bluuebunny/crossref_metadata_2025 huggingface dataset:
Perfusion computed tomography in the acute phase of mild head injury: Regional dysfunction and prognostic value
Authors: Metting Zwany , Rödiger Lars A. , Stewart Roy E. , Oudkerk Matthijs , De Keyser Jacques , van der Naalt Joukje
Published: June 2009

Objective

Traumatic brain injury is a major cause of disability and death. Most patients sustain a mild head injury with a subgroup that experiences disabling symptoms interfering with return to work. Brain imaging in the acute phase is not predictive of outcome, as 20% of noncontrast computed tomographic (CT) scans on admission is normal in patients with a suboptimal outcome. The aim of this study was to perform perfusion CT imaging in the acute phase of mild head injury in patients without intracranial abnormalities on the noncontrast CT, to assess whether these patients had cerebral perfusion abnormalities. Furthermore, the relation between perfusion CT parameters and severity of head injury and outcome was evaluated.

Methods

In patients with mild head injury and normal noncontrast CT, perfusion CT was performed directly after admission. The perfusion data were compared with data of 25 healthy control subjects. Outcome was determined 6 months after injury with the extended Glasgow Coma Outcome Scale score and return to work.

Results

Seventy‐six patients were included. In patients with a decreased Glasgow Coma Scale score, a significant decrease of cerebral blood flow and cerebral blood volume was detected in the frontal and occipital gray matter. In logistic regression analyses, decreased cerebral blood flow and cerebral blood volume in the frontal lobes predicted worse outcome according to the extended Glasgow Coma Outcome Scale score. CT perfusion parameters did not predict return to work.

Interpretation

In the acute phase of mild head injury, disturbed cerebral perfusion is seen in patients with normal noncontrast CT correlating with severity of injury and outcome. Ann Neurol 2009;66:809–816
Slowed progression in models of huntington disease by adipose stem cell transplantation
Authors: Lee Soon‐Tae , Chu Kon , Jung Keun‐Hwa , Im Woo‐Seok , Park Jeong‐Eun , Lim Hun‐Chang , Won Chong‐Hyun , Shin Seung‐Hyun , Lee Sang Kun , Kim Manho , Roh Jae‐Kyu
Published: June 2009

Objective

Adipose‐derived stem cells (ASCs) are readily accessible and secrete multiple growth factors. Here, we show that ASC transplantation rescues the striatal pathology of Huntington disease (HD) models.

Methods

ASCs were isolated from human subcutaneous adipose tissue. In a quinolinic acid (QA)‐induced rat model of striatal degeneration, human ASCs (1 million cells) were transplanted into the ipsilateral striatal border immediately after the QA injection. In 60‐day‐old R6/2 mice transgenic for HD, ASCs (0.5 million cells) were transplanted into each bilateral striata. In in vitro experiments, we treated mutant huntingtin gene‐transfected cerebral neurons with ASC‐conditioned media.

Results

In the QA model, human ASCs reduced apomorphine‐induced rotation behavior, lesion volume, and striatal apoptosis. In R6/2 transgenic mice, transplantation of ASCs improved Rota‐Rod performance and limb clasping, increased survival, attenuated the loss of striatal neurons, and reduced the huntingtin aggregates. ASC‐transplanted R6/2 mice expressed elevated levels of peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α) and reactive oxygen defense enzymes and showed activation of the Akt/cAMP‐response element‐binding proteins. ASC‐conditioned media decreased the level of N‐terminal fragments of mutant huntingtin and associated apoptosis, and increased PGC‐1α expression.

Interpretation

Collectively, ASC transplantation slowed striatal degeneration and behavioral deterioration of HD models, possibly via secreted factors. Ann Neurol 2009;66:671–681
Carbon‐nitrogen‐phosphorus removal and biofilm growth characteristics in an integrated wastewater treatment system involving a rotating biological contactor
Authors: Cabije Angelo H. , Agapay Ramelito C. , Tampus May V
Published: June 2009

A new rotating biological contactor‐packed media technology (RBC‐PMT) is locally innovated using light polyethylene Amazon screen material as disc media. A single‐stage co‐current fed of this type, which is connected with a series of equalization tanks as an integrated wastewater treatment system (IWWTS), showed good carbon‐nitrogen‐phosphorus (C‐N‐P) removal and unveiled biofilm growth characteristics noteworthy for treating pollutants in wastewater.

The equalization tanks approached facultative anaerobic conditions while the RBC‐PMT exhibited a completely aerated system, both with a slightly alkaline pH, whose temperatures are ranging from 21 to 24 °C, and both performed as biological nutrient removal systems. The combined nutrient removal efficiency at high organic loading rate (HOLR) and low organic loading rate (LOLR) showed fair chemical oxygen demand (COD) removal at 65.68 and 67.89%, respectively. Nitrate‐nitrogen removal demonstrated good removal at 79.17% at HOLR and 83.43% at LOLR. There was excellent phosphate‐phosphorus removal determined at 91.64 and 94.35% at high and low OLRs, respectively. This indicates that increasing the organic loading rate decreases the C‐N‐P removal in the IWWTS.

