Bibliography August 2008

1. Anonymous, In this issue: Proteomics 17/2008, Proteomics., Vol. 8(17)., 2008
   Organism:In this issue of Proteomics you will find the following highlighted articles:Slidin' and slipin': Substrates for autoantibody antigen arraysProteins do not have a reputation for being well-behaved. Given the number of sequence permutations possible for a particular length, it is no wonder that protein arrays have a notorious history. Balboni et al. report here on a systematic survey of supports and application methods for autoantibody antigen arrays. These arrays are central to studies of autoimmune diseases such as juvenile-onset (type I) diabetes, rheumatoid arthritis, multiple sclerosis, etc. Over 20 commercial and home-made slides were tested for background, smearing, streaking, adherence, and intra- and inter-slide variability (CVs). FAST(R) slides were ranked the best on the CV scores. Also acceptable were PATH(R) and SuperEpoxy2 slides. The authors note that other slide types may be better for specific antigens or detection methods.Balboni, I. et al, Proteomics 2008, 8, 3443-3449.Cheesy target for high resolution proteomicsWe are what we eat and sometimes that includes the leftovers from other organisms. "Yecch!" you say, but these are the products of a fermentome (to coin a new name), those proteins and organisms that ferment our food - grapes to wine, milk to yogurt, etc. - processes that need to be well understood for food safety and quality. Soufi et al. explore the phosphoproteome of Lactococcus lactis, an important commercial strain of bacteria, used in making a variety of fermented food products. L. lactis exhibits site-specific phosphorylation of serine, threonine and tryptophan residues similar to that found in eukaryotes. Unlike eukaryotes, bacteria usually have only one phosphorylation site per protein. The evidence presented suggests protein phosphorylation is a means to regulate gene expression in bacteria, albeit on a smaller scale than in higher organisms.Soufi, B. et al, Proteomics 2008, 8, 3486-3493.To see or not to see: That is not a questionOne of the most frequent healing complications of surgical repair of a detached retina is the overgrowth of membranes on both surfaces of the retina and the back side of the vitreous body (PVR) which can contract and rip the underlying tissue loose, creating major vision problems. Yu et al. applied proteomic tools to the problem and found the explanation lay in misregulation of a number of cytoskeleton and metabolism genes. Normal, moderate and severe PVR vitreous and serum samples were treated with trypsin and analyzed by strong cation exchange- and reverse phase-chromatography then nanoelectrospray-double quadrupole MS. Identity of vitreous proteins was verified by Western blots. The combined total of proteins identified was 255 but only 35 were common to both PVR and control samples, 24 were common to moderate and severe PVR. The regulation model is still a bit murky but should clear soon.Yu, J. et al., Proteomics 2008, 8, 3667-3678

2. AMINE B, ROSTOM S, BENBOUAZZA K, ABOUQAL Ret HAJJAJ-HASSOUNI N: Health related quality of life survey about children and adolescents with juvenile idiopathic arthritis, Rheumatol.Int., 2008
   Organism:el ayachi hospital, Sale, Morocco, amine_bouchra@yahoofr
   Abstract:This study aimed to investigate the proxy-reported Health related quality of life (HRQOL) and its determinants in patients with juvenile idiopathic arthritis (JIA). It was hypothesized that HRQOL would decrease with worsening disease and disability. Data were available in cross-sectional study on children and adolescents with JIA according to the ILAR criteria. Patient demographics, type of JIA, clinical determinants and laboratory parameters relating to JIA were obtained for each patient. Functional disability was assessed using the parent's or children's version of the child health assessment questionnaire (CHAQ). The HRQOL was evaluated using the juvenile arthritis quality of life questionnaire (JAQQ). These questionnaires were previously translated and validated in Moroccan children. A total of 80 participants were enrolled with mean age of 11 [6-17 years], and female predominance (59%). Many patients (42.5%) had oligoarticular subtype; 31.3% polyarticular subtypes and 26.2% systemic form. The mean global score of JAQQ was 2.6 +/- 1.3 (1-6). Patients with persistant oligoarticular had better gross motor function (P < 0.0001), better fine motor function (P < 0.0001), less psychosocial impact (P = 0.001), and less symptoms (P = 0.001) in comparison with polyarticular and systemic subtypes. The HRQOL assessed by the JAQQ was worse in adolescent patients in comparison with children except for symptoms (P = 0.15). The gender (P = 0.95), age at onset of JIA (P = 0.81), and evolution duration (P = 0.34) were not correlated with global score of JAQQ. The diagnosis delay was significantly associated with decrease of HRQOL (P = 0.001). The decrease of HRQOL was correlated with disease activity [pain (VAS), painful and swollen joints, erythrocyte sedimentation rate (for P < 0.0001)], with disability index (CHAQ) (P = 0.001) and presence of hip involvement (P = 0.01). This study suggests that JIA can have a significant adverse effect on the HRQOL of moroccan patients, particularly adolescents with polyarticular and systemic subtypes. Disease duration, disability score (CHAQ) and pain were the strongest determinants of poorer HRQOL

