bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacteria on Catheters in Patients Undergoing Peritoneal Dialysis
Authors: Pihl Maria , Davies Julia R. , Johansson Ann-Cathrine , Svensäter Gunnel
Published: August 2012

♦Background

Peritonitis is the leading cause of morbidity for peritoneal dialysis (PD) patients, and microbial biofilms have previously been identified on catheters from infected patients. However, few studies of catheters from patients without clinical signs of infection have been undertaken. The aim of the present study was to investigate the extent to which bacteria are present on catheters from PD patients with no symptoms of infection.

♦Methods

Microbiologic culturing under aerobic and anaerobic conditions and confocal laser scanning microscopy were used to determine the distribution of bacteria on PD catheters from 15 patients without clinical signs of infection and on catheters from 2 infected patients. The 16S rRNA gene sequencing technique was used to identify cultured bacteria.

♦Results

Bacteria were detected on 12 of the 15 catheters from patients without signs of infection and on the 2 catheters from infected patients. Single-species and mixed-microbial communities containing up to 5 species were present on both the inside and the outside along the whole length of the colonized catheters. The bacterial species most commonly found were the skin commensals Staphylococcus epidermidis and Propionibacterium acnes, followed by S. warneri and S. lugdunensis. The strains of these micro-organisms, particularly those of S. epidermidis, varied in phenotype with respect to their tolerance of the major classes of antibiotics.

♦Conclusions

Bacteria were common on catheters from patients without symptoms of infection. Up to 4 different bacterial species were found in close association and may represent a risk factor for the future development of peritonitis in patients hosting such micro-organisms.
Peritoneal Dialysis in Children with Acute Kidney Injury: A Developing Country Experience
Authors: Mishra Om P. , Gupta Aditya K. , Pooniya Vishal , Prasad Rajniti , Tiwary Narendra K. , Schaefer Franz
Published: August 2012

Background

Peritoneal dialysis (PD) is the preferred and convenient treatment modality for acute kidney injury (AKI) in children and hemodynamically unstable patients.

Methods

The outcome of acute PD was studied in 57 children (39 boys) with AKI, aged 1 month to 12 years, at a tertiary care center of a teaching hospital in India.

Results

Hemolytic uremic syndrome (36.8%) was the most common cause of AKI, followed by septicemia (24.6%) and acute tubular necrosis (19.3%). Treatment with PD was highly effective in lowering retention markers ( p < 0.001). Overall mortality was 36.8%. The risk of mortality by multivariate analysis was higher when patients were anuric [odds ratio (OR): 8.2; 95% confidence interval (CI): 1.3 to 49; p < 0.05], had septicemia (OR: 3.79; 95% CI: 1.55 to 25.8; p < 0.05), or severe infectious complications (OR: 8.2; 95% CI: 1.5 to 42.9; p < 001).

Conclusions

Because of its simplicity and feasibility, acute PD is still an appropriate treatment choice for children with AKI in resource-poor settings. Septicemia and severity of AKI are contributory factors to high mortality in pediatric acute kidney injury.
Comorbidities in Chronic Pediatric Peritoneal Dialysis Patients: A Report of the International Pediatric Peritoneal Dialysis Network
Authors: Neu Alicia M. , Sander Anja , Borzych–Dużałka Dagmara , Watson Alan R. , Vallés Patricia G. , Ha Il Soo , Patel Hiren , Askenazi David , Bałasz–Chmielewska Irena , Lauronen Jouni , Groothoff Jaap W. , Feber Janusz , Schaefer Franz , Warady Bradley A.
Published: August 2012

Background, Objectives, and Methods

Hospitalization and mortality rates in pediatric dialysis patients remain unacceptably high. Although studies have associated the presence of comorbidities with an increased risk for death in a relatively small number of pediatric dialysis patients, no large-scale study had set out to describe the comorbidities seen in pediatric dialysis patients or to evaluate the impact of those comorbidities on outcomes beyond the newborn period. In the present study, we evaluated the prevalence of comorbidities in a large international cohort of pediatric chronic peritoneal dialysis (CPD) patients from the International Pediatric Peritoneal Dialysis Network registry and began to assess potential associations between those comorbidities and hospitalization rates and mortality.

Results

Information on comorbidities was available for 1830 patients 0 – 19 years of age at dialysis initiation. Median age at dialysis initiation was 9.1 years [interquartile range (IQR): 10.9], median follow-up for calculation of hospitalization rates was 15.2 months (range: 0.2 – 80.9 months), and total follow-up time in the registry was 2095 patient–years. At least 1 comorbidity had been reported for 602 of the patients (32.9%), with 283 (15.5%) having cognitive impairment; 230 (12.6%), motor impairment; 167 (9.1%), cardiac abnormality; 76 (4.2%), pulmonary abnormality; 212 (11.6%), ocular abnormality; and 101 (5.5%), hearing impairment. Of the 150 patients (8.2%) that had a defined syndrome, 85% had at least 1 nonrenal comorbidity, and 64% had multiple comorbidities. The presence of at least 1 comorbidity was associated with a higher hospitalization rate [hospital days per 100 observation days: 1.7 (IQR: 5.8) vs 1.2 (IQR: 3.9), p = 0.001] and decreased patient survival (4-year survival rate: 73% vs 90%, p < 0.0001).

