bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum Osteopontin as a Predictive Marker of Responsiveness to Methotrexate in Juvenile Idiopathic Arthritis
Authors: MASI LAURA , RICCI LAURA , ZULIAN FRANCESCO , DEL MONTE FRANCESCA , SIMONINI GABRIELE , CAPANNINI SERENA , DE MARTINO MAURIZIO , BRANDI MARIA LUISA , FALCINI FERNANDA 
Published: August 2009

Objective.To evaluate if serum concentrations of osteopontin (OPN) at baseline in patients with juvenile idiopathic arthritis (JIA) represent a potential predictor of responsiveness to methotrexate (MTX).Methods.At diagnosis, 60 children with active JIA received MTX in addition to nonsteroidal antiinflammatory drugs. After 12 months of MTX treatment, 30 patients were defined as responders; the 30 nonresponders received anti-tumor necrosis factor-α therapy (etanercept) in addition to MTX; this group was then enrolled for an additional 12-month study period. No patient had received steroids within 6 weeks before entering the study. Fifty healthy children matched for sex and age acted as controls. OPN serum levels were measured at baseline, before MTX, and then at 6 and 12 months. In the nonresponder patients, OPN was evaluated again after 6 and 12 months of etanercept treatment.Results.At baseline, OPN values were significantly higher (p = 0.0003) in JIA patients than in controls, with no significant differences among the different JIA subtypes. At baseline, OPN levels were lower in responders than in nonresponder patients (14.16 ± 10.1 μg/ml vs 33.2 ± 18.1 μg/ml, respectively). After 12 months of MTX treatment, OPN levels were significantly reduced in comparison to baseline in both responder and nonresponder groups (p = 0.0017, p = 0.0048, respectively). In nonresponders, etanercept significantly reduced OPN levels at 6 and 12-month followup in comparison to baseline (p = 0.002, p = 0.008, respectively). No significant differences were found among OPN levels and disease activity.Conclusion.Serum levels of OPN at baseline represent a possible marker to predict the responsiveness to MTX in patients with JIA.
Association Between Interleukin 1 Gene Cluster Polymorphisms and Bilateral Distal Interphalangeal Osteoarthritis
Authors: SOLOVIEVA SVETLANA , KÄMÄRÄINEN OLLI-PEKKA , HIRVONEN ARI , HÄMÄLÄINEN SATU , LAITALA MARI , VEHMAS TAPIO , LUOMA KATARIINA , NÄKKI ANNU , RIIHIMÄKI HILKKA , ALA-KOKKO LEENA , MÄNNIKKÖ MINNA , LEINO-ARJAS PÄIVI 
Published: August 2009

Objective.To examine the association of the interleukin 1 gene (IL1) cluster polymorphisms and their haplotypes with bilateral distal interphalangeal joint osteoarthritis (DIP OA).Methods.Radiographs of both hands of 295 dentists and 248 teachers were examined and classified for the presence of OA using reference images. Bilateral DIP OA was defined by the presence of radiographic findings of grade 2 or more in at least 1 symmetrical pair of the DIP joints. We genotyped 10 single-nucleotide polymorphisms (SNP) in theIL1R1, IL1RL2, IL1A, IL1B,andIL1RNgenes using polymerase chain reaction-based methods. Haplotypes were statistically reconstructed using the PHASE program. The association between the genotypes/diplotypes and bilateral DIP OA was examined with logistic regression analysis.Results.TwoIL1BSNP (rs1143634 and rs1143633) were associated with bilateral DIP OA. The carriers of theIL1Brs1143634 minor allele had an increased OA risk [odds ratio (OR) 1.6; 95% confidence interval (CI) 1.08–2.26] compared to the noncarriers. The association was stronger in the dentists. The distribution of theIL1Brs1143633 genotype fit a recessive mode of inheritance (OR 3.03, 95% CI 1.35–6.83, p = 0.006). TwoIL1B-IL1RNextended haplotype alleles (211-1 and 121-1) were associated with bilateral DIP OA. An interaction between theIL1Brs1143634 and theIL1R1-IL1RL2andIL1B-IL1RNextended haplotypes and occupation (increased risk of OA among dentists only) was observed.Conclusion.Our results provide further evidence for the role ofIL1gene cluster polymorphisms in the etiology of OA and suggest that some of these may predispose DIP joints to the effects of mechanical overload.
Objective Measures of Disordered Sleep in Fibromyalgia
Authors: CHERVIN RONALD D. , TEODORESCU MIHAELA , KUSHWAHA RAMESH , DELINE ANDREA M. , BRUCKSCH CHRISTINE B. , RIBBENS-GRIMM CHRISTINE , RUZICKA DEBORAH L. , STEIN PHYLLIS K. , CLAUW DANIEL J. , CROFFORD LESLIE J. 
Published: August 2009