Biofilm growth was characterized by the selection and survival of microorganisms present under aerobic environmental conditions in the RBC‐PMT system and their respective metabolism in removing C‐N‐P substrates. Yeasts, coliform bacteria particularly E. coli, Cyanobacteria, and benthic diatoms were dominant microorganisms found upon oil‐immersion microscopy. Protozoans and algae including Chlorococcum, Chlorella, Diatoma, Tribonema, Oscillatoria, Euglena, and other motile rotifiers were also dominantly found in the biofilm samples. Biofilm growth is observed and its average thickness was measured to be 7.71 µm at HOLR and 2.81 µm at LOLR. Thicker biofilm at HOLR has caused the reduced rate of diffusion of the microorganisms and their metabolic products as manifested by the low C‐N‐P removal during HOLR. Copyright © 2009 Curtin University of Technology and John Wiley & Sons, Ltd.
Characterization and effect of modified surface on the morphology, structure and function of rabbit bone marrow‐derived mesenchymal stem cells 1
Authors: Song K. D. , Liu K. , Liu T. Q. , Ma X. H.
Published: June 2009

The surface morphologies modified with chitosan and gelatin respectively, the effects on cell spreading, adhesion and distribution of rabbit bone marrow‐derived mesenchymal stem cells (rMSCs) were observed under atomic force microscope (AFM). The structures and morphologies of rMSCs on coverslips were qualitatively and quantitatively assayed under AFM. Thereafter, the growth status and viability of rMSCs on the different coated surfaces were examined under inverted microscope and by Hoechst/PI double staining. The results showed that the surfaces modified with different materials presented different morphologies. The rMSCs adhered to the surfaces modified with 2 mg/ml chitosan and 0.5 mg/ml gelatin solution showed better viabilities than those of other groups, and the latter also presented the optimal cell adhesion, spreading and distribution with clear cellular structure such as cell nucleus, villus and interaction among various rMSCs. It is indicated that the surface modification played an important role on the development of cellular structure and function of rMSCs, and thus provided theoretical guidance to the fabrication and surface modification of embedded biomaterials in further clinical applications. Copyright © 2009 Curtin University of Technology and John Wiley & Sons, Ltd.
The isolation and characterization of lignin of kenaf fiber
Authors: Yan Tingting , Xu Yingqi , Yu Chongwen
Published: June 2009

In this article, milled wood lignin (MWL) was isolated and purified from retted kenaf fiber, the lignin obtained was characterized by elemental analysis, FTIR, 1H‐NMR, and 13C‐NMR spectroscopy. The C9 formula is calculated for kenaf fiber MWL as C9H9.32O3.69(OCH3)1.30. The spectra of FTIR, 1H‐NMR, and 13C‐NMR show the kenaf fiber lignin to be of the G/S type with high proportion of syringyl (S) unit. The numbers of phenolic and aliphatic hydroxyl groups in the kenaf fiber MWL are estimated to be 0.14 and 1.31, respectively, per C9 unit. The OHaliph is 90.3% in total numbers of hydroxyl groups of kenaf fiber MWL, and the OHph is 9.7%. It is evident that the β‐O‐4 structures are mainly linkage in the MWL of kenaf fiber, which contain more erythro stereochemistry type in β‐O‐4 units than thero stereochemistry type. In general, the characteristics of lignin of kenaf fiber are similar to that of hardwood. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Characterization and enzymatic degradation of PEG‐cross‐linked chitosan hydrogel films
Authors: Tanuma Hiroaki , Kiuchi Hiroki , Kai Weihua , Yazawa Koji , Inoue Yoshio
Published: June 2009

In our previous study (Kiuch et al., J Appl Polym Sci 2008, 107, 3823), poly(ethylene glycol) (PEG) cross‐linked chitosan hydrogel films with various PEG to chitosan ratio and PEG molecular weight have been successfully prepared and their thermal, mechanical and swelling properties at acidic pH were studied. These films are potential biodegradable polymeric materials, because their constituents, that is, chitosan and PEG, are well known as biodegradable polymers. In this study, glass transition temperature (Tg), contact angle, swelling behavior at physiological conditions and in vitro enzymatic degradation behavior were investigated for the PEG‐cross‐linked chitosan hydrogel films. These properties of chitosan hydrogel were found to change significantly upon introducing the PEG‐cross‐links. According to differential scanning calorimeter analysis, the Tg value increased with the PEG content in the hydrogel films, indicating the densification of the film by PEG‐crosslinking. The contact angle was decreased with increasing the number of crosslinks, reflecting that introduction of the cross‐linked structure induced the reduction of chitosan ordered structure. The swelling behavior depended on the PEG to chitosan ratio and the cross‐linked structure. The water content was changed with the number of PEG‐crosslinks. The rate of lysozyme‐catalyzed degradation was also influenced by the introduction of PEG‐cross‐linked structure. The surface morphology of the film was observed by the scanning electron microscopy. It was confirmed that the PEG‐cross‐linked chitosan hydrogel film was degraded by lysozyme from its surface area. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Characterization of rubber phase in acrylonitrile–butadiene–styrene polymers
Authors: Zamani A. , Abbasi F. , Agah A. M.
Published: June 2009

The performances of rubber‐toughened polymers like acrylonitrile–butadiene–styrene (ABS) are strongly affected by the type and amount of rubber phase. Characterization of rubber phase is an effective method to predict and control the physical and mechanical behaviors of ABS materials. In this work, different methods have been employed to determine the amount of rubber phase in ABS polymers. The first method was based on thermogravimetry using a particular step degradation of the polymer. In the second method, characteristic absorption bands in the Fourier transform infrared spectra were used to make a calibration curve to determine the rubber content of unknown ABS samples. The third method was based on variation of heat capacity of ABS polymers with increasing the rubber phase content. In the fourth method, a two‐step solvent extraction followed by centrifuging was used to separate the rubber particles of different ABS samples. Separation of hardened rubber particles was used to study the size and size distribution of rubber particles. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Synthesis of Novel 2,5‐Disubstituted 1,3,4‐Thiadiazoles for Their Potential Anticonvulsant Activity: Pharmacophoric Model Studies
Authors: Rajak Harish , Deshmukh Ravitas , Aggarwal Navneet , Kashaw Sushil , Kharya Murli Dhar , Mishra Pradeep
Published: June 2009