Conclusions

Nearly one third of pediatric CPD patients in a large international cohort had at least 1 comorbidity, and multiple comorbidities were frequently reported among patients with a defined syndrome. Preliminary analysis suggests an association between comorbidity and poor outcome in those patients. As this powerful international registry matures, further multivariate analyses will be important to more clearly define the impact of comorbidities on hospital-ization rates and mortality in pediatric CPD patients.
Impact of Global Economic Disparities on Practices and Outcomes of Chronic Peritoneal Dialysis in Children: Insights from the International Pediatric Peritoneal Dialysis Network Registry
Authors: Schaefer Franz , Borzych–Duzalka Dagmara , Azocar Marta , Munarriz Reyner Loza , Sever Lale , Aksu Nejat , Barbosa Lorena Sànchez , Galan Yajaira Silva , Xu Hong , Coccia Paula A. , Szabo Attila , Wong William , Salim Rosana , Vidal Enrico , Pottoore Stephen , Warady Bradley A.
Published: August 2012

Background, Objectives, and Methods

The number of patients on chronic peritoneal dialysis (CPD) is increasing rapidly on a global scale. We analyzed the International Pediatric Peritoneal Dialysis Network (IPPN) registry, a global database active in 33 countries spanning a wide range in gross national income (GNI), to identify the impact of economic conditions on CPD practices and outcomes in children and adolescents.

Results

We observed close associations of GNI with the fraction of very young patients on dialysis, the presence and number of comorbidities, the prevalence of patients with unexplained causes of end-stage kidney disease, and the rate of culture-negative peritonitis. The prevalence of automated PD increased with GNI, but was 46% even in the lowest GNI stratum. The GNI stratum also affected the use of biocompatible peritoneal dialysis fluids, enteral tube feeding, calcium-free phosphate binders, active vitamin D analogs, and erythropoiesis-stimulating agents (ESAs). Patient mortality was strongly affected by GNI (hazard ratio per $10 000: 3.3; 95% confidence interval: 2.0 to 5.5) independently of young patient age and the number of comorbidities present. Patients from low-income countries tended to die more often from infections unrelated to CPD (5 of 9 vs 15 of 61, p = 0.1). The GNI was also a strong independent predictor of standardized height ( p < 0.0001), adding to the impact of congenital renal disease, anuria, age at PD start, and dialysis vintage. Patients from the lower economic strata (GNI < $18 000) had higher serum parathyroid hormone (PTH) and lower serum calcium, and achieved lower hemoglobin concentrations. No impact of GNI was observed with regard to CPD technique survival or peritonitis incidence.

Conclusions

We conclude that CPD is practiced successfully, albeit with major regional variation related to economic differences, in children around the globe. The variations encompass the acceptance of very young patients and those with associated comorbidities to chronic dialysis programs, the use of automated PD and expensive drugs, and the diagnostic management of peritonitis. These variations in practice related to economic difference do not appear to affect PD technique survival; however, economic conditions seem to affect mortality on dialysis and standardized height, a marker of global child morbidity.
Formation of smectic phases in binary liquid crystal mixtures with a huge length ratio
Authors: Kapernaum Nadia , Knecht Friederike , Hartley C Scott , Roberts Jeffrey C , Lemieux Robert P , Giesselmann Frank
Published: August 2012

A system of two liquid-crystalline phenylpyrimidines differing strongly in molecular length was studied. The phase diagram of these two chemically similar mesogens, with a length ratio of 2, was investigated, and detailed X-ray diffraction and electrooptical measurements were performed. The phase diagram revealed a destabilization of the nematic phase, which is present in the pure short compound, while the smectic state was stabilized. The short compound forms smectic A and smectic C phases, whereas the longer compound forms a broad smectic C phase and a narrow higher-ordered smectic phase. Nevertheless, in the mixtures, the smectic C phase is destabilized and disappears rapidly, whereas smectic A is the only stable phase observed over a broad concentration range. In addition, the smectic translational order parameters as well as the tilt angles of the mixtures are reduced. The higher-ordered smectic phase of the longer mesogen was identified as a smectic F phase.
Efficacy and Tolerability of Celecoxib in the Treatment of Acute Gouty Arthritis: A Randomized Controlled Trial
Authors: SCHUMACHER H. RALPH , BERGER MANUELA F. , LI-YU JULIE , PEREZ-RUIZ FERNANDO , BURGOS-VARGAS RUBÉN , LI CHUNMING
Published: August 2012

Objective.

To evaluate the analgesic efficacy of high-dose celecoxib in the treatment of moderate to extreme pain and inflammation associated with acute gouty arthritis.

Methods.

A multinational, randomized, double-blind, double-dummy, active-controlled trial was done with patients (aged ≥ 18 years) with acute gouty monoarthritis or oligoarthritis (onset of pain ≤ 48 h before enrollment). Patients were treated for 8 days with 1 week followup and were randomized 1:1:1:1 to receive celecoxib 50 mg bid, celecoxib 400 mg (followed by 200 mg later on Day 1 and then 200 mg bid for 7 days), celecoxib 800 mg (followed by 400 mg later on Day 1 and then 400 mg bid for 7 days), or indomethacin 50 mg tid.

Results.

Of 443 patients screened, 402 were randomized and 400 received treatment. Baseline demographics were comparable among treatments. Patients receiving high-dose celecoxib (800/400 mg) experienced a significantly greater reduction in pain intensity on Day 2 compared with low-dose celecoxib 50 mg bid [least squares (LS) mean difference −0.46; p = 0.0014]. For high-dose celecoxib 800/400 mg, the change in pain scores from baseline to Day 2 was comparable with indomethacin 50 mg tid (LS mean difference 0.11; p = 0.4331). There were significant differences in adverse events when the combined celecoxib groups (29.5%) were compared with patients taking indomethacin (43.1%; p = 0.0116). There was no change in median serum creatinine levels for any treatment. There were more discontinuations due to adverse events (8.8% vs 3%; p = 0.0147) with indomethacin than with the combined celecoxib groups.

Conclusion.