Objective.Patients with fibromyalgia syndrome (FM) complain of inadequate sleep, which could contribute to common symptoms including sleepiness, fatigue, or pain. However, measures that consistently and objectively distinguish FM patients remain elusive.Methods.Fifteen women with FM and 15 age- and gender-matched controls underwent 3 nights of polysomnography; Multiple Sleep Latency Tests to assess sleepiness; testing of auditory arousal thresholds during non-REM stage 2 and stage 4 sleep; overnight assessment of urinary free cortisol; and analysis of 24-hour heart rate variability.Results.On the second night of polysomnography, women with FM in comparison to controls showed more stage shifts (p = 0.04) but did not differ significantly on any other standard polysomnographic measure or on the Multiple Sleep Latency Tests. Alpha EEG power during deep non-REM sleep, alone or as a proportion of alpha power during remaining sleep stages, also failed to distinguish the groups, as did auditory arousal thresholds. Urinary free cortisol did not differ between FM and control subjects in a consistent manner. However, decreased short-term heart rate variability (HRV) and especially ratio-based HRV among FM subjects suggested diminished parasympathetic and increased sympathetic activity, respectively. Other HRV measures suggested decreased complexity of HRV among the FM subjects.Conclusion.Standard measures of sleep, a gold-standard measure of sleepiness, quantified alpha-delta EEG power, auditory arousal thresholds, and urinary free cortisol largely failed to distinguish FM and control subjects. However, HRV analyses showed more promise, as they suggested both increased sympathetic activity and decreased complexity of autonomic nervous system function in FM.
Predictors for Treatment Success and Expression of Glucocorticoid Receptor in Giant Cell Arteritis and Polymyalgia Rheumatica
Authors: BRAUN NIKO , FRITZ PETER , RIETH ANJA , SCHROTH WERNER , KIMMEL MARTIN , BIEGGER DAGMAR , ZAKIM DAVID , ALSCHER MARK DOMINIK 
Published: August 2009

Objective.Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) generally respond well to treatment with glucocorticoids (GC). We sought to determine the value of clinical, histopathologic, immunohistochemical, and genetic findings and the expression of the glucocorticoid receptor (GR) for discriminating between patients who achieve complete remission, or partial remission, or who do not improve with glucocorticoid treatment.Methods.We examined biopsies of the temporal artery from 60 patients, of whom 27 had GCA, 13 PMR, and 20 arteriosclerosis.Results.Of the clinical variables evaluated, jaw claudication was correlated with the histologic classification of the biopsies (p < 0.0001). Erythrocyte sedimentation rate was significantly higher in patients with PMR and GCA than in patients with arteriosclerosis (p < 0.0001). There were significant differences between patients with GCA versus PMR in the numbers of CD3−, CD8−, and CD4-positive T cells, in CD68-positive monocytes (p < 0.0001), and antigen-presenting cells (p < 0.0001). CD138-positive and CD20-positive cells were absent in patients with PMR but present in patients with GCA (p < 0.0001). In GCA and chronic inflammation most monocytes and lymphocytes expressed GR (88.9%). The number of CD68-positive cells and the extent of GR-staining in chronic inflammation reflected the success of treatment in logistic regression analysis (p < 0.05). GR polymorphism showed that more than 90% of patients had the wild-type (homozygote) of the R23K or N363S polymorphism. There was no evidence that this polymorphism influenced response to treatment with GC (Fisher’s exact test 1.0).Conclusion.Expression of GR and the presence of CD20−, CD3−, CD4−, CD8−, CD68−, CD138-positive cells and antigen-presenting cells differ between GCA and PMR. The presence of CD68-positive cells and the extent of GR-staining in chronic inflammation are suitable to predict complete remission in GCA.
Metabolic Syndrome and the Incidence of Symptomatic Deep Vein Thrombosis Following Total Knee Arthroplasty
Authors: GANDHI RAJIV , RAZAK FAHAD , TSO PEGGY , DAVEY J. RODERICK , MAHOMED NIZAR N. 
Published: August 2009