A series of novel N1‐[5‐(4‐substituted phenyl)‐1,3,4‐thiadiazol‐2‐yl]‐N4‐(4‐substituted benzaldehyde)‐semicarbazone 1–12, N1‐[5‐(4‐substituted phenyl)‐1,3,4‐thiadiazol‐2‐yl]‐N4‐[1‐(4‐substituted phenyl)ethanone]‐semicarbazone 13‐16, and N1‐[5‐(4‐substituted phenyl)‐1,3,4‐thiadiazol‐2‐yl]‐N4‐[1‐(4‐substituted phenyl) (phenyl) methanone]‐semicarbazone 17–20 were synthesized for their anticonvulsant activity. The chemical structures of the compounds were proved by elemental and spectral (IR, 1H‐NMR, 13C‐NMR, and MS) analysis. The anticonvulsant potential of the compounds was investigated using maximal electroshock seizure (MES) and subcutaneous pentylenetrtrazole (scPTZ) models. Compound 19 was found to possess significant anticonvulsant activity in both the models employed for anticonvulsant evaluation. Compounds 8, 13, 15, and 16 also demonstrated a marked anticonvulsant property. The results of the present study validated that the pharmacophore model with four binding sites is essential for anticonvulsant activity. The efforts were also made to establish structure‐activity relationships among the synthesized compounds.
Sensitivity and specificity of spinal inflammatory lesions assessed by whole‐body magnetic resonance imaging in patients with ankylosing spondylitis or recent‐onset inflammatory back pain
Authors: Weber Ulrich , Hodler Juerg , Kubik Rahel A. , Rufibach Kaspar , Lambert Robert G. W. , Kissling Rudolf O. , Pfirrmann Christian W. A. , Maksymowych Walter P.
Published: June 2009

Objective

To determine the diagnostic utility of different spinal inflammatory lesions assessed by whole‐body magnetic resonance imaging (MRI) in patients with ankylosing spondylitis (AS) or with recent‐onset inflammatory back pain (IBP) compared with healthy controls.

Methods

We scanned 35 consecutive patients with AS fulfilling the modified New York criteria, 25 patients with IBP of <24 months' duration (both groups were age ≤45 years and had a Bath Ankylosing Spondylitis Disease Activity Index score ≥4), and 35 healthy age‐ and sex‐matched volunteers using whole‐body MRI STIR sequences of the spine. MRIs were independently assessed in random order by 3 readers blinded to patient identity. Inflammatory spinal lesions were recorded consistent with definitions proposed by the Canada/Denmark International MRI Working Group: vertebral corner inflammatory lesions (CIL) and noncorner inflammatory lesions in central sagittal slices and lateral inflammatory lesions (LIL) in lateral slices. Concordantly scored lesions for the 3 possible reader pairs were used in the analysis of sensitivity, specificity, likelihood ratios (LRs), and areas under the curve for the entire spine and by spinal segment.

Results

Diagnostic utility was optimal when ≥2 CIL were recorded (for patients with AS, values for sensitivity, specificity, and positive LR were 69%, 94%, and 12, respectively, and for patients with IBP were 32%, 96%, and 8, respectively). LIL had high specificity (97%) but low sensitivity (31%). Nine controls had ≥1 CIL, but only 2 controls had >2 CIL.

Conclusion

Diagnostic utility of STIR MRI for AS is optimal when ≥2 CIL are present. A single CIL can be found in up to 26% of healthy individuals.
Efficacy of intraarticular infliximab in patients with chronic or recurrent gonarthritis: A clinical randomized trial
Authors: van der Bijl A. E. , Teng Y. K. O. , van Oosterhout M. , Breedveld F. C. , Allaart C. F. , Huizinga T. W. J.
Published: June 2009

Objective

To evaluate the efficacy and safety of intraarticular infliximab compared with intraarticular methylprednisolone in patients with gonarthritis.

Methods

In 23 patients with recurrent gonarthritis despite previous intraarticular corticosteroid therapy, a total of 41 intraarticular injections (20 infliximab and 21 methylprednisolone) were performed in 28 knees. Initial therapy was randomly assigned, and crossover therapy was eligible within 3 months. The clinical effect was assessed during 6 months of followup. The primary outcome was event‐free survival, defined as the time after treatment until local retreatment was performed and/or nonimprovement of the knee joint score. Adverse effects were recorded during followup.

Results

All patients treated with intraarticular infliximab had an insufficient response. In contrast, 8 of the 21 intraarticular methylprednisolone injections were effective (P = 0.004). Between groups, no differences in the patients' age, disease duration, number of disease‐modifying antirheumatic drugs, or previous intraarticular methylprednisolone were observed. Reported adverse effects were not related to therapy.

Conclusion

Treatment with intraarticular infliximab injection was not effective in patients with a chronically inflamed knee joint. Intraarticular injection with methylprednisolone was superior despite previous intraarticular corticosteroid therapy. Further investigation is needed to provide these patients with a better alternative.
Validation of whole‐body against conventional magnetic resonance imaging for scoring acute inflammatory lesions in the sacroiliac joints of patients with spondylarthritis
Authors: Weber Ulrich , Maksymowych Walter P. , Jurik Anne G. , Pfirrmann Christian W. A. , Rufibach Kaspar , Kissling Rudolf O. , Khan Muhammad A. , Lambert Robert G. W. , Hodler Juerg
Published: June 2009

Objective

To compare the performance of whole‐body magnetic resonance imaging (MRI) versus conventional MRI in assessing acute inflammatory lesions of the sacroiliac (SI) joints in patients with established and active spondylarthritis (SpA) using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index. This study is validating whole‐body MRI against the current MRI standard for assessing active inflammatory lesions of the SI joints in patients with SpA.