High-dose celecoxib (800/400 mg) was significantly more effective than low-dose celecoxib (50 mg bid) and comparable to indomethacin in the treatment of moderate to extreme pain in patients with acute gouty arthritis. Further, celecoxib was well tolerated.
Access to Biologic Therapies in Canada for Children with Juvenile Idiopathic Arthritis
Authors: LEBLANC CLAIRE M.A. , LANG BIANCA , BENCIVENGA ALMA , CHETAILLE ANNE-LAURE , DANCEY PAUL , DENT PETER , MIETTUNEN PAIVI , OEN KIEM , ROSENBERG ALAN , ROTH JOHANNES , SCUCCIMARRI ROSIE , TSE SHIRLEY M.L. , BENSELER SUSANNE , CABRAL DAVID A. , CAMPILLO SARAH , CHÉDEVILLE GAËLLE , DUFFY CIARAN M. , DUFFY KAREN WATANABE , HADDAD ELIE , HUBER ADAM M. , LAXER RONALD , LEVY DEBORAH , JOHNSON NICOLE , RAMSEY SUZANNE , SHIFF NATALIE , SCHMELING HEINRIKE , SCHNEIDER RAYFEL , STRINGER ELIZABETH , YEUNG RAE S.M. , TUCKER LORI B.
Published: August 2012

Objective.

To compare access to biologic therapies for children with juvenile idiopathic arthritis (JIA) across Canada, and to identify differences in provincial regulations and criteria for access.

Methods.

Between June and August 2010, we compiled the provincial guidelines for reimbursement of biologic drugs for children with JIA and conducted a multicenter Canada-wide survey of pediatric rheumatologists to determine their experience with accessing biologic therapies for their patients.

Results.

There were significant difficulties accessing biologic treatments other than etanercept and abatacept for children. There were large discrepancies in the access criteria and coverage of biologic agents across provinces, notably with age restrictions for younger children.

Conclusion.

Canadian children with JIA may not receive optimal internationally recognized “standard” care because pediatric coverage for biologic drugs through provincial formularies is limited and inconsistent across the country. There is urgent need for public policy to improve access to biologic therapies for these children to ensure optimal short-term and longterm health outcomes.
Disease-modifying Antirheumatic Drug Use in the Treatment of Juvenile Idiopathic Arthritis: A Cross-sectional Analysis of the CARRA Registry
Authors: BEUKELMAN TIMOTHY , RINGOLD SARAH , DAVIS TREVOR E. , DeWITT ESI MORGAN , PELAJO CHRISTINA F. , WEISS PAMELA F. , KIMURA YUKIKO
Published: August 2012

Objective.

To characterize disease-modifying antirheumatic drug (DMARD) use for children with juvenile idiopathic arthritis (JIA) in the United States and to determine patient factors associated with medication use.

Methods.

We analyzed cross-sectional baseline enrollment data from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry from May 2010 through May 2011 for children with JIA. Current and prior medication use was included. We used parsimonious backward stepwise logistic regression models to calculate OR to estimate associations between clinical patient factors and medication use.

Results.

We identified 2748 children with JIA with a median disease duration of 3.9 years from 51 US clinical sites. Overall, 2023 (74%) had ever received a nonbiologic DMARD and 1246 (45%) had ever received a biologic DMARD. Among children without systemic arthritis, methotrexate use was most strongly associated with uveitis (OR 5.2, 95% CI 3.6–7.6), anticitrullinated protein antibodies (OR 4.5, 95% CI 1.7–12), and extended oligoarthritis (OR 4.1, 95% CI 2.5–6.6). Among children without systemic arthritis, biologic DMARD use was most strongly associated with rheumatoid factor (RF)-positive polyarthritis (OR 4.3, 95% CI 2.9–6.6), psoriatic arthritis (PsA; OR 3.0, 95% CI 2.0–4.4), and uveitis (OR 2.8, 95% CI 2.1–3.7). Among children with systemic arthritis, 160 (65%) ever received a biologic DMARD; tumor necrosis factor inhibitor use was associated with polyarthritis (OR 2.5, 95% CI 3.8–16), while interleukin 1 inhibitor use was not.

Conclusion.

About three-quarters of all children with JIA in the CARRA Registry received nonbiologic DMARD. Nearly one-half received biologic DMARD, and their use was strongly associated with RF-positive polyarthritis, PsA, uveitis, and systemic arthritis.
Efficacy of Incentive Spirometer Exercise on Pulmonary Functions of Patients with Ankylosing Spondylitis Stabilized by Tumor Necrosis Factor Inhibitor Therapy
Authors: SO MIN WOOK , HEO HYUN MI , KOO BON SAN , KIM YONG-GIL , LEE CHANG-KEUN , YOO BIN
Published: August 2012

Objective.

To evaluate the effect of combining incentive spirometer exercise (ISE) with a conventional exercise (CE) on patients with ankylosing spondylitis (AS) stabilized by tumor necrosis factor (TNF) inhibitor therapy by comparing a combination group with a CE-alone group.

Methods.

Forty-six patients (44 men, 2 women) were randomized to the combination group (ISE plus CE; n = 23) or the CE group (n = 23). The CE regimen of both groups consisted of 20 exercises performed for 30 min once a day. The ISE was performed once a day for 30 min. The trial duration was 16 weeks. Patients were assessed before and at the end of treatment by measuring the Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index (BASFI), chest expansion, finger to floor distance, pulmonary function measures, and 6-min walk distance.

Results.

Both groups improved significantly in terms of chest expansion (p < 0.01), finger to floor distance (p < 0.01), and BASFI (p < 0.05) after completing the exercise program. However, only the combination group showed significant improvements in the forced vital capacity (p < 0.05), total lung capacity (p < 0.01), and vital capacity (p < 0.05). Although this did not achieve statistical significance, the combination group was mildly superior to the CE-alone group in functional disability and pulmonary function measures.

Conclusion.

