bluuebunny/crossref_metadata_2025 huggingface dataset:
Sorption of Trace Metals by Standard and Micro Suction Cups in the Absence and Presence of Dissolved Organic Carbon
Authors: Rais D. , Nowack B. , Schulin R. , Luster J.
Published: January 2006

Both the bioavailability of a trace metal (TM) in a soil and the risk of leaching to the ground water are linked to the metals concentration in the soil solution. Sampling soil solution by tension lysimetry with suction cups is a simple and established technique that is increasingly used for monitoring dissolved TM in soils. Of major concern, however, is the sorption of TM by the walls of the samplers. Metal sorption by different materials used in suction cups can vary widely, depending also on the chemistry of the soil solution. We compared the sorption of Cu, Zn, Cd, and Pb by different standard‐size and micro suction cups in the laboratory at two pH values (4.5 and 7.5 or 8.0) in absence and presence of dissolved organic carbon (DOC). In addition, we investigated the sorption of DOC from different origins by the cup materials. At both pH values, the weakest sorption of all four TMs was exhibited by standard‐size suction cups based on nylon membranes and by hollow fibers made from polyvinyl alcohol (PVA). At alkaline pH, borosilicate glass, ceramic materials, and polytetrafluorethylene (PTFE) mixed with silicate were characterized by generally strong sorption of all investigated TMs. In addition, Cu and Pb were strongly sorbed at low pH by PTFE–silicate and a ceramic material used for the construction of standard‐size suction cups. On the other hand, sorption of Cu, Zn, and Cd by ceramic capillaries produced from pure aluminum oxide was negligible at low pH. Micro suction cups made of an unknown polymerous tube sorbed Cu strongly, but were well suited to monitor Zn, Cd, and Pb at low pH, and, in the presence of DOC, also at high pH. Major cations (Na+, Mg2+, K+, Ca2+) and anions (Cl−, NO3−, SO42−) were not or very weakly sorbed by all cup materials, except for Mg2+, K+, and Ca2+ by borosilicate glass at pH 7.5. Trace metal sorption by suction cups was generally greatly reduced in the presence of DOC, especially at alkaline pH. The sorption of DOC itself depended on its source. Dissolved organic carbon from leaf litter extracts with a probably large hydrophobic fraction was sorbed more strongly than mainly hydrophilic DOC from a mineral soil solution.
Getting Personal: How Early Childhood Teacher Education Troubles Students' and Teacher Educators' Identities regarding Subjectivity and Feminism
Authors: Taguchi Hillevi Lenz
Published: January 2006

This article constitutes an attempt to investigate how student teachers and teacher educators in the context of Swedish early childhood teacher education are invented and reinvented by practices that are inspired by feminist and post-structural thinking. I give examples of practice that explicitly make use of different aspects of the personal, such as subjectivities, voice and experience. These are theorized, problematized and troubled in relation to concepts of power, resistance and emancipation. The article questions the possibility of ‘getting outside’ of the regulatory regimes of power production through practices of ‘getting personal’, and asks just how much freedom is possible, even given overtly ‘emancipist’ teaching.
The Effectiveness of Cognitive Behavioral Treatment for Adult Offenders: A Methodological, Quality-Based Review
Authors: Allen Leana C. , MacKenzie Doris L. , Hickman Laura J.
Published: January 2006

Previous research on cognitive skills treatment programs has not included a comprehensive review of the effectiveness of these programs in reducing recidivism. This article reviews recent recidivism studies for two rehabilitation programs: Moral Reconation Therapy, which attempts to reduce recidivism by increasing the moral reasoning abilities of offenders, and Reasoning and Rehabilitation, which aims to educate offenders to change underlying criminogenic thoughts and attitudes. Using the Maryland Scale for Scientific Rigor, these studies were evaluated for their methodological strength and for the program’s success in reducing the recidivism of offenders. In considering the findings and the strength of the methods for each program, this review concludes that Moral Reconation Therapy and Reasoning and Rehabilitation programs appear to be successful approaches to reducing recidivism.
Managing Unacceptable Risk: Sex Offenders, Community Response, and Social Policy in the United States and Canada
Authors: Petrunik Michael G.
Published: January 2006

This article compares the community protection–risk management model for the control of sex offenders with the clinical and justice models that preceded it and with a restorative justice alternative based on the principle of community reintegration. The author discusses how this community protection–risk management model reflects the new penology as well as the fusion of panopticism and synopticism. The author also discusses the model’s actual and potential social costs. He concludes with a brief look at circles of support and accountability. This Canadian approach involves setting up support circles of volunteers who enter into a covenant with persons designated as high-risk sex offenders to help them both to integrate into the community and to reduce the likelihood that they will reoffend.
Residential Treatment Programs for Young Offenders in Hong Kong: A Report
Authors: Chui Wing Hong
Published: January 2006

Research evaluation of rehabilitation programs has used minimal contribution or participation from the ex-offenders who are the subjects or objects of study, and little attention has been paid to those who receive these services. This article looks at what young ex-offenders said about their experience of residential treatment programs in the probation homes and the detention center in Hong Kong. Based on in-depth, qualitative interviews with five young male ex-offenders, this small-scale study may shed light on how they perceive the advantages and disadvantages of treatment programs for them. Although loss of freedom, pains of detention, and doing time are a result of being locked up, some report their residential experiences as a fruitful way to enable them to grow out of crime and to cause them to reevaluate relationships with their families. Finally, an outline of what further research or policy evaluation could and should be done is given.
Capecitabine-Induced Severe Hypertriglyceridemia: Report of Two Cases
Authors: Kurt Mevlut , Babaoglu Melih O , Yasar Umit , Shorbagi Ali , Guler Nilufer
Published: January 2006

Objective:

To report 2 cases of severe hypertriglyceridemia associated with the use of oral capecitabine.