Methods

Thirty‐two SpA patients with clinically active disease (Bath Ankylosing Spondylitis Disease Activity Index score ≥4) fulfilling the modified New York criteria were scanned by whole‐body and conventional MRI of the SI joints. The MRIs were scored independently in random order by 3 readers blinded to patient identity. Active inflammatory lesions of the SI joints were recorded on a Web‐based SPARCC index. Pearson's correlation coefficients were used to compare scores for whole‐body and conventional MRI for each reader, whereas intraclass correlation coefficients (ICCs) were used to compare interobserver reliability.

Results

The Pearson's correlation coefficients between whole‐body and conventional MRI per rater were 0.94, 0.87, and 0.93. The mean sum scores for conventional versus whole‐body MRI were statistically significantly higher for all 3 readers, although all patients showing inflammatory lesions on conventional MRI also demonstrated them on whole‐body MRI. The ICCs(2,1) were 0.69, 0.78, and 0.95 for conventional MRI, and 0.79, 0.85, and 0.96 for whole‐body MRI for the 3 possible reader pairs.

Conclusion

Whole‐body and conventional MRI scores show a strong correlation and comparable reliability for the detection of inflammatory lesions of the SI joints.
Targeted ultrasound of the fifth metatarsophalangeal joint in an early inflammatory arthritis cohort
Authors: Sheane Barry J. , Beddy Peter , O'Connor Michelle , Miller Stanley , Cunnane Gaye
Published: June 2009

Objective

To determine whether targeted ultrasonographic (US) imaging of the fifth metatarsophalangeal (MTP) joint, compared with radiographs, could aid in the early diagnosis of rheumatoid arthritis (RA) by identifying erosions sooner in early inflammatory arthritis. Radiographic erosion in RA is a late indication of poor prognosis. The earlier detection of erosion may facilitate the timely initiation of disease‐modifying antirheumatic drug therapy, particularly in patients with undifferentiated synovitis.

Methods

Patients presenting with synovitis for the first time were invited to participate. Each patient underwent laboratory tests, radiographs of the hands and feet, and US imaging of both fifth MTP joints.

Results

Thirty patients (22 women) took part in the study. Seventeen patients (57%) had RA, and 13 (43%) had undifferentiated arthritis (UA). The mean ± SD time taken to scan both fifth MTP joints was 10.9 ± 4.4 minutes. Ten patients (33%) had US evidence of synovitis associated with a positive power Doppler (PD) signal (P = 0.04). Seven patients (23%) had radiographic erosions of the fifth MTP joint, and 17 patients (57%) had US evidence of fifth MTP joint erosions (P = 0.01). A positive PD signal at the fifth MTP joint was seen in 9 of 17 patients with RA and 1 of 13 patients with UA (P = 0.02). Patients with a definite diagnosis of RA were more likely to have fifth MTP joint erosions (11 [65%] of 17) compared with UA (6 [46%] of 13).

Conclusion

Targeted US is a rapid and useful tool in detecting erosive disease in early inflammatory arthritis. It gives a better indication of disease severity and prognosis compared with routinely available laboratory tests, even in the absence of a definite diagnosis.
The safety and efficacy of a JAK inhibitor in patients with active rheumatoid arthritis: Results of a double‐blind, placebo‐controlled phase IIa trial of three dosage levels of CP‐690,550 versus placebo
Authors: Kremer Joel M. , Bloom Bradley J. , Breedveld Ferdinand C. , Coombs John H. , Fletcher Mark P. , Gruben David , Krishnaswami Sriram , Burgos‐Vargas Rubén , Wilkinson Bethanie , Zerbini Cristiano A. F. , Zwillich Samuel H.
Published: June 2009

Objective

To determine the efficacy, safety, and tolerability of 3 different dosages of CP‐690,550, a potent, orally active JAK inhibitor, in patients with active rheumatoid arthritis (RA) in whom methotrexate, etanercept, infliximab, or adalimumab caused an inadequate or toxic response.

Methods

Patients (n = 264) were randomized equally to receive placebo, 5 mg of CP‐690,550, 15 mg of CP‐690,550, or 30 mg of CP‐690,550 twice daily for 6 weeks, and were followed up for an additional 6 weeks after treatment. The primary efficacy end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at 6 weeks.

Results

By week 6, the ACR20 response rates were 70.5%, 81.2%, and 76.8% in the 5 mg, 15 mg, and 30 mg twice daily groups, respectively, compared with 29.2% in the placebo group (P < 0.001). Improvements in disease activity in CP‐690,550–treated patients compared with placebo were seen in all treatment groups as early as week 1. ACR50 and ACR70 response rates significantly improved in all treatment groups by week 4. The most common adverse events reported were headache and nausea. The infection rate in both the 15 mg twice daily group and the 30 mg twice daily group was 30.4% (versus 26.2% in the placebo group). No opportunistic infections or deaths occurred. Increases in mean low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol levels, and increases in mean serum creatinine level (0.04–0.06 mg/dl) were seen in all CP‐690,550 treatment arms.

