

2017-08-01

Endothelial dysfunction and microvascular damage constitute the hallmarks of systemic sclerosis (SSc), explaining much of the pathophysiology and clinical manifestations of the disease. Nailfold videocapillaroscopy (NVC) is an established method for the assessment of the microvasculature, aiding in distinguishing different types of structural vascular abnormalities. Until recently, NVC was used in the diagnosis of SSc as well as in the assessment and follow-up of peripheral digital vasculopathy. On the top of digital ulcers, internal organ involvement such as myocardial dysfunction, pulmonary vascular and/or parenchymal lung disease characterizes severe SSc imparting a high risk of mortality. There is growing evidence suggesting that the extent of peripheral microvascular changes reflects the severity of the disease, especially in terms of life-threatening cardiopulmonary complications. The possible use of nailfold videocapillaroscopy as a useful, non-invasive modality to improve the ability to identify patients at higher risk for these devastating complications of the disease remains to be established. The aim of this review is to critically summarize and discuss current literature regarding the relationship between morphological alterations of nailfold dermal papillary vessels and several manifestations of SSc, focusing on visceral organ involvement, as well as their association with surrogate markers of macrovascular disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Supernatants from culture of type I collagen-stimulated PBMC from patients with cutaneous systemic sclerosis versus localized scleroderma demonstrate suppression of MMP-1 by fibroblasts.

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Brown, Monica; Postlethwaite, Arnold E; Myers, Linda K; Hasty, Karen A

2012-06-01

Systemic sclerosis (SSc) is a chronic fibrosing disease characterized by vasculopathy, autoimmunity, and an accumulation of collagen in tissues. Numerous studies have shown that compared to healthy or diseased controls, the peripheral blood mononuclear cells (PBMC) from patients with SSc produce a variety of cytokines or proliferate when cultured with solubilized type I collagen (CI) or constituent α1(II) and α2(I) polypeptide chains. The purpose of this study was to determine whether PBMC isolated from patients with SSc and cultured in vitro with soluble CI elaborated soluble mediators that inhibit the production of collagenase (i.e., matrix metalloproteinase, MMP-1) by fibroblasts. Supernatants of CI-stimulated PBMC from juvenile and adult diffuse cutaneous (dc)SSc patients significantly reduced MMP-1 production by SSc dermal fibroblasts, while supernatants of CI-stimulated PBMC from patients with localized scleroderma (LS) did not. CI-stimulated PBMC culture supernatants from patients with dcSSc in contrast to patients with LS exhibited increased levels of platelet-derived growth factor (PDGF)-AA, PDGF-BB, TNF-α, IL-13, and EGF. Prolonged culture of SSc dermal fibroblasts with recombinant PDGF-BB or IL-13 inhibited the induction of MMP-1 in response to subsequent TNF-α stimulation. These data suggest that therapies aimed at reducing these cytokines may decrease collagen accumulation in SSc, preventing the development of chronic fibrosis.

Digital ulcers and cutaneous subsets of systemic sclerosis: Clinical, immunological, nailfold capillaroscopy, and survival differences in the Spanish RESCLE Registry.

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Tolosa-Vilella, Carles; Morera-Morales, Maria Lluisa; Simeón-Aznar, Carmen Pilar; Marí-Alfonso, Begoña; Colunga-Arguelles, Dolores; Callejas Rubio, José Luis; Rubio-Rivas, Manuel; Freire-Dapena, Maika; Guillén-Del Castillo, Alfredo; Iniesta-Arandia, Nerea; Castillo-Palma, Maria Jesús; Egurbide-Arberas, Marivi; Trapiellla-Martínez, Luis; Vargas-Hitos, José A; Todolí-Parra, José Antonio; Rodriguez-Carballeira, Mónica; Marin-Ballvé, Adela; Pla-Salas, Xavier; Rios-Blanco, Juan José; Fonollosa-Pla, Vicent

2016-10-01

Digital ulcers (DU) are the most common vascular complication of systemic sclerosis (SSc). We compared the characteristics between patients with prior or current DU with those never affected and evaluated whether a history of DU may be a predictor of vascular, organ involvement, and/or death in patients with SSc. Data from SSc patients with or without prior or current DU were collected by 19 referral centers in an ongoing registry of Spanish SSc patients, named Registro de ESCLErodermia (RESCLE). Demographics, organ involvement, autoimmunity features, nailfold capillary pattern, survival time, and causes of death were analyzed to identify DU related characteristics and survival of the entire series and according to the following cutaneous subsets-diffuse cutaneous SSc (dcSSc), limited cutaneous SSc (lcSSc), and SSc sine scleroderma (ssSSc). Out of 1326, 552 patients enrolled in the RESCLE registry had prior or current DU, 88% were women, the mean age was 50 ± 16 years, and the mean disease duration from first SSc symptom was 7.6 ± 9.6 years. Many significant differences were observed in the univariate analysis between patients with and without prior/current DU. Multivariate analysis identified that history of prior/current DU in patients with SSc was independently associated to younger age at SSc diagnosis, diffuse cutaneous SSc, peripheral vascular manifestations such Raynaud's phenomenon, telangiectasia, and acro-osteolysis but no other vascular features such as pulmonary arterial hypertension or scleroderma renal crisis. DU was also associated to calcinosis cutis, interstitial lung disease, as well as worse survival. Multivariate analysis performed in the cutaneous subsets showed that prior/current DU were independently associated: (1) in dcSSc, to younger age at SSc diagnosis, presence of telangiectasia and calcinosis and rarely a non-SSc pattern on nailfold capillaroscopy; (2) in lcSSc, to younger age at SSc diagnosis, presence of Raynaud's phenomenon as

Electrical performance characteristics of the SSC Accelerator System String Test

International Nuclear Information System (INIS)

Robinson, W.; Burgett, W.; Dombeck, T.; Gannon, J.; Kraushaar, P.; McInturff, A.; Savord, T.; Tool, G.

1993-01-01

The string test facility was constructed to provide a development test bed for the arc regions of the Superconducting Super Collider (SSC). Significant effort has been devoted to the development and testing of superconducting magnets, spools, and accelerator control systems required for the SSC. The string test facility provides the necessary environment required to evaluate the operational performance of these components as they are configured as an accelerator lens in the collider. This discussion will review the results of high current testing of the string conducted to evaluate magnet element uniformity and compatibility, the splice resistance used to connect the magnets, and system response to various quench conditions. Performance results of the spools, energy bypass systems, energy dump, and the power supply system are also discussed

Electrical performance characteristics of the SSC Accelerator System String Test

International Nuclear Information System (INIS)

Robinson, W.; Burgett, W.; Dombeck, T.; Gannon, J.; Kraushaar, P.; McInturff, A.; Savord, T.; Tool, G.

1993-05-01

The string test facility was constructed to provide a development test bed for the arc regions of the Superconducting Super Collider (SSC). Significant effort has been devoted to the development and testing of superconducting magnets, spools, and accelerator control systems required for the SSC. The string test facility provides the necessary environment required to evaluate the operational performance of these components as they are configured as an accelerator lens in the collider. This discussion will review the results of high current testing of the string conducted to evaluate magnet element uniformity and compatibility, the splice resistance used to connect the magnets, and system response to various quench conditions. Performance results of the spools, energy bypass systems, energy dump, and the power supply system are also discussed

Psychological characteristics of systemic sclerosis patients and their correlation with major organ involvement and disease activity.

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Golemati, Christina V; Moutsopoulos, Haralampos M; Vlachoyiannopoulos, Panayiotis G

2013-01-01

The aim of this paper is to assess the psychological characteristics of personality, depression, anxiety, social support and coping strategies of systemic sclerosis (SSc) patients, their inter-correlations and their association with clinical symptoms. Patients with SSc (n=85) were interviewed and compared to rheumatoid arthritis (RA) patients (n=120) and healthy controls (HCs [n=125]). Psychological characteristics were assessed by the following psychometric scales: centre of epidemiological studies of depression (CES-D), hospital anxiety and depression scale (HAD), Eysenck personality questionnaire (EPQ), short form of social support (SSq), life experiences survey (LES) and ways of coping (WoC). Clinical data were collected at the same time of the interview. Both control groups were matched to SSc patients in terms of gender, age and educational status. Data were analysed with SPSS software. Compared to control groups, SSc patients expressed more symptoms of depression and anxiety, showed less extraversion and reported more negative life events. They coped less often with positive reappraisal, problem solving, seeking of support and assertiveness, while they sought more often divine help, and they expressed wishing and denial. Inactive disease was associated with a lower probability of reporting depressive symptoms and negative life events and with a higher probability of positively reevaluating a problem. Lung dysfunction, skin involvement, esophageal problems and oral aperture correlated with psychological features. Complications in psychological well-being characterise patients with SSc. This finding, as well as that of psychological characteristics correlating with organic factors, is an indication for designing supportive psycho-educational programmes as complementary therapies.

Regulatory T cells (CD4(+)CD25(bright)FoxP3(+)) expansion in systemic sclerosis correlates with disease activity and severity.

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Slobodin, Gleb; Ahmad, Mohammad Sheikh; Rosner, Itzhak; Peri, Regina; Rozenbaum, Michael; Kessel, Aharon; Toubi, Elias; Odeh, Majed

2010-01-01

The role and function of T regulatory (Treg) cells have not been fully investigated in patients with systemic sclerosis (SSc). Ten patients with SSc donated 20ml of peripheral blood. Activity (Valentini) and severity (Medsger) scores for SSc were calculated for all patients. Healthy volunteers (controls) were matched to each patient by gender and age. CD4(+) cells were separated using the MACS system. The numbers of Treg cells were estimated by flow cytometry after staining for CD4, CD25, and FoxP3 and calculated as patient-to-control ratio separately for each experiment. Correlations with activity and severity indices of the disease were performed. Twenty-four-hour production of TGF-beta and IL-10 by activated CD4(+) cells was measured by ELISA in culture supernatants. The numbers of Treg cells, expressed as patient-to-control ratio, correlated significantly with both activity and severity indices (r=0.71, p=0.034 and r=0.67, p=0.044, respectively). ELISA-measured production of TGF-beta and IL-10 by CD4(+) cells was similar in patients and controls. Increased numbers of Treg cells are present in patients with SSc, correlating with activity and severity of the disease. This expansion of Treg cells was not accompanied, however, by heightened TGF-beta or IL-10 production. Further studies to elaborate the causes and functional significance of Treg cell expansion in SSc are needed. 2010 Elsevier Inc. All rights reserved.

Practical suggestions on intravenous iloprost in Raynaud's phenomenon and digital ulcer secondary to systemic sclerosis: Systematic literature review and expert consensus.

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Ingegnoli, Francesca; Schioppo, Tommaso; Allanore, Yannick; Caporali, Roberto; Colaci, Michele; Distler, Oliver; Furst, Daniel E; Hunzelmann, Nicolas; Iannone, Florenzo; Khanna, Dinesh; Matucci-Cerinic, Marco

2018-04-04

Systemic sclerosis (SSc) is an autoimmune chronic disease characterized by vascular impairment, immune dysfunction and collagen deposition. Raynaud's phenomenon (RP) and digital ulcers (DU) are prominent features of SSc. Intravenous (IV) iloprost (ILO), according to the recently updated EULAR recommendations, is indicated for RP after failure of oral therapy. Moreover, IV ILO could be useful in DU healing. IV ILO is currently available mainly on the European market approved for RP secondary to SSc with 3-5 days infusion cycle. Unfortunately, data published varies regarding regimen (dosage, duration and frequency). Up to now, ILO has been studied in small cohorts of patients and in few randomized controlled trials. A systematic review of studies on IV ILO in patients with SSc complicated by DU and RP was performed. Insufficient data were available to perform a meta-analysis according to the GRADE system. We performed a three-stage internet-based Delphi consensus exercise. Three major indications were identified for IV ILO usage in SSc: RP non-responsive to oral therapy, DU healing, and DU prevention. IV ILO should be administered between 0.5 and 2.0ng/kg/min according to patient tolerability with a frequency depending on the indication. Although these suggestions are supported by this expert group to be used in clinical setting, it will be necessary to formally validate the present suggestions in future clinical trials. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

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

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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

Predictive value of isolated DLCO reduction in systemic sclerosis patients without cardio-pulmonary involvement at baseline

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M. Colaci

2016-05-01

Full Text Available Impaired diffusing capacity of the lung for carbon monoxide (DLCO was frequently observed in systemic sclerosis (SSc patients, generally related to the presence of interstitial lung disease (ILD and/or pulmonary arterial hypertension (PAH. However, in clinical practice abnormally low DLCO values may be found also in the absence of these SSc complications. The objective was to investigate the prospective clinical relevance of isolated DLCO reduction at baseline in SSc patients. Ninety-seven SSc female patients (age at the diagnosis: 51.3±14.5 years; disease duration: 10.4±6.6 years; limited/diffuse skin subsets: 92/5, without any clinical, radiological (high resolution computed tomography, and echocardiographic manifestations of ILD or PAH at baseline, nor other lung or heart diseases able to affect DLCO, were recruited at our Rheumatology Centre. Patients with DLCO <55% (15 patients; group A were compared with those with normal DLCO (82 patients; group B, at baseline and at the end of follow-up. At baseline, patients of group A showed significantly higher percentage of anticentromere autoantibodies compared to group B (13/15, 86.6% vs 48/82, 58.5%; p=0.044. More interestingly, at the end of long-lasting clinical follow-up (11.6±6.7 years, pre-capillary PAH (right heart catheterization solely developed in some patients of group A (3/15, 20% vs 0/82; p=0.003. In SSc patients, the presence at baseline of isolated, marked DLCO reduction (<55% of predicted and serum anticentromere autoantibodies might characterize a peculiar SSc subset that may precede the development of PAH. Therefore, careful clinical follow-up of patients with isolated moderate-severe DLCO reduction should be mandatory.

Design and analysis of the SSC [Superconducting Super Collider] dipole magnet suspension system

International Nuclear Information System (INIS)

Nicol, T.H.; Niemann, R.C.; Gonczy, J.D.

1989-03-01

The design of the suspension system for Superconducting Super Collider (SSC) dipole magnets has been driven by rigorous thermal and structural requirements. The current system, designed to meet those requirements, represents a significant departure from previous superconducting magnet suspension system designs. This paper will present a summary of the design and analysis of the vertical and lateral suspension as well as the axial anchor system employed in SSC dipole magnets. 5 refs., 9 figs., 4 tabs

Recovery from severe dysphagia in systemic sclerosis - myositis overlap: a case report.

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Chinniah, Keith J; Mody, Girish M

2017-06-01

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. A 56-year old African Black woman initially presented with systemic sclerosis (SSC) - myositis overlap and interstitial lung disease. She responded to high dose corticosteroids and cyclophosphamide followed by azathioprine, with improvement in her lung function and regression of the skin changes. Six years later she had a myositis flare with severe dysphagia. Her myositis improved after high doses of corticosteroids, azathioprine and two doses of intravenous immunoglobulin (IVIG). As her dysphagia persisted, she was fed via a percutaneous endoscopic gastrostomy (PEG) tube and given a course of rituximab. Her dysphagia gradually resolved and the PEG tube was removed within two months. She received another dose of rituximab six months later and continued low dose prednisone and azathioprine. Her muscle power improved, weight returned to normal and she remained well 20 months after hospital discharge. Our patient with SSC-myositis overlap and severe dysphagia requiring PEG feeding, improved with high dose corticosteroids, azathioprine, two courses of IVIG and rituximab, and remained in remission 20 months after hospital discharge.

Tolerability, safety and efficacy of Iloprost infusion without peristaltic pump in systemic sclerosis

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S. Tosi

2011-09-01

Full Text Available Objective. To evaluate safety, tolerability and efficacy on Raynaud’s phenomenon (Rp of iloprost infusion without peristaltic pump in patients with systemic sclerosis (SSc. Patients and methods. The inclusion criteria were diagnosis of SSc, age between 18 and 65 years, presence of Rp, and absence of any controindication to the use of iloprost. The treatment was carried out in a day hospital setting and consisted first of 5 consecutive days of iloprost infusion (from an initial dose of 1.0 ng/Kg/min up to 2 ng/kg/min, and then of 2 days of infusions at the maximum possible dose every 45 days for one year. All of the adverse events were carefully recorded and the changes in the Rp were measured by a 5 grade scale (worsened, unmodified, slightly improved, very improved, disappeared. Results. Thirty-eight SSc patients (all females, mean age 49 years (range 18.5-65, disease duration 1.5 years (range 0.5-10.8 were enrolled in the study. During the first cycle of therapy, 14 avderse events occurred in 11 (28.9% patients and during the next cycles, 3 adverse events were seen in 3 (7.9% patients. In all of the cases they were mild and transient. Rp was considered very improved in 15 (39.5% patients, slightly improved in 13 (34.2%, unmodified in 8 (21% and worse in 2 (5.2%. Discussion. In this study intravenous iloprost without peristaltic pump proved to be safe, well tolerated, and as effective as traditional infusion through peristaltic pump in improving Rp in patients with SSc.

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.

Combined measurement of carbon monoxide and nitric oxide lung transfer does not improve the identification of pulmonary hypertension in systemic sclerosis.

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Degano, Bruno; Soumagne, Thibaud; Delaye, Thomas; Berger, Patrick; Perez, Thierry; Guillien, Alicia; Pellegrin, Jean-Luc; Launay, David; Magy-Bertrand, Nadine; Agard, Christian; Tiev, Kiet Phong; Hua-Huy, Thông; Tardiff, Catherine; Diaz, Véronique; Chambellan, Arnaud; Dinh-Xuan, Anh Tuan

2017-10-01

Screening is important to determine whether patients with systemic sclerosis (SSc) have pulmonary hypertension because earlier pulmonary hypertension treatment can improve survival in these patients. Although decreased transfer factor of the lung for carbon monoxide ( T LCO ) is currently considered the best pulmonary function test for screening for pulmonary hypertension in SSc, small series have suggested that partitioning T LCO into membrane conductance (diffusing capacity) for carbon monoxide ( D MCO ) and alveolar capillary blood volume ( V C ) through combined measurement of T LCO and transfer factor of the lung for nitric oxide ( T LNO ) is more effective to identify pulmonary hypertension in SSc patients compared with T LCO alone. Here, the objective was to determine whether combined T LCO - T LNO partitioned with recently refined equations could more accurately detect pulmonary hypertension than T LCO alone in SSc.For that purpose, 572 unselected consecutive SSc patients were retrospectively recruited in seven French centres.Pulmonary hypertension was diagnosed with right heart catheterisation in 58 patients. T LCO , T LNO and V C were all lower in SSc patients with pulmonary hypertension than in SSc patients without pulmonary hypertension. The area under the receiver operating characteristic curve for the presence of pulmonary hypertension was equivalent for T LCO (0.82, 95% CI 0.79-0.85) and T LNO (0.80, 95% CI 0.76-0.83), but lower for V C (0.75, 95% CI 0.71-0.78) and D MCO (0.66, 95% CI 0.62-0.70).Compared with T LCO alone, combined T LCO - T LNO does not add capability to detect pulmonary hypertension in unselected SSc patients. Copyright ©ERS 2017.

STAT4 is a genetic risk factor for systemic sclerosis having additive effects with IRF5 on disease susceptibility and related pulmonary fibrosis.

Science.gov (United States)

Dieudé, P; Guedj, M; Wipff, J; Ruiz, B; Hachulla, E; Diot, E; Granel, B; Sibilia, J; Tiev, K; Mouthon, L; Cracowski, J L; Carpentier, P H; Amoura, Z; Fajardy, I; Avouac, J; Meyer, O; Kahan, A; Boileau, C; Allanore, Y

2009-08-01

Systemic sclerosis (SSc) belongs to the group of connective tissue disorders (CTDs), among which are several disorders characterized by a type I interferon (IFN) signature. The recent identification of an association between IRF5 and SSc further highlights a key role for IFN. STAT4, which encodes STAT-4, contributes to IFN signaling, and its genetic variants were found to be associated with CTDs. The aim of this study was to determine whether the STAT4 rs7574865 single-nucleotide polymorphism is associated with SSc, and whether it interacts with IRF5. Both the STAT4 rs7574865 and IRF5 rs2004640 polymorphisms were genotyped in 1,855 individuals of French Caucasian origin comprising a discovery set of 440 patients with SSc and 485 control subjects and a replication set of 445 patients with SSc and an additional 485 control subjects. STAT4 rs7574865 was shown to be associated with SSc (P=0.001, odds ratio [OR] 1.29, 95% confidence interval [95% CI] 1.11-1.51). This association was not restricted to a particular phenotype. An additive effect of the STAT4 rs7574865 T allele and the IRF5 rs2004640 T allele was observed, resulting in a multiple increased 1.28-fold risk of SSc. The OR for SSc was 2.72 (95% CI 1.86-3.99) for combinations of genotypes with >or=3 risk alleles. An additive effect was also detected for fibrosing alveolitis: carriage of at least 3 risk alleles appeared to be an independent risk factor (P=2.2x10(-4), OR 1.97, 95% CI 1.28-3.04). Our results establish STAT4 rs7574865 as a new SSc genetic susceptibility factor. STAT4 and IRF5 act with additive effects in terms of susceptibility to both SSc and SSc-related fibrosing alveolitis.

SSC-K code users manual (rev.1)

International Nuclear Information System (INIS)

Kwon, Y. M.; Lee, Y. B.; Chang, W. P.; Hahn, D.

2002-01-01

The Supper System Code of KAERI (SSC-K) is a best-estimate system code for analyzing a variety of off-normal or accidents in the heat transport system of a pool type LMR design. It is being developed at Korea Atomic Energy Research Institution (KAERI) on the basis of SSC-L, originally developed at BNL to analyze loop-type LMR transients. SSC-K can handle both designs of loop and pool type LMRs. SSC-K contains detailed mechanistic models of transient thermal, hydraulic, neutronic, and mechanical phenomena to describe the response of the reactor core, coolant, fuel elements, and structures to accident conditions. This report provides a revised User's Manual (rev.1) of the SSC-K computer code, focusing on phenomenological model descriptions for new thermal, hydraulic, neutronic, and mechanical modules. A comprehensive description of the models for pool-type reactor is given in Chapters 2 and 3; the steady-state plant characterization, prior to the initiation of transient is described in Chapter 2 and their transient counterparts are discussed in Chapter 3. Discussions on the intermediate heat exchanger (IHX) and the electromagnetic (EM) pump are described in Chapter 4 and 5, respectively. A model of passive safety decay heat removal system (PSDRS) is discussed in Chapter 6, and models for various reactivity feedback effects are discussed in Chapter 7. In Chapter 8, constitutive laws and correlations required to execute the SSC-K are described. New models developed for SSC-K rev.1 are two dimensional hot pool model in Chapter 9, and long term cooling model in Chapter 10. Finally, a brief description of MINET code adopted to simulate BOP is presented in Chapter 11. Based on test runs for typical LMFBR accident analyses, it was found that the present version of SSC-K would be used for the safety analysis of KALIMER. However, the further validation of SSC-K is required for real applications. It is noted that the user's manual of SSC-K will be revised later with the

Registry Evaluation of Digital Ulcers in Systemic Sclerosis

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Felice Galluccio

2010-01-01

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

Anti-Annexin V Antibodies: Association with Vascular Involvement and Disease Outcome in Patients with Systemic Sclerosis

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Iman A. Hassan

2010-04-01

Full Text Available Background: Systemic Sclerosis (SSc is characterized by skin thickening, fibrosis and vascular obliteration. The onset and course are heterogeneous. Prominent features include autoimmunity, inflammation and vascular damage. Aim of study: To measure the level of serum Anti-Annexin V antibodies in SSc patients and to study its significance in relation to vascular damage in these patients. Patients and methods: Twenty patients with SSc (12 with diffuse SSc and 8 with the limited form and 10 healthy age and sex matched volunteers as controls were all subjected to routine laboratory testing and immunological profiling including antinuclear, anti-Scl-70, anticentomere, anticardiolipin antibodies and anti-annexin V antibodies titres. Vascular damage was assessed by clinical examination and assessment of the disease activity score, nailfold capillaroscopy and colour flow Doppler of the renal arteries; Doppler echocardiography was used for assessing pulmonary hypertension. Results: Anti-annexin V antibodies were detected in 75% of patients. Comparisons between anti-annexin V in diffuse and limited subgroups showed no significance; however a statistically significant positive correlation was found between Anti-annexin V titre and the degree of vascular damage in SSc patients. Anti-annexin V increased significantly in patients with severe vascular damage in comparison with those less affected (15.3 ± 6.6 vs. 11.25 ± 3.6, P , 0.05. A significant positive correlation was found between Anti-annexin V titre and both the ACL titre (r = 0.79, P , 0.001 and the resistive index of the main renal artery (r = 0.42, P , 0.05. Conclusion: Anti-annexin V antibodies were significantly present in sera of patients with SSc. Patients with more severe forms of vascular damage had higher titres of these antibodies. Anti-annexin V antibodies are a sensitive predictor of vascular damage in SSc and could serve as a useful parameter in discriminating patients with a higher

Anti-Annexin V Antibodies: Association with Vascular Involvement and Disease Outcome in Patients with Systemic Sclerosis

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Reem A. Habeeb

2010-01-01

Full Text Available Background Systemic Sclerosis (SSc is characterized by skin thickening, fibrosis and vascular obliteration. The onset and course are heterogeneous. Prominent features include autoimmunity, inflammation and vascular damage. Aim of Study To measure the level of serum Anti-Annexin V antibodies in SSc patients and to study its significance in relation to vascular damage in these patients. Patients and Methods Twenty patients with SSc (12 with diffuse SSc and 8 with the limited form and 10 healthy age and sex matched volunteers as controls were all subjected to routine laboratory testing and immunological profiling including antinuclear, anti-Scl-70, anticentomere, anticardiolipin antibodies and anti-annexin V antibodies titres. Vascular damage was assessed by clinical examination and assessment of the disease activity score, nailfold capillaroscopy and colour flow Doppler of the renal arteries; Doppler echocardiography was used for assessing pulmonary hypertension. Results Anti-annexin V antibodies were detected in 75% of patients. Comparisons between anti-annexin V in diffuse and limited subgroups showed no significance; however a statistically significant positive correlation was found between Anti-annexin V titre and the degree of vascular damage in SSc patients. Anti-annexin V increased significantly in patients with severe vascular damage in comparison with those less affected (15.3 ± 6.6 vs. 11.25 ± 3.6, P < 0.05. A significant positive correlation was found between Anti-annexin V titre and both the ACL titre (r = 0.79, P < 0.001 and the resistive index of the main renal artery (r = 0.42, P < 0.05. Conclusion Anti-annexin V antibodies were significantly present in sera of patients with SSc. Patients with more severe forms of vascular damage had higher titres of these antibodies. Anti-annexin V antibodies are a sensitive predictor of vascular damage in SSc and could serve as a useful parameter in discriminating patients with a higher risk of

Doppler ultrasound study of penis in men with systemic sclerosis: a correlation with Doppler indices of renal and digital arteries.