Combining ISE with a CE can provide positive results in patients whose AS has been clinically stabilized by TNF inhibitor therapy.
Hydroxychloroquine Use Is Associated with Lower Odds of Persistently Positive Antiphospholipid Antibodies and/or Lupus Anticoagulant in Systemic Lupus Erythematosus
Authors: BRODER ANNA , PUTTERMAN CHAIM
Published: August 2012

Objective.

Antiphospholipid antibodies (aPL) play an active role in the pathogenesis of the antiphospholipid syndrome (APS). Primary prevention in APS may be aimed at decreasing existing elevated aPL levels, or preventing high aPL titers and/or lupus anticoagulant (LAC) from developing in the first place. Hydroxychloroquine (HCQ) has been shown in retrospective studies to decrease aPL titers in laboratory studies, and to decrease thrombosis risk in patients with systemic lupus erythematosus (SLE). We investigated an association between HCQ use and persistent aPL and/or LAC in SLE.

Methods.

We identified all patients over 21 years old with SLE from an urban tertiary care center who had aPL and LAC measured on at least 2 occasions at least 12 weeks apart. We defined the presence of persistent LAC+ and/or at least 1 aPL ≥ 40 U [immunoglobulin A (IgA), IgG, or IgM] as the main outcome variable.

Results.

Among 90 patients included in the study, 17 (19%) had persistent LAC+ and/or at least 1 aPL ≥ 40 U. HCQ use was associated with significantly lower odds of having persistent LAC+ and/or aPL ≥ 40 U (OR 0.21, 95% CI 0.05, 0.79, p = 0.02), adjusted for age, ethnicity, and sex.

Conclusion.

This is the first study to show that HCQ use is associated with lower odds of having persistently positive LAC and/or aPL. Data from this study provide a basis for the design of future prospective studies investigating the role of HCQ in primary and secondary prevention of APS.
Psoriatic Arthritis in Canadian Clinical Practice: The PsA Assessment in Rheumatology
Authors: GLADMAN DAFNA D. , CHANDRAN VINOD , THAVANESWARAN ARANE , ZUMMER MICHEL
Published: August 2012

Objective.

We aimed to determine disease severity and treatment of patients with psoriatic arthritis (PsA) in rheumatology practices in Canada through the PsA Assessment in Rheumatology (PAIR) study.

Methods.

Rheumatologists who were members of the Canadian Rheumatology Association were asked to complete a form for each patient addressing demographic questions, history, clinical examination, and patient-reported outcomes. Results were compared with a cohort seen in a PsA clinic during the same period.

Results.

From across Canada, 22 rheumatologists from 5 provinces submitted information about 233 consecutive patients with PsA [145 men (62.2%), 88 women (37.8%), mean age 53.2 yrs (± 12.7), 88.4% disease duration > 2 yrs]. A majority (80.7%) fulfilled ClASsification for Psoriatic ARthritis (CASPAR) criteria, and 30% had taken no disease-modifying antirheumatic drugs. Clinical joint damage was documented in 60% of the patients, active skin disease in 70%, and nail lesions in 32%. Only 22% were rated as having moderate to high disease activity, while 52% were rated as low disease activity and 26% were deemed in remission. The decision was based on joint counts, patient global assessment, physician global assessment, and acute-phase reactants. Twenty-seven percent of the patients were to have their medications changed based on the current visit, the majority for inadequate response to medications. Patients in the PAIR cohort had more inflamed joints but similar damage to those in the PsA clinic.

Conclusion.

Patients with PsA seen in regular rheumatology practice fulfill CASPAR criteria, have active disease, and more than half have joint damage. The majority have low activity or are in remission.
Knee Enthesitis and Synovitis on Magnetic Resonance Imaging in Patients with Psoriasis without Arthritic Symptoms
Authors: EMAD YASSER , RAGAB YASSER , GHEITA TAMER , ANBAR ASHRAF , KAMAL HODA , SAAD AHMED , DARWEESH HANAN , EL-SHAARAWY NASHWA , AZAB AMR , ISMAIL AHMED , RASKER JOHANNES J. , RASKER JOHANNES J.
Published: August 2012

Objective.

This case-control study was designed to evaluate magnetic resonance imaging (MRI) findings of knee joints in patients with psoriasis without clinical peripheral or axial joint involvement, and to correlate MRI findings with disease and demographic variables.

Methods.

In total 48 patients with psoriasis and no clinical evidence of synovitis or enthesitis in any peripheral or axial joints were enrolled. A random sample of 20 healthy subjects without knee or other joint complaints and matched for age and sex served as controls. All patients and controls underwent enhanced MRI studies of both knee joints, and MRI findings were compared.

Results.

Among 48 patients (96 knees), a total of 90 entheseal lesions were detected, with no enthesitis in 2 cases (6.3%). Signs of continuing inflammation bilaterally were frequently found: soft tissue edema (STE; n = 52), bone marrow edema (BME; n = 20), perientheseal BME (n = 3), cartilaginous erosions (n = 42), and bone erosions (n = 27). In controls, 2 (10%) subjects had BME and another 5 (25%) showed cartilaginous erosions. None showed evidence of enthesitis. Significant correlations were observed between the number of entheseal lesions of both knees vs STE (present vs absent; r = 0.314, p = 0.030) and STE (number of lesions; r = 0.351, p = 0.014). Enthesitis (unilateral vs bilateral) was significantly and positively correlated with STE (r = 0.304, p = 0.036), cartilaginous erosions (r = 0.304, p = 0.036), and villous projections (r = 0.347, p = 0.016).

Conclusion.

Subclinical synovitis and enthesitis are frequently found in the knee joint of patients with psoriasis. These may be an early sign of psoriatic arthritis.
Vitamin D Receptor Polymorphism rs2228570 (Fok1) Is Associated with Rheumatoid Arthritis in North American Natives
Authors: HITCHON CAROL A. , SUN YE , ROBINSON DAVID B. , PESCHKEN CHRISTINE A. , BERNSTEIN CHARLES N. , SIMINOVITCH KATHERINE A. , EL-GABALAWY HANI S.
Published: August 2012

Objective.