Conclusion

Our findings indicate that CP‐690,550 is efficacious in the treatment of RA, resulting in rapid, statistically significant, and clinically meaningful reductions in the signs and symptoms of RA. Further studies of CP‐690,550 in RA are warranted.
Mail‐delivered arthritis self‐management tool kit: A randomized trial and longitudinal followup
Authors: Goeppinger Jean , Lorig Kate R. , Ritter Philip L. , Mutatkar Sonal , Villa Frank , Gizlice Ziya
Published: June 2009

Objective

To determine the effectiveness of an intervention Tool Kit of arthritis self‐management materials to be sent once through the mail, and to describe the populations reached.

Methods

Spanish speakers (n = 335), non‐Hispanic English‐speaking African Americans (n = 156), and other non‐Hispanic English speakers (n = 404) were recruited separately and randomized within each of the 3 ethnic/racial categories to immediately receive the intervention Tool Kit (n = 458) or to a 4‐month wait‐list control status (n = 463). At the end of 4 months, controls were sent the Tool Kit. All subjects were followed in a longitudinal study for 9 months. Self‐administered measures included health status, health behavior, arthritis self‐efficacy, medical care utilization, and demographic variables. Using analyses of covariance and t‐tests, analyses were conducted for all participants and for Spanish‐ and English‐language groups.

Results

At 4 months, comparing all intervention subjects with randomized wait‐list controls, there were significant (P < 0.01) benefits in all outcomes except medical care utilization and self‐rated health. The results were maintained at 9 months compared with baseline. On average, the Tool Kit reached persons ages 50–56 years with 12–15 years of schooling. There were few differences between English‐ and Spanish‐language participants in either the effectiveness or reach variables.

Conclusion

A mailed Arthritis Self‐Management Tool Kit proved effective in improving health status, health behavior, and self‐efficacy variables for up to 9 months. It also reached younger persons in both English‐ and Spanish‐language groups and Spanish speakers with higher education levels than previous studies of the small‐group Arthritis Self‐Management Program.
Interleukin‐6 is a significant predictor of radiographic knee osteoarthritis: The Chingford study
Authors: Livshits Gregory , Zhai Guangju , Hart Deborah J. , Kato Bernet S. , Wang Huizhong , Williams Frances M. K. , Spector Tim D.
Published: June 2009

Objective

There is a great need for identification of biomarkers that could improve the prediction of early osteoarthritis (OA). We undertook this study to determine whether circulating levels of interleukin‐6 (IL‐6), tumor necrosis factor α (TNFα), and C‐reactive protein (CRP) can serve as useful markers of radiographic knee OA (RKOA) in a normal human population.

Methods

RKOA data were obtained from the cohort of the Chingford Study, a prospective population‐based study of healthy, middle‐aged British women. The RKOA‐affected status of the subjects was assessed using the Kellgren/Lawrence (K/L) grade as determined on radiographs obtained at baseline (n = 908) and at 10 years and 15 years thereafter. Serum levels of CRP, IL‐6, and TNFα were assayed at 5, 8, and 15 years, using high‐sensitivity commercial assays. A K/L grade of ≥2 in either knee was used as the outcome measure. Statistical analyses included analysis of variance for repeated measurements and logistic regression models, together with longitudinal modeling of dichotomous responses.

Results

During 15 years of followup, the prevalence of RKOA (K/L grade ≥2) increased from 14.7% to 48.7% (P < 0.00001 versus baseline). The body mass index (BMI) and circulating levels of CRP and IL‐6 were consistently and significantly higher in subjects diagnosed as having RKOA. When multiple logistic regression was applied to the data, the variables of older age (P = 3.93 × 10−5), higher BMI at baseline (P = 0.0003), and increased levels of IL‐6 at year 5 (P = 0.0129) were determined to be independent predictors of the appearance of RKOA at year 10. The results were fully confirmed using longitudinal modeling of repeated measurements of the data obtained at 3 visits. The odds ratio for RKOA in subjects whose IL‐6 levels were in the fourth quartile of increasing levels (versus the first quartile) was 2.74 (95% confidence interval 1.94–3.87).

Conclusion

This followup study showed that individuals were more likely to be diagnosed as having RKOA if they had a higher BMI and increased circulating levels of IL‐6. These results should stimulate more work on IL‐6 as a potential therapeutic target.
Subtype‐specific peripheral blood gene expression profiles in recent‐onset juvenile idiopathic arthritis
Authors: Barnes Michael G. , Grom Alexei A. , Thompson Susan D. , Griffin Thomas A. , Pavlidis Paul , Itert Lukasz , Fall Ndate , Sowders Dawn Paxson , Hinze Claas H. , Aronow Bruce J. , Luyrink Lorie K. , Srivastava Shweta , Ilowite Norman T. , Gottlieb Beth S. , Olson Judyann C. , Sherry David D. , Glass David N. , Colbert Robert A.
Published: June 2009

Objective

To identify differences in peripheral blood gene expression between patients with different subclasses of juvenile idiopathic arthritis (JIA) and healthy controls in a multicenter study of patients with recent‐onset JIA prior to treatment with disease‐modifying antirheumatic drugs (DMARDs) or biologic agents.

Methods

Peripheral blood mononuclear cells (PBMCs) from 59 healthy children and 136 patients with JIA (28 with enthesitis‐related arthritis [ERA], 42 with persistent oligoarthritis, 45 with rheumatoid factor [RF]–negative polyarthritis, and 21 with systemic disease) were isolated from whole blood. Poly(A) RNA was labeled using a commercial RNA amplification and labeling system (NuGEN Ovation), and gene expression profiles were obtained using commercial expression microarrays (Affymetrix HG‐U133 Plus 2.0).