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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.

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

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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.

Improved inter-assembly heat transfer modeling under low flow conditions for the Super System Code (SSC)

International Nuclear Information System (INIS)

Horak, W.C.; Guppy, J.G.

1984-01-01

The Super System Code (SSC) was developed at the Brookhaven National Laboratory (BNL) for the thermal hydraulic analysis of natural circulation transients, operational transients, and other system wide transients in nuclear power plants. SSC is a generic, best estimate code that models the in-vessel components, heat transport loops, plant protection systems and plant control systems. SSC also simulates the balance of plant when interfaced with the MINET code. SSC has been validated against both numerical and experimental data bases and is now used by several outside users. An important area of interest in LMFBR transient analysis is the prediction of the response of the reactor core under low flow conditions, such as experienced during a natural circulation event. Under these circumstances there are many physical phenomena which must be modeled to provide an adequate representation by a computer code simulation. The present version of SSC contains numerous models which account for most of the major phenomena. However, one area where the present model in SSC is being improved is in the representation of heat transfer and buoyancy effects under low flow operation. To properly improve the present version, the addition of models to represent certain inter-assembly effects is required

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

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Maria Giuseppina Onesti

2016-01-01

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

Increased Expression and Modulated Regulatory Activity of Coinhibitory Receptors PD-1, TIGIT, and TIM-3 in Lymphocytes From Patients With Systemic Sclerosis.

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Fleury, Michelle; Belkina, Anna C; Proctor, Elizabeth A; Zammitti, Christopher; Simms, Robert W; Lauffenburger, Douglas A; Snyder-Cappione, Jennifer E; Lafyatis, Robert; Dooms, Hans

2018-04-01

Immune dysfunction is an important component of the disease process underlying systemic sclerosis (SSc), but the mechanisms contributing to altered immune cell function in SSc remain poorly defined. This study was undertaken to measure the expression and function of the coinhibitory receptors (co-IRs) programmed cell death 1 (PD-1), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin and mucin domain 3 (TIM-3), and lymphocyte activation gene 3 (LAG-3) in lymphocyte subsets from the peripheral blood of patients with SSc. Co-IR expression levels on subsets of immune cells were analyzed using a 16-color flow cytometry panel. The functional role of co-IRs was determined by measuring cytokine production after in vitro stimulation of SSc and healthy control peripheral blood mononuclear cells (PBMCs) in the presence of co-IR-blocking antibodies. Supernatants from cultures of stimulated PBMCs were added to SSc fibroblasts, and their impact on fibroblast gene expression was measured. Mathematical modeling was used to reveal differences between co-IR functions in SSc patients and healthy controls. Levels of the co-IRs PD-1 and TIGIT were increased, and each was coexpressed, in distinct T cell subsets from SSc patients compared to healthy controls. Levels of TIM-3 were increased in SSc natural killer cells. PD-1, TIGIT, and TIM-3 antibody blockade revealed patient-specific roles of each of these co-IRs in modulating activation-induced T cell cytokine production. In contrast to healthy subjects, blockade of TIGIT and TIM-3, but not PD-1, failed to reverse inhibited cytokine production in SSc patients, indicating that enhanced T cell exhaustion is present in SSc. Finally, cytokines secreted in anti-TIM-3-treated PBMC cultures distinctly changed the gene expression profile in SSc fibroblasts. The altered expression and regulatory capacity of co-IRs in SSc lymphocytes may contribute to disease pathophysiology by modulating the cytokine-mediated cross-talk of

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

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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.

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

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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.

2013 American College of Rheumatology/European League against rheumatism classification criteria for systemic sclerosis outperform the 1980 criteria: data from the Canadian Scleroderma Research Group.

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Alhajeri, Hebah; Hudson, Marie; Fritzler, Marvin; Pope, Janet; Tatibouet, Solène; Markland, Janet; Robinson, David; Jones, Niall; Khalidi, Nader; Docherty, Peter; Kaminska, Elzbieta; Masetto, Ariel; Sutton, Evelyn; Mathieu, Jean-Pierre; Ligier, Sophie; Grodzicky, Tamara; LeClercq, Sharon; Thorne, Carter; Gyger, Geneviève; Smith, Douglas; Fortin, Paul R; Larché, Maggie; Baron, Murray

2015-04-01

The goal of this study was to determine the sensitivity of the new 2013 classification criteria for systemic sclerosis (SSc; scleroderma) in an independent cohort of SSc subjects and to assess the contribution of individual items of the criteria to the overall sensitivity. SSc subjects from the Canadian Scleroderma Research Group cohort were assessed. Sensitivity was determined in several subgroups of patients. In patients without the criterion of skin thickening proximal to the metacarpophalangeal (MCP) joints, we recalculated sensitivity after removing the individual criterion. A total of 724 SSc patients were included. Most were women (86%), mean age was 55.8 years, mean disease duration was 10.9 years, and 59% had limited cutaneous SSc (lcSSc). Overall, the sensitivity of the 2013 criteria was 98.3% compared to 88.3% for the 1980 criteria. This pattern was consistent among those with lcSSc (98.8% versus 85.6%), anticentromere antibodies (98.9% versus 79.8%), disease duration ≤3 years (98.7% versus 84.7%), and no skin involvement proximal to the MCP joints (97% versus 60%). In the latter subgroup, removing Raynaud's phenomenon and sclerodactyly from the criteria reduced the sensitivity to 77% and 79%, respectively. Removing both sclerodactyly and puffy fingers reduced the sensitivity to 62%. The 2013 SSc classification criteria classify more SSc patients than the 1980 criteria. The improvement in sensitivity is most striking in those with lcSSc, especially those without skin involvement proximal to the MCP joints. The addition of Raynaud's phenomenon and puffy fingers to the 2013 criteria accounts for important gains in sensitivity. Copyright © 2015 by the American College of Rheumatology.

SSC-K code user's manual

Energy Technology Data Exchange (ETDEWEB)

Kwon, Y.M.; Lee, Y.B.; Chang, W.P.; Hahn, D

2000-07-01

The Supper System Code of KAERI (SSC-K) is a best-estimate system code for analyzing a variety of off-normal or accidents in the heat transport system of a pool type LMR design. It is being developed at Korea Atomic Energy Research Inititution (KAERI) on the basis of SSC-L, originally developed at BNL to analyze loop-type LMR transients. SSC-K can handle both designs of loop and pool type LMRs. SSC-K contains detailed mechanistic models of transient thermal, hydraulic, neutronic, and mechanical phenomena to describe the response of the reactor core, coolant, fuel elements, and structures to accident conditions. This report provides an overview of recent model developmentsvfor the SSC-K computer code, focusing on phenomenological model descriptions for new thermal, hydraulic, neutronic, and mechnaical modules. A comprehensive description of the models for pool-type reactor is given in Chapters 2 and 3; the steady-state plant characterization, prior to the initiation of transient is described in Chapter 2 and their transient counterparts are discussed in Chapter 3. In Chapter 4, a discussion on the intermediate heat exchanger (IHX) is presented. The IHX model of SSC-K is similar to that used in the SSC-L, except for some changes required for the pool-type configuration of reactor vessel. In Chapter 5, an electromagnetic (EM) pump is modeled as a component. There are two pump choices available in SSC-K; a centrifugal pump which was originally imbedded into the SSC-L, and an EM pump which was introduced for the KALIMER design. In Chapter 6, a model of passive safety decay heat removal system(PSDRS) is discussed, which removes decay heat through the reactor and containment vessel walls to the ambient air heat sink. In Chapter 7, models for various reactivity feedback effects are discussed. Reactivity effects of importance in fast reactor include the Doppler effect, effects of sodium density changes, effects of dimensional changes in core geometry. Finally in Chapter 8

Characterization of the HLA-DRβ1 third hypervariable region amino acid sequence according to charge and parental inheritance in systemic sclerosis.

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Gentil, Coline A; Gammill, Hilary S; Luu, Christine T; Mayes, Maureen D; Furst, Dan E; Nelson, J Lee

2017-03-07

Specific HLA class II alleles are associated with systemic sclerosis (SSc) risk, clinical characteristics, and autoantibodies. HLA nomenclature initially developed with antibodies as typing reagents defining DRB1 allele groups. However, alleles from different DRB1 allele groups encode the same third hypervariable region (3rd HVR) sequence, the primary T-cell recognition site, and 3rd HVR charge differences can affect interactions with T cells. We considered 3rd HVR sequences (amino acids 67-74) irrespective of the allele group and analyzed parental inheritance considered according to the 3rd HVR charge, comparing SSc patients with controls. In total, 306 families (121 SSc and 185 controls) were HLA genotyped and parental HLA-haplotype origin was determined. Analysis was conducted according to DRβ1 3rd HVR sequence, charge, and parental inheritance. The distribution of 3rd HVR sequences differed in SSc patients versus controls (p = 0.007), primarily due to an increase of specific DRB1*11 alleles, in accord with previous observations. The 3rd HVR sequences were next analyzed according to charge and parental inheritance. Paternal transmission of DRB1 alleles encoding a +2 charge 3rd HVR was significantly reduced in SSc patients compared with maternal transmission (p = 0.0003, corrected for analysis of four charge categories p = 0.001). To a lesser extent, paternal transmission was increased when charge was 0 (p = 0.021, corrected for multiple comparisons p = 0.084). In contrast, paternal versus maternal inheritance was similar in controls. SSc patients differed from controls when DRB1 alleles were categorized according to 3rd HVR sequences. Skewed parental inheritance was observed in SSc patients but not in controls when the DRβ1 3rd HVR was considered according to charge. These observations suggest that epigenetic modulation of HLA merits investigation in SSc.

Immunohistochemical and morphometric evaluation of COX 1 and COX-2 in the remodeled lung in idiopathic pulmonary fibrosis and systemic sclerosis

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Edwin Roger Parra

2013-12-01

Full Text Available OBJECTIVE: To study the expression of COX-1 and COX-2 in the remodeled lung in systemic sclerosis (SSc and idiopathic pulmonary fibrosis (IPF patients, correlating that expression with patient survival.METHODS: We examined open lung biopsy specimens from 24 SSc patients and 30 IPF patients, using normal lung tissue as a control. The histological patterns included fibrotic nonspecific interstitial pneumonia (NSIP in SSc patients and usual interstitial pneumonia (UIP in IPF patients. We used immunohistochemistry and histomorphometry to evaluate the expression of COX-1 and COX-2 in alveolar septa, vessels, and bronchioles. We then correlated that expression with pulmonary function test results and evaluated its impact on patient survival.RESULTS: The expression of COX-1 and COX-2 in alveolar septa was significantly higher in IPF-UIP and SSc-NSIP lung tissue than in the control tissue. No difference was found between IPF-UIP and SSc-NSIP tissue regarding COX-1 and COX-2 expression. Multivariate analysis based on the Cox regression model showed that the factors associated with a low risk of death were younger age, high DLCO/alveolar volume, IPF, and high COX-1 expression in alveolar septa, whereas those associated with a high risk of death were advanced age, low DLCO/alveolar volume, SSc (with NSIP, and low COX-1 expression in alveolar septa.CONCLUSIONS: Our findings suggest that strategies aimed at preventing low COX-1 synthesis will have a greater impact on SSc, whereas those aimed at preventing high COX-2 synthesis will have a greater impact on IPF. However, prospective randomized clinical trials are needed in order to confirm that.

Comparison of laser Doppler imaging, fingertip lacticemy test, and nailfold capillaroscopy for assessment of digital microcirculation in systemic sclerosis.

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Correa, Marcelo Ju; Andrade, Luis Ec; Kayser, Cristiane

2010-01-01

Laser Doppler imaging (LDI) is a relatively new method for assessing the functional aspect of superficial skin blood flow in systemic sclerosis (SSc) and Raynaud's phenomenon. The present study investigated the dynamic behavior of digital skin microvascular blood flow before and after cold stimulus (CS) in SSc patients and in healthy controls by means of a comprehensive approach of the functional (LDI), morphological (nailfold capillaroscopy (NFC)), and biochemical (fingertip lacticemy (FTL)) microcirculation components. Forty-four SSc patients and 40 healthy controls were included. After acclimatization, all subjects underwent NFC followed by LDI and FTL measurement. NFC was performed with a stereomicroscope under 10× to 20× magnification in the 10 digits of the hands. Skin blood flow of the dorsum of four fingertips (excluding the thumb) of the left hand was measured using LDI at baseline and for 30 minutes after CS. The mean finger blood flow (FBF) of the four fingertips was expressed as arbitrary perfusion units. FTL was determined on the fourth left finger before (pre-CS-FTL) and 10 minutes after CS. LDI showed significantly lower mean baseline FBF in SSc patients as compared with controls (296.9 ± 208.8 vs. 503.6 ± 146.4 perfusion units; P < 0.001) and also at all time points after CS (P < 0.001). There was a significant decrease in mean FBF after CS as compared with baseline in SSc patients and in controls, followed by recovery of the blood flow 27 minutes after CS in healthy controls, but not in SSc patients. FBF tended to be lower in patients with digital scars and previous ulceration/amputation (P = 0.06). There was no correlation between mean baseline FBF and NFC parameters. Interestingly, there was a negative correlation between FTL and FBF measured by LDI in basal conditions and 10 minutes after CS in SSc patients. LDI showed lower digital blood flow in SSc patients when compared with healthy controls and correlated well with FTL both at baseline

Swallowing difficulties with medication intake assessed with a novel self-report questionnaire in patients with systemic sclerosis – a cross-sectional population study

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Messerli M

2017-09-01

Full Text Available Markus Messerli,1,2 Rebecca Aschwanden,1 Michael Buslau,2 Kurt E Hersberger,1 Isabelle Arnet1 1Pharmaceutical Care Research Group, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland; 2European Centre for the Rehabilitation of Scleroderma, Reha Rheinfelden, Rheinfelden, Switzerland Objectives: To assess subjective swallowing difficulties (SD with medication intake and their practical consequences in patients suffering from systemic sclerosis (SSc with a novel self-report questionnaire.Design and setting: Based on a systematic literature review, we developed a self-report questionnaire and got it approved by an expert panel. Subsequently, we sent the questionnaire by post mail to SSc patients of the European Center for the Rehabilitation of Scleroderma Rheinfelden, Switzerland.Participants: Patients were eligible if they were diagnosed with SSc, treated at the center, and were of age ≥18 years at the study start.Main outcome measures: Prevalence and pattern of SD with oral medication intake, including localization and intensity of complaints.Results: The questionnaire consisted of 30 items divided into five sections Complaints, Intensity, Localization, Coping strategies, and Adherence. Of the 64 SSc patients eligible in 2014, 43 (67% returned the questionnaire. Twenty patients reported SD with medication intake (prevalence 47%, either currently (11; 26% or in the past that had been overcome (9; 21%. Self-reported SD were localized mostly in the larynx (43% and esophagus (34%. They were of moderate (45% or strong to unbearable intensity (25%. Modification of the dosage form was reported in 40% of cases with SD. Adherence was poor for 20 (47% patients and was not associated with SD (p=0.148.Conclusion: Our novel self-report questionnaire is able to assess the pattern of complaints linked to medication intake, that is, localization and intensity. It may serve as a guide for health care professionals in selecting the most

Cutaneous chronic graft-versus-host disease does not have the abnormal endothelial phenotype or vascular rarefaction characteristic of systemic sclerosis.

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Jo Nadine Fleming

2009-07-01

Full Text Available The clinical and histologic appearance of fibrosis in cutaneous lesions in chronic graft-versus -host disease (c-GVHD resembles the appearance of fibrosis in scleroderma (SSc. Recent studies identified distinctive structural changes in the superficial dermal microvasculature and matrix of SSc skin. We compared the dermal microvasculature in human c-GVHD to SSc to determine if c-GVHD is a suitable model for SSc.We analyzed skin biopsies of normal controls (n = 24, patients with SSc (n = 30 and c-GVHD with dermal fibrosis (n = 133. Immunostaining was employed to identify vessels, vascular smooth muscle, dermal matrix, and cell proliferation. C-GVHD and SSc had similar dermal matrix composition and vascular smooth muscle pathology, including intimal hyperplasia. SSc, however, differed significantly from c-GVHD in three ways. First, there were significantly fewer (p = 0.00001 average vessels in SSc biopsies (9.8 when compared with c-GVHD (16.5. Second, in SSc, endothelial markers were decreased significantly (19/19 and 12/14 for VE cadherin and vWF (p = <0.0001 and <0.05, respectively. In contrast, 0/13 c-GVHD biopsies showed loss of staining with canonical endothelial markers. Third, c-GVHD contained areas of microvascular endothelial proliferation not present in the SSc biopsies.The sclerosis associated with c-GVHD appears to resemble wound healing. Focal capillary proliferation occurs in early c-GVHD. In contrast, loss of canonical endothelial markers and dermal capillaries is seen in SSc, but not in c-GVHD. The loss of VE cadherin in SSc, in particular, may be related to microvascular rarefaction because VE cadherin is necessary for angiogenesis. C-GVHD is a suitable model for studying dermal fibrosis but may not be applicable for studying the microvascular alterations characteristic of SSc.

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

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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.

Determinants of exercise-induced pulmonary arterial hypertension in systemic sclerosis.

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Voilliot, Damien; Magne, Julien; Dulgheru, Raluca; Kou, Seisyou; Henri, Christine; Laaraibi, Saloua; Sprynger, Muriel; Andre, Béatrice; Pierard, Luc A; Lancellotti, Patrizio

2014-05-15

Exercise-induced pulmonary arterial hypertension (EIPH) in systemic sclerosis (SSc) has already been observed but its determinants remain unclear. The aim of this study was to determine the incidence and the determinants of EIPH in SSc. We prospectively enrolled 63 patients with SSc (age 54±3years, 76% female) followed in CHU Sart-Tilman in Liège. All patients underwent graded semi-supine exercise echocardiography. Systolic pulmonary arterial pressure (sPAP) was derived from the peak velocity of the tricuspid regurgitation jet and adding the estimation of right atrial pressure, both at rest and during exercise. Resting pulmonary arterial hypertension (PH) was defined as sPAP > 35 mmHg and EIPH as sPAP > 50 mmHg during exercise. The following formulas were used: mean PAP (mPAP) = 0.61 × sPAP + 2, left atrial pressure (LAP)=1.9+1.24 × left ventricular (LV) E/e' and pulmonary vascular resistance (PVR)=(mPAP-LAP)/LV cardiac output (CO) and slope of mPAP-LVCO relationship=changes in mPAP/changes in LVCO. Resting PH was present in 3 patients (7%) and 21 patients developed EIPH (47%). Patients with EIPH had higher resting LAP (10.3 ± 2.2 versus 8.8 ± 2.3 mmHg; p = 0.03), resting PVR (2.6 ± 0.8 vs. 1.4 ± 1.1 Woods units; p=0.004), exercise LAP (13.3 ± 2.3 vs. 9 ± 1.7 mmHg; p exercise PVR (3.6 ± 0.7 vs. 2.1 ± 0.9 Woods units; p = 0.02) and slope of mPAP-LVCO (5.8 ± 2.4 vs. 2.9 ± 2.1 mmHg/L/min; p age and gender, exercise LAP (β=3.1 ± 0.8; p=0.001) and exercise PVR (β=7.9 ± 1.7; p=0.0001) were independent determinants of exercise sPAP. EIPH is frequent in SSc patients and is mainly related to both increased exercise LV filling pressure and exercise PVR. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations

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Bossini-Castillo, Lara; Martin, Jose-Ezequiel; Broen, Jasper; Gorlova, Olga; Simeón, Carmen P.; Beretta, Lorenzo; Vonk, Madelon C.; Luis Callejas, Jose; Castellví, Ivan; Carreira, Patricia; José García-Hernández, Francisco; Fernández Castro, Mónica; Coenen, Marieke J.H.; Riemekasten, Gabriela; Witte, Torsten; Hunzelmann, Nicolas; Kreuter, Alexander; Distler, Jörg H.W.; Koeleman, Bobby P.; Voskuyl, Alexandre E.; Schuerwegh, Annemie J.; Palm, Øyvind; Hesselstrand, Roger; Nordin, Annika; Airó, Paolo; Lunardi, Claudio; Scorza, Raffaella; Shiels, Paul; van Laar, Jacob M.; Herrick, Ariane; Worthington, Jane; Denton, Christopher; Tan, Filemon K.; Arnett, Frank C.; Agarwal, Sandeep K.; Assassi, Shervin; Fonseca, Carmen; Mayes, Maureen D.; Radstake, Timothy R.D.J.; Martin, Javier

2012-01-01

A single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in a previously published genome-wide association study (GWAS) in systemic sclerosis (SSc). Aiming to reveal the possible implication of the IL12RB2 gene in SSc, we conducted a follow-up study of this locus in different Caucasian cohorts. We analyzed 10 GWAS-genotyped SNPs in the IL12RB2 region (2309 SSc patients and 5161 controls). We then selected three SNPs (rs3790567, rs3790566 and rs924080) based on their significance level in the GWAS, for follow-up in an independent European cohort comprising 3344 SSc and 3848 controls. The most-associated SNP (rs3790567) was further tested in an independent cohort comprising 597 SSc patients and 1139 controls from the USA. After conditional logistic regression analysis of the GWAS data, we selected rs3790567 [PMH= 1.92 × 10−5 odds ratio (OR) = 1.19] as the genetic variant with the firmest independent association observed in the analyzed GWAS peak of association. After the first follow-up phase, only the association of rs3790567 was consistent (PMH= 4.84 × 10−3 OR = 1.12). The second follow-up phase confirmed this finding (Pχ2 = 2.82 × 10−4 OR = 1.34). After performing overall pooled-analysis of all the cohorts included in the present study, the association found for the rs3790567 SNP in the IL12RB2 gene region reached GWAS-level significant association (PMH= 2.82 × 10−9 OR = 1.17). Our data clearly support the IL12RB2 genetic association with SSc, and suggest a relevant role of the interleukin 12 signaling pathway in SSc pathogenesis. PMID:22076442

More severe nailfold capillaroscopy findings and anti-endothelial cell antibodies. Are they useful tools for prognostic use in systemic sclerosis?