Case Summaries:

The first patient was a 73-year-old woman with metastatic breast carcinoma who received capecitabine 2500 mg/m2/day in 2 divided doses for 2 weeks followed by a one week rest period. The baseline triglyceride level was 324 mg/dL; after 2 cycles of capecitabine, levels increased to 916 mg/dL. Although lipid-lowering treatment was initiated, triglyceride levels peaked at 1782 mg/dL by the end of the seventh cycle. Eight weeks after capecitabine treatment was stopped, triglyceride levels decreased to 118 mg/dL. The second patient was a 59-year-old man with metastatic colorectal carcinoma who was placed on capecitabine treatment at a dosage of 2500 mg/m2/day in 2 divided doses for 2 weeks followed by a one week rest period. The baseline triglyceride level was 244 mg/dL; levels peaked at 1455 mg/dL at the end of the fifth cycle. Capecitabine treatment was discontinued due to disease progression, and triglyceride levels decreased to 154 mg/dL after 11 weeks.

Discussion:

The most frequently reported adverse effects of capecitabine are gastrointestinal and hematologic effects and palmar-plantar erythrodysesthesia. Drug-induced hyperlipidemia may appear more readily in individuals with hereditary lipoprotein lipase deficiency because decreased lipoprotein lipase activity might make these individuals more susceptible to a rise in triglyceride levels. The Naranjo probability scale indicated a probable relationship between capecitabine and severe hypertriglyceridemia.

Conclusions:

Capecitabine should be prescribed with care, especially in patients with preexisting hypertriglyceridemia. The question of whether capecitabine actually causes hypertriglyceridemia needs careful consideration, and the possible mechanism by which it may cause this adverse effect requires further investigation.
Delinquency Risk as a Function of Number of Early Onset Problem Behaviors
Authors: Mason W. Alex , Windle Michael
Published: January 2006

This study examined delinquency risk as a function of number of early onset problem behaviors retrospectively self-reported by a sample of middle-adolescent boys and girls. Number of early first experiences of problem behaviors was linearly associated with increased frequency of delinquency among the predominantly White and middle-class high school students. In addition, number of early onset behaviors explained a small, but significant, amount of variance in self-reported frequency of delinquency over and above that explained by prior delinquency and additional psychosocial variables (e.g., peer deviance, family support). Finally, results demonstrated that the magnitude of risk for incarceration during adolescence increased in proportion to the number of early first experiences of problem behaviors. These findings are interpreted in light of the extant literature, and implications for the development of preventive interventions are discussed.
Murderous Parents
Authors: Palermo George B.
Published: January 2006

This article offers observations regarding some of the major manifestations of family violence, neonaticide, infanticide, and filicide with the purpose of aiding in the early identification of parents at risk. They are discussed within the past and present historical and cultural milieu. A brief review of pertinent literature is presented. Pertinent case studies from the forensic psychiatric practice of the author along with psychodynamic reflections are offered.
Comparison of Sex Offenders to Nonoffenders on Selected Psychological Measures
Authors: Fisher Dawn , Beech Anthony , Browne Kevin
Published: January 2006

A group of 140 child molesters (59 participating in community-based sex offender treatment programs and 81 incarcerated child molesters) were compared on a range of psychological measures to a group of 81 nonoffenders. Child molesters were found to be significantly lower in self-esteem, higher on emotional loneliness and personal distress, and to show deficits in victim empathy. Further differences were found between high- and low-deviancy offenders in terms of assertiveness, perspective taking, cognitive distortions regarding children, and emotional congruence with children. General empathy did not appear to be directly related to empathy for one’s own victim and the presence of cognitive distortions was only significant in high-deviancy child molesters. Some victim-blaming attitudes and distorted thinking regarding children and sex were found in the nonoffender group.
The Economics of Conservation Subdivisions
Authors: Mohamed Rayman
Published: January 2006

The environmental benefits of less land consumption and a growing interest in addressing the negative economic and social impacts of sprawl have resulted in calls for more sensitive subdivision designs. One such design is conservation subdivisions. However, not much is known about these subdivisions, in particular about their economics. This article addresses the issue by examining price premiums, investment costs, and absorption rates for lots in conservation versus those in conventional subdivisions. The results show that lots in conservation subdivisions carry a premium, are less expensive to build, and sell more quickly than lots in conventional subdivisions. The results suggest that designs that take a holistic view of ecology, aesthetics, and sense of community can assuage concerns about higher density. However, the potential negative consequences of conservation subdivisions require further study.
BAFF‐induced changes in B cell antigen receptor–containing lipid rafts in Sjögren's syndrome
Authors: d'Arbonneau Frédérique , Pers Jacques‐Olivier , Devauchelle Valérie , Pennec Yvon , Saraux Alain , Youinou Pierre
Published: December 2005

Objective

To determine the effect of excessive production of BAFF on the distribution and function of B cell subsets in patients with primary Sjögren's syndrome (SS).

Methods

The phenotype of B lymphocytes was analyzed by flow cytometry. Differences in the expression level of membrane IgD and CD38 were used to identify B lymphocyte subsets evolving from naive Bm1 through memory Bm5 cells. Based on our finding of a low expression of CD45RA, we sorted Bm2/Bm2′ cells to determine the time course of translocation of the CD19 molecule and the B cell receptor into lipid rafts, by confocal microscopy. Serum levels of BAFF were measured by an enzyme‐linked immunosorbent assay developed in‐house.

