bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood Pressure and Vascular Dysfunction Underlie Elevated Cerebral Blood Flow in Systemic Lupus Erythematosus
Authors: GASPAROVIC CHARLES , QUALLS CLIFFORD , GREENE ERNEST R. , SIBBITT WILMER L. , ROLDAN CARLOS A. 
Published: January 2012

Objective.In previous studies cerebral blood flow (CBF) was found to be altered in patients with systemic lupus erythematosus (SLE) compared to controls. We investigated the relationships between CBF and clinical data from subjects with SLE with the aim of determining the pathologic factors underlying altered CBF in SLE.Methods.A total of 42 SLE subjects and 19 age- and sex-matched healthy control subjects were studied. Dynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) was used to measure CBF. Patients and controls underwent complete clinical and laboratory evaluations in close proximity with their MRI studies.Results.A higher CBF was present in the SLE group and was independently associated in statistical models with higher systolic blood pressure (SBP; p < 0.01). The intensity of the relationships (slope of curve) between CBF and mean arterial blood pressure, diastolic blood pressure, or blood levels of tissue plasminogen activator in the SLE group was significantly blunted relative to the control group.Conclusion.These findings are consistent with an underlying cerebral hyperperfusion in SLE induced by elevated but nonhypertensive levels of SBP. The factors underlying this relationship may be functional and/or structural (atherosclerotic, thrombotic, thromboembolic, or vasculitic) cerebrovascular disease.
Involvement of the Femoropopliteal Arteries in Giant Cell Arteritis: Clinical and Color Duplex Sonography
Authors: CZIHAL MICHAEL , TATÒ FEDERICO , RADEMACHER ANTJE , KUHLENCORDT PETER , SCHULZE-KOOPS HENDRIK , HOFFMANN ULRICH 
Published: January 2012

Objective.To determine the extent and clinical significance of giant cell arteritis (GCA) of the femoropopliteal arteries.Methods.This was a retrospective clinical color duplex sonography (CDS) study; 60 of 112 consecutive patients with the diagnosis of GCA underwent complete clinical examination of the lower extremities including the vasculature, systolic ankle pressure measurement, and CDS scans of the femoropopliteal arteries within 1 year after diagnosis of GCA. Circumferential, hypoechogenic, homogenous wall thickening was regarded as a hallmark of femoropopliteal GCA.Results.GCA of femoropopliteal arteries was present in 32 (53.3%) of 60 patients. In general, femoropopliteal GCA developed bilaterally (100%) and 14 patients (23.3%) had significant lower extremity artery obstructions secondary to vasculitis, all leading to symptomatic lower extremity ischemia, with development of critical leg ischemia in 4 patients. Compared with subjects without lower extremity vasculitis, patients with femoropopliteal involvement had a significant time delay until diagnosis (mean 23.9 vs 11.1 weeks; p = 0.03) and a higher frequency of concomitant vasculitis of the arm arteries (74.2% vs 42.9%; p = 0.02).Conclusion.Femoropopliteal artery involvement appears to be a clinically relevant manifestation of GCA, frequently leading to symptomatic lower extremity ischemia. CDS of the femoropopliteal arteries is a noninvasive diagnostic tool for detection of lower extremity vasculitis in GCA.
Aggravation of ADAMTS and Matrix Metalloproteinase Production and Role of ERK1/2 Pathway in the Interaction of Osteoarthritic Subchondral Bone Osteoblasts and Articular Cartilage Chondrocytes — Possible Pathogenic Role in Osteoarthritis
Authors: PRASADAM INDIRA , CRAWFORD ROSS , XIAO YIN 
Published: January 2012

Objective.Degradative enzymes, such as A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) and matrix metalloproteinases (MMP), play key roles in development of osteoarthritis (OA). We investigated if crosstalk between subchondral bone osteoblasts (SBO) and articular cartilage chondrocytes (ACC) in OA alters the expression and regulation of ADAMTS5, ADAMTS4, MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and MMP-13, and also tested the possible involvement of mitogen-activated protein kinase (MAPK) signaling pathway during this process.Methods.ACC and SBO were isolated from normal and OA patients. An in vitro coculture model was developed to study the regulation of ADAMTS and MMP under normal and OA joint crosstalk conditions. The MAPK-ERK inhibitor PD98059 was applied to delineate the involvement of specific pathways during this interaction process.Results.Indirect coculture of OA SBO with normal ACC resulted in significantly increased expression of ADAMTS5, ADAMTS4, MMP-2, MMP-3, and MMP-9 in ACC, whereas coculture of OA ACC led to increased MMP-1 and MMP-2 expression in normal SBO. Upregulation of ADAMTS and MMP under these conditions was correlated with activation of the MAPK-ERK1/2 signaling pathway, and addition of the MAPK-ERK inhibitor PD98059 reversed the overexpression of ADAMTS and MMP in cocultures.Conclusion.These results add to the evidence that in human OA, altered bidirectional signals between SBO and ACC significantly influence the critical features of both cartilage and bone by producing abnormal levels of ADAMTS and MMP. We have demonstrated for the first time that this altered crosstalk was mediated by the phosphorylation of MAPK-ERK1/2 signaling pathway.
Morbidity, Mortality, and Organ Damage in Patients with Antiphospholipid Syndrome
Authors: GRIKA ELEFTHERIA P. , ZIAKAS PANAYIOTIS D. , ZINTZARAS ELIAS , MOUTSOPOULOS HARALAMPOS M. , VLACHOYIANNOPOULOS PANAYIOTIS G. 
Published: January 2012