Science.gov (United States)

Riccieri, V; Germano, V; Alessandri, C; Vasile, M; Ceccarelli, F; Sciarra, I; Di Franco, M; Spadaro, A; Valesini, G

2008-01-01

Anti-endothelial cell antibodies (AECA) have been described in systemic sclerosis (SSc) but their clinical relevance is unclear. Aim of this study was to measure serum levels of AECA in 62 SSc patients, examining the main clinical and laboratory features, including nailfold capillaroscopy (NC) abnormalities and looking for any significant association. Fourteen patients (23%) were AECA positive. An "early" NC pattern was observed in 21 patients (34%), an "active" pattern in 24 (39%) and a "late" pattern in 17 cases (27%). In those patients with AECA, a "late" NC pattern was significantly more frequent respect to the "early" and "late" patterns (p or =15) (p<0.04), while those cases with more aggressive NC patterns ("active" and "late") had a more frequent finding of arterial hypertension (p<0.05) and cardiac involvement (p<0.05) respect to those with "early" NC pattern. Thus, advanced NC findings were more frequently found in those patients with higher levels of AECA and their contemporary presence may consent to identify specific SSc subsets i.e., those with higher skin scores and cardiovascular involvement. These data suggest that AECA may have a role in the progression of the endothelial damage and their presence and titer should be considered as an adjunctive risk factor for a more severe disease. We also confirm the diagnostic and prognostic validity for NC in SSc, underlying the importance for an accurate capillaroscopic assessment. The contemporary assessment of these two diagnostic tools can be useful to better define different subset of SSc patients.

Whole-lung volume and density in spirometrically-gated inspiratory and expiratory CT in systemic sclerosis: correlation with static volumes at pulmonary function tests.

Science.gov (United States)

Camiciottoli, G; Diciotti, S; Bartolucci, M; Orlandi, I; Bigazzi, F; Matucci-Cerinic, M; Pistolesi, M; Mascalchi, M

2013-03-01

Spiral low-dose computed tomography (LDCT) permits to measure whole-lung volume and density in a single breath-hold. To evaluate the agreement between static lung volumes measured with LDCT and pulmonary function test (PFT) and the correlation between the LDCT volumes and lung density in restrictive lung disease. Patients with Systemic Sclerosis (SSc) with (n = 24) and without (n = 16) pulmonary involvement on sequential thin-section CT and patients with chronic obstructive pulmonary disease (COPD)(n = 29) underwent spirometrically-gated LDCT at 90% and 10% of vital capacity to measure inspiratory and expiratory lung volumes and mean lung attenuation (MLA). Total lung capacity and residual volume were measured the same day of CT. Inspiratory [95% limits of agreement (95% LoA)--43.8% and 39.2%] and expiratory (95% LoA -45.8% and 37.1%) lung volumes measured on LDCT and PFT showed poor agreement in SSc patients with pulmonary involvement, whereas they were in substantial agreement (inspiratory 95% LoA -14.1% and 16.1%; expiratory 95% LoA -13.5% and 23%) in SSc patients without pulmonary involvement and in inspiratory scans only (95% LoA -23.1% and 20.9%) of COPD patients. Inspiratory and expiratory LDCT volumes, MLA and their deltas differentiated both SSc patients with or without pulmonary involvement from COPD patients. LDCT lung volumes and density were not correlated in SSc patients with pulmonary involvement, whereas they did correlate in SSc without pulmonary involvement and in COPD patients. In restrictive lung disease due to SSc there is poor agreement between static lung volumes measured using LDCT and PFT and the relationship between volume and density values on CT is altered.

Dicty_cDB: SSC534 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available SS (Link to library) SSC534 (Link to dictyBase) - - - Contig-U13922-1 SSC534Z (Link... to Original site) - - SSC534Z 711 - - - - Show SSC534 Library SS (Link to library) Clone ID SSC534 (Link to dic... 1.3 FM992688_1247( FM992688 |pid:none) Candida dubliniensis CD36 chrom... 35 3.0 EU565733_1( EU565733 |pid:none) Unculture... 20.0 %: nuclear 16.0 %: vesicles of secretory system 12.0 %: mitochondrial 8.0 %: Golgi 8.0 %: endoplasmic reticul...kholderia multivorans ATCC 1... 33 6.6 AM260479_1383( AM260479 |pid:none) Ralstonia e

Proangiogenic hematopoietic cells of monocytic origin: roles in vascular regeneration and pathogenic processes of systemic sclerosis.

Science.gov (United States)

Yamaguchi, Yukie; Kuwana, Masataka

2013-02-01

New blood vessel formation is critical, not only for organ development and tissue regeneration, but also for various pathologic processes, such as tumor development and vasculopathy. The maintenance of the postnatal vascular system requires constant remodeling, which occurs through angiogenesis, vasculogenesis, and arteriogenesis. Vasculogenesis is mediated by the de novo differentiation of mature endothelial cells from endothelial progenitor cells (EPCs). Early studies provided evidence that bone marrow-derived CD14⁺ monocytes can serve as a subset of EPCs because of their expression of endothelial markers and ability to promote neovascularization in vitro and in vivo. However, the current consensus is that monocytic cells do not give rise to endothelial cells in vivo, but function as support cells, by promoting vascular formation and repair through their immediate recruitment to the site of vascular injury, secretion of proangiogenic factors, and differentiation into mural cells. These monocytes that function in a supporting role in vascular repair are now termed monocytic pro-angiogenic hematopoietic cells (PHCs). Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by excessive fibrosis and microvasculopathy, along with poor vascular formation and repair. We recently showed that in patients with SSc, circulating monocytic PHCs increase dramatically and have enhanced angiogenic potency. These effects may be induced in response to defective vascular repair machinery. Since CD14⁺ monocytes can also differentiate into fibroblast-like cells that produce extracellular matrix proteins, here we propose a new hypothesis that aberrant monocytic PHCs, once mobilized into circulation, may also contribute to the fibrotic process of SSc.

Validation of SSC using the FFTF natural-circulation tests

International Nuclear Information System (INIS)

Horak, W.C.; Guppy, J.G.; Kennett, R.J.

1982-01-01

As part of the Super System Code (SSC) validation program, the 100% power FFTF natural circulation test has been simulated using SSC. A detailed 19 channel, 2 loop model was used in SSC. Comparisons showed SSC calculations to be in good agreement with the Fast Flux Test Facility (FFTF), test data. Simulation of the test was obtained in real time

Evaluation of the Satisfaction with Appearance Scale and Its Short Form in Systemic Sclerosis: Analysis from the UCLA Scleroderma Quality of Life Study.

Science.gov (United States)

Mills, Sarah D; Fox, Rina S; Merz, Erin L; Clements, Philip J; Kafaja, Suzanne; Malcarne, Vanessa L; Furst, Daniel E; Khanna, Dinesh

2015-09-01

Changes in appearance are common in patients with systemic sclerosis (SSc) and can significantly affect well-being. The Satisfaction with Appearance Scale (SWAP) measures body image dissatisfaction in persons with visible disfigurement; the Brief-Satisfaction with Appearance Scale (Brief-SWAP) is its short form. The present study evaluated the reliability and validity of SWAP and Brief-SWAP scores in SSc. A sample of 207 patients with SSc participating in the University of California, Los Angeles Scleroderma Quality of Life Study completed the SWAP. Brief-SWAP scores were derived from the SWAP. The structural validity of both measures was investigated using confirmatory factor analysis. Internal consistency reliability of total and subscale scores was assessed with Cronbach's alpha coefficients. Convergent and divergent validity was evaluated using the Center for Epidemiological Studies Depression Scale, the Health Assessment Questionnaire-Disability Index, and the Medical Outcomes Study Short Form-36 questionnaire. SWAP and Brief-SWAP total scores were highly correlated (r = 0.97). The 4-factor structure of the SWAP fit well descriptively; the 2-factor structure of the Brief-SWAP fit well descriptively and statistically. Internal consistencies for total and subscale scores were good, and results supported convergent and divergent validity. Both versions are suitable for use in patients with SSc. The Brief-SWAP is most efficient; the full SWAP yields additional subscales that may be informative in understanding body image issues in patients with SSc.

Beam diagnostic system for SSC on HIRFL central console

International Nuclear Information System (INIS)

Zhang Guixu; Wang Zhen; Huang Tuanhua

1998-01-01

The SSC ion beam diagnostic system on the console of HIRFL in institute of modern physics is presented. The information between console and diagnostic system can be transferred via DECnet communication. The central computer for HIRFL console is VAX-8350, the working computer of diagnostic system is changed from IBM PC/XT to COMPAQ 486, and the operating program is rewritten from FORTRAN to C. In order to communicate information, DECnet TTT function is put into both programs on the VAX and PC

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...

An integrated 3D design, modeling and analysis resource for SSC detector systems

International Nuclear Information System (INIS)

DiGiacomo, N.J.; Adams, T.; Anderson, M.K.; Davis, M.; Easom, B.; Gliozzi, J.; Hale, W.M.; Hupp, J.; Killian, K.; Krohn, M.; Leitch, R.; Lajczok, M.; Mason, L.; Mitchell, J.; Pohlen, J.; Wright, T.

1989-01-01

Integrated computer aided engineering and design (CAE/CAD) is having a significant impact on the way design, modeling and analysis is performed, from system concept exploration and definition through final design and integration. Experience with integrated CAE/CAD in high technology projects of scale and scope similar to SSC detectors leads them to propose an integrated computer-based design, modeling and analysis resource aimed specifically at SSC detector system development. The resource architecture emphasizes value-added contact with data and efficient design, modeling and analysis of components, sub-systems or systems with fidelity appropriate to the task. They begin with a general examination of the design, modeling and analysis cycle in high technology projects, emphasizing the transition from the classical islands of automation to the integrated CAE/CAD-based approach. They follow this with a discussion of lessons learned from various attempts to design and implement integrated CAE/CAD systems in scientific and engineering organizations. They then consider the requirements for design, modeling and analysis during SSC detector development, and describe an appropriate resource architecture. They close with a report on the status of the resource and present some results that are indicative of its performance. 10 refs., 7 figs

[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.

SSC accelerator availability allocation

International Nuclear Information System (INIS)

Dixon, K.T.; Franciscovich, J.

1991-03-01

Superconducting Super Collider (SSC) operational availability is an area of major concern, judged by the Central Design Group to present such risk that use of modern engineering tools would be essential to program success. Experience has shown that as accelerator beam availability falls below about 80%, efficiency of physics experiments degrades rapidly due to inability to maintain adequate coincident accelerator and detector operation. For this reason, the SSC availability goal has been set at 80%, even though the Fermi National Accelerator Laboratory accelerator, with a fraction of the SSC's complexity, has only recently approached that level. This paper describes the allocation of the top-level goal to part-level reliability and maintainability requirements, and it gives the results of parameter sensitivity studies designed to help identify the best approach to achieve the needed system availability within funding and schedule constraints. 1 ref., 12 figs., 4 tabs

Does nailfold capillaroscopy help predict future outcomes in systemic sclerosis? A systematic literature review.

Science.gov (United States)

Paxton, Dolcie; Pauling, John D

2018-02-14

Nailfold capillaroscopy (NC) is an important diagnostic tool in systemic sclerosis (SSc). Confirmation of NC as a prognostic factor could facilitate earlier intervention and slow disease progression in SSc. We undertook a systematic literature review to evaluate the prognostic value of NC in predicting SSc disease progression. Standardised searches of EMBASE and MEDLINE were undertaken to identify longitudinal studies of adult subjects with SSc reporting the prognostic value of NC for any aspect of disease progression and/or survival. Non-English, non-original research, animal studies, non-adult studies and non-full length reports were excluded from the analysis (PROSPERO 2017:CRD42017071719). Wide heterogeneity in study design, prognostic factor measurement and study outcomes necessitated a qualitative data synthesis. The "QUality In Prognosis Studies" (QUIPS) risk-of-bias tool was used to assess study quality. Study selection, data extraction and risk-of-bias assessment were each undertaken independently by 2 reviewers and consensus reached where necessary. Of 942 retrieved articles, 18 studies fulfilled the inclusion criteria. The majority of studies (17/18, 94%) reported positive associations between baseline NC appearances (using a variety of qualitative, semi-quantitative and quantitative NC endpoints) and clinical outcomes including digital ulcer (DU) occurrence/healing, survival, disease progression (using domains of Medsger disease severity scale), calcinosis, skin progression, pulmonary arterial hypertension (PAH), and/or a composite analysis of "cardiovascular events". Application of the QUIPS tool identified a moderate-high risk of potential bias in 6/18 studies for study participation, 3/18 studies for study attrition, 10/18 for prognostic factor measurement, 5/18 for outcome measurement, 13/18 for confounders and 13/18 for statistical analyses. Study quality limited the strength of the conclusions drawn from these studies. The most important source of

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.

Assessment of esophageal involvement in systemic sclerosis and morphea (localized scleroderma) by clinical, endoscopic, manometric and pH metric features: a prospective comparative hospital based study.

Science.gov (United States)

Arif, Tasleem; Masood, Qazi; Singh, Jaswinder; Hassan, Iffat

2015-02-15

Systemic sclerosis (SSc) is a generalized disorder of unknown etiology affecting the connective tissue of the body. It affects the skin and various internal organs. Gastrointestinal tract involvement is seen in almost 90% of the patients. Esophagus is the most frequently affected part of the gastrointestinal tract. Esophageal motility disturbance classically manifests as a reduced lower esophageal sphincter pressure (LESP) and loss of distal esophageal body peristalsis. Consequently, SSc patients may be complicated by erosive esophagitis and eventually by Barrett's esophagus and esophageal adenocarcinoma. Morphea, also known as localized scleroderma, is characterized by predominant skin involvement, with occasional involvement of subjacent muscles and usually sparing the internal organs. The involvement of esophagus in morphea has been studied very scarcely. The proposed study will investigate the esophageal involvement in the two forms of scleroderma (systemic and localized), compare the same and address any need of upper gastrointestinal evaluation in morphea (localized scleroderma) patients. 56 and 31 newly and already diagnosed cases of SSc and morphea respectively were taken up for the study. All the patients were inquired about the dyspeptic symptoms (heartburn and/or acid regurgitation and/or dysphagia). Upper gastrointestinal endoscopy, esophageal manometry and 24-hour pH monitoring were done in 52, 47 and 41 patients of SSc; and 28, 25 and 20 patients of morphea respectively. Esophageal symptoms were present in 39 cases (69.6%) of SSc which were mild in 22 (39.3%), moderate in 14 (25%), severe in three (5.3%); while only four cases (7.1%) of morphea had esophageal symptoms all of which were mild in severity. Reflux esophagitis was seen in 17 cases (32.7%) of SSc and only two cases (7.14%) of morphea. Manometric abnormalities were seen in 32 cases (68.1%) of SSc and none in morphea. Ambulatory 24-hour esophageal pH monitoring documented abnormal reflux in

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.

Nailfold capillaroscopy in systemic sclerosis: data from the EULAR scleroderma trials and research (EUSTAR) database.

Science.gov (United States)

Ingegnoli, Francesca; Ardoino, Ilaria; Boracchi, Patrizia; Cutolo, Maurizio

2013-09-01

The aims of this study were to obtain cross-sectional data on capillaroscopy in an international multi-center cohort of Systemic Sclerosis (SSc) and to investigate the frequency of the capillaroscopic patterns and their disease-phenotype associations. Data collected between June 2004 and October 2011 in the EULAR Scleroderma Trials and Research (EUSTAR) registry were examined. Patients' profiles based on clinical and laboratory data were obtained by cluster analysis and the association between profiles and capillaroscopy was investigated by multinomial logistic regression. 62 of the 110 EUSTAR centers entered data on capillaroscopy in the EUSTAR database. 376 of the 2754 patients (13.65%) were classified as scleroderma pattern absent, but non-specific capillary abnormalities were noted in 55.48% of the cases. Four major patients' profiles were identified characterized by a progressive severity for skin involvement, as well as an increased number of systemic manifestations. The "early" and "active" scleroderma patterns were generally observed in patients with mild/moderate skin involvement and a low number of disease manifestations, while the "late" scleroderma pattern was found more frequently in the more severe forms of the disease. These data indicate the importance of capillaroscopy in SSc management and that capillaroscopic patterns are directly related to the extent of organ involvement. Copyright © 2013 Elsevier Inc. All rights reserved.

Association of interleukin-1 family cytokines single nucleotide polymorphisms with susceptibility to systemic sclerosis: an independent case-control study and a meta-analysis.

Science.gov (United States)

Huang, Xiao-Lei; Wu, Guo-Cui; Wang, Yu-Jie; Yang, Xiao-Ke; Yang, Guo-Jun; Tao, Jin-Hui; Duan, Yu; Yan, Jun-Wei; Li, Xiang-Pei; Ye, Dong-Qing; Wang, Jing

2016-08-01

The aim of our study was to investigate the association of five single nucleotide polymorphisms in interleukin-1 (IL-1) gene with susceptibility to systemic sclerosis (SSc) in a Chinese population. A total of 58 SSc patients and 113 healthy controls were enrolled. TaqMan allele discrimination assay was performed to detect the genotyping of IL-1A -889C/T (rs1800587), IL-1B -511C/T (rs16944), IL-18 -607C/A (rs1946518), IL-18 -137G/C (rs187238) and IL-33 rs7044343. The association between these SNPs and SSc risk was analyzed. Furthermore, a meta-analysis of relevant studies on the association of IL-1A -889C/T (rs1800587) and IL-1B -511C/T (rs16944) with the susceptibility to SSc was performed. Through the genotyping, significant associations for SSc were found for: IL-1A -889C/T genotype frequencies (P = 0.000), dominant model (P = 0.000), recessive model (P = 0.001) and allele T frequency (P = 0.000). Among SSc patients, dyspnea was significantly associated with IL-18 -607C/A genotype frequency and IL-33 rs7044343 allele frequency (P = 0.037, P = 0.042, respectively). In addition, elevated erythrocyte sedimentation rate was significantly associated with IL-18 -137G/C (rs187238) genotype and allele frequency (P = 0.019, P = 0.006, respectively). While meta-analysis showed there was no significant association between IL-1A -889C/T polymorphism and SSc, for IL-1B -511C/T (rs16944), significant associations were found in the comparison of allele C versus T (OR 1.267, 95 % CI 1.016-1.580) by combined different outcomes. Results showed that IL-1A -889C/T (rs1800587) was associated with SSc susceptibility in the Chinese population. However, this association was not supported by a meta-analysis of all relevant studies. Further investigations are required to verify our findings.

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.

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.

Tracking with wire chambers at the SSC

International Nuclear Information System (INIS)

Hanson, G.G.; Gundy, M.C.; Palounek, A.P.T.

1989-07-01

Limitations placed on wire chambers by radiation damage and rate requirements in the SSC environment are reviewed. Possible conceptual designs for wire chamber tacking systems that meet these requirements are discussed. Computer simulation studies of tracking in such systems are presented. Simulations of events from interesting physics at the SSC, including hits from minimum bias background events, are examined. Results of some preliminary pattern recognition studies are given. 13 refs., 11 fig., 1 tab

Multicentre randomised placebo-controlled trial of oral anticoagulation with apixaban in systemic sclerosis-related pulmonary arterial hypertension: the SPHInX study protocol.

Science.gov (United States)

Calderone, Alicia; Stevens, Wendy; Prior, David; Nandurkar, Harshal; Gabbay, Eli; Proudman, Susanna M; Williams, Trevor; Celermajer, David; Sahhar, Joanne; Wong, Peter K K; Thakkar, Vivek; Dwyer, Nathan; Wrobel, Jeremy; Chin, Weng; Liew, Danny; Staples, Margaret; Buchbinder, Rachelle; Nikpour, Mandana

2016-12-08

Systemic sclerosis (SSc) is a severe and costly multiorgan autoimmune connective tissue disease characterised by vasculopathy and fibrosis. One of the major causes of SSc-related death is pulmonary arterial hypertension (PAH), which develops in 12-15% of patients with SSc and accounts for 30-40% of deaths. In situ thrombosis in the small calibre peripheral pulmonary vessels resulting from endothelial dysfunction and an imbalance of anticoagulant and prothrombotic mediators has been implicated in the complex pathophysiology of SSc-related PAH (SSc-PAH), with international clinical guidelines recommending the use of anticoagulants for some types of PAH, such as idiopathic PAH. However, anticoagulation has not become part of standard clinical care for patients with SSc-PAH as only observational evidence exists to support its use. Therefore, we present the rationale and methodology of a phase III randomised controlled trial (RCT) to evaluate the efficacy, safety and cost-effectiveness of anticoagulation in SSc-PAH. This Australian multicentre RCT will compare 2.5 mg apixaban with placebo, in parallel treatment groups randomised in a 1:1 ratio, both administered twice daily for 3 years as adjunct therapy to stable oral PAH therapy. The composite primary outcome measure will be the time to death or clinical worsening of PAH. Secondary outcomes will include functional capacity, health-related quality of life measures and adverse events. A cost-effectiveness analysis of anticoagulation versus placebo will also be undertaken. Ethical approval for this RCT has been granted by the Human Research Ethics Committees of all participating centres. An independent data safety monitoring board will review safety and tolerability data for the duration of the trial. The findings of this RCT are to be published in open access journals. ACTRN12614000418673, Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence

Software methodologies for the SSC

International Nuclear Information System (INIS)

Loken, S.C.

1990-01-01

This report describes some of the considerations that will determine how the author developed software for the SSC. He begins with a review of the general computing problem for SSC experiments and recent experiences in software engineering for the present generation of experiments. This leads to a discussion of the software technologies that will be critical for the SSC experiments. He describes the emerging software standards and commercial products that may be useful in addressing the SSC needs. He concludes with some comments on how collaborations and the SSC Lab should approach the software development issue

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.

84 K nitrogen system for the SSC

International Nuclear Information System (INIS)

McAshan, M.; Thirumaleshwar, M.; Abramovich, S.; Ganni, V.; Scheidemantle, A.

1992-01-01

The nitrogen system for the Superconducting Super Collider (SSC) is designed to provide the 84 K (nominal) shield refrigeration for the collider rings. Liquid nitrogen is supplied to the collider tunnel from one, two, or more locations on the surface through the service shafts and is distributed along, the 87 km of both rings by the 84 K shield lines. Additional design requirements for the nitrogen distribution system include precooling, fluid supply to the helium plants, supplying makeup liquid nitrogen to the reservoirs located at the entrance of the main shafts, and providing an efficient cooldown means for the cold mass from 300 K to 90 K. The operational modes and possible emergency and maintenance conditions of the collider are taken into account for the nitrogen system design. The status of our work, including design considerations that address thermal aspects (heat load, recooling scheme, etc.) and hydraulic aspects (pressures, elevations, distances, etc.) of the nitrogen system will be discussed

Recent developments in wire chamber tracking at SSC

International Nuclear Information System (INIS)

Ogren, H.

1990-01-01

All of the major SSC proposed detectors use wire chambers in their tracking systems. The feasibility of wire chambers in an SSC detector has now been established by a number of groups planning detectors at SSC. The major advances during the past year in understanding straw tube drift chambers are presented and several innovations in gaseous wire chambers are discussed. The R and D section will concentrate on progress in drift cell design, electronics and signal processing, and engineering aspects of the tracking designs

SSC accelerator physics

International Nuclear Information System (INIS)

Anon.

1985-01-01

Accelerator physicists at LBL began intensive work on the SSC in 1983, in support of the proposed 6.5-T magnet design, which, in turn, became reference design A during the Reference Designs Study. In that same study, LBL physicists formed the core of the accelerator physics group led by Fermilab's Don Edwards. In a period of only a few months, that group established preliminary parameters for a near-optimal design, produced conceptual designs based on three magnet types, addressed all significant beam lifetime and stability issues, and identified areas requiring further R and D. Since the conclusion of the Reference Designs Study, work has focused on the key SSC design issue, namely, single-particle stability in an imperfect magnetic field. At the end of fiscal 1984, much of the LBL accelerator physics group took its place in the SSC Central Design Group, whose headquarters at LBL will be the focus of nationwide SSC R and D efforts over the next several years

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/

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.

Parameter selection for the SSC trade-offs and optimization

International Nuclear Information System (INIS)

Edwards, D.A.; Syphers, M.J.

1991-01-01

In November of 1988, a site was selected in the state of Texas for the SSC. In January of 1989, the SSC Laboratory was established in Texas to adapt the design of the collider to the site and to manage the construction of the project. This paper describes the evolution of the SSC design since site selection, notes the increased concentration on the injector system, and addresses the rationale for choice of parameters

Autoantibodies to the Rpp25 component of the Th/To complex are the most common antibodies in patients with systemic sclerosis without antibodies detectable by widely available commercial tests.