Results

A total of 9,501 differentially expressed probe sets were identified among the JIA subtypes and controls (by analysis of variance; false discovery rate 5%). Specifically, 193, 1,036, 873, and 7,595 probe sets were different in PBMCs from the controls compared with those from the ERA, persistent oligoarthritis, RF‐negative polyarthritis, and systemic JIA patients, respectively. In patients with persistent oligoarthritis, RF‐negative polyarthritis, and systemic JIA subtypes, up‐regulation of genes associated with interleukin‐10 (IL‐10) signaling was prominent. A hemoglobin cluster was identified that was underexpressed in ERA patients but overexpressed in systemic JIA patients. The influence of JAK/STAT, ERK/MAPK, IL‐2, and B cell receptor signaling pathways was evident in patients with persistent oligoarthritis. In systemic JIA, up‐regulation of innate immune pathways, including IL‐6, Toll‐like receptor/IL‐1 receptor, and peroxisome proliferator–activated receptor signaling, were noted, along with down‐regulation of gene networks related to natural killer cells and T cells. Complement and coagulation pathways were up‐regulated in systemic JIA, with a subset of these genes being differentially expressed in other subtypes as well.

Conclusion

Expression analysis identified differentially expressed genes in PBMCs obtained early in the disease from patients with different subtypes of JIA and in healthy controls, providing evidence of immunobiologic differences between these forms of childhood arthritis.
Relationship between elevated cerebrospinal fluid levels of plasminogen activator inhibitor 1 and neuronal destruction in patients with neuropsychiatric systemic lupus erythematosus
Authors: Kwieciński Jakub , Kłak Marcin , Trysberg Estelle , Blennow Kaj , Tarkowski Andrej , Jin Tao
Published: June 2009

Objective

A homeostatic imbalance between coagulation and fibrinolysis might occur intrathecally in neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no published data on levels of fibrinolytic factors in the cerebrospinal fluid (CSF) of patients with NPSLE. The present study was undertaken to assess CSF levels of fibrinolytic molecules, including urokinase plasminogen activator (uPA), tissue plasminogen activator (tPA), D‐dimer, and plasminogen activator inhibitor 1 (PAI‐1), in SLE patients with clinically verified neuropsychiatric involvement and to compare these levels with those in SLE patients without neuropsychiatric involvement and in healthy subjects.

Methods

Levels of uPA, tPA, and PAI‐1 were assessed in CSF from 94 patients with SLE (33 who had NPSLE, 56 who did not have NPSLE, and 5 who were positive for antiphospholipid antibody [not included in the NPSLE or non‐NPSLE group]) and from 53 age‐matched controls. Patients were evaluated clinically, with magnetic resonance imaging of the brain, analyses of neuronal/glial degradation products in CSF, and neuropsychiatric testing.

Results

In the group of patients with NPSLE, intrathecal PAI‐1 levels were significantly elevated compared with levels in SLE patients without overt neuropsychiatric involvement (P < 0.05) and in healthy controls (P < 0.001). In contrast, intrathecal levels of uPA did not differ significantly. Intrathecal levels of PAI‐1 correlated significantly with CSF levels of interleukin‐6 (IL‐6) (r = 0.34, P < 0.001) and IL‐8 (r = 0.33, P < 0.001). Importantly, increased PAI‐1 and D‐dimer levels were observed in SLE patients who had pathologically elevated levels of glial fibrillary acidic protein, neurofilament triplet protein, and tau protein in CSF.

Conclusion

Intrathecal release of PAI‐1 is increased in patients with NPSLE. This results in impaired fibrinolysis, which might contribute to neuronal and astrocytic damage in NPSLE.
Effectiveness of an early cognitive–behavioral treatment in patients with work disability due to musculoskeletal disorders
Authors: Leon Leticia , Jover Juan A. , Candelas Gloria , Lajas Cristina , Vadillo Cristina , Blanco Margarita , Loza Estibaliz , Perez Miguel Angel , Redondo Marta , Abasolo Lydia
Published: June 2009

Objective

To evaluate whether an early cognitive–behavioral treatment complementary to a rheumatologic care program, for patients with recent‐onset temporary work disability caused by musculoskeletal disorders (MSDs) is effective.

Methods

Patients with an MSD‐related temporary work disability episode from 3–8 weeks' duration who were in a rheumatologic care program were randomized into a control group (rheumatologic care program) or an intervention group (rheumatologic care program plus cognitive–behavioral treatment). Enrollment lasted 24 months and followup lasted 6–24 months. Efficacy variables included duration of temporary work disability episodes, total number of work days saved, relative efficacy, and relative rate to return to work. An economic evaluation was also performed.

Results

One hundred eighty‐one patients were included (66 control and 115 intervention patients), generating 222 episodes of MSD‐related temporary work disability. Episodes tended to be shorter in the intervention group than in the control group (mean 98 versus 127 days; P = 0.053), with a relative efficacy of 22.9%. There were no differences in duration of the first episode between groups (mean 105 versus 110 days; P = 0.79), but relapse episodes were significantly shorter in the intervention group (mean 63 days versus 197 days; P = 0.0002). Costs were also lower in the intervention group. To save 1 day of temporary work disability, $13.50 had to be invested in the program. Each dollar invested generated a benefit of $4.08. The program had a net benefit of $172,607.

Conclusion

Early cognitive–behavioral treatment complementary to a rheumatologic care program is cost‐effective, adds >20% efficacy to the rheumatologic care program, and reduces the duration of relapses.
Does the use of ordered values of subregional change in cartilage thickness improve the detection of disease progression in longitudinal studies of osteoarthritis?
Authors: Buck Robert J. , Wyman Bradley T. , Le Graverand Marie‐pierre hellio , Hudelmaier Martin , Wirth Wolfgang , Eckstein Felix ,   A9001140 Investigators
Published: June 2009

Objective

To propose a novel strategy for more efficiently measuring changes in cartilage thickness in osteoarthritis (OA) using magnetic resonance imaging, and to hypothesize that determining the magnitude of thickness change independent of the anatomic location provides improved discrimination between healthy subjects and OA participants longitudinally.