Vitamin D (VitD) has immunomodulatory activity relevant to rheumatoid arthritis (RA) and acts by binding nuclear receptors that regulate gene transcription. VitD receptor polymorphisms have been variably associated with RA. Because North American Native (NAN) populations have a high prevalence of RA with a strong genetic contribution, we studied potential associations of the rs2228570 (Fok1) VitD receptor polymorphism in a Canadian NAN population.

Methods.

The single-nucleotide polymorphism (SNP) Fok1 was tested by sequencing NAN patients with RA (n = 448) and unrelated NAN controls (n = 704). Associations were tested using genotypic, dominant, and recessive models.

Results.

The minor allele frequency (F/C) in the NAN control population was 0.44 and lower than reported in white subjects of the same geographical area. The Fok1 VitD receptor SNP was significantly associated with RA. Comparing patients with RA to unaffected NAN controls, the Fok1 SNP was associated with RA using both genotypic [FF vs Ff vs ff: RA 20%, 54%, 26% vs control 22%, 44%, 34% (chi-square 13.35, p = 0.003)] and dominant models [FF/Ff vs ff: RA 74% vs 26% control 66% vs 34% (OR 1.5, 95% CI 1.16–1.96, p = 0.003)]. This association was strongest in shared-epitope-positive RA.

Conclusion.

VitD receptor polymorphisms may contribute to the high prevalence of RA in NAN populations.
Interleukin 21 Correlates with T Cell and B Cell Subset Alterations in Systemic Lupus Erythematosus
Authors: TERRIER BENJAMIN , COSTEDOAT-CHALUMEAU NATHALIE , GARRIDO MARLÈNE , GERI GUILLAUME , ROSENZWAJG MICHELLE , MUSSET LUCILE , KLATZMANN DAVID , SAADOUN DAVID , CACOUB PATRICE
Published: August 2012

Objective.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by alterations of the B cell subset, global regulatory T cell (Treg) depletion, and an increase in Th17 cells. Interleukin 21 (IL-21) plays a critical role in T cell and B cell homeostasis. Our objective was to determine the implication of IL-21 and IL-21-producing CD4+ T cells in the pathogenesis of SLE.

Methods.

Twenty-five patients with SLE and 25 healthy donor controls were included. Analysis of CD4+ T cells producing IL-21, Th1, Th2, Th17, Treg, follicular helper T (TFH) cells, and B cells was performed in peripheral blood, and levels of cytokines were measured in culture supernatants.

Results.

Circulating CD4+ T cells producing IL-21 were markedly expanded in patients with SLE compared to controls and were correlated with increased Th17, decreased Treg, and increased memory B cells. CD4+ T cells producing IL-21 were composed of CXCR5+ and CXCR5–CD4+ T cell subsets. Both IL-21-producing CXCR5+CD4+ T cells and CXCR5–CD4+ T cells were increased in patients with SLE, the CXCR5–CD4+ subset correlating with Th17 cells and Treg, while the CXCR5+CD4+ subset was correlated with alterations of the B cell subset. The CXCR5+CD4+ subset comprised mainly circulating Bcl6+CXCR5+CD4+ TFH cells that were markedly expanded in patients with SLE and were correlated with increased circulating Bcl6+CXCR5+ germinal center B cells.

Conclusion.

These findings suggest that IL-21, produced by distinct cellular CD4+ T cells, correlates with alterations of T cell and B cell subsets in SLE, and that targeting IL-21 could provide beneficial effects on both T cell and B cell alterations.
Palindromic Rheumatism with Positive Anticitrullinated Peptide/Protein Antibodies Is Not Synonymous with Rheumatoid Arthritis. A Longterm Followup Study
Authors: SANMARTÍ RAIMON , CABRERA-VILLALBA SONIA , GÓMEZ-PUERTA JOSÉ A. , RUIZ-ESQUIDE VIRGINIA , HERNÁNDEZ M. VICTORIA , SALVADOR GEORGINA , RAMIREZ JULIO , VIÑAS ODETTE , CAÑETE JUAN D.
Published: August 2012

Objective.

To analyze longterm progression to rheumatoid arthritis (RA) and the predictive value of anticitrullinated peptide/protein antibodies (ACPA) in palindromic rheumatism (PR).

Methods.

We selected all patients in our clinic with PR who had at least 1 ACPA measurement. We included only patients with pure PR, defined as no evidence of associated rheumatic disease at the first serum ACPA measurement. Clinical characteristics, serum ACPA levels, duration of PR until serum ACPA measurement, and total followup time were recorded. The outcome variable was the definitive diagnosis of RA. The prognostic value of ACPA status in pure PR for a definite diagnosis of RA was analyzed by different statistical methods.

Results.

Seventy-one patients (54 women/17 men) with a PR diagnosis were included. Serum ACPA were positive in 52.1%. After a mean followup of 7.6 ± 4.7 years since the first ACPA measurement, 24 patients (33.8%) progressed to chronic disease: 22% RA, 5.6% systemic lupus erythematosus, and 5.6% other diseases. The positive likelihood ratio of ACPA status for RA was 1.45, and the area under the receiver-operating characteristic curve of ACPA titers was 0.60 (95% CI 0.45−0.75). Progression to RA was more frequently seen in ACPA-positive than in ACPA-negative patients (29.7% vs 14.7%), but the difference was not significant (hazard ratio 2.46, 95% CI 0.77−7.86). Mean ACPA levels of patients with pure PR did not differ significantly from those of patients who progressed to RA.

Conclusion.