Results

“Circulating” Bm2/Bm2′ cells were expanded in patients with primary SS compared with rheumatic disease controls and with normal controls. In addition, these B cell subsets were functionally abnormal. Prolonged residency of the B cell receptor in lipid rafts in these cells was associated with elevated CD19 expression in B cells, most notably, Bm2 and Bm2′ cells, obtained from the patients with primary SS. BAFF levels were higher in the patients than in the normal controls and correlated with the percentage of Bm2/Bm2′ cells and their expression of CD19 in primary SS patients. These correlations were confirmed by placing sorted Bm1 or Bm2 cells from normal controls in culture in the presence or absence of BAFF.

Conclusion

Bm2/Bm2′ cells express more CD19 molecules in primary SS patients than in normal controls. BAFF might participate in this elevated expression of CD19. These patients might be suitable candidates for treatment with BAFF antagonists.
The effectiveness of anti–tumor necrosis factor therapy in preventing progressive radiographic joint damage in rheumatoid arthritis: A population‐based study
Authors: Finckh Axel , Simard Julia F. , Duryea Jeffrey , Liang Matthew H. , Huang Jie , Daneel Synove , Forster Adrian , Gabay Cem , Guerne Pierre‐André
Published: December 2005

Objective

To compare the effectiveness of 3 therapeutic strategies in preventing progressive joint damage, in a population‐based cohort. The 3 strategies were infliximab with concomitant disease‐modifying antirheumatic drugs (DMARDs), etanercept with concomitant DMARDs, and etanercept alone.

Methods

We used sequential radiographs to assess all patients who were treated with infliximab or etanercept for >10 months. The rates of erosion progression and joint space narrowing (JSN) were analyzed using multivariate regression models for longitudinal data, with adjustment for potential confounders.

Results

A total of 372 patients treated with anti–tumor necrosis factor (TNF) therapies met the inclusion criteria. The baseline characteristics of the patients assigned to the 3 strategies were not significantly different, except that, as expected, more patients were receiving combination therapy with infliximab. The combination of infliximab plus DMARDs was significantly more effective than etanercept alone for controlling erosion progression (P< 0.001), but the effectiveness of the 2 combination‐treatment strategies was similar (P= 0.07). The combination of infliximab plus DMARDs was also more effective at controlling progressive JSN compared with etanercept alone (P= 0.04) or etanercept plus DMARDs (P= 0.02). Treatment with anti‐TNF agents (infliximab or etanercept) plus concomitant DMARDs was more effective than treatment with etanercept alone for controlling erosion progression (P= 0.045).

Conclusion

When combined with traditional DMARDs, both etanercept and infliximab appear to offer similar protection against progressive structural joint damage, and combination therapy with either of these agents appears to be more effective than treatment with etanercept alone.
Monocyte chemoattractant protein 1 released from glycosaminoglycans mediates its profibrotic effects in systemic sclerosis via the release of interleukin‐4 from T cells
Authors: Distler Jörg H. W. , Jüngel Astrid , Caretto David , Schulze‐Horsel Ursula , Kowal‐Bielecka Otylia , Gay Renate E. , Michel Beat A. , Müller‐Ladner Ulf , Kalden Joachim R. , Gay Steffen , Distler Oliver
Published: December 2005

Objective

Monocyte chemoattractant protein 1 (MCP‐1; CCL2) has been implicated in the pathogenesis of fibrotic diseases and is up‐regulated in patients with systemic sclerosis (SSc). The aim of the present study was to examine the mechanisms by which MCP‐1 mediates its profibrotic effects in the setting of SSc.

Methods

The expression of receptors for MCP‐1 on dermal fibroblasts was analyzed by real‐time polymerase chain reaction and fluorescence‐activated cell sorting. The ability of extracellular matrix proteins to bind and release MCP‐1 was quantified by enzyme‐linked immunosorbent assay. Th0 cells were isolated using a magnetic‐activated cell sorting system and were stimulated twice in the presence of MCP‐1. The synthesis of collagen was measured using the Sircol collagen assay kit.

Results

The glycosaminoglycan chondroitin sulfate, but not fibronectin or collagens, bound and released MCP‐1 in a time‐dependent manner. MCP‐1 that was released from chondroitin sulfate induced the differentiation of interleukin‐4 (IL‐4)–producing T cells in a dose‐dependent manner. In turn, dermal fibroblasts from patients with SSc expressed IL‐4 receptor, and stimulation with IL‐4 significantly increased the production of collagen in dermal fibroblasts. In contrast, CCR2a and CCR2b, as well as D6 and US28 (other potential receptors of MCP‐1), were not detectable in SSc and normal fibroblasts, and their expression was not induced by platelet‐derived growth factor, IL‐1β, or IL‐4. In addition, MCP‐1 had no direct effects on collagen production by fibroblasts.

Conclusion

MCP‐1 has no direct effects on dermal fibroblasts but contributes to fibrosis in patients with SSc by inducing the differentiation of IL‐4–producing T cells. Because MCP‐1 has both proinflammatory and profibrotic effects, pharmacologic targeting of MCP‐1 could be a promising therapeutic approach in SSc.
Association between protein tyrosine phosphatase 22 variant R620W in conjunction with the HLA–DRB1 shared epitope and humoral autoimmunity to an immunodominant epitope of cartilage‐specific type II collagen in early rheumatoid arthritis
Authors: Burkhardt Harald , Hüffmeier Ulrike , Spriewald Bernd , Böhm Beate , Rau Rolf , Kallert Stefan , Engström Åke , Holmdahl Rikard , Reis André
Published: December 2005

Objective

To analyze the genetic impact of allelic variants of the protein tyrosine phosphatase N22 (PTPN22) and HLA–DRB1 alleles on IgG autoantibody formation directed toward an immunodominant conformational epitope (C1III; amino acid residues 359–369) of type II collagen (CII) in early rheumatoid arthritis (RA).