3. BOUYAHIA O, NESSERINE N, GHARSALLAH L, MAZIGH SM, DAGHFOUS R, BOUKTHIR Set EL GHARBI AS: A case of anaphylactic reaction to ibuprofen in a child with Still's disease, Therapie., Vol. 63(2), 155-156., 2008
   Organism:

4. CAPARBO VF, PRADA F, SILVA CA, REGIO PLet PEREIRA RM: Serum from children with polyarticular juvenile idiopathic arthritis (pJIA) inhibits differentiation, mineralization and may increase apoptosis of human osteoblasts "in vitro", Clin.Rheumatol., 2008
   Organism:Rheumatology Division, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil
   Abstract:We examined the effects of polyarticular juvenile idiopathic arthritis (pJIA) serum on proliferation, differentiation, mineralization, and apoptosis of human osteoblast cells (hOb) in culture. The hOb were cultured with 10% serum from active pJIA and healthy controls (CT) and were tested for DNA synthesis, alkaline phosphatase (AP) activity, osteocalcin (OC) secretion, calcium levels, caspase 3 activity, and DNA fragmentation. None of the patients had used glucocorticoids for at least 1 month before the study, or any other drug that can affect bone mineral metabolism. Human inflammatory cytokine levels (IL-6, IL-8, IL-10, IL-1beta, TNF-alpha, and IL-12p70) were measured in pJIA and CT sera. Low levels of AP activity was observed in pJIA cultures compared with CT cultures (67.16 +/- 53.35 vs 100.11 +/- 50.64 mumol p-nitrophenol/h(-1) mg(-1) protein, P = 0.008). There was also a significant decrease in OC secretion (9.23 +/- 5.63 vs 12.82 +/- 7.02 ng/mg protein, P = 0.012) and calcium levels (0.475 +/- 0.197 vs 0.717 +/- 0.366 mmol/l, P = 0.05) in pJIA hOb cultures. No difference was observed in cell proliferation (323.56 +/- 108.23 vs 328.91 +/- 88.03 dpm/mg protein, P = 0.788). Osteoblasts cultured with JIA sera showed lower levels of DNA and increased fragmentation than osteoblasts cultured with CT sera. pJIA sera showed higher IL-6 values than CT (21.44 +/- 9.31 vs 3.58 +/- 2.38 pg/ml, P < 0.001), but no difference was observed related to IL-8, IL-10, IL-1beta, TNF-alpha, and IL-12p70 between pJIA and controls. This study suggests that serum from children with pJIA inhibits differentiation, mineralization and may increase apoptosis of hOb cultures, and inflammatory cytokines such as IL-6 might be a mechanism in this find. These results may represent an alternative therapeutic target for prevention and treatment of bone loss in JIA