Objective.To describe morbidity, organ damage, mortality, and cause of death in patients with antiphospholipid syndrome (APS).Methods.Descriptive analysis of 135 patients. Patients were clustered according to initial event: arterial thrombosis including stroke (AT; n = 46), venous thrombosis including pulmonary emboli (VT; n = 53), or pregnancy morbidity (PM; n = 36). Disease progression according to initial event and prevalence of organ damage was observed.Results.APS occurs among young individuals (mean age 33.3 ± 11.9 yrs). One-third of the patients have APS secondary to systemic lupus erythematosus (SLE) or SLE-like disease. A broad spectrum of clinical manifestations mark the disease onset even before diagnosis. The pattern of initial presentation is preserved with regard to second event; VT is followed by VT (84%), AT is followed by AT (95%), and PM is followed by PM (88.9%). The highest morbidity is attributed to neurologic damage. PM is more likely to be followed by a second event, yet is associated with less organ damage than AT and VT. After a mean followup of 7.55 years, 29% of patients experienced organ damage and 5 died, with Systemic Lupus International Collaborating Clinics score associated with increased mortality (HR 1.31, 95% CI 1.07–1.60, p = 0.01, per 1-unit increase); hematological malignancies occurred in 2 patients after a cumulative followup of 1020 person-years. Coexistent SLE adds significant damage in patients with APS.Conclusion.APS is a disease of young individuals, who experience increased morbidity. Neurologic damage is the most common cause of morbidity. AT at presentation as well as coexistent SLE are associated with poor outcome.
Adverse Events During Longterm Low-dose Glucocorticoid Treatment of Polymyalgia Rheumatica: A Retrospective Study
Authors: MAZZANTINI MAURIZIO , TORRE CLAUDIA , MICCOLI MARIO , BAGGIANI ANGELO , TALARICO ROSARIA , BOMBARDIERI STEFANO , DI MUNNO OMBRETTA 
Published: January 2012

Objective.To assess the occurrence of adverse events in a cohort of patients with polymyalgia rheumatica (PMR), treated with low-dose glucocorticoids (GC).Methods.This was a retrospective study by review of medical records.Results.We identified 222 patients who had a mean duration of followup of 60 ± 22 months and a mean duration of GC therapy of 46 ± 22 months. We found that 95 patients (43%) had at least 1 adverse event after a mean duration of GC therapy of 31 ± 22 months and a mean cumulative dose of 3.4 ± 2.4 g. In particular, 55 developed osteoporosis, 31 had fragility fractures; 27 developed arterial hypertension; 11 diabetes mellitus; 9 acute myocardial infarction; 3 stroke; and 2 peripheral arterial disease. Univariate analysis showed that the duration of GC treatment was significantly associated with osteoporosis (p < 0.0001), fragility fractures (p < 0.0001), arterial hypertension (p < 0.005), and acute myocardial infarction (p < 0.05). Cumulative GC dose was significantly associated with osteoporosis (p < 0.0001), fragility fractures (p < 0.0001), and arterial hypertension (p < 0.01). The adverse events occurred more frequently after 2 years of treatment. Multivariate analysis showed that GC duration was significantly associated with osteoporosis (adjusted OR 1.02, 95% CI 1.02–1.05) and arterial hypertension (adjusted OR 1.03, 95% CI 1.01–1.06); GC cumulative dose was significantly associated with fragility fractures (adjusted OR 1.4, 95% CI 1.03–1.8).Conclusion.Longterm, low-dose GC treatment of PMR is associated with serious adverse events such as osteoporosis, fractures, and arterial hypertension; these adverse events occur mostly after 2 years of treatment.
Identification of the Clinical Features Distinguishing Psoriatic Arthritis and Fibromyalgia
Authors: MARCHESONI ANTONIO , ATZENI FABIOLA , SPADARO ANTONIO , LUBRANO ENNIO , PROVENZANO GIUSEPPE , CAULI ALBERTO , OLIVIERI IGNAZIO , MELCHIORRE DANIELA , SALVARANI CARLO , SCARPA RAFFAELE , SARZI-PUTTINI PIERCARLO , MONTEPAONE MONICA , PORRU GIOVANNI , D’ANGELO SALVATORE , CATANOSO MARIAGRAZIA , COSTA LUISA , MANARA MARIA , VARISCO VALENTINA , ROTUNNO LAURA , DE LUCIA ORAZIO , DE MARCO GABRIELE 
Published: January 2012