Methods

Sera obtained at study inclusion from an inception cohort of RA patients (n = 221; mean symptom duration 6 months) were analyzed for circulating anti–C1III IgG autoantibodies. An enzyme‐linked immunosorbent assay based on solid‐phase–coupled synthetic triple‐helical collagen peptides was used to quantify humoral autoimmune responses. HLA–DRB1 genotypes were determined by allele‐specific polymerase chain reaction amplification of genomic DNA and sequence‐specific hybridization. PTPN22*620W genotyping was performed using an allelic discrimination TaqMan assay.

Results

Anti–C1III IgG autoantibody titers were significantly elevated in patients with early RA as compared with those in healthy controls (n = 70). The increased titers were more pronounced in RA patients harboring alleles of the RA‐associated HLA–DRB1 shared epitope (SE) consensus sequence than in those lacking the SE. In addition, the PTPN22*620W variant was strongly associated with a vigorous humoral autoimmune response to the cartilage‐specific CII determinant C1III.

Conclusion

Allelic variants encoding the binding pocket for peptide presentation (SE) to T cells and a functional domain of a negative regulator of T cell receptor signaling (PTPN22*620W), respectively, synergize in early RA to break self tolerance toward C1III, an evolutionarily conserved cartilage determinant that is also frequently targeted in arthritogenic humoral autoimmunity in mice.
The PREMIER study: A multicenter, randomized, double‐blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment
Authors: Breedveld Ferdinand C. , Weisman Michael H. , Kavanaugh Arthur F. , Cohen Stanley B. , Pavelka Karel , Vollenhoven Ronald van , Sharp John , Perez John L. , Spencer‐Green George T.
Published: December 2005

Objective

To compare the efficacy and safety of adalimumab plus methotrexate (MTX) versus MTX monotherapy or adalimumab monotherapy in patients with early, aggressive rheumatoid arthritis (RA) who had not previously received MTX treatment.

Methods

This was a 2‐year, multicenter, double‐blind, active comparator–controlled study of 799 RA patients with active disease of <3 years' duration who had never been treated with MTX. Treatments included adalimumab 40 mg subcutaneously every other week plus oral MTX, adalimumab 40 mg subcutaneously every other week, or weekly oral MTX. Co‐primary end points at year 1 were American College of Rheumatology 50% improvement (ACR50) and mean change from baseline in the modified total Sharp score.

Results

Combination therapy was superior to both MTX and adalimumab monotherapy in all outcomes measured. At year 1, more patients receiving combination therapy exhibited an ACR50 response (62%) than did patients who received MTX or adalimumab monotherapy (46% and 41%, respectively; both P < 0.001). Similar superiority of combination therapy was seen in ACR20, ACR70, and ACR90 response rates at 1 and 2 years. There was significantly less radiographic progression (P ≤ 0.002) among patients in the combination treatment arm at both year 1 and year 2 (1.3 and 1.9 Sharp units, respectively) than in patients in the MTX arm (5.7 and 10.4 Sharp units) or the adalimumab arm (3.0 and 5.5 Sharp units). After 2 years of treatment, 49% of patients receiving combination therapy exhibited disease remission (28‐joint Disease Activity Score <2.6), and 49% exhibited a major clinical response (ACR70 response for at least 6 continuous months), rates approximately twice those found among patients receiving either monotherapy. The adverse event profiles were comparable in all 3 groups.

Conclusion

In this population of patients with early, aggressive RA, combination therapy with adalimumab plus MTX was significantly superior to either MTX alone or adalimumab alone in improving signs and symptoms of disease, inhibiting radiographic progression, and effecting clinical remission.
Activation of receptor for advanced glycation end products in osteoarthritis leads to increased stimulation of chondrocytes and synoviocytes
Authors: Steenvoorden Marjan M. C. , Huizinga Tom W. J. , Verzijl Nicole , Bank Ruud A. , Ronday H. Karel , Luning Hilco A. F. , Lafeber Floris P. J. G. , Toes René E. M. , DeGroot Jeroen
Published: December 2005

Objective

The major risk factor for osteoarthritis (OA) is aging, but the mechanisms underlying this risk are only partly understood. Age‐related accumulation of advanced glycation end products (AGEs) could be one of these mechanisms. We undertook this study to investigate the role of the receptor for AGEs (RAGE) in mediating the cellular effects of AGEs on chondrocytes and fibroblast‐like synoviocytes (FLS).

Methods

AGE levels in human cartilage were determined by fluorescence, browning, and pentosidine levels. Chondrocyte activation by AGEs was assessed as the release of proteoglycans and the synthesis of matrix metalloproteinase 1 (MMP‐1) and type II collagen messenger RNA (mRNA). The activation of FLS by AGEs was measured by MMP‐1 production and invasion through matrix proteins.

Results

Patients with focal degeneration of cartilage showed increased AGE levels in their healthy cartilage compared with the levels in healthy cartilage from donors without cartilage degeneration (P < 0.01 for both fluorescence and browning; P not significant for pentosidine content). Stimulation of bovine chondrocytes with glycated albumin increased the release of proteoglycans by 110% (P < 0.001) and the production of MMP‐1 mRNA by 200% (P = 0.028). In addition, OA FLS produced 240% more MMP‐1 when stimulated with glycated albumin (P < 0.001). Glycated matrix or albumin increased the catabolic activity of OA FLS, which was assessed as invasive behavior, by 150% and 140% (P = 0.001 and P = 0.010), respectively. Effects of stimulation with AGEs were blocked by a neutralizing antibody against RAGE, but not by an isotype control.