5. COSTENBADER KH, CHANG SC, LADEN F, PUETT Ret KARLSON EW: Geographic variation in rheumatoid arthritis incidence among women in the United States, Arch.Intern.Med., Vol. 168(15), 1664-1670., 2008
   Organism:Section of Clinical Sciences, Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA KCostenbader@partnersorgFAU - Costenbader, Karen H
   Abstract:BACKGROUND: The geographic variation in rheumatoid arthritis (RA) incidence in the United States is unknown. METHODS: We studied residential region from January 1, 1921, to May 31, 1976, and RA risk in a prospective cohort of women, the Nurses' Health Study. Information on state of residence was collected at baseline in 1976 (when participants were aged 30-55 years) and on state of residence at birth, at age 15 years, and at age 30 years in 1992. Among 83,546 participants reporting residence for all 4 time points, 706 incident RA cases from June 1, 1976, to May 31, 2004, were confirmed by screening questionnaire and record review for American College of Rheumatology criteria. Residential region was classified as West, Midwest, mid-Atlantic, New England, and Southeast. Multivariate Cox proportional hazards regression models were used to assess relationships between region and RA risk, adjusting for age, smoking, body mass index, parity, breastfeeding, postmenopausal status, postmenopausal hormone use, father's occupation, race, and physical activity. Analyses were performed in participants who lived in the same regions, or moved, over time. RESULTS: Compared with those in the West, women in New England had a 37% to 45% elevated risk of RA in multivariate models at each time point (eg, state of residence in 1976: rate ratio [RR], 1.42; 95% confidence interval [CI], 1.10-1.82). In analyses of women who lived in the same region at birth, age 15 years, and age 30 years, living in the Midwest was associated with greater risk (RR, 1.47; 95% CI, 1.05-2.05), as was living in New England (RR, 1.40; 95% CI, 0.98-2.00). Compared with living in the West at birth, age 15 years, and age 30 years, RA risk was higher in the East. CONCLUSIONS: In this large cohort of US women, significant geographic variation in incident RA existed after controlling for confounders. Potential explanations include regional variation in behavioral factors, climate, environmental exposures, RA diagnosis, and genetic factors

6. DIVITO Aet KAN JH: Juvenile idiopathic arthritis with rice bodies, Pediatr.Radiol., 2008
   Organism:Department of Radiology, University of Tennessee Medical Center, Knoxville, TN, 37920, USA, adivito@mcutmckedu
   Abstract:

7. GAO P, LU C, ZHANG F, SANG P, YANG D, LI X, KONG H, YIN P, TIAN J, LU X, LU Aet XU G: Integrated GC-MS and LC-MS plasma metabonomics analysis of ankylosing spondylitis, Analyst., Vol. 133(9), 1214-1220., 2008
   Organism:National Chromatographic R & A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaFAU - Gao, Peng
   Abstract:Ankylosing spondylitis (AS) is a chronic inflammatory arthritis that predominantly affects the axial skeleton in adolescent patients. The natural history of the disease remains poorly characterized. In this study, we combined GC-MS and LC-MS techniques to evaluate the major metabolic changes in the plasma of AS patients in view of metabonomics. Univariate and multivariate analysis were employed for altered metabolite comparison and pattern recognition. Application of supervised partial least-squares discrminant analysis to either GC-MS or LC-MS data allowed accurate discrimination of AS patients from normal controls, demonstrating its potential diagnostic utilization. In addition, AS patients presented elevated plasma concentrations of proline, glucose, phosphate, urea, glycerol, phenylalanine and homocysteine but reduced levels of phosphocholines, tryptophan and a bipeptide - phenylalanyl-phenylalanine. In the context of their involved metabolic pathways, the identified metabolites were discussed accordingly. This investigation primarily proved that integrated chromatography-mass spectrometry and integrated uni- and multi-variate statistical analysis facilitated metabonomics to be a more promising tool in disease research

8. ILOWITE NT: Update on biologics in juvenile idiopathic arthritis, Curr.Opin.Rheumatol., Vol. 20(5), 613-618., 2008
   Organism:Albert Einstein College of Medicine, Division of Rheumatology, Children's Hospital at Montefiore, Department of Pediatrics, Bronx, New York 10467-2490, USA nilowite@montefioreorgFAU - Ilowite, Norman T
   Abstract:PURPOSE OF REVIEW: The purpose of this review is to summarize the recent data on biologic therapies in juvenile rheumatoid arthritis. The armamentarium for treatment of juvenile idiopathic arthritis is expanding at a rapid rate, and improved physical and functional outcomes are anticipated. New data from large prospective randomized trials have demonstrated efficacy of anti-tumor necrosis factor agents and a costimulator signal inhibitor. RECENT FINDINGS: The results of a pivotal trial of infliximab in polyarticular juvenile idiopathic arthritis suggested efficacy, but the primary outcome was not significantly different from placebo. Important information regarding dosing in children was obtained, however. A pivotal trial of adalimumab did prove efficacy, and resulted in U.S. Food and Drug Administration (FDA) approval. The monoclonal antibodies to tumor necrosis factor appear to be more effective in treating chronic uveitis associated with juvenile idiopathic arthritis than etanercept. Anti-IL-1 and anti-IL-6 therapy, particularly for systemic disease patients, looks very promising, as well. The costimulation modifier abatacept was shown to be effective and relatively well tolerated in the short term, also resulting in FDA approval this year. Continued experience with these agents and appropriate systems-based methods such as formal registries, to complement existing FDA procedures for monitoring safety, will improve our ability to identify short-term and long-term toxicities of these new agents. SUMMARY: As experience is gained, and longer-term safety is demonstrated, it is likely that biologics will be introduced as therapy earlier in the course of patients who inadequately respond to conventional disease-modifying antirheumatic drugs