Objective.To identify the clinical features that can help to distinguish between psoriatic arthritis (PsA) and fibromyalgia (FM).Methods.Our cross-sectional study was carried out in 10 Italian rheumatology centers between January and September 2009, and enrolled all consecutive patients with PsA and FM who agreed to participate. Standard clinical and laboratory data for PsA and FM were collected from all patients. Records were made of somatic symptoms, response to nonsteroidal antiinflammatory drugs (NSAID), self-evaluated pain, general health, disability, and responses to the Fibromyalgia Impact Questionnaire. Data were statistically analyzed by univariate and multivariate analyses, and receiver-operating characteristic curves. The analysis concentrated on the clinical features shared by the 2 conditions.Results.Two hundred sixty-six patients with PsA (mean age 51.7 yrs; disease duration 10.2 yrs) and 120 patients with FM (mean age 50.2 yrs; disease duration 5.6 yrs) were evaluated. Univariate analysis showed that patients with FM had higher mean tender point and enthesitis scores, more somatic symptoms, and responded less to NSAID. Multivariate analysis showed that the presence of ≥ 6 FM-associated symptoms and ≥ 8 tender points was the best predictor of FM.Conclusion.The shared clinical features of PsA and FM that had the greatest discriminating power for FM were the number of FM-associated symptoms and tender point count.
Utility of Interferon-α as a Biomarker in Central Neuropsychiatric Involvement in Systemic Lupus Erythematosus
Authors: FRAGOSO-LOYO HILDA , ATISHA-FREGOSO YEMIL , NÚÑEZ-ALVAREZ CARLOS A. , LLORENTE LUIS , SÁNCHEZ-GUERRERO JORGE 
Published: January 2012

Objective.To assess the utility of interferon-α (IFN-α) in serum and cerebrospinal fluid (CSF) as a biomarker of disease activity in central neuropsychiatric systemic lupus erythematosus (cNPSLE).Methods.Serum and CSF samples were drawn at hospitalization in 34 patients with cNPSLE, 16 surgical SLE, 4 primary neuropsychiatric conditions, and 25 with nonautoimmune conditions, except in 44 non-NPSLE patients in whom only serum was studied. Six months later, serum/CSF and serum samples were taken in 20 cNPSLE and 35 non-NPSLE patients, respectively. SLE activity was assessed at hospitalization, and 6 months later in cNPSLE and non-NPSLE patients. IFN-α was detected by Luminex technology.Results.The mean ± SD age of patients with cNPSLE was 31.4 ± 12.2 years, which was similar across the study groups (p = 0.46). Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores among cNPSLE, non-NPSLE, and SLE-surgical patients were 15.3 ± 8.2, 12.4 ± 8.2, and 3.8 ± 1.5, respectively. IFN-α levels in serum were higher in cNPSLE than in nonautoimmune patients (p = 0.02), but were similar to non-NPSLE and SLE-surgical groups. In CSF samples, IFN-α levels were higher in cNPSLE than in nonautoimmune patients (p = 0.03), and were nonsignificantly higher than in SLE-surgical and primary neuropsychiatric patients. Six months later, serum levels of IFN-α did not vary from baseline values despite a significant decrease in SLEDAI-2K score in cNPSLE and non-NPSLE patients. IFN-α levels in the CSF of patients with cNPSLE also remained stable. Among specific cNPSLE syndromes, CSF IFN-α levels were significantly higher among patients with acute confusional syndrome.Conclusion.IFN-α does not seem to represent a useful biomarker of cNPSLE syndromes; its utility in specific cNPSLE manifestations merits further investigation.
Safety and Efficacy of Various Dosages of Ocrelizumab in Japanese Patients with Rheumatoid Arthritis with an Inadequate Response to Methotrexate Therapy: A Placebo-controlled Double-blind Parallel-group Study
Authors: HARIGAI MASAYOSHI , TANAKA YOSHIYA , MAISAWA SHINGO ,   the JA21963 Study Group
Published: January 2012