Conclusion

This study shows that AGEs trigger RAGE on chondrocytes and FLS, leading to increased catabolic activity and therefore to cartilage degradation. AGEs, via RAGE, could therefore contribute to the development and/or progression of OA.
Increased expression of receptor for advanced glycation end products by synovial tissue macrophages in rheumatoid arthritis
Authors: Sunahori Katsue , Yamamura Masahiro , Yamana Jiro , Takasugi Koji , Kawashima Masanori , Makino Hirofumi
Published: December 2005

Objective

The accumulation of advanced glycation end products (AGEs), S100A12, and high mobility group box chromosomal protein 1 has been associated with joint inflammation in rheumatoid arthritis (RA). This study was undertaken to determine the induction of the receptor for these proteins, termed receptor for AGEs (RAGE), in synovial tissue (ST) macrophages from RA patients.

Methods

RAGE and CD68 expression in ST were determined by 2‐color immunofluorescence labeling. Cell surface and messenger RNA (mRNA) expression of RAGE were examined by flow cytometry and reverse transcriptase–polymerase chain reaction (PCR) or real‐time PCR, respectively.

Results

CD68+ lining macrophages, like the vasculature, expressed high levels of RAGE in inflamed ST from RA patients. RAGE mRNA expression was significantly higher in RA ST than in ST from patients with osteoarthritis. RAGE mRNA levels were significantly higher in ST macrophages and normal endothelial cells than in ST CD4+ T cells and synovial fibroblasts stimulated with tumor necrosis factor α and interleukin‐1β (IL‐1β). Cell surface RAGE was highly induced on normal monocytes after a 24‐hour incubation with a 20% concentration of RA ST cell culture supernatants. RAGE mRNA expression in adherent monocytes was augmented by various cytokines, most potently by IL‐1β.

Conclusion

These results indicate that RAGE overexpression in lining macrophages may be induced, at least in part, by cytokines such as IL‐1, leading to the amplification of inflammatory responses mediated by RAGE ligands that are abundant in RA joints.
Association of higher levels of serum cartilage oligomeric matrix protein and N‐telopeptide crosslinks with the development of radiographic hip osteoarthritis in elderly women
Authors: Kelman A. , Lui L. , Yao W. , Krumme A. , Nevitt M. , Lane N. E.
Published: December 2005

Objective

To examine the association of baseline concentrations of serum cartilage oligomeric matrix protein (COMP) and serum N‐telopeptide crosslinks (NTX) with the development and progression of radiographic hip osteoarthritis (RHOA) in elderly women.

Methods

Pelvic radiographs were obtained a mean of 8.3 years apart from white women ≥65 years of age enrolled in the Study of Osteoporotic Fractures. Random sampling from a cohort of 5,928 subjects was performed, with subjects (∼200 per group) assigned to nested case–control studies, one focusing on RHOA incidence and the other on RHOA progression. Baseline serum levels of COMP and NTX were measured by enzyme‐linked immunosorbent assay in duplicate. Odds ratios (ORs) and 95% confidence intervals (95% CIs), indicating the likelihood of baseline serum COMP and NTX levels to be predictive of the development or progression of RHOA, were calculated using logistic regression analysis, with adjustment for potential covariates.

Results

At baseline, incident cases of RHOA were associated with higher serum levels of COMP and NTX (P < 0.05 for each) compared with the no RHOA control group. Higher baseline serum COMP and NTX levels were associated with an increased risk of incident RHOA compared with the no RHOA group, with an adjusted OR of 1.31 per SD increase in COMP (95% CI 1.02–1.68) and adjusted OR of 1.38 per SD increase in NTX (95% CI 1.07–1.79). In this community‐based cohort, progression of RHOA was modest. However, there was a trend toward increased risk of RHOA progression with higher baseline COMP and NTX levels.

Conclusion

These data suggest that serum levels of COMP and NTX are modest risk markers for the development of RHOA in a community‐based cohort of elderly white women.
Fibromyalgia diagnosis: A comparison of clinical, survey, and American College of Rheumatology criteria
Authors: Katz Robert S. , Wolfe Frederick , Michaud Kaleb
Published: December 2005

Objective

The American College of Rheumatology (ACR) criteria for fibromyalgia are the de facto criteria used for research. However, ACR criteria are not generally utilized by nonrheumatologists, and rheumatologists may diagnose fibromyalgia in patients who do not satisfy the ACR criteria. We undertook this study to determine concordance between ACR criteria and clinician diagnosis and between proposed survey criteria and clinician diagnosis.

Methods

Consecutive patients in a clinical practice setting were evaluated by tender point examination, survey criteria for fibromyalgia (Regional Pain Scale score ≥8 and fatigue score ≥6), and clinical diagnosis.

Results

Among the 206 patients, the clinician diagnosed fibromyalgia in 49.0%, while 29.1% satisfied ACR criteria and 40.3% satisfied survey criteria. Clinical and survey criteria were concordant in 74.8% of cases (κ = 0.49 [95% confidence interval 0.36, 0.60]). Clinical criteria and ACR criteria were concordant in 75.2% of cases (κ = 0.50 [95% confidence interval 0.35, 0.59]), and survey criteria and ACR criteria were concordant in 72.3% (κ = 0.40 [95% confidence interval 0.25, 0.51]). The ACR tender point criterion (≥11) was not a factor in clinical and survey criteria. However, the tender point count was useful in clinical diagnosis.