Objective.We asked if patients with metabolic syndrome undergoing total knee replacement (TKR) have an increased risk for symptomatic deep vein thrombosis (DVT) at 3 months followup.Methods.We reviewed 1460 patients from our joint registry undergoing primary, unilateral TKR between 1998–2006. Demographic variables of age, sex, comorbidity, and education were retrieved. Metabolic syndrome was defined as body mass index above 30 kg/m2, diabetes, hypertension, and hypercholesterolemia. Logistic regression was used to examine the relationship of metabolic syndrome on the incidence of DVT.Results.The overall incidence of symptomatic DVT was 4.4% (65/1460). Patients with metabolic syndrome had an increased incidence of DVT compared to those without metabolic syndrome (15.5% vs 3.4%). Adjusted analysis showed that the risk of symptomatic DVT in patients with metabolic syndrome was 3.2 times [odds ratio 3.2, 95% CI (1.0,15.4), p = 0.04] the risk in those without metabolic syndrome.Conclusion.Hospital protocols developed for prophylactic anticoagulation following TKR should give special consideration to patients with metabolic syndrome.
Functional Association of Interleukin 18 Gene −607 (C/A) Promoter Polymorphisms with Disease Course in Chinese Patients with Adult-onset Still’s Disease
Authors: CHEN DER-YUAN , CHEN YI-MING , CHEN HSIN-HUA , HSIEH CHIA-WEI , LIN CHI-CHEN , LAN JOUNG-LIANG 
Published: August 2009

Objective.Interleukin 18 (IL-18) has a central role in the pathogenesis of adult-onset Still’s disease (AOSD). We investigated the functional association of −607 (C/A) IL-18 promoter polymorphisms with disease course in Chinese patients with AOSD.Methods.Sequence-specific primer polymerase chain reaction and the restriction fragment-length polymorphism method were used to analyze the genotypes of IL-18 promoter polymorphism at position −607 in 96 unrelated patients with AOSD and 164 ethnically-matched healthy controls. Serum IL-18 levels were determined using ELISA in patients with active untreated AOSD.Results.Significantly lower frequencies of single-nucleotide polymorphism −607/AA were observed in patients with AOSD compared to healthy controls (18.8% vs 31.1%, respectively; p < 0.05). Median levels of serum IL-18 were significantly lower in AOSD patients with AA genotype compared to those with CA genotype or CC genotype (147.5 pg/ml vs 410.5 pg/ml or 262.4 pg/ml, respectively; both p < 0.05). Significantly lower IL-18 levels were demonstrated in AOSD patients with a monocyclic systemic course than in those with a polycyclic systemic course or a chronic articular course. The AA genotype was more frequently observed in patients with monocyclic systemic course, which had the best prognosis, than in those with the other 2 disease courses. In contrast, a lower frequency of the AA genotype than the CA or the CC genotype was observed in patients with chronic disabling arthritis (5.5% vs 25.0% or 19.2%, respectively).Conclusion.The SNP −607/AA genotype with lower IL-18 levels might be a genetically protective factor for the occurrence of AOSD in the Chinese population, against progression of chronic disabling arthritis.
Preface: Message from the Director, PGIM
Authors: Sheriff Rezvi 
Published: August 2009

It gives me enormous pleasure as an Academic and Director of the Postgraduate Institute of Medicine (PGIM) to inaugurate the series of Postgraduate Institute Journals in different branches of medicine. The new discipline of Critical Care is taking the lead and this issue of the Sri Lanka Journal of Critical Care (SLJCC) will be the first one. The idea to establish a new peer-reviewed journal in critical care under the PGIM was based on a proposal made in 2008 by Dr Senaka Rajapakse, Head, Department of Clinical Medicine, Faculty of Medicine, University of Colombo. I congratulate the Editors, Dr. Senaka Rajapakse, Dr. Aruna Munasinghe, Consultant Physician, General Hospital Matara, and Dr Anuja Abeydeera, Senior Lecturer in Anaesthesiology, Faculty of Medicine, University of Colombo for their untiring efforts in getting the journal off the ground. I hope this will be a regular publication with easy access and of high standard and high impact. My sincere good wishes go to the Editors and the Editorial Board. Vidyajyothi Professor Rezvi Sheriff,Director, Postgraduate Institute of MedicineDOI: 10.4038/sljcc.v1i1.935
Initial Management Of Patients With Community-Acquired Pneumonia In A Tertiary Hospital In Sri Lanka
Authors: Haniffa Rashan , Ariyaratne Hemal , Fernando Shyam , Rajapakse Senaka 
Published: August 2009