Objective.To evaluate the safety and efficacy of ocrelizumab (OCR) in Japanese patients with rheumatoid arthritis (RA) with an inadequate response to methotrexate (MTX).Methods.RA patients with an inadequate response to MTX 6–8 mg/week received an infusion of 50, 200, or 500 mg OCR or placebo on Days 1 and 15 and were observed for 24 weeks. The double-blind period was prematurely terminated because of a possible risk for serious infection from OCR.Results.A total of 152 patients were randomized into the study. The incidence of infection was 37.7% (43/114) in the OCR groups combined, compared to 18.9% (7/37) in the placebo group. Serious infections occurred in 7 patients in the OCR groups combined; there were no serious infections in the placebo group. Among the serious infections, Pneumocystis jirovecii pneumonia occurred in 2 patients in the OCR 200 mg group. The American College of Rheumatology 20% response rates at Week 24 (the primary endpoint) of the OCR 50, 200, and 500 mg groups were 54.1% (p = 0.0080), 55.6% (p = 0.0056), and 47.2% (p = 0.044), respectively, all significantly higher than that of the placebo group (25.0%).Conclusion.These results suggest inappropriate benefit-risk balance of OCR in this patient population. Because rituximab is not approved for treatment of RA in Japan, it will be necessary to investigate safety and efficacy of other anti-B cell therapies in Japanese patients with RA. (ClinicalTrials.govNCT00779220).
Orthopedic Surgery Among Patients with Rheumatoid Arthritis 1980–2007: A Population-based Study Focused on Surgery Rates, Sex, and Mortality
Authors: SHOURT COURTNEY A. , CROWSON CYNTHIA S. , GABRIEL SHERINE E. , MATTESON ERIC L. 
Published: January 2012

Objective.To describe current trends in arthritis-related joint surgery among a population-based cohort of patients with rheumatoid arthritis (RA) and to examine the influence of joint surgery on mortality.Methods.A retrospective medical record review was performed of all orthopedic surgeries following diagnosis in cases of adult-onset RA in Olmsted County, Minnesota, USA, in 1980–2007. Surgeries included primary total joint arthroplasty, joint reconstructive procedures (JRP), soft tissue procedures (STP), and revision arthroplasty. Cumulative incidence of surgery was estimated using Kaplan-Meier methods. Time trends, sex differences, and mortality were examined using Cox models with time-dependent covariates for surgery.Results.A total of 189 of 813 patients underwent at least 1 surgical procedure involving joints during followup. The cumulative incidence of any joint surgery at 10 years after RA incidence for the 1980–94 cohort was 27.3% compared to 19.5% for the 1995–2007 cohort (p = 0.08). The greatest reduction was in STP, which decreased from 12.1% in 1980–94 to 6.0% in 1995–2007 at 10 years after RA incidence (p = 0.012). Women had more surgery (cumulative incidence 26.6% at 10 years for women; 20.4% for men; p = 0.049), as did obese patients. JRP were significantly associated with mortality (hazard ratio 2.6; 95% CI 1.8, 3.9; p < 0.001) compared to patients not requiring JRP.Conclusion.The rates of joint surgery continue to decrease for patients more recently diagnosed with RA. JRP is associated with increased mortality. These findings may reflect improved treatments for RA as well as continued higher disease burden among some patients.
Synergism between Curdlan and GM-CSF Confers a Strong Inflammatory Signature to Dendritic Cells
Authors: Min Lin , Mohammad Isa Siti Aminah Bte , Fam Wee Nih , Sze Siu Kwan , Beretta Ottavio , Mortellaro Alessandra , Ruedl Christiane 
Published: January 2012