Conclusion

Clinical diagnosis and ACR and survey criteria are moderately concordant (72–75%) and address a common pool of symptoms and physical findings. Because there is no gold standard for fibromyalgia diagnosis and because fibromyalgia is often viewed as a trait diagnosis, all methods of diagnosis have utility. The survey method has the advantage that it does not require physical examination.
A functional haplotype of thePADI4gene associated with increased rheumatoid arthritis susceptibility in Koreans
Authors: Kang Changsoo Paul , Lee Hye‐Soon , Ju Hyoungseok , Cho Hyunmi , Kang Changwon , Bae Sang‐Cheol
Published: December 2005

Objective

Anticitrullinating autoantibodies are specific markers for rheumatoid arthritis (RA). A functional haplotype of 4 exonic single‐nucleotide polymorphisms (SNPs) in a citrullinating enzyme, peptidylarginine deiminase 4 (PADI4), was shown to be associated with susceptibility to RA in a Japanese population and was shown to increase the stability ofPADI4messenger RNA. However, the association was not confirmed in 4 subsequent studies involving Caucasian RA patients living in the UK, a French Caucasian population, and a Spanish population. The aim of the current study was to investigate the association of SNPs in thePADI4gene with RA in a Korean population.

Methods

Four exonic SNPs of thePADI4gene (padi4_89, padi4_90, padi4_92, and padi4_104) were genotyped in 545 unrelated patients with RA and 392 controls, using the MassArray SNP genotyping system. Allelic, genotypic, and haplotypic associations of the SNPs with RA susceptibility were examined using the chi‐square test and multivariate logistic regression analyses.

Results

Increased RA susceptibility was significantly associated with the minor alleles of padi4_89 (P= 2.3 × 10−5), padi4_90 (P= 2.3 × 10−5), padi4_92 (P= 2.1 × 10−5), and padi4_104 (P= 1.1 × 10−3) and the haplotype carrying the 4 minor alleles (P= 1.0 × 10−4). Genotypes carrying the minor alleles and HLA–DRB1 shared epitope (SE) alleles (P= 9.4 × 10−21) were also associated with increased RA susceptibility. The genotypic associations were sustained among individuals who did not carry any SE alleles, except in the case of padi4_104. Individuals carrying the risk SNPs and/or SE alleles were more susceptible to RA than were individuals carrying neither risk SNPs nor SE alleles.

Conclusion

ThePADI4SNPs and haplotypes are associated with RA susceptibility in Koreans. Thus, the association ofPADI4with RA may depend on genetic heterogeneity between Asians and Europeans.
More pronounced inhibition of cyclooxygenase 2, increase in blood pressure, and reduction of heart rate by treatment with diclofenac compared with celecoxib and rofecoxib
Authors: Hinz Burkhard , Dormann Harald , Brune Kay
Published: December 2005

Objective

Recent findings suggest that permanent blockade of cyclooxygenase 2 (COX‐2) is one factor contributing to the cardiovascular side effects of selective COX‐2 inhibitors (coxibs) and nonsteroidal antiinflammatory drugs (NSAIDs). The present study compared the extent and time course of COX‐2 inhibition and the effects on cardiovascular parameters (changes in blood pressure and heart rate) between various antirheumatic doses of diclofenac, celecoxib, and rofecoxib in healthy elderly volunteers.

Methods

A randomized, parallel‐group study was conducted in volunteers receiving 75 mg diclofenac twice daily, 200 mg celecoxib twice daily, or 25 mg rofecoxib once daily for 8 days. Blood samples were obtained predose and at specified time points postdose, on days 1 and 8, for assay of drug plasma concentrations and COX‐2 inhibition. Lipopolysaccharide‐induced prostaglandin E2synthesis was measured ex vivo as an index of COX‐2 activity in human whole blood.

Results

COX‐2 inhibition was significantly less pronounced after treatment with celecoxib and rofecoxib than with diclofenac. Maximal inhibitions after a single dose and at steady state, respectively, were as follows: 99% and 99% with diclofenac, 70% and 81% with celecoxib, and 56% and 72% with rofecoxib. At steady state, only diclofenac caused virtually complete COX‐2 inhibition over the whole dose interval, and this corresponded to the highest increase in systolic blood pressure and greatest reduction in heart rate.

Conclusion

Diclofenac elicited the most pronounced COX‐2 inhibition, blood pressure elevation, and suppression of heart rate. It is assumed that the extent and time course of intravascular COX‐2 inhibition may determine the differential profile of cardiovascular side effects associated with NSAIDs and coxibs, but this has to be proven in future studies.
Variations of neuronal nitric oxide synthase in systemic sclerosis skin
Authors: Ibba‐Manneschi Lidia , Niissalo Sirkku , Milia Anna Franca , Allanore Yannick , Rosso Angela Del , Pacini Alessandra , Manetti Mirko , Toscano Annarita , Cipriani Paola , Liakouli Vasiliki , Giacomelli Roberto , Kahan André , Konttinen Yrjö T. , Matucci‐Cerinic Marco
Published: December 2005

Objective

In systemic sclerosis (SSc), derangement of the peripheral nervous system is linked to vascular tone dysfunction. Nitric oxide (NO) produced by neuronal nitric oxide synthase (nNOS, NOS‐I) might play a dynamic role in the control of vascular tone. This study was performed to verify, by immunohistochemical and biochemical analyses, the presence and expression of nNOS and protein gene product 9.5 (PGP 9.5) in SSc skin, in different subsets and various phases of the disease.

Methods

Biopsy samples of clinically involved skin from 32 SSc patients (12 with limited cutaneous SSc [lcSSc] and 20 with the diffuse form [dcSSc]) and skin samples from 6 healthy controls were either immunostained with anti–PGP 9.5 and anti‐nNOS antibodies or analyzed by semiquantitative reverse transcription–polymerase chain reaction and Western blotting.