Introduction: We studied the choice of antibiotic/s prescribed on admission and microbiological investigations, in patients hospitalised with community-acquired pneumonia, and compared such choice with published consensus guidelines. Methods: Adult patients admitted to medical wards of the National Hospital of Sri Lanka with clinical features of pneumonia, with subsequent radiological confirmation, were eligible for inclusion (n=112). Patients who had been in hospital within 10 days of admission, and those with diagnoses of lung malignancy, lung fibrosis, bronchiectasis or tuberculosis were excluded. We obtained data from the patients' case records regarding indicators of severity, the antibiotic prescribed on admission, and route of administration. The microbiological investigations performed were also recorded. We compared the practices with guidelines for management of community-acquired pneumonia published by the British Thoracic Society in 2001. Results: The respiratory rate, a core clinical adverse prognostic feature, was documented in only 13% of case records. Oral amoxicillin was the most common antibiotic prescribed on admission, with 29% of hospitalized patients receiving it. Erythromycin was included in the drug regimen in only 18% of all patients. Intravenous antibiotics were started for 44% of cases without any documented adverse prognostic features on admission. Sputum was sent for acid-fast bacilli staining in 48% of patients and for bacterial culture in 11%. Blood culture was performed in 5% of patients. Conclusion: Documentation of severity criteria is often incomplete. There is inadequate utilization of oral macrolide antibiotics to cover atypical pathogens. Intravenous antibiotics are overused in hospitalized patients with community-acquired pneumonia. DOI: 10.4038/sljcc.v1i1.941
A Computer-Based ICU Patient Alert And Decision Support System
Authors: Gunawardane Shashi , Koggalage Ravindra , Rodrigo Ranga , Rajapakse Senaka 
Published: August 2009

The safety of critically ill patients in intensive care units is an important aspect of medical care. Many human factors contribute to deficiencies and errors in patient care in the intensive care setting, such as long working hours, high levels of stress, lack of enough people, may cause human errors and affecting the effectiveness of the decisions of the physician. Several attempts have been made to increase the effectiveness of such decisions by issuing early alerts on adverse patient conditions. However, such alerts are based on single parameter variations, and not on the relationship between multiple parameter variations. We developed a computer-based model is an integrated solution which identifies adverse patient events based on multiple parameter variations, and then provides predictive treatment suggestions based on the likely clinical conditions which result in the parameter variations. The proposed system follows an interactive communication cycle in order to properly notify the responsible treating physicians at different tiers of responsibility. Our model is capable of early identification of adverse conditions and providing suitable treatment suggestions, thus acting as a decision support system to assist the treating physician. DOI: 10.4038/sljcc.v1i1.942
Expression of Tolerance Associated Gene-1, a Mitochondrial Protein Inhibiting T Cell Activation, Can Be Used to Predict Response to Immune Modulating Therapies
Authors: Keeren Kathrin , Friedrich Markus , Gebuhr Inga , Philipp Sandra , Sabat Robert , Sterry Wolfram , Brandt Christine , Meisel Christian , Grütz Gerald , Volk Hans-Dieter , Sawitzki Birgit 
Published: August 2009

Abstract
Immune modulating therapies gain increasing importance in treatment of patients with autoimmune diseases such as psoriasis. None of the currently applied biologics achieves significant clinical improvement in all treated patients. Because the therapy with biologics is cost intensive and sometimes associated with side effects, noninvasive diagnostic tools for early prediction of responders are of major interest. We studied the effects of Alefacept (LFA3Ig), an approved drug for treatment of psoriasis, on leukocytes in vitro and in vivo to identify gene markers predictive for treatment response and to further investigate its molecular mechanisms of action. In an open-label study, 20 psoriasis patients were treated weekly with 15 mg Alefacept over 12 wk. We demonstrate that transcription of the tolerance-associated gene (TOAG-1) is significantly up-regulated whereas receptor for hyaluronic acid mediated migration (RHAMM) transcription is down-regulated in PBMCs of responding patients before clinical improvement. TOAG-1 is exclusively localized within mitochondria. Overexpression of TOAG-1 in murine T cells leads to increased susceptibility to apoptosis. Addition of Alefacept to stimulated human T cells in vitro resulted in reduced frequencies of activated CD137+ cells, increased TOAG-1 but reduced RHAMM expression. This was accompanied by reduced proliferation and enhanced apoptosis. Inhibition of proliferation was dependent on enhanced PDL1 expression of APCs. Thus, peripheral changes of TOAG-1 and RHAMM expression can be used to predict clinical response to Alefacept treatment in psoriasis patients. In the presence of APCs Alefacept can inhibit T cell activation and survival by increasing expression of TOAG-1 on T cells and PDL1 on APCs.
Galactoxylomannan-Mediated Immunological Paralysis Results from Specific B Cell Depletion in the Context of Widespread Immune System Damage
Authors: De Jesus Magdia , Nicola André Moraes , Frases Susana , Lee Ian R. , Mieses Steven , Casadevall Arturo 
Published: August 2009