9. IMUNDO L: Hodgkin's lymphoma associated with anti-TNF use in juvenile idiopathic arthritis: supplemental case report, J.Rheumatol., Vol. 35(8), 1681, 2008
   Organism:

10. JACOBSON JA, GIRISH G, JIANG Yet SABB BJ: Radiographic evaluation of arthritis: degenerative joint disease and variations, Radiology., Vol. 248(3), 737-747., 2008
    Organism:Department of Radiology, University of Michigan Medical Center, 1500 E Medical Center Dr, TC-2910L, Ann Arbor, MI 48109-0326, USA jjacobsn@umicheduFAU - Jacobson, Jon A
    Abstract:In the presence of joint space narrowing, it is important to differentiate inflammatory from degenerative conditions. The presence of osteophytes, bone sclerosis, and subchondral cysts and the absence of inflammatory features such as erosions suggest osteoarthritis. Typical osteoarthritis involves specific joints at a particular patient age. When osteoarthritis involves an atypical joint, occurs at an early age, or has an unusual radiographic appearance, then other causes for cartilage destruction should be considered, such as trauma, crystal deposition, neuropathic joint, and hemophilia. There are several types of arthritis, such as juvenile chronic arthritis and gouty arthritis, that may have a variable appearance compared with that of other common inflammatory arthritides

11. JANIC D, LONCAREVIC S, KRSTOVSKI N, DOKMANOVIC L, LAZIC Jet RODIC P: Bone marrow findings in juvenile idiopathic arthritis, Pediatr.Hematol.Oncol., Vol. 25(6), 575-581., 2008
    Organism:University Children's Hospital, Belgrade, SerbiaFAU - Janic, Dragana
    Abstract:The diagnosis of juvenile idiopathic arthritis (JIA) is an exclusion one due to heterogeneous clinical presentation and lack of specific laboratory tests. The authors investigated bone marrow of 25 untreated children with JIA at the onset of the disease. Bone marrow smears were evaluated for cell populations as well as myelodysplastic features and compared to two control groups. The characteristic of bone marrow in JIA was myeloid hyperplasia and elevated plasmocyte count. There was no difference between JIA patients and control groups in terms of myelodysplastic features. These findings can be helpful in explaining hematological alterations in JIA

12. KEENAN JD, TESSLER HHet GOLDSTEIN DA: Granulomatous inflammation in juvenile idiopathic arthritis-associated uveitis, J.AAPOS., 2008
    Organism:PURPOSE: The uveitis that is associated with juvenile idiopathic arthritis (JIA) has typically been described as nongranulomatous. This study reports the prevalence of granulomatous disease in a population with JIA-associated uveitis. METHODS: We conducted a retrospective analysis of all patients with JIA-associated uveitis seen between 1973 and 2006 at a hospital-based uveitis service. Patients with uveitis were included if they were diagnosed with JIA by a specialist and experienced at least 6 weeks of arthritis starting before the age of 16 years. Granulomatous disease was defined as Busacca or angle nodules, mutton-fat keratic precipitates (KP), or hyalinized "ghost" KPs. Statistical tests were performed to seek associations between granulomatous disease and various clinical factors. RESULTS: Seventy-one patients with JIA-associated uveitis were included. Granulomatous uveitis was observed in 28% of the population, with 7% exhibiting mutton-fat KP, and 21% "ghost" KP. There was no association between the presence of granulomatous disease and age of arthritis onset, age of uveitis onset, sex, antinuclear antibody status, or whether the arthritis was pauciarticular or polyarticular. In this population, 67% of black patients had granulomatous disease compared with 25% of nonblack patients (p < 0.05), and 24% of white patients showed granulomatous disease compared with 56% of nonwhite patients (p = 0.11). CONCLUSIONS: Granulomatous disease is more common in JIA-associated uveitis than previously thought and may be more common in black patients. Although it is necessary to exclude other forms of granulomatous uveitis, such as sarcoidosis, the presence of granulomatous uveitis is not inconsistent with a diagnosis of JIA-associated uveitis