Results

Immunohistochemical and biochemical data showed a decrease in PGP 9.5 and nNOS innervation and in their messenger RNA (mRNA) levels in lcSSc and dcSSc skin. In the edematous phase of SSc, a light alteration in cutaneous innervation was initiated and slowly progressed into the sclerotic phase, becoming most evident in the atrophic phase. Levels of nNOS mRNA were significantly lower between the edematous phase and the sclerotic phase in both dcSSc and lcSSc skin, which was attributable to the earlier occurrence of more severe pathologic alterations.

Conclusion

Total cutaneous innervation and nNOS innervation slowly disappear in the skin of SSc patients. Expression of nNOS depends on the severity of tissue damage in SSc, and increased synthesis of NO also contributes to this process. It remains to be determined whether the changes in cutaneous innervation are due to the disease itself or whether these changes contribute to the pathogenesis and evolution of SSc.
Ultrasonographic and radiographic results from a two‐year controlled trial of immediate or one‐year–delayed addition of infliximab to ongoing methotrexate therapy in patients with erosive early rheumatoid arthritis
Authors: Taylor P. C. , Steuer A. , Gruber J. , McClinton C. , Cosgrove D. O. , Blomley M. J. K. , Marsters P. A. , Wagner C. L. , Maini R. N.
Published: December 2005

Objective

To compare the impact of immediate and delayed introduction of anti–tumor necrosis factor therapy on inflammation and structural damage in methotrexate (MTX)–treated patients with early rheumatoid arthritis (RA).

Methods

Twenty‐four patients with erosive early RA (duration <3 years) who were receiving MTX were randomized to receive infliximab 5 mg/kg or placebo infusions at weeks 0, 2, and 6, and then every 8 weeks through week 46. Beginning at week 54 and thereafter, all patients received infliximab 5 mg/kg. Metacarpophalangeal joints were scanned using high‐frequency ultrasonography and power Doppler imaging. Radiographs were evaluated using the modified Sharp/van der Heijde scoring system.

Results

From baseline to week 54, total synovial thickness was significantly improved in the infliximab + MTX group compared with the placebo + MTX group (median reduction 95.8% versus 37.5%; P = 0.005), as was the total color Doppler area (CDA; vascularity assessment) (median reduction 100% and 47.1%, respectively; P = 0.025). From week 0 to week 110, no significant between‐group difference was observed in the change from baseline for total synovial thickening or the total CDA. At week 54, greater progression in the Sharp/van der Heijde score was apparent in patients receiving placebo + MTX compared with those receiving infliximab + MTX. Although radiographic progression in the placebo + MTX group was greatly reduced in the second year (after initiation of infliximab therapy), marked differences were observed between the infliximab + MTX group (median change in the Sharp/van der Heijde score 4.0) and the placebo + MTX group (median change 14.5) from baseline to week 110 (P = 0.076).

Conclusion

The results indicate that the efficacy of 2 years of combination therapy with infliximab + MTX for inhibiting cumulative structural damage was superior to that of 1 year of treatment with MTX alone followed by the addition of infliximab.
The impact of a diagnosis of fibromyalgia on health care resource use by primary care patients in the UK: An observational study based on clinical practice
Authors: Hughes Gwenda , Martinez Carlos , Myon Eric , Taïeb Charles , Wessely Simon
Published: December 2005

Objective

To investigate the impact of a diagnosis of fibromyalgia (FM) in clinical practice on health care resource use in the UK.

Methods

Rates of visits, prescriptions, referral, and diagnostic testing were estimated in patients who had been diagnosed as having FM between 1998 and March 2003 in UK primary care and compared with those in matched controls. Rates were calculated in 6‐month intervals from 10 years before until 4 years after the FM diagnosis.

Results

Patients (2260) were newly diagnosed as having FM; 81.3% were women. Their mean age was 49 years. FM patients had considerably higher rates of visits, prescriptions, and testing from at least 10 years prior to diagnosis compared with controls. By the time of diagnosis, FM patients had 25 visits and 11 prescriptions per year compared with 12 visits and 4.5 prescriptions per year in controls. Visit rates were highest for depression, followed by fatigue, chest pain, headache, and sleep disturbance. Following diagnosis, visits for most symptoms and health care use markers declined, but within 2–3 years, most visits rose to levels at or higher than those at diagnosis.

Conclusion

Primary care patients who had been diagnosed as having FM reported higher rates of illness and health care resource use for at least 10 years prior to their diagnosis, which suggests that illness behavior may play a role. Being diagnosed as having FM may help patients cope with some symptoms, but the diagnosis has a limited impact on health care resource use in the longer term, possibly because there is little effective treatment.
Transforming growth factor β1 in the pathogenesis of autoimmune congenital complete heart block: Lesson from twins and triplets discordant for the disease
Authors: Cimaz Rolando , Orietta Borghi Maria , Gerosa Maria , Biggioggero Martina , Raschi Elena , Meroni Pier Luigi
Published: December 2005

Objective

Clinical evidence and experimental evidence suggest that anti‐Ro/La autoantibodies are necessary but not sufficient for the development of congenital complete heart block (CCHB). Maternal, fetal, and environmental factors may also contribute to heart damage in CCHB. The aim of our study was to investigate polymorphisms of transforming growth factor β1 (TGFβ1) and tumor necrosis factor α (TNFα) genes in twins and triplets discordant for CCHB whose mothers are anti‐Ro/La positive.