Science.gov (United States)

Mahler, Michael; Satoh, Minoru; Hudson, Marie; Baron, Murray; Chan, Jason Y F; Chan, Edward K L; Wick, James; Fritzler, Marvin J

2014-07-01

Antinuclear antibodies (ANA) occur in up to 95% of patients with systemic sclerosis (SSc). In most, SSc-associated antibodies are detected (i.e., centromere, topoisomerase I, RNA polymerase III, PM/Scl, Ro52/TRIM21, and U1RNP). Ribonuclease P protein subunit p25, (Rpp25) is an autoantigenic component of the Th/To complex. The contribution of anti-Th/To and anti-Rpp25 antibodies to ANA positivity in patients with SSc remains unknown. Sera from 873 patients with SSc were tested for ANA, and SSc-associated antibodies were measured. Samples without antibodies to extractable nuclear antigens (ENA; n = 53, ANA+/ENA-), were analyzed by immunoprecipitation (IP) and metabolically labeled proteins and for anti-Rpp25 antibodies (n = 50) by a chemiluminescent immunoassay (CLIA) and Rpp25 ELISA. Anti-Th/To antibodies occurred in 19/53 (36%), as determined by IP, and were the most common autoantibody in ANA+/ENA- SSc. Of those samples, 50/53 were available for additional testing by CLIA and ELISA. Anti-Rpp25 antibodies were detected in 12 (24% CLIA) or 10 (20% ELISA) of 50 patients. Receiver-operating characteristic curve analysis showed similar discrimination between Th/To IP-positive (n = 19) and -negative samples (n = 31) by CLIA and ELISA (area under the curve 0.90 vs 0.87; p = 0.6691). The positive percent agreement between IP and CLIA or ELISA was 12/19 (63.2%, 95% CI 38.4-83.7%) or 10/19 (52.6%, 95% CI 73.3-94.2%), respectively. Negative percent agreement was 100% for both assays. Autoantibodies to the Th/To autoantigen are important in patients with SSc who have been considered negative for SSc-specific or SSc-associated antibodies by widely available commercial assays. Rpp25 can be considered a major target of anti-Th/To antibodies. Assays detecting anti-Th/To and anti-Rpp25 antibodies may be important in SSc.

Prognostic Role of Exhaled Breath Condensate pH and Fraction Exhaled Nitric Oxide in Systemic Sclerosis Related Interstitial Lung Disease.

Science.gov (United States)

Guillen-Del Castillo, Alfredo; Sánchez-Vidaurre, Sara; Simeón-Aznar, Carmen P; Cruz, María J; Fonollosa-Pla, Vicente; Muñoz, Xavier

2017-03-01

Interstitial lung disease (ILD) is one of the major causes of death in systemic sclerosis (SSc). This study investigated exhaled breath (EB) and exhaled breath condensate (EBC) biomarkers in patients with SSc and analyzed their role as a prognostic tool in SSc-related ILD. Fraction exhaled nitric oxide (FeNO) and exhaled carbon monoxide (eCO) measured in EB, together with pH, nitrite, nitrate and interleukin-6 levels measured in EBC were prospectively analyzed in 35 patients with SSc. Twelve patients had established ILD by chest high-resolution computed tomography (HRCT), and 23 patients showed no evidence of ILD. EB and EBC biomarkers were determined at inclusion, and pulmonary function tests were annually performed during 4 years of follow-up. No differences at baseline biomarkers levels were found between groups. In all patients studied, low EBC pH levels were associated with a decreased diffusing capacity for carbon monoxide (DLCO) during follow-up. Low FeNO levels were correlated with lower forced vital capacity (FVC) at baseline, 4years of follow-up and with a decrease in FVC and DLCO during monitoring. Among ILD patients, high eCO levels were correlated with lower baseline FVC. In the global cohort, a worse progression-free survival was identified in patients with EBC pH values lower than 7.88 and FeNO levels lower than 10.75ppb (Log Rank P=.03 and P<.01, respectively). EB and EBC could help to detect patients likely to present a deterioration on lung function during follow up. Copyright © 2016 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

Validation of the Social Appearance Anxiety Scale in Patients with Systemic Sclerosis: A Scleroderma Patient-centered Intervention Network Cohort Study.

Science.gov (United States)

Mills, Sarah D; Kwakkenbos, Linda; Carrier, Marie-Eve; Gholizadeh, Shadi; Fox, Rina S; Jewett, Lisa R; Gottesman, Karen; Roesch, Scott C; Thombs, Brett D; Malcarne, Vanessa L

2018-01-17

Systemic sclerosis (SSc) is an autoimmune disease that can cause disfiguring changes in appearance. This study examined the structural validity, internal consistency reliability, convergent validity, and measurement equivalence of the Social Appearance Anxiety Scale (SAAS) across SSc disease subtypes. Patients enrolled in the Scleroderma Patient-centered Intervention Network Cohort completed the SAAS and measures of appearance-related concerns and psychological distress. Confirmatory factor analysis (CFA) was used to examine the structural validity of the SAAS. Multiple-group CFA was used to determine if SAAS scores can be compared across patients with limited and diffuse disease subtypes. Cronbach's alpha was used to examine internal consistency reliability. Correlations of SAAS scores with measures of body image dissatisfaction, fear of negative evaluation, social anxiety, and depression were used to examine convergent validity. SAAS scores were hypothesized to be positively associated with all convergent validity measures, with correlations significant and moderate to large in size. A total of 938 patients with SSc were included. CFA supported a one-factor structure (CFI: .92; SRMR: .04; RMSEA: .08), and multiple-group CFA indicated that the scalar invariance model best fit the data. Internal consistency reliability was good in the total sample (α = .96) and in disease subgroups. Overall, evidence of convergent validity was found with measures of body image dissatisfaction, fear of negative evaluation, social anxiety, and depression. The SAAS can be reliably and validly used to assess fear of appearance evaluation in patients with SSc, and SAAS scores can be meaningfully compared across disease subtypes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A data acquisition architecture for the SSC

International Nuclear Information System (INIS)

Partridge, R.

1990-01-01

An SSC data acquisition architecture applicable to high-p T detectors is described. The architecture is based upon a small set of design principles that were chosen to simplify communication between data acquisition elements while providing the required level of flexibility and performance. The architecture features an integrated system for data collection, event building, and communication with a large processing farm. The interface to the front end electronics system is also discussed. A set of design parameters is given for a data acquisition system that should meet the needs of high-p T detectors at the SSC

Patient phenotypes in fibromyalgia comorbid with systemic sclerosis or rheumatoid arthritis: influence of diagnostic and screening tests. Screening with the FiRST questionnaire, diagnosis with the ACR 1990 and revised ACR 2010 criteria.

Science.gov (United States)

Perrot, Serge; Peixoto, Mariana; Dieudé, Philippe; Hachulla, Eric; Avouac, Jerome; Ottaviani, Sebastien; Allanore, Yannick

2017-01-01

Fibromyalgia (FM) may occur with rheumatoid arthritis (RA) and systemic sclerosis (SSc), and debate remains about its diagnosis. We aimed to use three FM tools (a screening tool (FiRST), diagnostic criteria (ACR 1990 and revised 2010), to compare FM prevalence between RA and SSc patients, to describe the phenotypes of patients with comorbid FM, and to analyze links between FM and secondary Sjögren's syndrome (SS). Consecutive adult patients with confirmed RA or SSc from four university hospitals were tested with the three FM tools. FiRST detected FM in 22.6% of the 172 RA patients, with confirmation in 22.1% (ACR1990) and 19.1% (ACR2010). ACR1990FM+ RA patients had more diffuse pain, whereas ACR2010FM+ RA patients had higher BMI and pain intensity, more diffuse pain, active disease, disability, and associated SS. FiRST detected FM in 27.8% of the 122 SSc patients, with confirmation in 30.3% (ACR1990) and 23.7% (ACR2010). ACR1990FM+ SSc patients had greater disability and pain intensity, and more diffuse pain, whereas ACR2010FM+ SSc patients had higher BMI, pain intensity, more disability and diffuse pain, and associated SS. Correlations between FM diagnostic and screening tool results were modest in both conditions. Secondary SS was associated with comorbid FM. The prevalence of FM is high in SSc and RA, whatever the FM diagnostic tool used. Secondary SS is associated with FM in both RA and SSc. The revised ACR 2010 FM criteria and FiRST screening tool reveal specific phenotypes potentially useful for improving disease management.

Avaliação da pressão venosa periférica na esclerose sistêmica Peripheral venous pressure in systemic sclerosis

Directory of Open Access Journals (Sweden)

João Potério-Filho

2004-02-01

Full Text Available OBJETIVO: Estabelecer a utilidade da medida indireta da pressão venosa periférica (PVP na avaliação de pacientes com esclerose sistêmica (ES, comparando com uma população controle normal. MÉTODOS: Estudo prospectivo avaliando 18 pacientes esclerodérmicas do sexo feminino (sendo oito delas com úlcera cutânea isquêmica submetidas à medida indireta da PVP (por pletismografia. Os dados foram comparados a um grupo controle normal de 18 mulheres hígidas, pareadas para idade. RESULTADOS: Os níveis de pressão arterial foram semelhantes nos dois grupos. Os valores de PVP estavam significativamente diminuídos nos pacientes com ES (58.9 ± 11.6 mmHg no grupo ES e 96.9 ± 7.1 mmHg no grupo controle; p OBJECTIVE: The aim of this prospective study was to establish the usefulness of indirect measurement of peripheral venous pressure (PVP in the evaluation of patients with systemic sclerosis (SSc, comparing them with a normal control population. METHODS: Eighteen female SSc patients (eight patients presenting cutaneous ischemic ulcers were submitted to indirect measurement of the PVP (by plethysmography, and data were compared with a control group of 18 healthy women, paired by age. RESULTS: Arterial pressure levels were similar in both groups. PVP levels were significantly decreased in the SSc patients (58.9 ± 11.6 mmHg in the SSc group and 96.9 ± 7.1 mmHg in the control group; p < 0.0001; in the SSc group, patients with ischemic ulcers presented PVP levels significantly decreased compared with those patients without ulcers (50.6 ± 10.8 mmHg in the ulcer group and 65.5 ± 7.2 mmHg in the group without ulcers; p = 0.006. CONCLUSIONS: It can be concluded that decreased PVP in SSc is associated with a decrease in the blood flow of these patients, predisposing them to cutaneous ischemic ulcers.

First beam extracted from the SSC

International Nuclear Information System (INIS)

Anon.

1986-01-01

On the 25th July 1986 the first 2,8 μA 66 MeV proton beam was successfully extracted from the separated sector cyclotron (SSC) at the National Accelerator Centre at Faure, South Africa. The beam has now also been transported for the first time down the high-energy beamline up to the last Faraday cup in front of the neutron therapy vault. A brief description of the extraction system of the SSC, consisting of an electrostatic extraction channel and two septum magnets is given

Cabling for an SSC silicon tracking system

International Nuclear Information System (INIS)

Ziock, H.; Boissevain, J.; Cooke, B.; Miller, W.

1990-01-01

As part of the Superconducting Super Collider Laboratory (SSCL) funded silicon tracking subsystem R ampersand D program, we examine the problems associated with cabling such a system. Different options for the cabling plant are discussed. A silicon microstrip tracking detector for an SSC experiment is an extremely complex system. The system consists of approximately 10 7 detector channels, each of which requires a communication link with the outside world and connections to the detector bias voltage supply, to a DC power supply for the onboard electronics, and to an adjustable discrimination level. The large number of channels and the short time between beam interactions (16 nanoseconds) dictates the need for high speed and large bandwidth communication channels, and a power distribution system that can handle the high current draw of the electronics including the large AC component due to their switching. At the same time the constraints imposed by the physics measurements require that the cable plant have absolutely minimal mass and radiation length. 4 refs., 2 figs

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...

SSC [Superconducting Super Collider] site evaluations

International Nuclear Information System (INIS)

1988-11-01

With this report, the SSC Site Task Force forwards to the Director, Office of Energy Research, US Department of Energy (DOE), its evaluation of the technical criteria and life-cycle costs for the proposed SSC sites judged to be the best qualified. The criteria against which each site was evaluated are those set forth in the Invitation for Site Proposals for the Superconducting Super Collider (DOE/ER-0315) (Invitation) which was prepared by the Task Force and issued in April 1987. The methodology followed by the Task Force in this report and in all other phases of the proposal evaluation has been consistent with the SSC site selection process approved by DOE's Energy System Acquisition Advisory Board (ESAAB). The goal of the site selection process is to identify a site that will permit the highest level of research productivity and overall effectiveness of the SSC at a reasonable cost of construction and operation and with minimial impact on the environment. The Task Force acknowledges that all seven sites are, indeed, highly qualified locations for the construction and operation of the SSC on the basis of technical and cost considerations. In performing its evaluation, which is presented in this paper, the Task Force took an in-depth look at each site on the basis of site visits and extensive technical analyses. A consensus rating for each technical evaluation criterion and subcriterion was developed for each site

Decoupling schemes for the SSC Collider

International Nuclear Information System (INIS)

Cai, Y.; Bourianoff, G.; Cole, B.; Meinke, R.; Peterson, J.; Pilat, F.; Stampke, S.; Syphers, M.; Talman, R.

1993-05-01

A decoupling system is designed for the SSC Collider. This system can accommodate three decoupling schemes by using 44 skew quadrupoles in the different configurations. Several decoupling schemes are studied and compared in this paper

Radiation effects at the SSC

Energy Technology Data Exchange (ETDEWEB)

Gilchriese, M.G.D. [ed.] [Superconducting Super Collider Lab., Dallas, TX (United States)

1988-06-01

This report contains a preliminary study of the effects of the radiation levels expected at the SSC on potential detector components and a subset of materials to be used in the SSC accelerators. The report does not contain a discussion of radiation damage to electronics components that may be used at the SSC. We have investigated many of the effects of radiation on silicon detectors, on wire chambers, on scintillating materials and the associated readout, on optical fibers for data transmission and on structural or other materials to be used in detector or accelerator components. In the SSC accelerator complex, in particular the storage rings, radiation damage will not present significant problems different than those now faced by existing high energy accelerators. We find that the effects of radiation damage on SSC detector components will be significant at the design luminosity of the ssc and will limit, or determine, many of the options for different detector components. In this regard the reader should keep in mind that, in the absence of a specific detector design, it is not possible to form definitive conclusions regarding the viability of the detector components. Since the radiation levels in experiments at the SSC will depend on the geometry and composition of the apparatus, simple yes /no generalizations about the feasibility of a detector component are not possible.

Human adipose mesenchymal stem cells as potent anti-fibrosis therapy for systemic sclerosis.

Science.gov (United States)

Maria, Alexandre T J; Toupet, Karine; Maumus, Marie; Fonteneau, Guillaume; Le Quellec, Alain; Jorgensen, Christian; Guilpain, Philippe; Noël, Danièle

2016-06-01

Displaying immunosuppressive and trophic properties, mesenchymal stem/stromal cells (MSC) are being evaluated as promising therapeutic options in a variety of autoimmune and degenerative diseases. Although benefits may be expected in systemic sclerosis (SSc), a rare autoimmune disease with fibrosis-related mortality, MSC have yet to be evaluated in this specific condition. While autologous approaches could be inappropriate because of functional alterations in MSC from patients, the objective of the present study was to evaluate allogeneic and xenogeneic MSC in the HOCl-induced model of diffuse SSc. We also questioned the source of human MSC and compared bone marrow- (hBM-MSC) and adipose-derived MSC (hASC). HOCl-challenged BALB/c mice received intravenous injection of BM-MSC from syngeneic BALB/c or allogeneic C57BL/6 mice, and xenogeneic hBM-MSC or hASC (3 donors each). Skin thickness was measured during the experiment. At euthanasia, histology, immunostaining, collagen determination and RT-qPCR were performed in skin and lungs. Xenogeneic hBM-MSC were as effective as allogeneic or syngeneic BM-MSC in decreasing skin thickness, expression of Col1, Col3, α-Sma transcripts, and collagen content in skin and lungs. This anti-fibrotic effect was not associated with MSC migration to injured skin or with long-term MSC survival. Interestingly, compared with hBM-MSC, hASC were significantly more efficient in reducing skin fibrosis, which was related to a stronger reduction of TNFα, IL1β, and enhanced ratio of Mmp1/Timp1 in skin and lung tissues. Using primary cells isolated from 3 murine and 6 human individuals, this preclinical study demonstrated similar therapeutic effects using allogeneic or xenogeneic BM-MSC while ASC exerted potent anti-inflammatory and remodeling properties. This sets the proof-of-concept prompting to evaluate the therapeutic efficacy of allogeneic ASC in SSc patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Productivity Losses and Costs in the Less-Common Systemic Autoimmune Rheumatic Diseases.

Science.gov (United States)

McCormick, Natalie; Marra, Carlo A; Aviña-Zubieta, J Antonio

2017-10-30

We synthesised the literature on productivity losses and costs in the less-common systemic autoimmune rheumatic diseases: Sjogren's syndrome (SjS), systemic sclerosis (SSc), poly/dermatomyositis (PM/DM), and systemic vasculitides (SV). Of 29 studies located, 12 were published 2012 onwards (SSc = 6, SjS = 2, PM/DM = 2, SV = 2). In these, 25% of PM/DM, and 21-26% of SV, were work disabled, 22% of SSc stopped work within 3 years of diagnosis, and annual costs of absenteeism in SSc averaged $12,024 2017 USD. Very few studies reported on costs, presenteeism (working at reduced levels), or unpaid productivity loss. Across multiple systemic autoimmune rheumatic diseases (SARDs), major drivers of lost productivity were generalised items like pain, depression, and fatigue, rather than disease-specific factors. Evidence suggests that work disability is common in SSc and strikes quickly. However, in SSc and other SARDs, more comprehensive estimates are needed, which include absenteeism and presenteeism from paid and unpaid work, costs, and drivers of productivity loss.

High IL-17E and low IL-17C dermal expression identifies a fibrosis-specific motif common to morphea and systemic sclerosis.

Directory of Open Access Journals (Sweden)

Paola Adele Lonati

Full Text Available 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 14 SSc, 5 morphea and 8 healthy donors (HD undergoing plastic surgery. Immunohistochemistry/immunofluorescence techniques were coupled to a semi-automated imaging quantification approach to determine the presence of the IL-17 family members in the skin. The in vitro effects induced by the IL-17 family members on fibroblasts from normal and SSc individuals were assessed by ELISA and RIA. RESULTS: Positive cells for each of the IL-17 isoforms investigated were present in the dermis of all the individuals tested, though with variable frequencies. SSc individuals had increased frequency of IL-17A+ (p = 0.0237 and decreased frequency of IL-17F+ (p = 0.0127 and IL-17C+ cells (p = 0.0008 when compared to HD. Similarly, morphea individuals had less frequent IL-17C+ cells (p = 0.0186 in their skin but showed similar number of IL-17A+ and IL-17F+ cells when compared to HD. Finally, IL-17E+ cells were more numerous in morphea (p = 0.0109 and tended to be more frequent in SSc than in HD. Fibroblast production of IL-6, MMP-1 and MCP-1 was enhanced in a dose-dependent manner in the presence of IL-17E and IL-17F, but not in the presence of IL-17C. None of the cytokine tested had significant effect on type I collagen production. Of interest, in SSc the frequency of both IL-17A and IL-17F positive cells increased with disease duration. CONCLUSIONS: The frequency of IL-17A and IL-17F distinguish SSc to morphea individuals while dermal expression of IL-17C (low and IL-17E (high

Can the Cancer-related Fatigue Case-definition Criteria Be Applied to Chronic Medical Illness? A Comparison between Breast Cancer and Systemic Sclerosis.

Science.gov (United States)

Kwakkenbos, Linda; Minton, Ollie; Stone, Patrick C; Alexander, Susanna; Baron, Murray; Hudson, Marie; Thombs, Brett D

2015-07-01

Fatigue is a crucial determinant of quality of life across rheumatic diseases, but the lack of agreed-upon standards for identifying clinically significant fatigue hinders research and clinical management. Case definition criteria for cancer-related fatigue were proposed for inclusion in the International Classification of Diseases. The objective was to evaluate whether the cancer-related fatigue case definition performed equivalently in women with breast cancer and systemic sclerosis (SSc) and could be used to identify patients with chronic illness-related fatigue. The cancer-related fatigue interview (case definition criteria met if ≥ 5 of 9 fatigue-related symptoms present with functional impairment) was completed by 291 women with SSc and 278 women successfully treated for breast cancer. Differential item functioning was assessed with the multiple indicator multiple cause model. Items 3 (concentration) and 10 (short-term memory) were endorsed significantly less often by women with SSc compared with cancer, controlling for responses on other items. Omitting these 2 items from the case definition and requiring 4 out of the 7 remaining symptoms resulted in a similar overall prevalence of cancer-related fatigue in the cancer sample compared with the original criteria (37.4% vs 37.8%, respectively), with 97.5% of patients diagnosed identically with both definitions. Prevalence of chronic illness-related fatigue was 36.1% in SSc using 4 of 7 symptoms. The cancer-related fatigue criteria can be used equivalently to identify patients with chronic illness-related fatigue when 2 cognitive fatigue symptoms are omitted. Harmonized definitions and measurement of clinically significant fatigue will advance research and clinical management of fatigue in rheumatic diseases and other conditions.

Fermilab R and D test facility for SSC magnets

International Nuclear Information System (INIS)

Strait, J.; Bleadon, M.; Hanft, R.; Lamm, M.; McGuire, K.; Mantsch, P.; Mazur, P.O.; Orris, D.; Pachnik, J.

1989-01-01

The test facility used for R and D testing of full scale development dipole magnets for the SSC is described. The Fermilab Magnet Test Facility, originally built for production testing of Tevatron magnets, has been substantially modified to allow testing also of SSC magnets. Two of the original six test stands have been rebuilt to accommodate testing of SSC magnets at pressures between 1.3 Atm and 4 Atm and at temperatures between 1.8 K and 4.8 K and the power system has been modified to allow operation to at least 8 kA. Recent magnets have been heavily instrumented with voltage taps to allow detailed study of quench location and propagation and with strain gage based stress, force and motion transducers. A data acquisition system has been built with a capacity to read from each SSC test stand up to 220 electrical quench signals, 32 dynamic pressure, temperature and mechanical transducer signals during quench and up to 200 high precision, low time resolution, pressure, temperature and mechanical transducer signals. The quench detection and protection systems is also described. 23 refs., 4 figs. 2 tabs

Dicty_cDB: SSC474 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available SS (Link to library) SSC474 (Link to dictyBase) - - - Contig-U07719-1 SSC474P (Link... to Original site) SSC474F 368 SSC474Z 238 SSC474P 606 - - Show SSC474 Library SS (Link to library) Clone ID SSC474 (Link to dict...yBase) Atlas ID - NBRP ID - dictyBase ID - Link to Contig Contig-U07719-1 Original site URL http://dict...logy vs DNA Score E Sequences producing significant alignments: (bits) Value N ( AU071762 ) Dictyostelium di...scoideum slug cDNA, clone SSC474. 448 e-121 1 ( AU060185 ) Dictyostelium discoideum slug cDNA, clone SLA535.

Chiral Lagrangians and the SSC

International Nuclear Information System (INIS)

Dawson, S.

1991-09-01

In the event that the SSC does not observe any resonances such as a Higgs boson or a techni-rho meson, we would like to know if the SSC can still discover something about the nature of the electroweak symmetry breaking. We will use chiral Lagrangian techniques to address this question and analyze their utility for studying events containing W and Z gauge bosons at the SSC. 20 refs., 4 figs

Gene-level association analysis of systemic sclerosis: A comparison of African-Americans and White populations.