13. KLEPPER SE: Exercise in pediatric rheumatic diseases, Curr.Opin.Rheumatol., Vol. 20(5), 619-624., 2008
    Organism:Program in Physical Therapy, Columbia University College of Physicians and Surgeons, Department of Pediatric Rheumatology, Children's Hospital of New York, New York, New York 10032, USA sek44@columbiaeduFAU - Klepper, Susan E
    Abstract:PURPOSE OF REVIEW: The present review discusses the current knowledge about exercise capacity and physical activity in children with rheumatic disease and examines the role of exercise in managing these conditions. RECENT FINDINGS: Recent studies suggest exercise capacity is significantly impaired in a large proportion of children with juvenile idiopathic arthritis and other rheumatic diseases. These deficits are not limited to children with active inflammation. Children, especially girls, with rheumatoid factor positive polyarticular juvenile idiopathic arthritis, have the greatest deficits. Poor fitness and low levels of weight-bearing physical activity contribute to low bone mass and strength. Children and adolescents with juvenile dermatomyositis and systemic lupus erythematosus also exhibit impaired exercise capacity. There is some evidence that structured aerobic and neuromuscular training may improve exercise capacity, functional performance, and quality of life in children and adolescents with rheumatic disease. SUMMARY: A sedentary lifestyle contributes to secondary impairments in aerobic and muscular fitness, bone health, and functional limitations in children and adolescents with rheumatic disease despite advances in the pharmacological management of these inflammatory conditions. Increased levels of moderate to vigorous physical activity and structured exercise may improve exercise capacity, performance of daily activities, and overall quality of life

14. LAAS K, ROINE R, RASANEN P, SINTONEN Het LEIRISALO-REPO M: Health-related quality of life in patients with common rheumatic diseases referred to a university clinic, Rheumatol.Int., 2008
    Organism:Division of Rheumatology, Department of Medicine, Helsinki University Central Hospital, Kasarmikatu 11-13, HUS, P O Box 263, 00029, Helsinki, Finland, karinlaas@helsinkifi
    Abstract:The aim of the present study was to assess the health-related quality of life (HRQoL) in patients with common rheumatic diseases referred to a rheumatology clinic and to compare it to the HRQoL of the general population. All patients with a new referral to the Department of Rheumatology of the Helsinki University Central Hospital were asked to participate in the study during the period from May 2002 to April 2003. A total of 295 patients with various rheumatic diseases were included in the analysis: 99 patients with rheumatoid arthritis (RA), 47 with arthralgia and fibromyalgia, 43 with other chronic arthritis (spondyloarthritis, psoriatic arthritis, enteropathic arthritis), 44 with osteoarthritis (OA), 22 with active reactive arthritis (ReA), 17 with systemic rheumatic diseases, 9 adults with juvenile idiopathic arthritis (JIA) and 14 with other diagnoses. HRQoL was measured by a disease specific instrument, the Stanford health assessment questionnaire (HAQ) and by a generic instrument, 15D. The mean baseline 15D score of the 295 included patients (0.822, SD 0.114) was significantly lower than of the general population (0.903, SD 0.098). Patients with OA and chronic arthritis reported the poorest HRQoL scores (both 0.810 on a 0-1 scale). In patients with RA and ReA the 15D score improved in a statistically significant and clinically important manner during the 8-month follow-up. Discomfort and symptoms caused by the disease were alleviated in a statistically significant manner in patients with RA as well as in those with arthralgia and fibromyalgia, chronic arthritis, ReA and systemic rheumatic diseases. HAQ score improved significantly in patients with RA, arthralgia and fibromyalgia, and ReA. The HRQoL of patients with common rheumatic diseases at referral to rheumatology clinic is significantly lower than the HRQoL of age-standardized general population. The most affected patients are those with OA, chronic arthritis and RA. A significant improvement in HRQoL with conventional interventions was achieved in patients with RA and ReA