Abstract
The mechanisms responsible for polysaccharide-induced immunological paralysis have remained unexplained almost a century after this phenomenon was first described. Cryptococcus neoformans capsular polysaccharides glucuronoxylomannan and galactoxylomannan (GalXM) elicit little or no Ab responses. This study investigates the immunological and biological effects of GalXM in mice. GalXM immunization elicits a state of immunological paralysis in mice characterized by the disappearance of Ab-producing cells in the spleen. Immunological paralysis and lack of immunogenicity could not be overcome by immunization with GalXM conjugated to a protein carrier, Bacillus anthracis protective Ag. Additionally, immunization with GalXM in either complete or IFA was associated with spleen enlargement in BALB/c mice. TUNEL and flow cytometry revealed widespread apoptosis in the spleen after GalXM administration. Administration of a cocktail of caspase-3 inhibitor Z-DEVD-FMK and general caspase inhibitor Z-VAD-FMK or Fas-deficient mice abrogated the complete disappearance of Ab-producing cells. Analysis of spleen cytokine expression in response to GalXM systemic injection revealed that GalXM down-regulated the production of inflammatory cytokines. Hence, we conclude that GalXM-induced immune paralysis is a result of specific B cell depletion mediated by its proapoptotic properties in the context of widespread dysregulation of immune function.
TC1(C8orf4) Is a Novel Endothelial Inflammatory Regulator Enhancing NF-κB Activity
Authors: Kim Jungtae , Kim Yunlim , Kim Hyun-Taek , Kim Dong Wook , Ha Yunhi , Kim Jihun , Kim Cheol-Hee , Lee Inchul , Song Kyuyoung 
Published: August 2009

Abstract
Endothelial inflammation is regulated by a complex molecular mechanism. TC1(C8orf4) is a novel regulator implicated in cancer and inflammation. It is a small protein conserved well among vertebrates. In zebrafish embryos, it is mostly expressed in angio-hematopoietic system and the overexpression induces edema. In human aortic endothelial cells and umbilical vein endothelial cells, TC1 transfection up-regulates key inflammatory cytokines, enzymes, and adhesion proteins including IL-6, IL-1α, COX-2, CXCL1, CCL5, CCL2, IL-8, ICAM1, VCAM1, and E-selectin, while TC1 knockdown down-regulates them. TC1 also enhances inflammatory parameters such as monocyte-endothelial adhesion and endothelial monolayer permeability. TC1 is up-regulated by IL-1β, TNF-α, LPS, and phorbol ester, and the up-regulation is inhibited by I-κB-kinase inhibitors. TC1, in turn, enhances the nuclear translocation of RelA and the DNA binding activity, suggesting a biological role of amplifying NF-κB signaling via a positive feedback. Our findings suggest that TC1 is a novel endothelial inflammatory regulator that might be implicated in inflammatory vascular diseases.
Cutting Edge: Candida albicans Hyphae Formation Triggers Activation of the Nlrp3 Inflammasome
Authors: Joly Sophie , Ma Ning , Sadler Jeffrey J. , Soll David R. , Cassel Suzanne L. , Sutterwala Fayyaz S. 
Published: August 2009

Abstract
The proinflammatory cytokine IL-1β plays an important role in antifungal immunity; however, the mechanisms by which fungal pathogens trigger IL-1β secretion are unclear. In this study we show that infection with Candida albicans is sensed by the Nlrp3 inflammasome, resulting in the subsequent release of IL-1β. The ability of C. albicans to switch from a unicellular yeast form into a filamentous form is essential for activation of the Nlrp3 inflammasome, as C. albicans mutants incapable of forming hyphae were defective in their ability to induce macrophage IL- 1β secretion. Nlrp3-deficient mice also demonstrated increased susceptibility to infection with C. albicans, which is consistent with a key role for Nlrp3 in innate immune responses to the pathogen C. albicans.