ACPA are frequently found in the sera of patients with PR, and a significant proportion of these patients do not progress to RA in the long term.
The Acute-phase Response Is Not Predictive for the Development of Arthritis in Seropositive Arthralgia – A Prospective Cohort Study
Authors: LIMPER MAARTEN , van de STADT LOTTE , BOS WOUTER , de KRUIF MARTIJN , SPEK ARNOLD , WOLBINK GERTJAN , van SCHAARDENBURG DIRKJAN , van GORP ERIC
Published: August 2012

Objective.

To evaluate whether markers of the acute-phase response in patients presenting with arthralgia and positive anticitrullinated protein antibodies (ACPA) and/or immunoglobulin M rheumatoid factor (IgM-RF) could be predictive for the development of arthritis.

Methods.

In total, 137 ACPA- and/or IgM-RF-positive patients were included. Patients were followed annually for the development of arthritis, defined as presence of 1 or more swollen joints at clinical examination. High-sensitivity C-reactive protein (hsCRP), procalcitonin (PCT), secretory phospholipase A2 (SPLA2), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), IL-12p70, IL-10, and interferon-γ (IFN-γ) were measured in baseline serum samples. Gene expression focusing on a predefined panel of genes coding for inflammatory molecules was measured by multiplex ligation-dependent probe amplification.

Results.

Thirty-five patients (26%) developed arthritis within a median time of 11 months (interquartile range 3.7–18 mo). Circulating levels of cytokines, SPLA2, hsCRP, and PCT were not different between patients with progression to clinical arthritis and those without progression. However, a trend for IL-12p70, TNF-α, IL-10, IL-6, and SPLA2 was observed. No correlation between messenger RNA (mRNA) expression levels of inflammatory genes and progression to arthritis was found. Subgroup analysis of patients with early progression to arthritis showed higher levels of mRNA expression of poly(A)-specific ribonuclease and polycomb complex protein BMI-1 compared to patients without progression to arthritis.

Conclusion.

Although low-grade inflammation is present before onset of clinical arthritis in large cohorts and can be detected using consecutive measurements, a single measurement of acute-phase reactants seems to have limited value for prediction of development of arthritis in individual patients.
Une notion encombrante dans l'histoire de la sculpture grecque : le « dédalisme »
Authors: Aurigny Hélène
Published: August 2012

Résumé L’utilisation récurrente du mot « dédalique » dans les études récentes sur la sculpture grecque du haut-archaïsme fait apparaître une grande diversité dans le contenu de cette notion, formée à l’origine d’après le nom de l’artisan légendaire Dédale. « Dédalique » peut ainsi avoir un sens stylistique, géographique et, surtout, un sens chronologique plus ou moins précis. Mais ces différents emplois reposent sur un ensemble de présupposés et de conceptions anciennes qui ne sont pour ainsi dire jamais explicitées. Si l’on veut comprendre pourquoi les chercheurs continuent de s’y référer, malgré la confusion qui en résulte, il paraît donc nécessaire de retracer les différentes étapes de l’histoire de la notion même de « dédalisme ». On pourra ainsi s’interroger sur son utilité réelle et se demander si elle est encore susceptible de nous aider à comprendre la sculpture grecque du haut-archaïsme.
Les premiers voyageurs et la dorure du Parthénon : mise au point sur une controverse ancienne
Authors: Zambon Alessia
Published: August 2012

Résumé Au‑delà des sources anciennes, les arguments régulièrement avancés en faveur d’une dorure des marbres du Parthénon tiennent aux récits des voyageurs de la fin du xviii e et du début du xix e  s. Les noms le plus souvent évoqués à ce sujet sont ceux de Haygarth, Dodwell, Clarke, Brøndsted, Cockerell, Fauvel et Millin. L’auteur soumet leurs témoignages et ceux de quelques autres voyageurs à une critique rigoureuse pour en vérifier la nature exacte. Il apparaît ainsi que, bien que les remarques des premiers voyageurs aient contribué à forger les avis sur l’emploi de la polychromie et de la dorure dans l’Antiquité, elles ne reposent pas toujours sur des observations de première main.
Verres de l'Antiquité gréco‑romaine : trois ans de publication (2008‑2010)
Authors: Nenna Marie-Dominique
Published: August 2012

Résumé Recension des publications parues dans les années 2008‑2010 sur le verre de l’Antiquité ( viii e  s. av. J.‑C.- vii e  s. apr. J.‑C.) : ouvrages généraux, bibliographies et sites internet, expositions, méthodologie et terminologie, colloques, collections, ventes, musées, études thématiques par technique et par fonction, production et commerce, clientèle et centres de consommation.
El índice de credibilidad: una propuesta metodológica para incrementar la eficacia de los planes de empresa
Authors: Retolaza José Luis , San José Leire , Iturralde Txomin
Published: August 2012

El instrumento más utilizado para realizar la previsión de éxito en la creación de empresas, el plan de empresa, no tiene un alto grado de garantía y, por tanto, su credibilidad es mínima. En este trabajo se desarrolla una metodología con objeto de proporcionar una eficiencia relativa mayor que la de metodologías previas, para lo cual se efectúa un proceso de benchmarking a través del DEA (Data Envelopment Analysis –Análisis Envolvente de Datos–). Las principales aportaciones de este trabajo son dos: por un lado, se propone una metodología que permite valorar un nuevo proyecto empresarial mediante la comparación de la eficiencia de las empresas; por otro, esta metodología permite obtener un índice de credibilidad del propio proyecto de viabilidad o plan de empresa, lo que aporta valor añadido al tradicional plan, que carece de indicadores que ofrezcan información sobre las garantías de éxito empresarial del proyecto. Esta metodología no está exenta de limitaciones. Las principales son la necesidad de establecer un grupo de empresas de referencia, con los problemas que ello conlleva, y la falta de contraste empírico que valide esta metodología.