15. LIPIEC E, GRALEK Met NIWALD A: [The dry eye syndrome in children with juvenile idiopatic arthritis], Klin.Oczna., Vol. 110(1-3), 35-39., 2008
    Organism:Z Kliniki Okulistyki Dzieciecej Katedry Pediatrii Zabiegowej Uniwersytetu Medycznego w LodziFAU - Lipiec, Ewa
    Abstract:PURPOSE: The aim of the study was to evaluate the dry eye syndrome in children with juvenile idiopathic arthritis (JIA), and its relation to the immunological markers of the JIA (antynuclear antybodies ANA and rheumatoid factor RF). MATERIAL AND METHODS: The study included 62 children with JIA. The age of patients during the first ophthalmic examination ranged from 9 to 18 years (62 children). A control group consisted of 49 healthy children. The time of observation was 18 months during which the children and adolescents were subjected to complex ophthalmic examinations (including a history of eye discomfort and Schirmer and BUT tests), in the intervals of 9 months. The diagnosis towards dry eye syndrome was made (including a history of eye discomfort and Schirmer and BUT tests). RESULTS: The majority of children with JIA complained of discomfort in the eyes. The difference appeared to be statistically significant between the group of children with JIA and the control group in the range of 5 features. The results of Schirmer test were found to be inadequate in 7 children (13%) and of BUT test in 9 children (15%). In total, inadequate results of Schirmer and/or BUT tests and a high score of discomfort evaluation were detected in 11 patients (17.7%). CONCLUSIONS: 1. The dry eye syndrome may occur in the course of JIA in children without any distinct clinical signs, resulting in subjective symptoms and decreasing the quality of life. 2. No correlation between immunological markers of the JIA and ocular changes was observed

16. LOVELL DJ, RUPERTO N, GOODMAN S, REIFF A, JUNG L, JAROSOVA K, NEMCOVA D, MOUY R, SANDBORG C, BOHNSACK J, ELEWAUT D, FOELDVARI I, GERLONI V, ROVENSKY J, MINDEN K, VEHE RK, WEINER LW, HORNEFF G, HUPPERTZ HI, OLSON NY, MEDICH JR, CARCERERI-DE-PRATI R, MCILRAITH MJ, GIANNINI EHet MARTINI A: Adalimumab with or without methotrexate in juvenile rheumatoid arthritis, N.Engl.J.Med., Vol. 359(8), 810-820., 2008
    Organism:Cincinnati Children's Hospital Medical Center, Division of Rheumatology, Location E, Rm 2-129, MLC 4010, 3333 Burnet Ave, Cincinnati, OH 45229-3039, USA daniellovell@cchmcorgFAU - Lovell, Daniel J
    Abstract:BACKGROUND: Tumor necrosis factor (TNF) has a pathogenic role in juvenile rheumatoid arthritis. We evaluated the efficacy and safety of adalimumab, a fully human monoclonal anti-TNF antibody, in children with polyarticular-course juvenile rheumatoid arthritis. METHODS: Patients 4 to 17 years of age with active juvenile rheumatoid arthritis who had previously received treatment with nonsteroidal antiinflammatory drugs underwent stratification according to methotrexate use and received 24 mg of adalimumab per square meter of body-surface area (maximum dose, 40 mg) subcutaneously every other week for 16 weeks. We randomly assigned patients with an American College of Rheumatology Pediatric 30% (ACR Pedi 30) response at week 16 to receive adalimumab or placebo in a double-blind fashion every other week for up to 32 weeks. RESULTS: Seventy-four percent of patients not receiving methotrexate (64 of 86) and 94% of those receiving methotrexate (80 of 85) had an ACR Pedi 30 response at week 16 and were eligible for double-blind treatment. Among patients not receiving methotrexate, disease flares (the primary outcome) occurred in 43% of those receiving adalimumab and 71% of those receiving placebo (P=0.03). Among patients receiving methotrexate, flares occurred in 37% of those receiving adalimumab and 65% of those receiving placebo (P=0.02). At 48 weeks, the percentages of patients treated with methotrexate who had ACR Pedi 30, 50, 70, or 90 responses were significantly greater for those receiving adalimumab than for those receiving placebo; the differences between patients not treated with methotrexate who received adalimumab and those who received placebo were not significant. Response rates were sustained after 104 weeks of treatment. Serious adverse events possibly related to adalimumab occurred in 14 patients. CONCLUSIONS: Adalimumab therapy seems to be an efficacious option for the treatment of children with juvenile rheumatoid arthritis. (ClinicalTrials.gov number, NCT00048542.)