Science.gov (United States)

Gorlova, Olga Y; Li, Yafang; Gorlov, Ivan; Ying, Jun; Chen, Wei V; Assassi, Shervin; Reveille, John D; Arnett, Frank C; Zhou, Xiaodong; Bossini-Castillo, Lara; Lopez-Isac, Elena; Acosta-Herrera, Marialbert; Gregersen, Peter K; Lee, Annette T; Steen, Virginia D; Fessler, Barri J; Khanna, Dinesh; Schiopu, Elena; Silver, Richard M; Molitor, Jerry A; Furst, Daniel E; Kafaja, Suzanne; Simms, Robert W; Lafyatis, Robert A; Carreira, Patricia; Simeon, Carmen Pilar; Castellvi, Ivan; Beltran, Emma; Ortego, Norberto; Amos, Christopher I; Martin, Javier; Mayes, Maureen D

2018-01-01

Gene-level analysis of ImmunoChip or genome-wide association studies (GWAS) data has not been previously reported for systemic sclerosis (SSc, scleroderma). The objective of this study was to analyze genetic susceptibility loci in SSc at the gene level and to determine if the detected associations were shared in African-American and White populations, using data from ImmunoChip and GWAS genotyping studies. The White sample included 1833 cases and 3466 controls (956 cases and 2741 controls from the US and 877 cases and 725 controls from Spain) and the African American sample, 291 cases and 260 controls. In both Whites and African Americans, we performed a gene-level analysis that integrates association statistics in a gene possibly harboring multiple SNPs with weak effect on disease risk, using Versatile Gene-based Association Study (VEGAS) software. The SNP-level analysis was performed using PLINK v.1.07. We identified 4 novel candidate genes (STAT1, FCGR2C, NIPSNAP3B, and SCT) significantly associated and 4 genes (SERBP1, PINX1, TMEM175 and EXOC2) suggestively associated with SSc in the gene level analysis in White patients. As an exploratory analysis we compared the results on Whites with those from African Americans. Of previously established susceptibility genes identified in Whites, only TNFAIP3 was significant at the nominal level (p = 6.13x10-3) in African Americans in the gene-level analysis of the ImmunoChip data. Among the top suggestive novel genes identified in Whites based on the ImmunoChip data, FCGR2C and PINX1 were only nominally significant in African Americans (p = 0.016 and p = 0.028, respectively), while among the top novel genes identified in the gene-level analysis in African Americans, UNC5C (p = 5.57x10-4) and CLEC16A (p = 0.0463) were also nominally significant in Whites. We also present the gene-level analysis of SSc clinical and autoantibody phenotypes among Whites. Our findings need to be validated by independent studies, particularly

A front-end system for industrial type controls at the SSC

International Nuclear Information System (INIS)

Haenni, D.R.

1992-01-01

The SSC control system is tasked with coordinating the operation of many different accelerator subsystems, a number of which use industrial type process controls. The design of a high-performance control system front end is presented which serves both as a data concentrator and a distributed process controller. In addition it provides strong support for a centralized control system architecture, allows for regional control systems, and simplifies the construction of inter-subsystem controls. An implementation of this design will be discussed which uses STD-Bus for accelerator hardware interfacing, a time domain multiplexing (TDM) communications transport system, and a modified reflective memory interface to the rest of the control system. (author)

Tracking simulation and wire chamber requirements for the SSC

International Nuclear Information System (INIS)

Hanson, G.G.; Niczyporuk, B.B.; Palounek, A.P.T.

1988-11-01

Limitations placed on wire chambers by radiation damage and rate requirements in the SSC environment are reviewed. Possible conceptual designs for wire chamber tracking systems which meet these requirements are discussed. Computer simulation studies of tracking in such systems are presented. Simulations of events from interesting physics at the SSC, including hits from minimum bias background events, are examined. Results of some preliminary pattern recognition studies are given. 16 refs., 16 figs., 2 tabs

A dynamic model for beam tube vacuum effects on the SSC cryogenic system

International Nuclear Information System (INIS)

Carcagno, R.H.; Schiesser, W.E.; Shih, H.J.; Xu, X.; Yuecel, A.

1992-01-01

The dynamic interaction between the beam-gas scattering induced energy deposition and the SSC cryogenic system is studied by integrating a cryogenic system dynamic simulator with an adsorption model and a beam-gas scattering and energy deposition model. Simulation results are obtained for a 1km long SSC arc section where the beam tube pressure in one of the dipoles is increased up to 150 times its nominal operating pressure. The beam-gas scattering induced heat loads arising from such high pressure perturbations can be very high locally but do not overload the cryogenic system. They are more likely to induce a magnet quench as they result in coil temperatures that largely exceed the desired operating limit. Simulations are also carried out for the case where a large external heat load of 1W/m is imposed on the coldmass of a half-cell in the section. Results show that the coldmass temperatures rise significantly with the added heat load but the energy deposition in the cold mass due to beam-gas scattering remains low despite the increase in the beam tube temperature

A dynamic model for beam tube vacuum effects on the SSC cryogenic system

International Nuclear Information System (INIS)

Carcagno, R.H.; Schiesser, W.E.; Shih, H.J.; Xu, X.; Yuecel, A.

1992-03-01

The dynamic interaction between the beam-gas scattering induced energy deposition and the SSC cryogenic system is studied by integrating a cryogenic system dynamic simulator with an adsorption model and a beam-gas scattering and energy deposition model. Simulation results are obtained for a 1 km long SSC arc section where the beam tube pressure in one of the dipoles in increased up to 150 times its nominal operating pressure. The beam-gas scattering induced heat loads arising from such high pressure perturbations can be very locally but do not overload the cryogenic system. They are more likely to induce a magnet quench as they result in coil temperatures that largely exceed the desired operating limit. Simulations are also carried out for the case where a large external heat load of 1 W/m is imposed on the coldmass of a half-cell in the section. Results show that the coldmass temperatures rise significantly with the added heat load but the energy deposition in the coldmass due to beam-gas scattering remains low despite the increase in the beam tube temperature

Developing the Polish Educational Needs Assessment Tool (Pol-ENAT) in rheumatoid arthritis and systemic sclerosis: a cross-cultural validation study using Rasch analysis.

Science.gov (United States)

Sierakowska, Matylda; Sierakowski, Stanisław; Sierakowska, Justyna; Horton, Mike; Ndosi, Mwidimi

2015-03-01

To undertake cross-cultural adaptation and validation of the educational needs assessment tool (ENAT) for use with people with rheumatoid arthritis (RA) and systemic sclerosis (SSc) in Poland. The study involved two main phases: (1) cross-cultural adaptation of the ENAT from English into Polish and (2) Cross-cultural validation of Polish Educational Needs Assessment Tool (Pol-ENAT). The first phase followed an established process of cross-cultural adaptation of self-report measures. The second phase involved completion of the Pol-ENAT by patients and subjecting the data to Rasch analysis to assess the construct validity, unidimensionality, internal consistency and cross-cultural invariance. An adequate conceptual equivalence was achieved following the adaptation process. The dataset for validation comprised a total of 278 patients, 237 (85.3 %) of which were female. In each disease group (145, RA and 133, SSc), the 7 domains of the Pol-ENAT were found to fit the Rasch model, X (2)(df) = 16.953(14), p = 0.259 and 8.132(14), p = 0.882 for RA and SSc, respectively. Internal consistency of the Pol-ENAT was high (patient separation index = 0.85 and 0.89 for SSc and RA, respectively), and unidimensionality was confirmed. Cross-cultural differential item functioning (DIF) was detected in some subscales, and DIF-adjusted conversion tables were calibrated to enable cross-cultural comparison of data between Poland and the UK. Using a standard process in cross-cultural adaptation, conceptual equivalence was achieved between the original (UK) ENAT and the adapted Pol-ENAT. Fit to the Rasch model, confirmed that the construct validity, unidimensionality and internal consistency of the ENAT have been preserved.

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

Science.gov (United States)

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

2014-10-09

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. Eight-finger NVC was performed in 107 patients with SSc, and the total number of MHE/MT, GC, and the mean number of Cs were counted and defined as number of micro-haemorrhages (NEMO), GC and Cs scores, respectively. The European Scleroderma Study Group (ESSG) index constituted the gold standard for DA assessment, and scores ≥ 3.5 and = 3 were considered indicative of high and moderate activity, respectively. NEMO and GC scores were positively correlated with ESSG index (R = 0.65, P < 0.0001, and R = 0.47, P <0.0001, respectively), whilst Cs score showed a negative correlation with that DA index (R = -0.30, P <0.001). The area under the curve (AUC) of receiver operating characteristic plots, obtained by NEMO score sensitivity and specificity values in classifying patients with ESSG index ≥ 3.5, was significantly higher than the corresponding AUC derived from either GC or Cs scores (P <0.03 and P <0.0006, respectively). A modified score, defined by the presence of a given number of MHE/MT and GC, had a good performance in classifying active patients (ESSG index ≥ 3, sensitivity 95.1%, specificity 84.8%, accuracy 88.7%). MHE/MT and GC appear to be good indicators of DA in SSc, and enhances the role of NVC as an easy technique to identify active patients.

Diagnosis and Management of Systemic Sclerosis: A Practical Approach.

Science.gov (United States)

Lee, Jason J; Pope, Janet E

2016-02-01

Systemic sclerosis is a devastating multisystem rheumatologic condition that is characterized by autoimmunity, tissue fibrosis, obliterative vasculopathy and inflammation. Clinical presentation and course of the condition vary greatly, which complicates both diagnosis and corresponding treatment. In this regard, recent advances in disease understanding, both clinically and biochemically, have led to newer classification criteria for systemic sclerosis that are more inclusive than ever before. Still, significant disease modifying therapies do not yet exist for most patients. Therefore, organ-based management strategies are employed and research has been directed within this paradigm focusing on either the most debilitating symptoms, such as Raynaud's phenomenon, digital ulcers and cutaneous sclerosis, or life-threatening organ involvement such as interstitial lung disease and pulmonary arterial hypertension. The current trends in systemic sclerosis diagnosis, evidence-based treatment recommendations and potential future directions in systemic sclerosis treatment are discussed.

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)

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.

Tomography patterns of lung disease in systemic sclerosis

International Nuclear Information System (INIS)

Bastos, Andrea de Lima; Correa, Ricardo de Amorim; Ferreira, Gilda Aparecida

2016-01-01

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)

Experimentally-derived fibroblast gene signatures identify molecular pathways associated with distinct subsets of systemic sclerosis patients in three independent cohorts.

Directory of Open Access Journals (Sweden)

Michael E Johnson

Full Text Available Genome-wide expression profiling in systemic sclerosis (SSc has identified four 'intrinsic' subsets of disease (fibroproliferative, inflammatory, limited, and normal-like, each of which shows deregulation of distinct signaling pathways; however, the full set of pathways contributing to this differential gene expression has not been fully elucidated. Here we examine experimentally derived gene expression signatures in dermal fibroblasts for thirteen different signaling pathways implicated in SSc pathogenesis. These data show distinct and overlapping sets of genes induced by each pathway, allowing for a better understanding of the molecular relationship between profibrotic and immune signaling networks. Pathway-specific gene signatures were analyzed across a compendium of microarray datasets consisting of skin biopsies from three independent cohorts representing 80 SSc patients, 4 morphea, and 26 controls. IFNα signaling showed a strong association with early disease, while TGFβ signaling spanned the fibroproliferative and inflammatory subsets, was associated with worse MRSS, and was higher in lesional than non-lesional skin. The fibroproliferative subset was most strongly associated with PDGF signaling, while the inflammatory subset demonstrated strong activation of innate immune pathways including TLR signaling upstream of NF-κB. The limited and normal-like subsets did not show associations with fibrotic and inflammatory mediators such as TGFβ and TNFα. The normal-like subset showed high expression of genes associated with lipid signaling, which was absent in the inflammatory and limited subsets. Together, these data suggest a model by which IFNα is involved in early disease pathology, and disease severity is associated with active TGFβ signaling.

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.

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.

WLWL scattering at the SSC

International Nuclear Information System (INIS)

Bagger, J.; Valencia, G.

1990-01-01

We use higher-order chiral Lagrangians to study W L W L scattering at the SSC. We analyze a model that is consistent with crossing, unitarity and chiral symmetry, with no resonant behavior at SSC energies. The only signal is a slightly enhanced rate for W L W L scattering. Our results indicate the level of sensitivity that must be reached before the SSC can be assured of discovering the mechanism for electroweak symmetry breaking. 19 refs., 4 figs., 2 tabs

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

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Anusha Venkataraman

2015-01-01

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

An engineering design network for SSC detector development

International Nuclear Information System (INIS)

DiGiacomo, N.J.

1990-01-01

The detector systems that are being proposed to exploit the capabilities of the SSC are of a scale and scope that will make them among the most complex devices ever built. To successfully design and build these systems over the next decade, the authors must make use of integrated state of the art computer aided engineering and design (CAE/CAD) tools that have been developed and employed in industry. The challenge is to made these tools and associated engineering resources available to the spectrum of institutions - large and small universities, industries and national labs - involved in SSC detector development in such a way that each may contribute and participate in the most effective manner. The authors believe that powerful workstations running sophisticated modeling, analysis and simulation software, linked by high speed data networks and governed by modern configuration management methods offer the ideal means of arriving at the optimum detector configuration for physics at the SSC

Systemic sclerosis without antinuclear antibodies or Raynaud's phenomenon

DEFF Research Database (Denmark)

Schneeberger, D.; Tyndall, A.; Walker, U.A.

2013-01-01

Objective: To assess patients with SSc who present without circulating antinuclear antibodies (ANA) or Raynaud’s phenomenon (RP). Methods: 5390 patients who fulfilled the ACR criteria for SSc and were enrolled in the EULAR Scleroderma Trials And Research (EUSTAR) database were screened for the ab......Objective: To assess patients with SSc who present without circulating antinuclear antibodies (ANA) or Raynaud’s phenomenon (RP). Methods: 5390 patients who fulfilled the ACR criteria for SSc and were enrolled in the EULAR Scleroderma Trials And Research (EUSTAR) database were screened...

Can Serum Surfactant Protein D or CC-Chemokine Ligand 18 Predict Outcome of Interstitial Lung Disease in Patients with Early Systemic Sclerosis?

Science.gov (United States)

Elhaj, Mona; Charles, Julio; Pedroza, Claudia; Liu, Xiaochun; Zhou, Xiaodong; Estrada-Y-Martin, Rosa M.; Gonzalez, Emilio B.; Lewis, Dorothy E.; Draeger, Hilda T.; Kim, Sarah; Arnett, Frank C.; Mayes, Maureen D.; Assassi, Shervin

2013-01-01

Objective To examine the predictive significance of 2 pneumoproteins, surfactant protein D (SP-D) and CC-chemokine ligand 18 (CCL18), for the course of systemic sclerosis (SSc)-related interstitial lung disease. Methods The pneumoproteins were determined in the baseline plasma samples of 266 patients with early SSc enrolled in the GENISOS observational cohort. They also were measured in 83 followup patient samples. Pulmonary function tests were obtained annually. The primary outcome was decline in forced vital capacity (FVC percentage predicted) over time. The predictive significance for longterm change in FVC was investigated by a joint analysis of longitudinal measurements (sequentially obtained FVC percentage predicted) and survival data. Results SP-D and CCL18 levels were both higher in patients with SSc than in matched controls (p < 0.001 and p = 0.015, respectively). Baseline SP-D levels correlated with lower concomitantly obtained FVC (r = −0.27, p < 0.001), but did not predict the short-term decline in FVC at 1 year followup visit or its longterm decline rate. CCL18 showed a significant correlation with steeper short-term decline in FVC (p = 0.049), but was not a predictor of its longterm decline rate. Similarly, a composite score of SP-D and CCL18 was a significant predictor of short-term decline in FVC but did not predict its longterm decline rate. Further, the longitudinal change in these 2 pneumoproteins did not correlate with the concomitant percentage change in FVC. Conclusion SP-D correlated with concomitantly obtained FVC, while CCL18 was a predictor of short-term decline in FVC. However, neither SP-D nor CCL18 was a longterm predictor of FVC course in patients with early SSc. PMID:23588945

Relationship between adiponectin, leptin, IGF-1 and total lipid peroxides plasma concentrations in patients with systemic sclerosis: possible role in disease development.

Science.gov (United States)

Winsz-Szczotka, Katarzyna; Kuźnik-Trocha, Kornelia; Komosińska-Vassev, Katarzyna; Kucharz, Eugeniusz; Kotulska, Anna; Olczyk, Krystyna

2016-07-01

The relationship between adiponectin, leptin, insulin-like growth factor-1 (IGF-1) and total lipid peroxide (TLP) concentrations, and its possible role in the development of diffuse cutaneous systemic sclerosis (dcSSc), were evaluated in this study. Plasma adipokines and IGF-1 levels were determined using the enzyme-linked immunosorbent assay method, whereas TLP levels were determined using a photometric test, in 36 dcSSc patients and 40 healthy controls matched by age, sex and body mass index (BMI). Plasma levels of adipokines were significantly lowered, while TLP and IGF-1 were increased in dcSSc patients compared to controls. Adiponectin correlated significantly with leptin (r = 0.44), TLP (r = -0.54), CRP (r = -0.47), erythrocyte sedimentation rate (ESR) (r = -0.40) and duration of disease (r = -0.44). A significant relationship was found between leptinemia and IGF-1 (r = -0.40), TLP (r = 0.44), duration of disease (r = -0.38) and BMI (r = 0.65). TLP correlated with IGF-1 (r = -0.43), C-reactive protein (r = 0.47), ESR (r = 0.49) and duration of disease (r = 0.46), while IGF-1 correlated with ESR (r = -0.40). Adipose tissue may play a complex role in the development of dcSSc, affecting both the metabolic state of the organism, as well as free radical-induced connective tissue degradation. Although, leptin seems to exert a pro-oxidative effect and both adiponectin and IGF-1 appear to prevent free radical damage, confirmation of the above effects requires further research. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Educational opportunities from the SSC

International Nuclear Information System (INIS)

Doddy, G.J.; Rider, A.H.; Halff, A.H.

1990-01-01

High energy physics and education are very closely interwoven. Most physics laboratories are located at universities or are operated by consortiums of universities. Fermilab and the SSC are operated by the Universities Research Association, URA, a consortium of 69 major research universities and 3 associate members. Another example of this laboratory and universities relationship is the Continuous Electron Beam Accelerator Facility, CEBAF, which is operated by the Southeastern Universities Research Association, SURA, another consortium of 39 major universities. The education potential inherent in the planning, construction and operation of the SSC is immense. The SSC, as the world's largest scientific instrument and, as the most power accelerator, will have a natural attraction as the preeminent institution in the scientific community. In addition to the primary objective of probing the fundamental composition of matter, the SSC will appear to a broad segment of the population and will create the opportunity for both passive and active educational experiences on the part of staff, students and visitors. On the esoteric level, the SSC will be a magnet for the scientific community and will attract from around the world the finest minds in the field of high energy physics. On the human level, the laboratory will become an integral part of the community and will be an object of great interest to local residents and visitors. The SSC planners should recognize the opportunity to be a contributing institution to both the local and the world community

Cross-Language Measurement Equivalence of the Center for Epidemiologic Studies Depression (CES-D) Scale in Systemic Sclerosis: A Comparison of Canadian and Dutch Patients

Science.gov (United States)

Kwakkenbos, Linda; Arthurs, Erin; van den Hoogen, Frank H. J.; Hudson, Marie; van Lankveld, Wim G. J. M.; Baron, Murray; van den Ende, Cornelia H. M.; Thombs, Brett D.

2013-01-01

Objectives Increasingly, medical research involves patients who complete outcomes in different languages. This occurs in countries with more than one common language, such as Canada (French/English) or the United States (Spanish/English), as well as in international multi-centre collaborations, which are utilized frequently in rare diseases such as systemic sclerosis (SSc). In order to pool or compare outcomes, instruments should be measurement equivalent (invariant) across cultural or linguistic groups. This study provides an example of how to assess cross-language measurement equivalence by comparing the Center for Epidemiologic Studies Depression (CES-D) scale between English-speaking Canadian and Dutch SSc patients. Methods The CES-D was completed by 922 English-speaking Canadian and 213 Dutch SSc patients. Confirmatory factor analysis (CFA) was used to assess the factor structure in both samples. The Multiple-Indicator Multiple-Cause (MIMIC) model was utilized to assess the amount of differential item functioning (DIF). Results A two-factor model (positive and negative affect) showed excellent fit in both samples. Statistically significant, but small-magnitude, DIF was found for 3 of 20 items on the CES-D. The English-speaking Canadian sample endorsed more feeling-related symptoms, whereas the Dutch sample endorsed more somatic/retarded activity symptoms. The overall estimate in depression scores between English and Dutch was not influenced substantively by DIF. Conclusions CES-D scores from English-speaking Canadian and Dutch SSc patients can be compared and pooled without concern that measurement differences may substantively influence results. The importance of assessing cross-language measurement equivalence in rheumatology studies prior to pooling outcomes obtained in different languages should be emphasized. PMID:23326538

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.

Physics possibilities at LHC/SSC

International Nuclear Information System (INIS)

Hinchliffe, I.

1991-01-01

This document reviews some recent work on physics simulations for SSC/LHC. Included are reviews of some of the recent developments in physics simulations for the SSC/LHC and comments upon the requirements that are placed upon detectors by the need to extract specific physics signatures. The material in the various EOI/LOI documents submitted to the SCC Laboratory and the work done at the Aachen LHC workshop are discussed. In the following discussion 1 SSC (LHC) year corresponds to an integrated luminosity of 10 (100) fb -1 . 41 refs., 14 figs

Overview of a robotic system for azimuthal dimensions of SSC dipole coils

International Nuclear Information System (INIS)

Assell, D.L.; Cahill, J.M.; Carson, J.A.; Connolly, D.F.; Pawlak, S.K.; Rihel, R.K.; Robatzek, W.R.; Robotham, W.F.; Skweres, T.M.; Schmitz, E.; Sims, R.; Ullmark, R.

1992-01-01

This system measures the azimuthal dimensions of SSC dipole long coils automatically, taking over 500 measurements in less than four hours. These measurements are then analyzed and displayed via software reports which reveal coil statistics, point by point dimensional graphics, modulus of elasticity measurements, comparisons with previous coils and pre-collaring shimming information. The rapid turnaround of this system yields the ability to spot process variables and fine tune the fabrication techniques. This process will aid in producing coils to the required precision

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

Relational databases for SSC design and control

International Nuclear Information System (INIS)

Barr, E.; Peggs, S.; Saltmarsh, C.

1989-01-01

Most people agree that a database is A Good Thing, but there is much confusion in the jargon used, and in what jobs a database management system and its peripheral software can and cannot do. During the life cycle of an enormous project like the SSC, from conceptual and theoretical design, through research and development, to construction, commissioning and operation, an enormous amount of data will be generated. Some of these data, originating in the early parts of the project, will be needed during commissioning or operation, many years in the future. Two of these pressing data management needs-from the magnet research and industrialization programs and the lattice design-have prompted work on understanding and adapting commercial database practices for scientific projects. Modern relational database management systems (rDBMS's) cope naturally with a large proportion of the requirements of data structures, like the SSC database structure built for the superconduction cable supplies, uses, and properties. This application is similar to the commercial applications for which these database systems were developed. The SSC application has further requirements not immediately satisfied by the commercial systems. These derive from the diversity of the data structures to be managed, the changing emphases and uses during the project lifetime, and the large amount of scientific data processing to be expected. 4 refs., 5 figs

The treatment of diffuse cutaneous systemic sclerosis with autologous hemopoietic stem cells transplantation (HSCT: our experience on 2 cases

Directory of Open Access Journals (Sweden)

A. Tyndall

2011-09-01

Full Text Available Objectives: Autologous hematopoietic stem cell transplantation (HSCT is a treatment option which may be considered for severe diffuse cutaneous systemic sclerosis (dcSSc patients not responding to cyclophophamide (CY. We present two cases of dcSSc not responding to CY >10 g who were successfully treated with HSCT. Patients and methods: Two dcSSc patients were unresponsive to monthly i.v. pulse of CYC (0.75 g m2. Both patients had significant reduction of DLCO and mild-moderate pulmonary hypertension and HSCT was considered due to the rapid progression of the disease. Following informed consent and ethics committee approval, HSCT was performed. Mobilisation was performed with CY 4g/m2 and recombinant human granulocyte colony stimulating factor (rHu GCSF followed by a successful apheresis (CD34+ cells, >7X106. Conditioning regimens were: CY 100mg/kg body weight plus thiotepa 10 mg/ kg in the first patient and CY 200 mg/kg in the second. Both graft products were CD34 selected. No arrythmias occurred during the procedure and no other severe side effects were observed during hospitalisation. Results: Follow up: Patients underwent a monthly follow up with physical examination, pulmonary function tests and echocardiography every 3 months. Chest CT has been performed 6 months post transplantation. The following was observed: skin score (from 40 to 10 for the first patient and from 38 to 12 for the second one, LVEF and pulmonary function remained stable, PAP decreased from 45 mmHg to 35 mmHg and from 40 to 32 mmHg. No late complications or cardiac toxicity was observed. Conclusion: These two dcSSc cases demonstrate that HSCT may be successfully performed without serious side effects in cases in whom despite a cumulative CY dose was ineffective. This suggests an “immunological threshold” effect which may be exploited in other severe, therapy refractory autoimmune cases.

Overview and status of RF systems for the SSC Linac

International Nuclear Information System (INIS)

Mynk, J.; Grippe, J.; Cutler, R.I.; Rodriguez, R.