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The business plan, the most frequently tool used for the provision of the success of entrepreneurship has not a high degree of assurance, and therefore its credibility is minimal. This paper develops a methodology in order to provide a relative efficiency greater than previous methods for which a benchmarking process is carried out through the DEA (Data Envelopment Analysis). The main contributions of this paper are twofold. On the one hand, we propose a methodology to assess a new business plan by comparing the efficiency of enterprises. On the other hand, this methodology would produce an index of credibility of own project feasibility or business plan; what adds value to the traditional plan with lack of indicators that provide information about the guarantee of business success of the project. This methodology is not without limitations. The main ones are: the need to establish a reference group of companies with the problems that this entails and the lack of empirical test to validate this methodology.
Airway Epithelial Expression of TLR5 Is Downregulated in Healthy Smokers and Smokers with Chronic Obstructive Pulmonary Disease
Authors: Wang Rui , Ahmed Joumana , Wang Guoqing , Hassan Ibrahim , Strulovici-Barel Yael , Salit Jacqueline , Mezey Jason G. , Crystal Ronald G.
Published: August 2012

The TLRs are important components of the respiratory epithelium host innate defense, enabling the airway surface to recognize and respond to a variety of insults in inhaled air. On the basis of the knowledge that smokers are more susceptible to pulmonary infection and that the airway epithelium of smokers with chronic obstructive pulmonary disease (COPD) is characterized by bacterial colonization and acute exacerbation of airway infections, we assessed whether smoking alters expression of TLRs in human small airway epithelium, the primary site of smoking-induced disease. Microarrays were used to survey the TLR family gene expression in small airway (10th to 12th order) epithelium from healthy nonsmokers (n = 60), healthy smokers (n = 73), and smokers with COPD (n = 36). Using the criteria of detection call of present (P call) ≥50%, 6 of 10 TLRs (TLRs 1–5 and 8) were expressed. Compared with nonsmokers, the most striking change was for TLR5, which was downregulated in healthy smokers (1.4-fold, p < 10−10) and smokers with COPD (1.6-fold, p < 10−11). TaqMan RT-PCR confirmed these observations. Bronchial biopsy immunofluorescence studies showed that TLR5 was expressed mainly on the apical side of the epithelium and was decreased in healthy smokers and smokers with COPD. In vitro, the level of TLR5 downstream genes, IL-6 and IL-8, was highly induced by flagellin in TLR5 high-expressing cells compared with TLR5 low-expressing cells. In the context that TLR5 functions to recognize pathogens and activate innate immune responses, the smoking-induced downregulation of TLR5 may contribute to smoking-related susceptibility to airway infection, at least for flagellated bacteria.
Rapid Differentiation of Monocytes into Type I IFN-Producing Myeloid Dendritic Cells as an Antiviral Strategy against Influenza Virus Infection
Authors: Cao Weiping , Taylor Andrew K. , Biber Renata E. , Davis William G. , Kim Jin Hyang , Reber Adrian J. , Chirkova Tatiana , De La Cruz Juan A. , Pandey Aseem , Ranjan Priya , Katz Jacqueline M. , Gangappa Shivaprakash , Sambhara Suryaprakash
Published: August 2012

Myeloid dendritic cells (mDCs) have long been thought to function as classical APCs for T cell responses. However, we demonstrate that influenza viruses induce rapid differentiation of human monocytes into mDCs. Unlike the classic mDCs, the virus-induced mDCs failed to upregulate DC maturation markers and were unable to induce allogeneic lymphoproliferation. Virus-induced mDCs secreted little, if any, proinflammatory cytokines; however, they secreted a substantial amount of chemoattractants for monocytes (MCP-1 and IP-10). Interestingly, the differentiated mDCs secreted type I IFN and upregulated the expression of IFN-stimulated genes (tetherin, IFITM3, and viperin), as well as cytosolic viral RNA sensors (RIG-I and MDA5). Additionally, culture supernatants from virus-induced mDCs suppressed the replication of virus in vitro. Furthermore, depletion of monocytes in a mouse model of influenza infection caused significant reduction of lung mDC numbers, as well as type I IFN production in the lung. Consequently, increased lung virus titer and higher mortality were observed. Taken together, our results demonstrate that the host responds to influenza virus infection by initiating rapid differentiation of circulating monocytes into IFN-producing mDCs, which contribute to innate antiviral immune responses.
V(D)J Recombinase-Mediated TCR β Locus Gene Usage and Coding Joint Processing in Peripheral T Cells during Perinatal and Pediatric Development
Authors: Murray Janet M. , Messier Terri , Rivers Jami , O’Neill J. Patrick , Walker Vernon E. , Vacek Pamela M. , Finette Barry A.
Published: August 2012

The generation of TCR proteins is the result of V(D)J recombinase-mediated genomic rearrangements at recombination signal sequences (RSS) in human lymphocytes. V(D)J recombinase can also mediate rearrangements at nonimmune or “cryptic” RSS in normal and leukemic human peripheral T cells. We previously demonstrated age- and gender-specific developmental differences in V(D)J coding joint processing at cryptic RSS within the HPRT locus in peripheral T cells from healthy children (Murray et al. 2006. J. Immunol. 177: 5393–5404). In this study, we investigated developmentally specific V(D)J recombinase TCRβ immune gene rearrangements and coding joint processing at RSS in peripheral T cells in the same pediatric population. This approach provided a unique opportunity to investigate site-specific V(D)J recombinase rearrangements and coding joint processing at immune and nonimmune genes from the same individual T cell population. We determined the genomic sequence of 244 TCRβ coding junctions from 112 (63 male, 49 female) subjects from the late stages of fetal development through 9 y of age. We observed both age- and gender-specific V(D)J recombinase-mediated TCRβ gene usage and coding joint processing at immune RSS. To the best of our knowledge, these data represent the first description of age- and gender-specific developmental differences in TCR gene usage and coding joint processing that could directly influence TCR diversity and immune specificity. It will be important for future studies to ascertain the mechanistic etiology of these developmental and gender differences in TCR diversity and specificity, as well as their importance with respect to the age and gender risks for infectious and autoimmune diseases in humans.
B Cell Memory to a Serogroup C Meningococcal Conjugate Vaccine in Childhood and Response to Booster: Little Association with Serum IgG Antibody
Authors: Perrett Kirsten P. , Jin Celina , Clutterbuck Elizabeth , John Tessa M. , Winter Amy P. , Kibwana Elizabeth , Yu Ly-Mee , Curtis Nigel , Pollard Andrew J.
Published: August 2012