17. NAKAJIMA S, NARUTO T, MIYAMAE T, IMAGAWA T, MORI M, NISHIMAKI Set YOKOTA S: Improvement of reduced serum cartilage oligomeric matrix protein levels in systemic juvenile idiopathic arthritis patients treated with the anti-interleukin-6 receptor monoclonal antibody tocilizumab, Mod.Rheumatol., 2008
    Organism:Department of Pediatrics, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa, 236-0004, Japan
    Abstract:In this study, we determined serum cartilage oligomeric matrix protein (COMP) levels in systemic juvenile idiopathic arthritis (sJIA) patients during both the active and the remission phases to investigate how the growth cartilage turnover changed under tocilizumab treatment. Specimens were collected from 201 healthy children under 16 years of age with no growth impairment, and paired sera were collected from 11 sJIA patients treated with tocilizumab. Disease activity was assessed from white blood cell count, erythrocyte sedimentation rate, C-reactive protein, and ferritin, and the COMP concentration was determined by sandwich enzyme-linked immunosorbent assay. Serum COMP concentrations were found independent of age, and the mean value in healthy children was 17.74 +/- 5.6 U/L. The mean serum COMP in sJIA patients during the active phase was 10.75 +/- 3.9 U/L, lower than that of healthy children. The mean serum COMP in the remission phase (14.89 +/- 3.9 U/L) was significantly higher than that in the active period (P < 0.05). These results suggested that in sJIA patients, a reduced serum COMP concentration is a useful marker of active disease and growth impairment, and that the growth cartilage turnover suppressed during the active phase is improved in the remission phase under tocilizumab treatment

18. NEUHAUSEN SL, STEELE L, RYAN S, MOUSAVI M, PINTO M, OSANN KE, FLODMAN Pet ZONE JJ: Co-occurrence of celiac disease and other autoimmune diseases in celiacs and their first-degree relatives, J.Autoimmun., 2008
    Organism:Department of Epidemiology, University of California Irvine, 224 Irvine Hall, Irvine, CA 92697-7550, USA
    Abstract:The occurrence of other autoimmune diseases in celiac disease families has not been previously reported in a North American population. We investigated the familial aggregation of rheumatoid arthritis (RA), juvenile rheumatoid arthritis/juvenile idiopathic arthritis (JRA/JIA), hypothyroidism, insulin dependent diabetes mellitus (IDDM), and alopecia areata (AA) among individuals in families with celiac disease (CD). Family history information, obtained from questionnaires from the University of California Irvine Celiac Disease study, was reviewed for reports of RA, JRA/JIA, hypothyroidism, IDDM, and AA in celiac disease cases and their first-degree relatives. Reports of disease were compared with prevalence data from the literature and analyzed by calculating the standardized ratio (SR) with 95% confidence limits. We analyzed: (1) subjects with confirmed celiac disease or dermatitis herpetiformis (205 probands and 203 affected first-degree relatives) and (2) first-degree relatives of celiac disease cases (n=1272). We found a significantly increased number of cases, relative to the expected number, of IDDM in both groups and hypothyroidism among subjects with celiac disease. JRA/JIA was increased among first-degree relatives of celiacs. These results indicate that the presence of IDDM within our celiac disease families may be due to shared genetic susceptibility predisposing to these diseases or autoimmune diseases in general