Abstract
A simultaneous engagement of different pathogen recognition receptors provides a tailor-made adaptive immunity for an efficient defense against distinct pathogens. For example, cross-talk of TLR and C-type lectin signaling effectively shapes distinct gene expression patterns by integrating the signals at the level of NF-κB. In this study, we extend this principle to a strong synergism between the dectin-1 agonist curdlan and an inflammatory growth factor, GM-CSF. Both together act in synergy in inducing a strong inflammatory signature that converts immature dendritic cells (DCs) to potent effector DCs. A variety of cytokines (IL-1β, IL-6, TNF-α, IL-2, and IL-12p70), costimulatory molecules (CD80, CD86, CD40, and CD70), chemokines (CXCL1, CXCL2, CXCL3, CCL12, CCL17), as well as receptors and molecules involved in fugal recognition and immunity such as Mincle, dectin-1, dectin-2, and pentraxin 3 are strongly upregulated in DC treated simultaneously with curdlan and GM-CSF. The synergistic effect of both stimuli resulted in strong IκBα phosphorylation, its rapid degradation, and enhanced nuclear translocation of all NF-κB subunits. We further identified MAPK ERK as one possible integration site of both signals, because its phosphorylation was clearly augmented when curdlan was coapplied with GM-CSF. Our data demonstrate that the immunomodulatory activity of curdlan requires an additional signal provided by GM-CSF to successfully initiate a robust β-glucan–specific cytokine and chemokine response. The integration of both signals clearly prime and tailor a more effective innate and adaptive response against invading microbes and fungi.
Experience of Participation as Described by People with Hand Deformity Caused by Rheumatic Disease
Authors: Nicklasson Marit , Jonsson Hans 
Published: January 2012

Objective: Participation as a concept has come into focus as an important aspect of wellbeing and derives from the International Classification of Functioning, Disability and Health. This qualitative study aimed to increase understanding of how hand deformities caused by rheumatic disease influence the individual's potential to continue participating in society by taking into account other people's attitudes. Method: Interviews were carried out with 11 participants with hand deformity associated with a rheumatic disease. Analyses were conducted using comparative methodology and hermeneutic interpretation. Findings: Participation was described as an experience that arises during involvement in an activity or a social context. All the participants experienced restricted participation across a variety of situations. Hand deformity, combined with physical environment, personal attributes and the attitudes of others, was an obstacle to the achievement of full participation. It also became obvious that the participants were not able to consider only the impact of hand deformity without acknowledging other consequences of their rheumatic condition. Conclusion: Personal and contextual factors intertwine and influence the lived experience of participation and the ability to participate. A perspective in rehabilitation that addresses only functions or performance might hinder taking the experience of participation into consideration.
Multivariate analysis of anxiety disorders yields further evidence of linkage to chromosomes 4q21 and 7p in panic disorder families
Authors: Logue Mark W. , Bauver Sarah R. , Knowles James A. , Gameroff Marc J. , Weissman Myrna M. , Crowe Raymond R. , Fyer Abby J. , Hamilton Steven P. 
Published: January 2012

AbstractReplication has been difficult to achieve in linkage studies of psychiatric disease. Linkage studies of panic disorder have indicated regions of interest on chromosomes 1q, 2p, 2q, 3, 7, 9, 11, 12q13, 12q23, and 15. Few regions have been implicated in more than one study. We examine two samples, the Iowa (IA) and the Columba panic disorder families. We use the fuzzy‐clustering method presented by Kaabi et al. [Kaabi et al. (2006); Am J Hum Genet 78: 543–553] to summarize liability to panic disorder, agoraphobia, simple phobia, and social phobia. Kaabi et al. applied this method to the Yale panic disorder linkage families and found evidence of linkage to chromosomes 4q21, 4q32, 7p, and 8. When we apply the same method to the IA families, we obtain overlapping evidence of linkage to chromosomes 4q21 and 7p. Additionally, we find evidence of linkage on chromosomes 1, 5, 6, 16, and 22. The Columbia (CO) data does not indicate linkage to any of the Kaabi et al. peaks, instead implicating chromosomes 2 and 22q11 (2 Mb from COMT). There is some evidence of overlapping linkage between the IA and CO datasets on chromosomes 1 and 14. While use of fuzzy clustering has not produced complete concordance across datasets, it has produced more than previously seen in analyses of panic disorder proper. We conclude that chromosomes 4q21 and 7p should be considered strong candidate regions for panic and fear‐associated anxiety disorder loci. More generally, this suggests that analyses including multiple aspects of psychopathology may lead to greater consistency across datasets. © 2012 Wiley Periodicals, Inc.
Newborn screening for Pompe disease: An update, 2011
Authors: Burton Barbara K. 
Published: January 2012

AbstractThere is mounting evidence in support of universal newborn screening for Pompe disease. Early treatment of children with infantile Pompe disease, prior to clinical diagnosis, is clearly of benefit in prolonging survival and improving cardiac and motor function. Several testing methods applicable to newborn screening using dried blood spots have been described and several are currently being tested in pilot screening programs. Although challenges remain, particularly in identification of the best strategy for follow‐up and management of later onset Pompe disease, these challenges can surely be overcome as they have been with other disorders added to the newborn screening panel. It is anticipated that the results of the several pilot programs currently ongoing or in the planning stages in the United States will provide the data necessary to recommend universal newborn screening for Pompe disease for all infants. © 2012 Wiley Periodicals, Inc.