Methods

A total of 148 women were imaged; 90 were Kellgren/Lawrence (K/L) grade 0, 30 were K/L grade 2, and 28 were K/L grade 3. Magnetic resonance images (3T) were acquired at baseline and at 24 months. Changes in femorotibial cartilage thickness were determined in 5 tibial and 3 femoral medial and lateral subregions, respectively (conventional approach). The new strategy provided ordered values of subregional change in each compartment, ranked according to the direction and magnitude of change.

Results

Using the new ordered values approach, the minimal P value for the differences in 2‐year change in medial cartilage thickness of K/L grade 3 and K/L grade 0 participants was 0.001 (Wilcoxon test), with 4 ordered medial subregions differing significantly between both groups. With the conventional approach, only 1 medial subregion differed significantly between K/L grade 3 and K/L grade 0 (P = 0.037). Cartilage thickening was significantly greater in K/L grade 2 versus K/L grade 0 participants in 1 medial subregion using the conventional approach (P = 0.016), and in 2 medial subregions (minimal P = 0.007) using the ordered values approach.

Conclusion

The novel ordered values approach is more sensitive in detecting cartilage thinning in K/L grade 3 and cartilage thickening in K/L grade 2 versus K/L grade 0 participants. The new method may be particularly useful in the context of other comparisons, e.g., a group treated with a disease‐modifying OA drug versus one treated with a placebo.
Sociodemographic, disease, and symptom correlates of fatigue in systemic sclerosis: Evidence from a sample of 659 Canadian Scleroderma Research Group Registry patients
Authors: Thombs Brett D. , Hudson Marie , Bassel Marielle , Taillefer Suzanne S. , Baron Murray ,   Canadian Scleroderma Research Ggroup
Published: June 2009

Objective

To assess fatigue levels and demographic, socioeconomic, disease, and psychosocial correlates of fatigue in patients with systemic sclerosis (SSc).

Methods

We conducted a cross‐sectional, multicenter study of 659 patients with SSc from the Canadian Scleroderma Research Group Registry. Fatigue was assessed during annual Registry visits with the Short Form 36 (SF‐36) health survey vitality subscale. Patients completed measures of depressive symptoms and pain and underwent clinical histories and medical examinations. Kendall's tau was used to assess bivariate association of sociodemographic, medical, and psychosocial variables with fatigue. Multivariable associations of demographic (step 1), socioeconomic (step 2), global disease (step 3), specific disease and lifestyle (step 4), and psychosocial (step 5) factors with fatigue were assessed using hierarchical multiple linear regression.

Results

The mean ± SD score of the patients on the SF‐36 vitality subscale was 45.6 ± 10.8, substantially lower (indicating more fatigue) than the mean ± SD score for the Canadian general population (65.8 ± 18.0). In multivariate analysis, higher fatigue was significantly associated with the number of medical comorbidities (standardized β = −0.11, P = 0.004), breathing problems (standardized β = −0.23, P < 0.001), the number of gastrointestinal (GI) symptoms (standardized β = −0.27, P < 0.001), and current smoking (standardized β = −0.08, P = 0.018). As a group, specific symptom and lifestyle variables predicted the most incremental variance in fatigue (▵R2 = 21.6%, P < 0.001), despite being added to the model after demographic, socioeconomic, and global disease duration/severity indicators. Symptoms of depression (β = −0.42) and pain (β = −0.21) were also independently associated with fatigue (P < 0.001).

Conclusion

High levels of fatigue are common in patients with SSc and are independently associated with clinical variables, including number of comorbidities, breathing problems, GI symptoms, and smoking.
Factors associated with depression and suicidal ideation among individuals with arthritis or rheumatism: Findings from a representative community survey
Authors: Fuller‐Thomson Esme , Shaked Yael
Published: June 2009

Objective

To investigate factors associated with depression and suicidal ideation among individuals with arthritis or rheumatism.

Methods

The nationally representative Canadian Community Health Survey 2000–2001 included 130,880 respondents (response rate 84.7%). Respondents were diagnosed as depressed using a subset of items from the Composite International Diagnostic Interview. There were 23,405 respondents age ≥20 years who reported that they had been diagnosed with arthritis or rheumatism by a health professional. Logistic regression analyses were conducted to investigate depression and suicidal ideation.

Results

One in 10 Canadians with arthritis had clinically relevant levels of major depression. The age‐ and sex‐adjusted odds ratios (ORs) of major depression (OR 2.24, 95% confidence interval [95% CI] 2.11–2.38) and suicidal ideation (OR 2.01, 95% CI 1.75–2.31) among those with arthritis were approximately twice that of those without arthritis. The adjusted ORs of major depression among those with arthritis were significantly higher among women, the unmarried, younger, and poorer individuals. Individuals in pain, with limitations in activities of daily living, with limitations in instrumental activities of daily living, and with greater numbers of chronic conditions had higher odds of major depression. Less than half of those with major depression had consulted a mental health professional. One in 5 individuals with arthritis and major depression had been suicidal in the past year.