The maintenance of adequate serum Ab levels following immunization has been identified as the most important mechanism for individual long-term protection against rapidly invading encapsulated bacteria. The mechanisms for maintaining adequate serum Ab levels and the relationship between Ag-specific memory B cells and Ab at steady state are poorly understood. We measured the frequency of circulating serogroup C meningococcal (MenC)-specific memory B cells in 250 healthy 6- to 12-y-old children 6 y following MenC conjugate vaccine priming, before a booster of a combined Haemophilus influenzae type b–MenC conjugate vaccine and then 1 wk, 1 mo, and 1 y after the booster. We investigated the relationship between circulating MenC-specific memory B cell frequencies and Ab at baseline and following the booster vaccine. We found very low frequencies of circulating MenC-specific memory B cells at steady state in primary school-aged children and little association with MenC IgG Ab levels. Following vaccination, there were robust memory B cell booster responses that, unlike Ab levels, were not dependent on age at priming with MenC. Measurement of B cell memory in peripheral blood does not predict steady state Ab levels nor the capacity to respond to a booster dose of MenC Ag.
Systemic Analysis of PPARγ in Mouse Macrophage Populations Reveals Marked Diversity in Expression with Critical Roles in Resolution of Inflammation and Airway Immunity
Authors: Gautier Emmanuel L. , Chow Andrew , Spanbroek Rainer , Marcelin Genevieve , Greter Melanie , Jakubzick Claudia , Bogunovic Milena , Leboeuf Marylene , van Rooijen Nico , Habenicht Andreas J. , Merad Miriam , Randolph Gwendalyn J.
Published: August 2012

Although peroxisome proliferator-activated receptor γ (PPARγ) has anti-inflammatory actions in macrophages, which macrophage populations express PPARγ in vivo and how it regulates tissue homeostasis in the steady state and during inflammation remains unclear. We now show that lung and spleen macrophages selectively expressed PPARγ among resting tissue macrophages. In addition, Ly-6Chi monocytes recruited to an inflammatory site induced PPARγ as they differentiated to macrophages. When PPARγ was absent in Ly-6Chi–derived inflammatory macrophages, initiation of the inflammatory response was unaffected, but full resolution of inflammation failed, leading to chronic leukocyte recruitment. Conversely, PPARγ activation favored resolution of inflammation in a macrophage PPARγ-dependent manner. In the steady state, PPARγ deficiency in red pulp macrophages did not induce overt inflammation in the spleen. By contrast, PPARγ deletion in lung macrophages induced mild pulmonary inflammation at the steady state and surprisingly precipitated mortality upon infection with Streptococcus pneumoniae. This accelerated mortality was associated with impaired bacterial clearance and inability to sustain macrophages locally. Overall, we uncovered critical roles for macrophage PPARγ in promoting resolution of inflammation and maintaining functionality in lung macrophages where it plays a pivotal role in supporting pulmonary host defense. In addition, this work identifies specific macrophage populations as potential targets for the anti-inflammatory actions of PPARγ agonists.
Dendritic Cell Sphingosine 1-Phosphate Receptor-3 Regulates Th1–Th2 Polarity in Kidney Ischemia–Reperfusion Injury
Authors: Bajwa Amandeep , Huang Liping , Ye Hong , Dondeti Krishna , Song Steven , Rosin Diane L. , Lynch Kevin R. , Lobo Peter I. , Li Li , Okusa Mark D.
Published: August 2012

Dendritic cells (DCs) are central to innate and adaptive immunity of early kidney ischemia–reperfusion injury (IRI), and strategies to alter DC function may provide new therapeutic opportunities. Sphingosine 1-phosphate (S1P) modulates immunity through binding to its receptors (S1P1–5), and protection from kidney IRI occurs in S1P3-deficient mice. Through a series of experiments we determined that this protective effect was owing in part to differences between S1P3-sufficient and -deficient DCs. Mice lacking S1P3 on bone marrow cells were protected from IRI, and S1P3-deficient DCs displayed an immature phenotype. Wild-type (WT) but not S1P3-deficient DCs injected into mice depleted of DCs prior to kidney IR reconstituted injury. Adoptive transfer (i.e., i.v. injection) of glycolipid (Ag)-loaded WT but not S1P3-deficient DCs into WT mice exacerbated IRI, suggesting that WT but not S1P3-deficient DCs activated NKT cells. Whereas WT DC transfers activated the Th1/IFN-γ pathway, S1P3-deficient DCs activated the Th2/IL-4 pathway, and an IL-4–blocking Ab reversed protection from IRI, supporting the concept that IL-4 mediates the protective effect of S1P3-deficient DCs. Administration of S1P3-deficient DCs 7 d prior to or 3 h after IRI protected mice from IRI and suggests their potential use in cell-based therapy. We conclude that absence of DC S1P3 prevents DC maturation and promotes a Th2/IL-4 response. These findings highlight the importance of DC S1P3 in modulating NKT cell function and IRI and support development of selective S1P3 antagonists for tolerizing DCs for cell-based therapy or for systemic administration for the prevention and treatment of IRI and autoimmune diseases.