1993-05-01

The Superconducting Super Collider (SSC) Linear Accelerator (Linac) produces a 600-MeV, 35-μs, H-beam at a 10-Hz repetition rate. The beam is accelerated by a series of RF cavities. These consist of a Radio Frequency Quadrupole (RFQ), two bunchers, and four Drift Tube Linac (DTL) tanks at 427.617 MHz, and two bunchers, nine side-coupled Linac modules, and an energy compressor at 1282.851 MHz. The RFQ amplifier and the low-frequency buncher cavity amplifiers use gridded tubes, while the other cavities use klystron amplifier systems. The RF control system consists of a reference line and cavity feedback and feedforward loops for each amplifier. The RF amplifier system for each of these accelerator cavities is described, and the current status of each system is presented

Plans for industrial production of the SSC magnets

International Nuclear Information System (INIS)

Karpenko, V.N.; Rardin, D.C.

1986-01-01

The Universities Research Association through its Central Design Group is currently conducting research and development for the Department of Energy on a superconducting super collider (SSC). The proposed SSC is a device in which protons would be accelerated around a ring approximately 50 miles in circumference. The protons would be kept in their path by means of thousands of powerful superconducting magnets. Two such rings of magnets would be housed in a common underground tunnel, allowing groups of protons to be accelerated in opposite directions and collided, in order to study the fundamental nature of matter and energy. The magnet system is a major element of the SSC in terms of technical requirements, quantity of components and cost. In order to meet technical and production requirements imposed by this system early participation of industry is necessary. The program plans were developed with the objective to involve industry in the early stages of research and development of superconducting magnets, leading to cost effective processes of potential mass production of high quality accelerator magnets by industry. While a decision has not been made by the Department of Energy on whether or not to request construction of the SSC project, if such a request is made and the project is authorized and funded, it would lead to industrial manufacture of a large quantity of superconducting magnets

Cooldown and warmup computer simulations of the SSC ring

International Nuclear Information System (INIS)

Carcagno, R.H.; Schiesser, W.E.; Yuecel, A.

1991-06-01

The Superconducting Super Collider (SSC) consists of two stacked rings of superconducting magnets; each ring is about 86 km in circumference. The total mass to be cooled to liquid helium temperature amounts to about 1 x 10 8 kg, and the total helium inventory under nominal operating conditions (4.15 K and 4 atm) is about 2.8 x 10 5 kg. The cooldown and warmup process of a long string of magnets has to be well understood in order to design a cryogenic system that can satisfy the requirements of helium inventory handling, magnet temperature gradients, and process time for the different cooldown and warmup scenarios being planned for the SSC. A system that can be convincingly simulated can be understood, controlled, operated and improved in a systematic way. In this paper, we introduce two numerical models, a lumped model and a distributed model, for cooldown and warmup of the SSC ring, and present simulation results for an SSC string (4320 m long, or 1/20th of the full ring circumference). The models cover the temperature range between room and liquid helium temperature; the distributed model includes radial temperature distribution in the cold mass. Low temperature range simulations are particularly important to study inventory handling strategies because of the relationship between rapid changes in density and the system mass flow rate. 9 refs., 9 figs

SSC muon detector group report

International Nuclear Information System (INIS)

Carlsmith, D.; Groom, D.; Hedin, D.; Kirk, T.; Ohsugi, T.; Reeder, D.; Rosner, J.; Wojcicki, S.

1986-01-01

We report here on results from the Muon Detector Group which met to discuss aspects of muon detection for the reference 4π detector models put forward for evaluation at the Snowmass 1986 Summer Study. We report on: suitable overall detector geometry; muon energy loss mechanisms; muon orbit determination; muon momentum and angle measurement resolution; raw muon rates and trigger concepts; plus we identify SSC physics for which muon detection will play a significant role. We conclude that muon detection at SSC energies and luminosities is feasible and will play an important role in the evolution of physics at the SSC

SSC muon detector group report

Energy Technology Data Exchange (ETDEWEB)

Carlsmith, D.; Groom, D.; Hedin, D.; Kirk, T.; Ohsugi, T.; Reeder, D.; Rosner, J.; Wojcicki, S.

1986-01-01

We report here on results from the Muon Detector Group which met to discuss aspects of muon detection for the reference 4..pi.. detector models put forward for evaluation at the Snowmass 1986 Summer Study. We report on: suitable overall detector geometry; muon energy loss mechanisms; muon orbit determination; muon momentum and angle measurement resolution; raw muon rates and trigger concepts; plus we identify SSC physics for which muon detection will play a significant role. We conclude that muon detection at SSC energies and luminosities is feasible and will play an important role in the evolution of physics at the SSC.

Measuring structure functions at SSC energies

International Nuclear Information System (INIS)

Morfin, J.G.; Owens, J.F.

1985-01-01

Topics discussed include measuring Λ, tests of QCD using hard scattering processes, and measuring parton distributions. In each case, any opportunities and advantages afforded by the unique features of the SSC are emphasized. The working group on structure functions was charged with investigating two specific questions: (1) How well are the various parton distributions known in the kinematic region relevant to calculations for the SSC. (2) What new information can be learned about parton distributions at the SSC. Especially for this working group, the advantages of having a fixed-target facility at the SSC for the measurement of the parton distributions with multi-TeV leptons, were to be examined. 15 references

Overview and statistical failure analyses of the electrical insulation system for the SSC long dipole magnets from an industrialization point of view

International Nuclear Information System (INIS)

Roach, J.F.

1992-01-01

The electrical insulation system of the SSC long dipole magnets is reviewed and potential dielectric failure modes discussed. Electrical insulation fabrication and assembly issues with respect to rate production manufacturability are addressed. The automation required for rate assembly of electrical insulation components will require critical online visual and dielectric screening tests to insure production quality. Storage and assembly areas must bc designed to prevent foreign particles from becoming entrapped in the insulation during critical coil winding, molding, and collaring operations. All hand assembly procedures involving dielectrics must be performed with rigorous attention to their impact on insulation integrity. Individual dipole magnets must have a sufficiently low probability of electrical insulation failure under all normal and fault mode voltage conditions such that the series of magnets in the SSC rings have acceptable Mean Time Between Failure (MTBF) with respect to dielectric mode failure events. Statistical models appropriate for large electrical system breakdown failure analysis are applied to the SSC magnet rings. The MTBF of the SSC system is related to failure data base for individual dipole magnet samples

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.

Prospects for SSC physics

International Nuclear Information System (INIS)

Paige, F.E.

1986-03-01

The SSC is primarily designed to explore the physics of the 1 TeV mass scale. Since new heavy particles will decay either into other new particles or into the quanta of the standard model, the main goal of SSC experiments will be to identify and to measure these quanta well. Progress in simulating events and in understanding the signature and backgrounds for standard-model physics is described. 51 refs

Proposal for a cryogenic magnetic field measurement system for SSC dipole magnets

International Nuclear Information System (INIS)

Green, M.I.; Hansen, L.

1991-03-01

This proposal describes the research and development required, and the subsequent fabrication of, a system capable of making integrated magnetic multipole measurements of cryogenic 40-mm-bore SSC dipole magnets utilizing a cryogenic probe. Our experience and some preliminary studies indicate that it is highly unlikely that a 16-meter-long probe can be fabricated that will have a twist below several milliradians at cryogenic temperatures. We would anticipate a twist of several milliradians just as a result of cooldown stresses. Consequently, this proposal describes a segmented 16-meter-long probe, for which we intend to calibrate the phase of each segment to within 0.1 milliradians. The data for all segments will be acquired simultaneously, and integrated data will be generated from the vector sums of the individual segments. The calibration techniques and instrumentation required to implement this system will be described. The duration of an integral measurement at one current is expected to be under 10 seconds. The system is based on an extrapolation of the techniques used at LBL to measure cryogenic 1-meter models of SSC magnets with a cryogenic probe. It should be noted that the expansion of the dipole bore from 40 to 50 mm may make a warm-finger device practical at a cost of approximately one quarter of the cryogenic probe. A warm quadrupole measurement system can be based upon the same principles. 5 refs., 9 figs., 1 tab

Dicty_cDB: SSC836 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available SS (Link to library) SSC836 (Link to dictyBase) - - - - SSC836E (Link to Original s...ite) - - - - - - SSC836E 502 Show SSC836 Library SS (Link to library) Clone ID SSC836 (Link to dictyBase) Atlas ID - NBRP ID - dict...yBase ID - Link to Contig - Original site URL http://dictycdb.biol.tsukuba.ac.jp/CSM/...t alignments: (bits) Value N M77492 |M77492.1 Dictyostelium discoideum glycoprotein phosphorylase 2 (glpD) g...ene, complete cds. 779 0.0 1 AC116984 |AC116984.2 Dictyostelium discoideum chromo

Cryogenic systems for the SSC and the status of their development

International Nuclear Information System (INIS)

Fietz, W.A.; Ganni, V.; Abramovich, S.; Niehaus, T.

1993-07-01

The Superconducting Super Collider (SSC) consists of two parallel magnet rings, each 87,120 m in circumference, constructed in a tunnel 25 to 74 m underground. Protons are injected into these ring from the high energy booster (HEB), which contains a separate magnet ring 10,800 m in circumference constructed in a tunnel 14 m above the collider tunnel. The magnets will be operated at a controlled low temperature in order to maintain the windings in the superconducting state. Therefore the magnet cryostat is designed with a high vacuum insulating chamber, multilayer insulation (MLI), and thermal shields at 84 K and 20 K nominal temperatures. The major portion of the heat load is from thermal radiation and conduction through the supports, and is intercepted and absorbed by the shields. The cryogenic system for the machine is divided into sectors of nominally equal length: ten for the collider and two for the HEB. Each sector has a dedicated cryogenic system (SCS) as well as some level of redundancy from the neighboring SCS. The helium refrigeration plants will be installed at the midpoint of each sector. Each cryogenic sector in the collider is divided into four strings, two upper and two lower, about 4000 m long. Each string is subdivided into sections of about 1080 m, the smallest modules that can be isolated for maintenance, or for warmup and cooldown. Each section is subdivided into cells and half cells. The half cell, containing six main magnets and a spool piece is 90 m long. The SSC cryogenic system for each sector consists of a sector refrigerator surface system (SRS) and a sector refrigerator tunnel system (SRT). Proposals for the SRS systems' are presently in review for vendor selection. In this paper the SRT subsystems requirements and their status will be reviewed

The impact of slice-reduced computed tomography on histogram-based densitometry assessment of lung fibrosis in patients with systemic sclerosis.

Science.gov (United States)

Nguyen-Kim, Thi Dan Linh; Maurer, Britta; Suliman, Yossra A; Morsbach, Fabian; Distler, Oliver; Frauenfelder, Thomas

2018-04-01

To evaluate usability of slice-reduced sequential computed tomography (CT) compared to standard high-resolution CT (HRCT) in patients with systemic sclerosis (SSc) for qualitative and quantitative assessment of interstitial lung disease (ILD) with respect to (I) detection of lung parenchymal abnormalities, (II) qualitative and semiquantitative visual assessment, (III) quantification of ILD by histograms and (IV) accuracy for the 20%-cut off discrimination. From standard chest HRCT of 60 SSc patients sequential 9-slice-computed tomography (reduced HRCT) was retrospectively reconstructed. ILD was assessed by visual scoring and quantitative histogram parameters. Results from standard and reduced HRCT were compared using non-parametric tests and analysed by univariate linear regression analyses. With respect to the detection of parenchymal abnormalities, only the detection of intrapulmonary bronchiectasis was significantly lower in reduced HRCT compared to standard HRCT (P=0.039). No differences were found comparing visual scores for fibrosis severity and extension from standard and reduced HRCT (P=0.051-0.073). All scores correlated significantly (Phistogram parameters derived from both, standard and reduced HRCT. Significant higher values of kurtosis and skewness for reduced HRCT were found (both Phistogram parameters from reduced HRCT showed significant discrimination at cut-off 20% fibrosis (sensitivity 88% kurtosis and skewness; specificity 81% kurtosis and 86% skewness; cut-off kurtosis ≤26, cut-off skewness ≤4; both Phistogram parameters derived from the approach of reduced HRCT could discriminate at a threshold of 20% lung fibrosis with high sensitivity and specificity. Hence it might be used to detect early disease progression of lung fibrosis in context of monitoring and treatment of SSc patients.

Low vitamin D serum levels in diffuse systemic sclerosis: a correlation with worst quality of life and severe capillaroscopic findings.

Science.gov (United States)

Sampaio-Barros, Marília M; Takayama, Liliam; Sampaio-Barros, Percival D; Bonfá, Eloísa; Pereira, Rosa Maria R

2016-01-01

The aim of this study was to analyze the correlation of vitamin D levels with clinical parameters, bone mineral density (BMD), quality of life (QoL) and nailfold capillaroscopy (NC) in patients with diffuse systemic sclerosis (SSc). Thirty-eight female patients with diffuse SSc were analyzed regarding 25-hydroxyvitamin D (25OHD) serum levels. At inclusion, organ involvement, autoantibodies, modified Rodnan skin score (mRSS), Medsger Disease Severity Index (MDSI), body mass index (BMI), BMD, NC, Short-Form-36 Questionnaire (SF-36), and Health Assessment Questionnaire (HAQ), were performed through a standardized interview, physical examination and electronic chart review. Mean 25OHD serum level was 20.66±8.20ng/mL. Eleven percent of the patients had 25OHD levels ≤10ng/mL, 50% ≤20ng/mL and 87% ≤30ng/mL. Vitamin D serum levels were positively correlated with BMI (r=0.338, p=0.038), BMD-total femur (r=0.340, p=0.037), BMD-femoral neck (r=0.384, p=0.017), SF-36-Vitality (r=0.385, p=0.017), SF-36-Social Function (r=0.320, p=0.050), SF-36-Emotional Role (r=0.321, p=0.049) and SF-36-Mental Health (r=0.531, p=0.0006) and were negatively correlated with HAQ-Reach (r=-0.328, p=0.044) and HAQ-Grip Strength (r=-0.331, p=0.042). A negative correlation with NC-diffuse devascularization (p=0.029) and NC-avascular area (p=0.033) was also observed. The present study provides novel evidence demonstrating that low levels of 25OHD have a negative impact in diffuse SSc QoL and further studies are needed to define whether vitamin D supplementation can improve health related QoL in these patients. The additional observation of a correlation with severe NC alterations suggests a possible role of 25OHD in the underlying SSc vascular involvement. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Low vitamin D serum levels in diffuse systemic sclerosis: a correlation with worst quality of life and severe capillaroscopic findings

Directory of Open Access Journals (Sweden)

Marília M. Sampaio-Barros

Full Text Available ABSTRACT Objective: The aim of this study was to analyze the correlation of vitamin D levels with clinical parameters, bone mineral density (BMD, quality of life (QoL and nailfold capillaroscopy (NC in patients with diffuse systemic sclerosis (SSc. Methods: Thirty-eight female patients with diffuse SSc were analyzed regarding 25-hydroxyvitamin D (25OHD serum levels. At inclusion, organ involvement, autoantibodies, modified Rodnan skin score (mRSS, Medsger Disease Severity Index (MDSI, body mass index (BMI, BMD, NC, Short-Form-36 Questionnaire (SF-36, and Health Assessment Questionnaire (HAQ, were performed through a standardized interview, physical examination and electronic chart review. Results: Mean 25OHD serum level was 20.66 ± 8.20 ng/mL. Eleven percent of the patients had 25OHD levels ≤10 ng/mL, 50% ≤20 ng/mL and 87% ≤30 ng/mL. Vitamin D serum levels were positively correlated with BMI (r = 0.338, p = 0.038, BMD-total femur (r = 0.340, p = 0.037, BMD-femoral neck (r = 0.384, p = 0.017, SF-36-Vitality (r = 0.385, p = 0.017, SF-36-Social Function (r = 0.320, p = 0.050, SF-36-Emotional Role (r = 0.321, p = 0.049 and SF-36-Mental Health (r = 0.531, p = 0.0006 and were negatively correlated with HAQ-Reach (r = −0.328, p = 0.044 and HAQ-Grip Strength (r = −0.331, p = 0.042. A negative correlation with NC-diffuse devascularization (p = 0.029 and NC-avascular area (p = 0.033 was also observed. Conclusion: The present study provides novel evidence demonstrating that low levels of 25OHD have a negative impact in diffuse SSc QoL and further studies are needed to define whether vitamin D supplementation can improve health related QoL in these patients. The additional observation of a correlation with severe NC alterations suggests a possible role of 25OHD in the underlying SSc vascular involvement.

Malignancies in Patients with Anti-RNA Polymerase III Antibodies and Systemic Sclerosis: Analysis of the EULAR Scleroderma Trials and Research Cohort and Possible Recommendations for Screening.

Science.gov (United States)

Lazzaroni, Maria-Grazia; Cavazzana, Ilaria; Colombo, Enrico; Dobrota, Rucsandra; Hernandez, Jasmin; Hesselstrand, Roger; Varju, Cecilia; Nagy, Gabriella; Smith, Vanessa; Caramaschi, Paola; Riccieri, Valeria; Hachulla, Eric; Balbir-Gurman, Alexandra; Chatelus, Emmanuel; Romanowska-Próchnicka, Katarzyna; Araújo, Ana Carolina; Distler, Oliver; Allanore, Yannick; Airò, Paolo

2017-05-01

To analyze the characteristics of anti-RNA polymerase III antibodies (anti-RNAP3)- positive patients with systemic sclerosis (SSc) in the European League Against Rheumatism Scleroderma Trials and Research group (EUSTAR) registry with a focus on the risk of cancer and the characteristics of malignancies, and the aim to provide guidelines about potential cancer screening in these patients. (1) Analysis of the EUSTAR database: 4986 patients with information on their anti-RNAP3 status were included. (2) Case-control study: additional retrospective data, including malignancy history, were queried in 13 participating EUSTAR centers; 158 anti-RNAP3+ cases were compared with 199 local anti-RNAP3- controls, matched for sex, cutaneous subset, disease duration, and age at SSc onset. (3) A Delphi exercise was performed by 82 experts to reach consensus for cancer screening in anti-RNAP3+ patients. In the EUSTAR registry, anti-RNAP3 were associated in multivariable analysis with renal crisis and diffuse cutaneous involvement. In the case-control study, anti-RNAP3 were associated with gastric antral vascular ectasia, rapid progression of skin involvement, and malignancies concomitant to SSc onset (OR 7.38, 95% CI 1.61-33.8). When compared with other anti-RNAP3+ patients, those with concomitant malignancies had older age (p < 0.001) and more frequent diffuse cutaneous involvement (p = 0.008). The Delphi exercise highlighted the need for malignancy screening at the time of diagnosis for anti-RNAP3+ patients and tight followup in the following years. Anti-RNAP3+ patients with SSc have a high risk of concomitant malignancy. These results have implications for clinical practice and suggest regular screening for cancer in anti-RNAP3+ patients.

The SSC superconducting air core toroid design development

International Nuclear Information System (INIS)

Fields, T.; Carroll, A.; Chiang, I.H.; Frank, J.S.; Haggerty, J.; Littenberg, L.; Morse, W.; Strand, R.C.; Lau, K.; Weinstein, R.; McNeil, R.; Friedman, J.; Hafen, E.; Haridas, P.; Kendall, H.W.; Osborne, L.; Pless, I.; Rosenson, L.; Pope, B.; Jones, L.W.; Luton, J.N.; Bonanos, P.; Marx, M.; Pusateri, J.A.; Favale, A.; Gottesman, S.; Schneid, E.; Verdier, R.

1990-01-01

Superconducting air core toroids show great promise for use in a muon spectrometer for the SSC. Early studies by SUNY at Stony Brook funded by SSC Laboratory, have established the feasibility of building magnets of the required size. The toroid spectrometer consists of a central toroid with two end cap toroids. The configuration under development provides for muon trajectory measurement outside the magnetic volume. System level studies on support structure, assembly, cryogenic material selection, and power are performed. Resulting selected optimal design and assembly is described. 4 refs., 6 figs

Correlation between pretreatment or follow-up CT findings and therapeutic effect of autologous peripheral blood stem cell transplantation for interstitial pneumonia associated with systemic sclerosis

Energy Technology Data Exchange (ETDEWEB)

Yabuuchi, Hidetake, E-mail: yabuuchi@shs.kyushu-u.ac.jp [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Matsuo, Yoshio [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Tsukamoto, Hiroshi [Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Sunami, Shunya; Kamitani, Takeshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Sakai, Shuji [Department of Health Sciences, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Hatakenaka, Masamitsu [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Nagafuji, Koji; Horiuchi, Takahiko; Harada, Mine; Akashi, Koichi [Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Honda, Hiroshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

2011-08-15

Purpose: To evaluate what is useful among various parameters including CT findings, laboratory parameters (%VC, %DLco, KL-6), patients related data (age, sex, duration of disease) to discriminate between responder and non-responder in patients who received autologous peripheral blood stem cell transplantation (auto-PBSCT) for interstitial pneumonia (IP) with systemic sclerosis (SSc). Method: Auto-PBSCT and follow-up of at least one year by chest CT, serum KL-6, %VC, and %DLco were performed in 15 patients for IP with SSc. Analyzed CT findings included extent of ground-glass opacity (GGO), intralobular reticular opacity, number of segments that showed traction bronchiectasis, and presence of honeycombing. We regarded the therapeutic response of patients as responders when TLC or VC increase over 10% or DLco increase more than 15%, otherwise we have classified as non-responder. We applied univariate and multivariate analyses to find the significant indicators to discriminate responders from non-responders. P < 0.05 was considered statistically significant. Results: Univariate and multivariate analyses showed that the significant parameter to discriminate responders from non-responders were pretreatment KL-6, presence of honeycombing, extent of GGO, and early change in extent of GGO. Among them, extent of GGO and early change in extent of GGO were the strongest discriminators between responders and non-responders (P = 0.001, 0.001, respectively). Conclusion: Several CT findings and pretreatment KL-6 may be useful to discriminate between responder and non-responder in patients who received auto-PBSCT for IP with SSc.

Subcooler assembly for SSC single magnet test program

International Nuclear Information System (INIS)

Wu, K.C.; Brown, D.P.; Sondericker, J.H.; Farah, Y.; Zantopp, D.; Nicoletti, A.

1991-01-01

A subcooler assembly has been designed, constructed and installed in the MAGCOOL magnet test area at Brookhaven National Laboratory. Since July 1989, it has been used for testing SSC magnets. This subcooler assembly and cryogenic system are the first of its kind ever built. Today, with more than 5000 hours of operating time, the subcooler has proved to be a reliable unit with individual components meeting design expectations. The lowest temperatures achieved with one SSC dipole are 3.0 K at the suction of the cold vacuum pump and 3.2 K at the return of the magnet. The system performs well in both steady state operation and during magnet quench, subcooling, cooldown and warmup. 4 refs., 7 figs

Simulation of the SSC refrigeration system using the ASPEN/SP process simulator

International Nuclear Information System (INIS)

Rasson, J.; Dweck, J.

1990-01-01

The SSC Magnet must be maintained at a superconducting temperature of 4 K. The proposed refrigeration cooling processes consist of fairly simple closed cycles which take advantage of the Joule-Thompson effect via a series of expansions and compressions of helium gas which has been precooled by liquid nitrogen. The processes currently under consideration consist of three cycles, the 20 K shield cooling, the 4.0 K helium refrigerator and the helium liquefier. The process units which are to be employed are compressors, turbines, expanders, mixers, flashes, two stream heat exchangers and multiple stream heat exchangers. The cycles are to be operated at or near steady state. Due to the large number of competing cooling sector designs to be considered and the high capital and operating costs of the proposed processes, the SSC Laboratory requires a software tool for the validation and optimization of the individual designs and for the performance of cost-benefit analyses among competing designs. Since these processes are steady state flow processes involving primarily standard unit operations, a decision was made to investigate the application of a commercial process simulator to the task. Several months of internal evaluations by the SSC Laboratory revealed that while the overall structure and calculation approach of a number of the commercial simulators were appropriate for this task, all were lacking essential capabilities in the areas of thermodynamic property calculations for cryogenic systems and modeling of complex, multiple stream heat exchangers. An acceptable thermodynamic model was provided and a series of simple, but three software vendors. Based on the results of the benchmark tests, the ASPEN/SP process simulator was selected for future modeling work. 2 refs., 4 figs

Dicty_cDB: SSC538 [Dicty_cDB

Lifescience Database Archive (English)

Full Text Available SS (Link to library) SSC538 (Link to dictyBase) - - - Contig-U13922-1 SSC538Z (Link... to Original site) - - SSC538Z 712 - - - - Show SSC538 Library SS (Link to library) Clone ID SSC538 (Link to dic...SHR34... 36 1.3 FM992688_1247( FM992688 |pid:none) Candida dubliniensis CD36 chrom... 35 3.0 EU565733_1( EU565733 |pid:none) Uncultur...9385_2728( AP009385 |pid:none) Burkholderia multivorans ATCC 1... 33 6.6 AM260479_1383( AM260479 |pid:none) ... reticulum 4.0 %: extracellular, including cell wall 4.0 %: cytoskeletal 4.0 %: vacu

Do scleroderma patients look young?: Evaluation by using facial imaging system.