Conclusion

The majority of individuals with arthritis and major depression were not receiving adequate treatment for major depression. Clients should be screened for major depression and suicidal ideation, particularly if they fall into the identified vulnerable groups.
Functional analysis of the osteoarthritis susceptibility–associated GDF5 regulatory polymorphism
Authors: Egli Rainer J. , Southam Lorraine , Wilkins James M. , Lorenzen Inken , Pombo‐Suarez Manuel , Gonzalez Antonio , Carr Andrew , Chapman Kay , Loughlin John
Published: June 2009

Objective

Single‐nucleotide polymorphism (SNP) rs143383 (T to C) in the 5′‐untranslated region (5′‐UTR) of GDF5 has recently been reported to be associated with osteoarthritis (OA) susceptibility, with lower expression of the risk‐associated T allele observed in vitro and in vivo. The in vivo studies were performed on cartilage tissue from OA patients. The present study was undertaken to expand the analysis of the effect of this SNP on GDF5 allelic expression to more joint tissue types, to investigate for cis and trans factors that interact with the SNP, and to examine novel cis‐acting GDF5 regulatory polymorphisms.

Methods

Tissue samples were collected from OA patients undergoing joint replacement of the hip or knee. Nucleic acid was extracted, and, using rs143383 and an assay that discriminates and quantifies allelic expression, the relative amount of GDF5 expression from the T and C alleles was measured. Additional common variants in the GDF5 transcript sequence were interrogated as potential regulatory elements using allelic expression and luciferase reporter assays, and electrophoretic mobility shift assays were used to search for trans factors binding to rs143383.

Results

We observed a consistent allelic expression imbalance of GDF5 in all tissues tested, implying that the functional effect mediated by rs143383 on GDF5 expression is joint‐wide. We identified a second polymorphism, located in the 3′‐UTR of GDF5, that influenced allelic expression of the gene independent of rs143383. Finally, we observed differential binding of deformed epidermal autoregulatory factor 1 (DEAF‐1) to the 2 alleles of rs143383.

Conclusion

These findings show that the OA susceptibility mediated by polymorphism in GDF5 is not restricted to cartilage, emphasizing the need to consider the disease as involving the whole joint. The existence of an additional cis‐acting regulatory polymorphism highlights the complexity of the regulation of expression of this important OA susceptibility locus. DEAF‐1 is a trans‐acting factor that merits further investigation as a potential tool for modulating GDF5 expression.
Severe gouty arthritis and mild neurologic symptoms due to F199C, a newly identified variant of the hypoxanthine guanine phosphoribosyltransferase
Authors: Ea Hang‐Korng , Bardin Thomas , Jinnah H. A. , Aral Bernard , Lioté Frédéric , Ceballos‐Picot Irène
Published: June 2009

A deficiency in hypoxanthine guanine phosphoribosyltransferase (HPRT) activity leads to overproduction of uric acid. According to the degree of enzymatic deficiency, a large spectrum of neurologic features can also be observed, ranging from mild or no neurologic involvement to complete Lesch‐Nyhan disease. Herein, we describe a patient with hyperuricemia, juvenile‐onset gouty arthritis, nephrolithiasis, and mild neurologic symptoms, attributed to a newly identified variant of the hprt gene, c.596T>G, resulting in the amino acid change p.F199C. Residual HPRT activity (8%) protected against severe neurologic involvement in this patient. Modeling of the mutated protein was used to predict the mechanisms that led to partial enzymatic activity. Careful neurologic examination is warranted in juvenile and middle‐aged patients with gout, in order to detect mild symptoms that may lead to a diagnosis of HPRT deficiency.
Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis
Authors: Prahalad Sampath , Hansen Sterling , Whiting April , Guthery Stephen L. , Clifford Bronte , McNally Bernadette , Zeft Andrew S. , Bohnsack John F. , Jorde Lynn B.
Published: June 2009

Objective

Subtypes of juvenile idiopathic arthritis (JIA) share phenotypic features with other autoimmune disorders. We investigated several genetic variants associated with rheumatoid arthritis (RA) and other autoimmune disorders for association with JIA to test the hypothesis that clinically distinct phenotypes share common genetic susceptibility factors.

Methods

Cases were 445 children with JIA, and controls were 643 healthy adults. Using the TaqMan assay, subjects were genotyped for 8 single‐nucleotide polymorphisms in 7 loci including rs10499194 and rs6920220 in the TNFAIP3 locus, rs6679677 in the RSBN1 locus, rs17696736 in the C12orf30 locus, rs3761847 in the TRAF1/C5 locus, rs2104286 in the IL2RA locus, rs7574865 in the STAT4 locus, and rs2542151 in the PTPN2 locus. Alleles and genotypes were analyzed for association with JIA and JIA subtypes. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.

Results

The strongest associations with JIA risk or protection were observed for TNFAIP3 variants rs10499194 (OR 0.74 [95% CI 0.61–0.91], P < 0.004) and rs6920220 (OR 1.30 [95% CI 1.05–1.61], P = 0.015). We also observed associations between JIA and both STAT4 (OR 1.24 [95% CI 1.02–1.51], P = 0.029) and C12orf30 (OR 1.20 [95% CI 1.01–1.43], P = 0.041) variants. The PTPN2 variant rs2542151 deviated from Hardy‐Weinberg equilibrium and was excluded from analyses. Variants in IL2RA, TRAF1/C5, and RSBN1 were not associated with JIA. After stratification by JIA subtype, the TNFAIP3 and C12orf30 variants were associated with oligoarticular JIA, while the STAT4 variant was associated primarily with polyarticular JIA.

Conclusion

We have demonstrated associations between JIA and variants in the TNFAIP3, STAT4, and C12orf30 regions that have previously shown associations with other autoimmune diseases, including RA and systemic lupus erythematosus. Our results suggest that clinically distinct autoimmune phenotypes share common genetic susceptibility factors.