Methods

We studied 2 families in which 1 of the mothers gave birth to triplets and the other gave birth to twins. Only 1 child in each family was affected by CCHB, although 1 of the triplets had incomplete heart block. We analyzed TNFα and TGFβ1 polymorphisms in the 2 babies with CCHB and their siblings. TNFα polymorphisms at the promoter region and TGFβ1 polymorphisms at codons 10 and 25 were determined using polymerase chain reaction–restriction fragment length polymorphism analysis. In addition, the production of TGFβ1 and TNFα by resting or mitogen‐stimulated peripheral blood mononuclear cells in cell culture supernatants was evaluated by enzyme‐linked immunosorbent assay.

Results

The profibrotic TGFβ1 genotype was detected in the twin with CCHB but not in the healthy twin, while all of the triplets displayed the same TGFβ1 genotype at codon 10. Peripheral blood mononuclear cells from the children with CCHB displayed higher spontaneous and mitogen‐stimulated TGFβ1 secretion than was observed in their siblings. No differences regarding TNFα polymorphisms and secretion of TNFα were observed.

Conclusion

The results of this study suggest that, besides anti‐Ro/La autoantibodies, a fetal profibrotic response might contribute to the development of CCHB, but additional pathogenic mechanism(s) are also likely to play a role.
Antiphospholipid antibodies from patients with the antiphospholipid syndrome induce monocyte tissue factor expression through the simultaneous activation of NF‐κB/Rel proteins via the p38 mitogen‐activated protein kinase pathway, and of the MEK‐1/ERK pathway
Authors: López‐Pedrera Chary , Buendía Paula , José Cuadrado Maria , Siendones Emilio , Angeles Aguirre Maria , Barbarroja Nuria , Montiel‐Duarte Cristina , Torres Antonio , Khamashta Munther , Velasco Francisco
Published: December 2005

Objective

Antiphospholipid syndrome (APS) is characterized by thrombosis and the presence of antiphospholipid antibodies (aPL). In patients with primary APS, expression of tissue factor (TF) on the surface of monocytes is increased, which may contribute to thrombosis in these patients. However, the intracellular mechanisms involved in aPL‐mediated up‐regulation of TF on monocytic cells are not understood. This study was undertaken to investigate the intracellular signals induced by aPL that mediate TF activation in monocytes from APS patients.

Methods

We analyzed, both in vivo and in vitro, aPL interactions with proteins that have signaling functions, including mitogen‐activated protein kinases (MAP kinases) and NF‐κB/Rel proteins.

Results

In vivo studies demonstrated significantly higher levels of both TF messenger RNA and TF protein in monocytes from APS patients compared with controls. At the molecular level, increased proteolysis of IκBα and activation of NF‐κB were observed. Constitutive activation of both p38 and ERK‐1 MAP kinases was also found. Treatment of normal monocytes with aPL activated ERK‐1 and p38 MAP kinases, as well as the IκB/NF‐κB pathway, in a dose‐dependent manner. NF‐κB activation and IκBα degradation induced by aPL were inhibited by the NF‐κB inhibitor SN50 and the p38 MAP kinase inhibitor SB203580, thus suggesting crosstalk between these pathways. However, the MEK‐1/ERK inhibitor PD98059 did not affect aPL‐induced NF‐κB binding activity. TF expression induced by aPL was significantly inhibited by combined treatment with the 3 inhibitors.

Conclusion

Our results suggest that aPL induces TF expression in monocytes from APS patients by activating, simultaneously and independently, the phosphorylation of MEK‐1/ERK proteins, and the p38 MAP kinase–dependent nuclear translocation and activation of NF‐κB/Rel proteins.
Production of a novel class of polyreactive pathogenic autoantibodies in BXD2 mice causes glomerulonephritis and arthritis
Authors: Hsu Hui‐Chen , Zhou Tong , Kim Helen , Barnes Stephen , Yang PingAr , Wu Qi , Zhou Juling , Freeman Bruce A. , Luo Ming , Mountz John D.
Published: December 2005

Objective

The BXD2 mouse strain spontaneously develops glomerulonephritis and erosive arthritis. The goal of this study was to identify the antigenic target proteins and epitopes and to unravel the mechanisms by which the related conditions arise in BXD2 mice.

Methods

Individual hybridomas isolated from the spleen of a 10‐month‐old BXD2 mouse were injected intraperitoneally into nonautoimmune mice for evaluation of pathogenicity of each autoantibody. Autoantigens were immunoprecipitated with the pathogenic autoantibody L3A4. Autoantigens were identified using enzyme‐linked immunosorbent assay, Western blotting, 2‐dimensional gel electrophoresis, and matrix‐assisted laser desorption ionization–time‐of‐flight mass spectrometry (MS) and tandem MS. Antigenic epitopes were determined using a high‐throughput epitope mapping method.

Results

The production of autoantibodies in BXD2 mice occurred in an orderly progression, with peak levels of autoantibodies to nitrotyrosine (NT)–modified enolase, Ro, α‐actin, and heat‐shock proteins (HSPs) preceding peak levels of antihistone, anti‐DNA, and rheumatoid factor. Two monoclonal autoantibodies, L3A4 and T56G10, were identified that could induce immune complexes, renal disease, and/or arthritis. Both L3A4 and T56G10 were polyreactive, and each reacted with separate sets of autoantigens. The antigenic targets of L3A4 consisted of NT‐modified enolase, ATP5b, α‐actin, and Hsp70 family proteins including Hspa5 and Hsp74. The antigenic epitopes of NT‐modified enolase and Hspa5 exhibited sequence homology and cross‐reactivity, suggesting that epitope spreading may occur through a molecular mimicry mechanism.

Conclusion

The polyreactivity of autoantibodies that target a novel class of autoantigens may enable these autoantibodies to induce erosive arthritis or glomerulonephritis either by direct pathogenic mechanisms or indirectly via Fc or immune complex deposition.