Science.gov (United States)

Sawamura, Soichiro; Jinnin, Masatoshi; Kajihara, Ikko; Makino, Katsunari; Aoi, Jun; Ichihara, Asako; Makino, Takamitsu; Fukushima, Satoshi; Ihn, Hironobu

2017-01-01

These days various collagen supplements have widely been marketed. However, it has not been scientifically proved whether increasing collagen can actually prevent skin aging. Systemic sclerosis (SSc) is an autoimmune disease that is characterized by thickening of the skin caused by accumulation of collagen. In this study, we tried to evaluate facial skin characteristics and skin aging of SSc patients by using digital imaging system. As the result, the severity of wrinkles, texture and pores were significantly lower in SSc patients than control subjects. Among them, wrinkles showed better correlation with skin thickness score. Therefore, increased amount of collagen in scleroderma skin may directly affect wrinkles. In conclusion, attempt on collagen induction itself is reasonable and effective strategy in order to keep young appearance, although oral collagen supplementation may not directly reach to the skin.

EMPACT: An alternative approach to a high PT SSC experiment

International Nuclear Information System (INIS)

Marx, M.; State Univ. of New York, Stony Brook, NY

1989-05-01

A survey of high P T detector concepts advanced for the SSC reveals two striking facts -- first, the scale of most detectors is set by the muon detection system; and second, that the performance of these muon systems is limited in comparison to electron or jet capabilities, either in resolution or in rapidity acceptance. I propose here an alternative concept for an SSC experiment which will provide enhanced muon performance at a level to that obtainable through calorimetric means for electrons and jets, while drastically reducing the tonnage of the experiment

SSC lattice database and graphical interface

International Nuclear Information System (INIS)

Trahern, C.G.; Zhou, J.

1991-11-01

When completed the Superconducting Super Collider will be the world's largest accelerator complex. In order to build this system on schedule, the use of database technologies will be essential. In this paper we discuss one of the database efforts underway at the SSC, the lattice database. The SSC lattice database provides a centralized source for the design of each major component of the accelerator complex. This includes the two collider rings, the High Energy Booster, Medium Energy Booster, Low Energy Booster, and the LINAC as well as transfer and test beam lines. These designs have been created using a menagerie of programs such as SYNCH, DIMAD, MAD, TRANSPORT, MAGIC, TRACE3D AND TEAPOT. However, once a design has been completed, it is entered into a uniform database schema in the database system. In this paper we discuss the reasons for creating the lattice database and its implementation via the commercial database system SYBASE. Each lattice in the lattice database is composed of a set of tables whose data structure can describe any of the SSC accelerator lattices. In order to allow the user community access to the databases, a programmatic interface known as dbsf (for database to several formats) has been written. Dbsf creates ascii input files appropriate to the above mentioned accelerator design programs. In addition it has a binary dataset output using the Self Describing Standard data discipline provided with the Integrated Scientific Tool Kit software tools. Finally we discuss the graphical interfaces to the lattice database. The primary interface, known as OZ, is a simulation environment as well as a database browser

A GEM of an SSC detector

International Nuclear Information System (INIS)

Anon.

1992-01-01

The SSC Laboratory has decided to support the GEM (Gammas, Electrons, and Muons) detector collaboration in the next stage of its work, development of a Technical Design Report. Initial ideas for GEM as the second major SSC detector were aired last year

The prevalence of median neuropathy at wrist in systemic sclerosis patients at Srinagarind Hospital

Directory of Open Access Journals (Sweden)

Thanaporn Nimitbancha

2015-01-01

Full Text Available Objectives: To determine the prevalence and factor related with median neuropathy at wrist (MNW in systemic sclerosis patients. Study Design: Cross-sectional study. Setting: Srinagarind Hospital, Khon Kaen, Thailand. Participants: Systemic sclerosis patients who attended the Scleroderma Clinic, Srinagarind Hospital. Materials and Methods: Seventyfive systemic sclerosis patients were prospectively evaluated by questionnaire, physical examination, and electrodiagnostic study. The questionnaire consisted of the symptoms, duration, and type of systemic sclerosis. The physical examination revealed skin score of systemic sclerosis, pinprick sensation of median nerve distribution of both hands, and weakness of both abductor pollicis brevis muscles. The provocative test which were Tinel′s sign and Phalen′s maneuver were also examined. Moreover, electrodiagnostic study of the bilateral median and ulnar nerves was conducted. Results: The prevalence of MNW in systemic sclerosis patients was 44% - percentage of mild, moderate, and severe were 28%, 9.3%, and 6.7%, respectively. The prevalence of asymptomatic MNW was 88%. There were no association between the presence of MNW and related factors of systemic sclerosis. Conclusions: MNW is one of the most common entrapment neuropathies in systemic sclerosis patients. Systemic sclerosis patients should be screened for early signs of MNW.

Uses of the chiral Lagrangian at the SSC

International Nuclear Information System (INIS)

Dawson, S.

1992-09-01

In the event that the SSC does not observe any resonances such as a Higgs boson or a techni-rho meson, we would like to know if the SSC can still discover something about the nature of the electroweak symmetry breaking. In particular, we consider the question of whether there is a ''no-lose'' corollary at the SSC. We will use chiral Lagrangian techniques to address this question and analyze their utility for studying events containing W and Z gauge bosons at the SSC

Quantitative outcome measures for systemic sclerosis-related Microangiopathy - Reliability of image acquisition in Nailfold Capillaroscopy.

Science.gov (United States)

Dinsdale, Graham; Moore, Tonia; O'Leary, Neil; Berks, Michael; Roberts, Christopher; Manning, Joanne; Allen, John; Anderson, Marina; Cutolo, Maurizio; Hesselstrand, Roger; Howell, Kevin; Pizzorni, Carmen; Smith, Vanessa; Sulli, Alberto; Wildt, Marie; Taylor, Christopher; Murray, Andrea; Herrick, Ariane L

2017-09-01

Nailfold capillaroscopic parameters hold increasing promise as outcome measures for clinical trials in systemic sclerosis (SSc). Their inclusion as outcomes would often naturally require capillaroscopy images to be captured at several time points during any one study. Our objective was to assess repeatability of image acquisition (which has been little studied), as well as of measurement. 41 patients (26 with SSc, 15 with primary Raynaud's phenomenon) and 10 healthy controls returned for repeat high-magnification (300×) videocapillaroscopy mosaic imaging of 10 digits one week after initial imaging (as part of a larger study of reliability). Images were assessed in a random order by an expert blinded observer and 4 outcome measures extracted: (1) overall image grade and then (where possible) distal vessel locations were marked, allowing (2) vessel density (across the whole nailfold) to be calculated (3) apex width measurement and (4) giant vessel count. Intra-rater, intra-visit and intra-rater inter-visit (baseline vs. 1week) reliability were examined in 475 and 392 images respectively. A linear, mixed-effects model was used to estimate variance components, from which intra-class correlation coefficients (ICCs) were determined. Intra-visit and inter-visit reliability estimates (ICCs) were (respectively): overall image grade, 0.97 and 0.90; vessel density, 0.92 and 0.65; mean vessel width, 0.91 and 0.79; presence of giant capillary, 0.68 and 0.56. These estimates were conditional on each parameter being measurable. Within-operator image analysis and acquisition are reproducible. Quantitative nailfold capillaroscopy, at least with a single observer, provides reliable outcome measures for clinical studies including randomised controlled trials. Copyright © 2017 Elsevier Inc. All rights reserved.

Pediatric Scleroderma –Systemic and Localized Forms

Science.gov (United States)

Torok, Kathryn S.

2012-01-01

Synopsis statement Pediatric scleroderma includes two major groups of clinical entities, systemic sclerosis (SSc) and localized scleroderma (LS). Although both share a common pathophysiology, with an initial inflammatory phase associated with endothelial activation, and a later fibrotic phase evidenced by collagenization of tissue and appreciable skin thickness, their clinical manifestations differ. LS is typically confined to the skin and underlying subcutis, and though not fatal like SSc, up to a quarter of the patients may have extracutaneous disease manifestations, such as arthritis and uveitis. While any organ may be affected in SSc, vascular (Raynaud’s phenomenon), cutaneous (skin thickening), GI, pulmonary and musculoskeletal involvement are most commonly seen in children. Auto-antibody profiles in childhood onset SSc can assist in predicting internal organ involvement. Treatment for both forms of scleroderma targets the active inflammatory stage and halts disease progression; however, progress still needs to be made towards the development of a more effective anti-fibrotic therapy to help reverse disease damage. PMID:22560576

Fermilab R and D test facility for SSC [Superconducting Super Collider] magnets

International Nuclear Information System (INIS)

Strait, J.; Bleadon, M.; Hanft, R.; Lamm, M.; McGuire, K.; Mantsch, P.; Mazur, P.O.; Orris, D.; Pachnik, J.

1989-02-01

The test facility used for R and D testing of full scale development dipole magnets for the SSC is described. The Fermilab Magnet Test Facility, originally built for production testing of Tevatron magnets, has been substantially modified to allow testing also of SSC magnets. Two of the original six test stands have been rebuilt to accommodate testing of SSC magnets at pressures between 1.3 Atm and 4 Atm and at temperatures between 1.8 K and 4.8 K and the power system has been modified to allow operation to at least 8 kA. Recent magnets have been heavily instrumented with voltage taps to allow detailed study of quench location and propagation and with strain gage based stress, force and motion transducers. A data acquisition system has been built with a capacity to read from each SSC test stand up to 220 electrical quench signals, 32 dynamic pressure, temperature and mechanical transducer signals during quench and up to 200 high precision, low time resolution, pressure, temperature and mechanical transducer signals. The quench detection and protection systems is also described. 23 refs., 4 figs., 2 tabs

A parallel non-neural trigger tracker for the SSC

International Nuclear Information System (INIS)

Farber, R.M.; Kennison, W.; Lapedes, A.S.

1991-01-01

The Superconducting Super Collider (SSC) is a major project promising to open the vistas of very high particle physics. When the SSC is in operation, data will be produced at a staggering rate. Current estimates place the raw data coming our of the proposed silicon detector system at 2.5 x 10 16 bits/second. Clearly, storing all events for later off-line processing is totally impracticable. A hierarchy of triggers, firing only on events meeting increasingly specific criteria, are planned to cull interesting events from the flood of information. Each event consists of a sequence of isolated ''hits'', caused by particles hitting various parts of the detector. Collating these hits into the tracks of the approximately 500 particles/event, and then quickly deciding which events meet the criteria for later processing, is essential if the SSC is to produce usable information. This paper addresses the need for real-time triggering and track reconstruction. A benchmarked and buildable algorithm, operable at the required data rates, is described. The use of neural nets, suggested by other researchers, is specifically avoided as unnecessary and impractical. Instead, a parallel algorithm, and associated hardware architecture using only conventional technology, is presented. The algorithm has been tested on fully scaled up, extensively detailed, simulated SSC events, with extremely encouraging results. Preliminary hardware analysis indicate that the trigger/tracker may be built within proposed SSC budget guidelines. 7 refs., 4 figs

Pediatric scleroderma: systemic or localized forms.

Science.gov (United States)

Torok, Kathryn S

2012-04-01

Pediatric scleroderma includes 2 major groups of clinical entities, systemic sclerosis (SSc) and localized scleroderma (LS). Although both share a common pathophysiology, their clinical manifestations differ. LS is typically confined to the skin and underlying subcutis, with up to a quarter of patients showing extracutaneous disease manifestations such as arthritis and uveitis. Vascular, cutaneous, gastrointestinal, pulmonary, and musculoskeletal involvement are most commonly seen in children with SSc. Treatment of both forms targets the active inflammatory stage and halts disease progression; however, progress needs to be made toward the development of more effective antifibrotic therapy to help reverse disease damage. Copyright © 2012 Elsevier Inc. All rights reserved.

Serum nitric oxide metabolites and disease activity in patients with systemic sclerosis.

Science.gov (United States)

Mok, Mo Yin; Fung, Peter Chin Wah; Ooi, Clara; Tse, Hung Fat; Wong, Yik; Lam, Yui Ming; Wong, Woon Sing; Lau, Chak Sing

2008-03-01

There is no surrogate marker in serum for defining disease activity in scleroderma (SSc). Nitric oxide (NO), which regulates vasodilation and possesses pro-inflammatory actions, has been implicated in the pathogenesis of SSc. We compared serum NO(x) (total nitrate and nitrite) level in SSc patients to healthy controls and evaluated its correlation with detailed symptomatology and scoring systems for various organ involvement. Symptoms and physical findings that suggested disease activity in regard to various organs were documented. Lung function test, high-resolution computed tomographic (HRCT) scan of thorax and echocardiography were performed. Serum NO(x) was measured by chemiluminescence. Serum NO(x) levels in SSc (n = 43) were significantly higher (72.4 +/- 47.8 microM) than age- and sex-matched controls (n = 41; 37.1 +/- 13.5 microM; p n = 9; OR 145.3, p = 0.01) were predictive factors for elevated serum NO(x). Prednisolone use was associated with lower serum NO(x) level (OR 0.06, p = 0.04). Elevated PAP of increasing severity was found to be associated with higher level of serum NO(x) (p = 0.004 by trend). Serum NO(x) in SSc patients were elevated compared to healthy controls. Serum NO(x) level was determined by multiple factors including age, prednisolone use, and elevated PAP.

Development and preliminary validation of the Scleroderma Support Group Leader Self-efficacy Scale

NARCIS (Netherlands)

Pal, N.E.; Gumuchian, S.T.; Delisle, V.C.; Pé pin, M.; Malcarne, V.L.; Carrier, M.E.; Kwakkenbos, C.M.C.; Pelá ez, S.; El-Baalbaki, G.; Thombs, B.D.

2018-01-01

Support groups are an important resource for people living with systemic sclerosis (SSc; scleroderma). Peer support group leaders play an important role in the success and sustainability of SSc support groups, but face challenges that include a lack of formal training. An SSc support group leader

[Large vessels vasculopathy in systemic sclerosis].

Science.gov (United States)

Tejera Segura, Beatriz; Ferraz-Amaro, Iván

2015-12-07

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

Preliminary study of an integral harmonic analysis magnetic field measurement system for long SSC magnets

International Nuclear Information System (INIS)

Green, M.I.

1991-04-01

We described the research and development required to design and build a prototype system capable of making integrated magnetic multipole measurements of warm and cryogenic 50 mm bore SSC dipole and quadrupole magnets utilizing a warm probe in a warm finger. Our experience and some preliminary studies indicate that it is highly unlikely that a 16 meter long probe can be fabricated that will have a twist below several milliradians at any temperature. Consequently we describe a segmented 16 meter long probe for which we intend to calibrate the phase of each segment to within 0.1 milliradians. The data for all segments will be acquired simultaneously, and integrated data will be generated from the vector sums of the individual segments. The calibration techniques and instrumentation required to implement this system are described. The duration of an integral measurement at one current is less than ten seconds, which is three orders of magnitude shorter than that required by the mole technique presently being used. The system is based on an extrapolation of the techniques used at LBL to measure cryogenic 1 meter models of SSC magnets with a cryogenic probe. 3 refs., 3 figs

Present status and physics prospects of SSC

International Nuclear Information System (INIS)

Sugimoto, Shojiro

1990-01-01

Physics prospects of Superconducting Super Collider (SSC) are discussed, referring to other coming colliders. In addition, the present status of the SSC project and detector proposals for the experiments are described. (author)

A development environment for the SSC control system

International Nuclear Information System (INIS)

Murray, Doug; Martinsen, Garth; Wang, Judy

1994-01-01

The SSC is developing a design environment for control system development within the context of EPICS. The environment is aimed at developers of applications using the EPICS Input/Output Controller (IOC). The unique aspect of this effort is our emphasis on providing a simple and intuitive development environment compared with tools currently available. Our most important goal in this effort has been to hide the complexity of EPICS IOC development from the developers. This paper describes two tools which are under development; The Function Block Editor (FBE) and the State Machine Editor (SME). The FBE provides a visual editing environment for graphically describing control processes as a set of related functional blocks. The configuration of functional blocks is then translated into IOC records and executed. SME allows the user to visually construct a sequence using a notation we are modeling after Grafcet [1]. State machines are translated into EPICS State Notation Language programs and executed. Future extensions will be described. ((orig.))

Association between systemic lupus erythematosus and multiple sclerosis: lupoid sclerosis; Asociacion de LES y esclerosis multiple: esclerosis lupoide.

Energy Technology Data Exchange (ETDEWEB)

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

2010-07-01

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.

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.

Qualification of technical personnel for employment during construction and operation of the SSC

International Nuclear Information System (INIS)

Johnson, C.D.; Wolf, L.J.

1991-01-01

In the early stages of the SSC design it became apparent that construction will have a significant impact on post-secondary technical/vocational education in Texas. Present estimates are that from 2,000 to 3,000 employees will be needed in the traditional fields of civil, mechanical, electrical technology, computers as well as exotic technologies such as cryogenics and high vacuum. In this paper an on-going project is described which is directed toward assuring that graduates of Texas post-secondary technical and vocational education programs will be competitive for employment in these jobs. The project involves development of SSC pedagogical material at a level appropriate to the students, education of teachers about the SSC and development of delivery systems for education about the SSC

Accelerator physics issues at the SSC

International Nuclear Information System (INIS)

Dugan, G.F.

1993-05-01

Realization of the design energy and luminosity goals of the Superconducting Super Collider (SSC) will require proper resolutions of a number of challenging problems in accelerator physics. The status of several salient issues in the design of the SSC will be reviewed and updated in this paper. The emphasis will be on the superconducting accelerators

Measurements of ground motion and SSC dipole vibrations

International Nuclear Information System (INIS)

Parkhomchuk, V.V.; Shiltsev, V.D.; Weaver, H.J.

1993-06-01

The results of seismic ground measurements at the Superconducting Super Collider (SSC) site and investigations of vibrational properties of superconducting dipoles for the SSC are presented. Spectral analysis of the data obtained in the large frequency band from 0.05 Hz to 2000 Hz is done. Resonant behavior and the dipole-to-ground transform ratio are investigated. The influence of measured vibrations on SSC operations is considered

Localized Scleroderma, Systemic Sclerosis and Cardiovascular Risk: A Danish Nationwide Cohort Study.

Science.gov (United States)

Hesselvig, Jeanette Halskou; Kofoed, Kristian; Wu, Jashin J; Dreyer, Lene; Gislason, Gunnar; Ahlehoff, Ole

2018-03-13

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, systemic sclerosis is a significant cardiovascular disease risk factor, while patients with localized scleroderma are not at increased risk of cardiovascular disease.

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.

Intrinsic Chevrolets at the SSC

International Nuclear Information System (INIS)

Brodsky, S.J.; Collins, J.C.; Ellis, S.D.; Gunion, J.F.; Mueller, A.H.

1984-01-01

The possibility of the production at high energy of heavy quarks, supersymmetric particles and other large mass colored systems via the intrinsic twist-six components in the proton wave function is discussed. While the existing data do not rule out the possible relevance of intrinsic charm production at present energies, the extrapolation of such intrinsic contributions to very high masses and energies suggests that they will not play an important role at the SSC

The SSC dipole: Its conceptual origin and early design history

International Nuclear Information System (INIS)

Dahl, P.F.

1992-05-01

The magnet system for the Superconducting Super Collider will likely remain the most ambitions-and challenging-application of superconducting technology for the foreseeable future. The centerpiece of the system is the behemoth collider dipole magnet. Its design, still evolving in its detailed features, dates from the mid-1980's when it emerged as the winter in an early technical showdown that occupied the fledgling SSC project. In the present report we chronicle the origins and chief milestones in the development of certain SSC dipole design concepts. Unfortunately, the chronicle must remain incomplete, with the design not yet frozen as we go to press and still subject to important modifications as the SSC Laboratory settles in near its future home in Ellis County, Texas, hard on the heels of a wide-ranging design review in the closing days of the SSC Central Design Group in (CDG) Berkeley. Be that as it may, in what follows we concentrate on the early years in an attempt to recapitulate the birth of the dipole, taking as our point of departure the SSC Reference Designs Study (RDS) of 1984. In Section 3 we touch on the background for the various RDS options, including ISABELLE/CBA and the Tevatron. In Section 4 the narrative focuses on the two final protagonists, a high-field cosine theta (cos θ) magnet and a low-field superferric magnet. Section 5 recounts the circumstances surrounding the selection of a particular magnet ''style'' for further development, and the ups and downs of the first model magnets. We conclude with a smattering of progress highlights in refining the design during the final push under the reign of the CDG. Beyond that, the ongoing chronicle must be left for others to amplify and complete

Heavy particle production at the SSC

International Nuclear Information System (INIS)

Brodsky, S.J.; Haber, H.E.; Gunion, J.F.

1984-03-01

Predictions for the production of heavy quarks, supersymmetric particles, and other colored systems at high energy due to intrinsic twist-six components in the proton wavefunction are given. We also suggest the possibility of using asymmetric collision energies (e.g., via intersecting rings at the SSC) in order to facilitate the study of forward and diffractive particle production processes. 9 references

An assessment of the measurement equivalence of English and French versions of the Center for Epidemiologic Studies Depression (CES-D Scale in systemic sclerosis.

Directory of Open Access Journals (Sweden)

Vanessa C Delisle

Full Text Available Center for Epidemiologic Studies Depression (CES-D Scale scores in English- and French-speaking Canadian systemic sclerosis (SSc patients are commonly pooled in analyses, but no studies have evaluated the metric equivalence of the English and French CES-D. The study objective was to examine the metric equivalence of the CES-D in English- and French-speaking SSc patients.The CES-D was completed by 1007 English-speaking and 248 French-speaking patients from the Canadian Scleroderma Research Group Registry. Confirmatory factor analysis (CFA was used to assess the factor structure in both samples. The Multiple-Indicator Multiple-Cause (MIMIC model was utilized to assess differential item functioning (DIF.A two-factor model (Positive and Negative affect showed excellent fit in both samples. Statistically significant, but small-magnitude, DIF was found for 3 of 20 CES-D items, including items 3 (Blues, 10 (Fearful, and 11 (Sleep. Prior to accounting for DIF, French-speaking patients had 0.08 of a standard deviation (SD lower latent scores for the Positive factor (95% confidence interval [CI]-0.25 to 0.08 and 0.09 SD higher scores (95% CI-0.07 to 0.24 for the Negative factor than English-speaking patients. After DIF correction, there was no change on the Positive factor and a non-significant increase of 0.04 SD on the Negative factor for French-speaking patients (difference = 0.13 SD, 95% CI-0.03 to 0.28.The English and French versions of the CES-D, despite minor DIF on several items, are substantively equivalent and can be used in studies that combine data from English- and French-speaking Canadian SSc patients.

An assessment of the measurement equivalence of English and French versions of the Center for Epidemiologic Studies Depression (CES-D) Scale in systemic sclerosis.

Science.gov (United States)

Delisle, Vanessa C; Kwakkenbos, Linda; Hudson, Marie; Baron, Murray; Thombs, Brett D

2014-01-01

Center for Epidemiologic Studies Depression (CES-D) Scale scores in English- and French-speaking Canadian systemic sclerosis (SSc) patients are commonly pooled in analyses, but no studies have evaluated the metric equivalence of the English and French CES-D. The study objective was to examine the metric equivalence of the CES-D in English- and French-speaking SSc patients. The CES-D was completed by 1007 English-speaking and 248 French-speaking patients from the Canadian Scleroderma Research Group Registry. Confirmatory factor analysis (CFA) was used to assess the factor structure in both samples. The Multiple-Indicator Multiple-Cause (MIMIC) model was utilized to assess differential item functioning (DIF). A two-factor model (Positive and Negative affect) showed excellent fit in both samples. Statistically significant, but small-magnitude, DIF was found for 3 of 20 CES-D items, including items 3 (Blues), 10 (Fearful), and 11 (Sleep). Prior to accounting for DIF, French-speaking patients had 0.08 of a standard deviation (SD) lower latent scores for the Positive factor (95% confidence interval [CI]-0.25 to 0.08) and 0.09 SD higher scores (95% CI-0.07 to 0.24) for the Negative factor than English-speaking patients. After DIF correction, there was no change on the Positive factor and a non-significant increase of 0.04 SD on the Negative factor for French-speaking patients (difference = 0.13 SD, 95% CI-0.03 to 0.28). The English and French versions of the CES-D, despite minor DIF on several items, are substantively equivalent and can be used in studies that combine data from English- and French-speaking Canadian SSc patients.

Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase I trial.

Science.gov (United States)

Granel, Brigitte; Daumas, Aurélie; Jouve, Elisabeth; Harlé, Jean-Robert; Nguyen, Pierre-Sébastien; Chabannon, Christian; Colavolpe, Nathalie; Reynier, Jean-Charles; Truillet, Romain; Mallet, Stéphanie; Baiada, Antoine; Casanova, Dominique; Giraudo, Laurent; Arnaud, Laurent; Veran, Julie; Sabatier, Florence; Magalon, Guy

2015-12-01

In patients with systemic sclerosis (scleroderma, SSc), impaired hand function greatly contributes to disability and reduced quality of life, and is insufficiently relieved by currently available therapies. Adipose tissue-derived stromal vascular fraction (SVF) is increasingly recognised as an easily accessible source of regenerative cells with therapeutic potential in ischaemic or autoimmune diseases. We aimed to measure for the first time the safety, tolerability and potential efficacy of autologous SVF cells local injections in patients with SSc with hand disability. We did an open-label, single arm, at one study site with 6-month follow-up among 12 female SSc patients with Cochin Hand Function Scale score >20/90. Autologous SVF was obtained from lipoaspirates, using an automated processing system, and subsequently injected into the subcutaneous tissue of each finger in contact with neurovascular pedicles. Primary outcome was the number and the severity of adverse events related to SVF-based therapy. Secondary endpoints were changes in hand disability and fibrosis, vascular manifestations, pain and quality of life from baseline to 2 and 6 months after cell therapy. All enrolled patients had surgery, and there were no dropouts or patients lost to follow-up. No severe adverse events occurred during the procedure and follow-up. Four minor adverse events were reported and resolved spontaneously. A significant improvement in hand disability and pain, Raynaud's phenomenon, finger oedema and quality of life was observed. This study outlines the safety of the autologous SVF cells injection in the hands of patients with SSc. Preliminary assessments at 6 months suggest potential efficacy needing confirmation in a randomised placebo-controlled trial on a larger population. GFRS (Groupe Francophone de Recherche sur la Sclérodermie). NCT01813279. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to

SSC seeks aid

CERN Multimedia

1990-01-01

The chairman of the science committee in the US House of representatives will ask Congress to pass a law requiring that at least a quarter of the funds for the SSC come from foreign money (2 paragraphs).

Lymphatic microangiopathy of the skin in systemic sclerosis.

Science.gov (United States)

Leu, A J; Gretener, S B; Enderlin, S; Brühlmann, P; Michel, B A; Kowal-Bielecka, O; Hoffmann, U; Franzeck, U K

1999-03-01

The cutaneous capillary lymphatic system in patients with systemic sclerosis was investigated using fluorescence microlymphography. The distal upper limbs of 16 healthy controls (mean age 62.3+/-13.1 yr) and 16 patients with systemic sclerosis (mean age 58.9+/-13.6 yr) were examined and the following parameters were evaluated: (a) single lymphatic capillaries; (b) lymphatic capillary network and cutaneous backflow; (c) extension of the stained lymphatics; (d) diameter of single lymphatic capillaries. At the finger level, lymphatic capillaries were lacking in five patients, while they were present in all controls (P < 0.05). Extension of the stained lymphatics was increased in 11 patients (8.1+/-6.0 mm) compared to the 16 healthy controls (2.0+/-1.2 mm) (P < 0.0001). Cutaneous backflow was observed in three patients (P < 0.05). At the hand level, lymphatic network extension was significantly different between patients (3.8+/-2.4 mm) and controls (1.2+/-0.8 mm) (P < 0.01); however, no significant differences were found at the forearm level. Lesional skin in patients with systemic sclerosis exhibits evidence of lymphatic microangiopathy.

Reactivity feedback models for SSC-K

Energy Technology Data Exchange (ETDEWEB)

Han, Do Hee; Kwon, Young Min; Kim, Kyung Du; Chang, Won Pyo [Korea Atomic Energy Research Institute, Taejon (Korea)

1998-06-01

Safety of KALIMER is assured by the inherent safety of the core and passive safety of the safety-related systems. For the safety analysis of a new reactor design such as KALIMER, analysis models, which are consistent with the design, have to be developed for a plant-wide transient and safety analysis code. Efforts for the development of reactivity feedback models for SSC-K, which is now being developed for the safety analysis of KALIMER, is described in this report. Models for Doppler, sodium density/void, fuel axial expansion, core radial expansion, and CRDL expansion have been developed. Test runs have been performed for the unprotected accident for the verification of the models. Use of KALIMER reactivity coefficients and future development of models for GEM and PSDRS would make it possible to analyze the response of KALIMER under TOP as well as LOF and LOHS accident conditions using SSC-K. (author). 5 refs., 64 figs., 2 tabs.

Evaluation of the extent of ground-glass opacity on high-resolution CT in patients with interstitial pneumonia associated with systemic sclerosis: Comparison between quantitative and qualitative analysis

International Nuclear Information System (INIS)

Yabuuchi, H.; Matsuo, Y.; Tsukamoto, H.; Horiuchi, T.; Sunami, S.; Kamitani, T.; Jinnouchi, M.; Nagao, M.; Akashi, K.; Honda, H.

2014-01-01

Aim: To verify whether quantitative analysis of the extent of ground-glass opacity (GGO) on high-resolution computed tomography (HRCT) could show a stronger correlation with the therapeutic response of interstitial pneumonia (IP) associated with systemic sclerosis (SSc) compared with qualitative analysis. Materials and methods: Seventeen patients with IP associated with SSc received autologous peripheral blood stem cell transplantation (auto-PBSCT) and were followed up using HRCT and pulmonary function tests. Two thoracic radiologists assessed the extent of GGO on HRCT using a workstation. Therapeutic effect was assessed using the change of vital capacity (VC) and diffusing capacity of the lung for carbon monoxide (DLco) before and 12 months after PBSCT. Interobserver agreement was assessed using Spearman's rank correlation coefficient and the Bland–Altman method. Correlation with the therapeutic response between quantitative and qualitative analysis was assessed with Pearson's correlation coefficients. Results: Spearman's rank correlation coefficient showed good agreement, but Bland–Altman plots showed that proportional error could be suspected. Quantitative analysis showed stronger correlation than the qualitative analysis based on the relationships between the change in extent of GGO and VC, and change in extent of GGO and DLco. Conclusion: Quantitative analysis of the change in extent of GGO showed stronger correlation with the therapeutic response of IP with SSc after auto-PBSCT than with the qualitative analysis. - Highlights: • Quantitative analysis of GGO in IP showed strong correlation with therapeutic effect. • Qualitative analysis might be limited by interobserver variance. • Other parameters including reticular opacities remain in a future investigation

Fixed target facility at the SSC

Energy Technology Data Exchange (ETDEWEB)

Loken, S.C.; Morfin, J.G.

1985-01-01

The question of whether a facility for fixed target physics should be provided at the SSC must be answered before the final technical design of the SSC can be completed, particularly if the eventual form of extraction would influence the magnet design. To this end, an enthusiastic group of experimentalists, theoreticians and accelerator specialists have studied this point. The accelerator physics issues were addressed by a group led by E. Colton whose report is contained in these proceedings. The physics addressable by fixed target was considered by many of the Physics area working groups and in particular by the Structure Function Group. This report is the summary of the working group which considered various SSC fixed target experiments and determined which types of beams and detectors would be required. 13 references, 5 figures.

Fixed target facility at the SSC

International Nuclear Information System (INIS)

Loken, S.C.; Morfin, J.G.

1985-01-01

The question of whether a facility for fixed target physics should be provided at the SSC must be answered before the final technical design of the SSC can be completed, particularly if the eventual form of extraction would influence the magnet design. To this end, an enthusiastic group of experimentalists, theoreticians and accelerator specialists have studied this point. The accelerator physics issues were addressed by a group led by E. Colton whose report is contained in these proceedings. The physics addressable by fixed target was considered by many of the Physics area working groups and in particular by the Structure Function Group. This report is the summary of the working group which considered various SSC fixed target experiments and determined which types of beams and detectors would be required. 13 references, 5 figures

Design of SSC collider structures

International Nuclear Information System (INIS)

Monsees, J.E.

1994-01-01

The authors would like to set the record straight. To date, underground construction contracts on the SSC main ring have been bid at a savings of $77 million dollars or 33 percent below the baseline cost estimate. The SSC is the largest single underground project ever built anywhere in the world. When completed it will have approximately 70 miles of tunnels, 60 shafts, two huge underground experiment halls -- each the size of a football stadium -- and numerous other structures, each of which would be considered a major facility on any other project

Computing facility at SSC for detectors

International Nuclear Information System (INIS)

Leibold, P.; Scipiono, B.

1990-01-01

A description of the RISC-based distributed computing facility for detector simulaiton being developed at the SSC Laboratory is discussed. The first phase of this facility is scheduled for completion in early 1991. Included is the status of the project, overview of the concepts used to model and define system architecture, networking capabilities for user access, plans for support of physics codes and related topics concerning the implementation of this facility

Coil measurement data acquisition and curing press control system for SSC dipole magnet coils

International Nuclear Information System (INIS)

Dickey, C.E.

1989-03-01

A coil matching program, similar in theory to the methods used to match Tevatron coils, is being developed at Fermilab. Modulus of elasticity and absolute coil size will be determined at 18-inch intervals along the coils while in the coil curing press immediately following the curing process. A data acquisition system is under construction to automatically acquire and manage the large quantities of data that result. Data files will be transferred to Fermilab's VAX Cluster for long-term storage and actual coil matching. The data acquisition system will also provide the control algorithm for the curing press hydraulic system. A description of the SSC Curing Press Data Acquisition and Controls System will be reported. 20 figs

Advanced thermohydraulic simulation code for transients in LMFBRs (SSC-L code)

Energy Technology Data Exchange (ETDEWEB)

Agrawal, A.K.

1978-02-01

Physical models for various processes that are encountered in preaccident and transient simulation of thermohydraulic transients in the entire liquid metal fast breeder reactor (LMFBR) plant are described in this report. A computer code, SSC-L, was written as a part of the Super System Code (SSC) development project for the ''loop''-type designs of LMFBRs. This code has the self-starting capability, i.e., preaccident or steady-state calculations are performed internally. These results then serve as the starting point for the transient simulation.

Advanced thermohydraulic simulation code for transients in LMFBRs (SSC-L code)

International Nuclear Information System (INIS)

Agrawal, A.K.

1978-02-01

Physical models for various processes that are encountered in preaccident and transient simulation of thermohydraulic transients in the entire liquid metal fast breeder reactor (LMFBR) plant are described in this report. A computer code, SSC-L, was written as a part of the Super System Code (SSC) development project for the ''loop''-type designs of LMFBRs. This code has the self-starting capability, i.e., preaccident or steady-state calculations are performed internally. These results then serve as the starting point for the transient simulation

Sleep disturbances in systemic sclerosis: evidence for the role of gastrointestinal symptoms, pain and pruritus.

Science.gov (United States)

Milette, Katherine; Hudson, Marie; Körner, Annett; Baron, Murray; Thombs, Brett D

2013-09-01

SSc is a rare autoimmune CTD characterized by thickening and fibrosis of skin and internal organs. There is significant mortality and no cure. Sleep disturbance has been identified as an important contributor to poor quality of life. The objective was to investigate socio-demographic and medical factors potentially associated with sleep disturbance in SSc. The sample consisted of patients from the Canadian Scleroderma Research Group's (CSRG) 15-centre, pan-Canadian Registry assessed with the 8-item Patient-Reported Outcome Measurement Information System (PROMIS) sleep disturbance scale short form, version 1.0. Pearson's correlations were used to assess bivariate association of socio-demographic and medical variables with PROMIS sleep scores. The independent association of PROMIS sleep disturbance scores and factors previously identified as associated with sleep disturbance in the general population, in SSc and other rheumatic diseases, was assessed using multiple linear regression. Among 397 patients in the study (88% female, mean age 57.5 years), 25% (n = 98) had diffuse cutaneous SSc. Mean duration since onset of non-RP symptoms was 10.6 years. Number of gastrointestinal symptoms (standardized regression coefficient β = 0.19, P = 0.001), pain severity (β = 0.21, P sleep disturbance. Gastrointestinal symptoms, pain and pruritus were associated with sleep disturbance in SSc. Additional research is needed on sleep in SSc so that well-informed sleep interventions can be developed and tested.

The SSC dipole: Its conceptual origin and early design history

International Nuclear Information System (INIS)

Dahl, P.F.

1990-06-01

The magnet system for the Superconducting Super Collider will likely remain the most ambitious -- and challenging -- application of superconducting technology for the foreseeable future. The centerpiece of the system is the behemoth collider dipole magnet. Its design, still evolving in its detailed features, dates from the mid-1980's when it emerged as the winner in an early technical showdown that occupied the fledgling SSC project. However, some of its gross features can be traced back to three path-breaking superconducting accelerator initiatives under way a decade earlier -- on the East Coast, on the West Coast, and in the Midwest. Other features have a still earlier legacy. In the present report we chronicle the origins and chief milestones in the development of certain SSC dipole design concepts. Unfortunately, the chronicle must remain incomplete, with the design not yet frozen as we go to press and still subject to important modifications as the SSC Laboratory settles in near its future home in Ellis County, Texas, hard on the heels of a wide-ranging design review in the closing days of the SSC Central Design Group in (CDG) Berkeley. Be that as it may, in what follows we concentrate on the early years in an attempt to recapitulate the birth of the dipole, taking as our point of departure the SSC Reference Designs Study (RDS) of 1984. In Section 3 we touch on the background for the various RDS options, including ISABELLE/CBA and the Tevatron. In Section 4 the narrative focuses on the two final protagonists, a high-field cosine theta (cos θ) magnet and a low-field superferric magnet. Section 5 recounts the circumstances surrounding the selection of a particular magnet ''style'' for further development, and the ups and downs of the first model magnets. We conclude with a smattering of progress highlights in refining the design during the final push under the reign of the CDG

Forward spectrometers at the SSC

International Nuclear Information System (INIS)

Bjorken, J.D.

1986-01-01

Most of SSC phase space and a great deal of physics potential is in the forward/backward region (absolute value of theta < 100 mrad). Comprehensive open-geometry spectrometers are feasible and very cost effective. Examples of such devices are sketched. Because such spectrometers are very long and may operate at high β and longer bunch spacing, they impact now on SSC interaction - region design. The data acquisition load is as heavy as for central detectors, although there may be less emphasis on speed and more emphasis on sophisticated parallel and/or distributed processing for event selection, as well as on high-capacity buffering

Simulating supersymmetry at the SSC

International Nuclear Information System (INIS)

Barnett, R.M.; Haber, H.E.

1984-08-01

Careful study of supersymmetric signatures at the SSC is required in order to distinguish them from Standard Model physics backgrounds. To this end, we have created an efficient, accurate computer program which simulates supersymmetric particle production and decay (or other new particles). We have incorporated the full matrix elements, keeping track of the polarizations of all intermediate states. (At this time hadronization of final-state partons is ignored). Using Monte Carlo techniques this program can generate any desired final-state distribution or individual events for Lego plots. Examples of the results of our study of supersymmetry at SSC are provided

Study of passive and active protection system for the SSC [Superconducting Super Collider] R ampersand D dipole magnet

International Nuclear Information System (INIS)

Lopez, G.; Snitchler, G.

1990-06-01

A comparative study of Passive versus Active Protection Systems is made using the computer programs SSC*, designed especially for this proposal. These programs track the quench evolution of each conductor independently, the axial quench velocity is given by a modified expression which correctly fits the experimental data, the phenomenological turn-to-turn transversal quench propagation is considered as an input parameter of the programs. The results of the simulations for a 40 mm dipole indicate that a single dipole is widely self-protected, which suggests that a Cold Diode Passive Protection System is a safe method to protect the magnet (no heaters are needed), and also that two or three magnets (Conceptual Design) will be a safe Active Protection System is the heater-time-delay to cause other quenching is sufficiently brief (τ h < 50 ms). Assuming the same turn-to-turn quench propagation for the 50 mm SSC R ampersand D Dipole Magnet, the predictions for this magnet will have much lower axial quench velocity and the above results will be still valid for this new magnet. 10 refs., 30 figs

Engineered design of SSC cooling ponds

International Nuclear Information System (INIS)

Bear, J.B.

1993-05-01

The cooling requirements of the SSC are significant and adequate cooling water systems to meet these requirements are critical to the project's successful operation. The use of adequately designed cooling ponds will provide reliable cooling for operation while also meeting environmental goals of the project to maintain streamflow and flood peaks to preconstruction levels as well as other streamflow and water quality requirements of the Texas Water Commission and the Environmental Protection Agency

Development and validation of the Body Concealment Scale for Scleroderma

NARCIS (Netherlands)

Jewett, L.R.; Malcarne, V.L.; Kwakkenbos, C.M.C.; Harcourt, D.; Rumsey, N.; Körner, A.; Steele, R.J.; Hudson, M.; Baron, M.; Haythornthwaite, J.A.; Heinberg, L.; Wigley, F.M.; Thombs, B.D.

2016-01-01

Objective: Body concealment is a component of social avoidance among people with visible differences from disfiguring conditions, including systemic sclerosis (SSc). The study objective was to develop a measure of body concealment related to avoidance behaviors in SSc. Methods: Initial items for the

One year in review 2017: systemic sclerosis.

Science.gov (United States)

Barsotti, Simone; Bruni, Cosimo; Orlandi, Martina; Della Rossa, Alessandra; Marasco, Emiliano; Codullo, Veronica; Guiducci, Serena

2017-01-01

Systemic sclerosis is a rare acquired systemic disease characterised by heterogeneous evolution and outcome. Each year novel insights into the pathogenesis, diagnosis and treatment of this severe disease have been published. We herewith provide our overview of the most significant literature contributions published over the last year.

A fixed target facility at the SSC

International Nuclear Information System (INIS)

Loken, S.; Morfin, J.G.

1984-01-01

The question of whether a facility for fixed target physics should be provided at the SSC must be answered before the final technical design of the SSC can be completed, particularly if the eventual form of extraction would influence the magnet design. To this end, an enthusiastic group of experimentalists, theoreticians and accelerator specialists have studied this point. The accelerator physics issues were addressed by a group whose report is contained in these proceedings. The physics addressable by fixed target was considered by many of the Physics area working groups and in particular by the Structure Function Group. This report is the summary of the working group which considered various SSC fixed target experiments and determined which types of beams and detectors would be required

Esophageal transit scintigraphy in systemic sclerosis

Directory of Open Access Journals (Sweden)

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.

SUPERCOLLIDER: SDC for SSC

Energy Technology Data Exchange (ETDEWEB)

Anon.

1992-03-15

On a scale to match the 87-kilometre Superconducting Supercollider (SSC) planned for Ellis County, Texas, the Solenoidal Detector Collaboration (SDC) is designing a large general purpose detector to pursue a broad range of physics goals.

SUPERCOLLIDER: SDC for SSC

International Nuclear Information System (INIS)

Anon.

1992-01-01

On a scale to match the 87-kilometre Superconducting Supercollider (SSC) planned for Ellis County, Texas, the Solenoidal Detector Collaboration (SDC) is designing a large general purpose detector to pursue a broad range of physics goals

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.

SSC design update

International Nuclear Information System (INIS)

Syphers, M.J.

1992-11-01

Recent developments in the design and construction of the SSC are presented. Topics include status of the 20 TeV Collider rings, including interaction regions, utility regions, and main arcs, plus some remarks on the injector accelerators. Remaining issues facing the design of the colliding beams synchrotron and its injectors are discussed

Genome Wide Association Studies (GWAS Identify QTL on SSC2 and SSC17 Affecting Loin Peak Shear Force in Crossbred Commercial Pigs.

Directory of Open Access Journals (Sweden)

Chunyan Zhang

Full Text Available Of all the meat quality traits, tenderness is considered the most important with regard to eating quality and market value. In this study we have utilised genome wide association studies (GWAS for peak shear force (PSF of loin muscle as a measure of tenderness for 1,976 crossbred commercial pigs, genotyped for 42,721 informative SNPs using the Illumina PorcineSNP60 Beadchip. Four 1 Mb genomic regions, three on SSC2 (at 4 Mb, 5 Mb and 109 Mb and one on SSC17 (at 20 Mb, were detected which collectively explained about 15.30% and 3.07% of the total genetic and phenotypic variance for PSF respectively. Markers ASGA0008566, ASGA0008695, DRGA0003285 and ASGA0075615 in the four regions were strongly associated with the effects. Analysis of the reference genome sequence in the region with the most important SNPs for SSC2_5 identified FRMD8, SLC25A45 and LTBP3 as potential candidate genes for meat tenderness on the basis of functional annotation of these genes. The region SSC2_109 was close to a previously reported candidate gene CAST; however, the very weak LD between DRGA0003285 (the best marker representing region SSC2_109 and CAST indicated the potential for additional genes which are distinct from, or interact with, CAST to affect meat tenderness. Limited information of known genes in regions SSC2_109 and SSC17_20 restricts further analysis. Re-sequencing of these regions for informative animals may help to resolve the molecular architecture and identify new candidate genes and causative mutations affecting this trait. These findings contribute significantly to our knowledge of the genomic regions affecting pork shear force and will potentially lead to new insights into the molecular mechanisms regulating meat tenderness.

Variance component analysis of quantitative trait loci for pork carcass composition and meat quality on SSC4 and SSC11

NARCIS (Netherlands)

Wijk, van H.J.; Dibbits, B.W.; Liefers, S.C.; Buschbell, H.; Harlizius, B.; Heuven, H.C.M.; Knol, E.F.; Bovenhuis, H.; Groenen, M.A.M.

2007-01-01

In a previous study, QTL for carcass composition and meat quality were identified in a commercial finisher cross. The main objective of the current study was to confirm and fine map the QTL on SSC4 and SSC11 by genotyping an increased number of individuals and markers and to analyze the data using a

Orofacial Manifestations and Temporomandibular Disorders of Systemic Scleroderma: An Observational Study

Directory of Open Access Journals (Sweden)

Vito Crincoli

2016-07-01

Full Text Available Scleroderma is a disorder involving oral and facial tissues, with skin hardening, thin lips, deep wrinkles, xerostomia, tongue rigidity, and microstomia. The aim of this study was to investigate the prevalence of oral manifestations and temporomandibular disorders (TMD in Systemic Sclerosis (SSc patients compared with healthy people. Eighty patients (6 men, 74 women fulfilling ACR/EULAR SSc Criteria were enrolled. A randomly selected group of 80 patients, matched by sex and age served as control group. The examination for TMD signs and symptoms was based on the standardized Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD through a questionnaire and clinical examination. SSc patients complained more frequently (78.8% of oral symptoms (Xerostomia, dysgeusia, dysphagia and stomatodynia than controls (28.7% (χ2 = 40.23 p = 0.001. TMD symptoms (muscle pain on chewing, difficulty in mouth opening, headaches were complained by 92.5% of SSc patients and by 76.2% of controls (χ2 = 8.012 p = 0.005. At the clinical examination, 85% of SSc patients showed restricted opening versus 20.0% of controls (χ2 = 67.77 p = 0.001, 81.2% of SSc showed reduced right lateral excursion versus 50% of controls (χ2 = 17.316 p = 0.001; 73.8% of SSc showed limited left lateral excursion versus 53.8% of controls (χ2 = 6.924 p = 0.009; and 73.8% of SSc had narrow protrusion versus 56.2% of controls (χ2 = 5.385 p = 0.02.

Real time control of the SSC string magnets

International Nuclear Information System (INIS)

Calvo, O.; Flora, R.; MacPherson, M.

1987-01-01

The system described in this paper, called SECAR, was designed to control the excitation of a test string of magnets for the proposed Superconducting Super Collider (SSC) and will be used to upgrade the present Tevatron Excitation, Control and Regulation (TECAR) hardware and software. It resides in a VME orate and is controlled by a 68020/68881 based CPU running the application software under a real time operating system named VRTX

Report of the Ad Hoc Committee on SSC physics

International Nuclear Information System (INIS)

1990-04-01

The Ad Hoc Committee on SSC Physics has reexamined the relationship between beam energy, machine luminosity, and physics capability. In the next section, the physics motivation for the SSC is reviewed in general terms. This is followed by a discussion of the ability to detect a number of specific processes as a function of the SSC energy and luminosity. The viability of various detector technologies is then assessed as a function of luminosity. The report ends with a brief summary and some conclusions