19. NOLLE B, BOTH M, HELLER Met ROIDER JB: [Typical questions from the rheumatologist to the ophthalmologist and cooperating radiologist.], Z.Rheumatol., Vol. 67(5), 360-371., 2008
    Organism:Interdisziplinares Vaskulitiszentrum am Universitatsklinikum Schleswig-Holstein, Kiel, Deutschland, bnoelle@ophthalmoluni-kieldeFAU - Nolle, B
    Abstract:Patients with rheumatic disorders may suffer from various acute or chronic ocular symptoms. In addition to pain and motility disorders, loss of vision, and irreversible deterioration of the eye may occur. Red eye, a symptom easily identified, can be a sign of rheumatic involvement, but can also have a variety of other causes. Dry eye is frequently present in rheumatic patients. It is always important that infections and masquerade syndromes are ruled out in the differential diagnoses of any ocular inflammation. In cases of ocular inflammation the ophthalmologist should determine the diagnostic procedure on the basis of his clinical experience. Uveitis is a common complication of juvenile idiopathic arthritis depending on the subtype of arthritis. Patients with episcleritis rarely suffer from systemic inflammation, while inflammation is found in half of all cases of scleritis. Corneal ulceration should always be managed as an emergency case and, in addition to systemic medication, surgical intervention is often indicated. The degree of orbital or ocular involvement can be objectively monitored using modern imaging techniques. Medications against rheumatic inflammation may rarely result in ocular side effects, which should be detected early by the eye specialist

20. PAGALAVAN Let ONG SG: Demography, clinical and laboratory features of systemic sclerosis in a Malaysian rheumatology centre, Med.J.Malaysia., Vol. 62(2), 117-121., 2007
    Organism:Rheumatology Unit, Department of Medicine, Hospital Selayang, 68100 Batu Caves, SelangorFAU - Pagalavan, L
    Abstract:A six year retrospective study of the demography, clinical and laboratory features of patients with systemic sclerosis (SSc) was carried out in Selayang Hospital. There were 61 cases seen between January 2000 and December 2005. Of these, 55 (90.2%) were females and 6 (9.8%) were males. Twenty-eight (45.9%) were Malays, 24 (39.3%) were Chinese and 9 (14.8%) were Indians. The mean age of onset was 38.8 years. Thirty-nine (64.0%) had limited cutaneous SSc, 21 (34.4%) had diffuse cutaneous SSc and one had localized morphoea. Raynaud's phenomenon was present in 82.6%, telangiectasia in 45.9%, calcinosis in 11.5%, sclerodactyly in 83.6%, digital pitting scars in 42.6%, digital infarcts/ulcers/gangrene in 23.0%, arthralgia/arthritis in 49.2% and gastroesophageal reflux disease (GERD) in 47.5%. Forty-three (70.5%) patients had interstitial lung disease. Seven patients had associated myositis, 7 systemic lupus erythematosus and 2 rheumatoid arthritis. Three had two other connective tissue diseases. Antinuclear antibodies were positive in 83.6% and anti-Scl 70 antibodies in 34.4%. This study demonstrates that limited cutaneous SSc is more common and there is a high incidence of interstitial lung disease in our population

21. PASSO MHet TAYLOR J: Quality improvement in pediatric rheumatology: what do we need to do?, Curr.Opin.Rheumatol., Vol. 20(5), 625-630., 2008
    Organism:Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USAFAU - Passo, Murray H
    Abstract:PURPOSE OF REVIEW: Quality improvement is a mandate for all individuals and institutions in medicine. Quality improvement has spread to the specialty certifying boards, resident education accreditation, licensure boards, and hospital medical staff offices. This review summarizes the thrust of quality improvement, provides justification for the conduct of quality improvement work, and reviews the progress in development of quality measures in rheumatology to date. RECENT FINDINGS: The American College of Rheumatology, quality of care, and quality measure committees have developed quality indicators for rheumatoid arthritis, gout, osteoporosis, and drug safety. Pediatric rheumatology is charged with developing quality measures for juvenile idiopathic arthritis; thus, there is a commitment to improve the processes and patient outcomes. Quality improvement science has progressed over the last decade and employs methodology that utilizes small number and rapid improvement cycles. Examples of this quality improvement methodology are elaborated in this review. SUMMARY: The review summarizes the history and current mandates for quality improvement in the medical community, progress made in the development of quality measures for adult rheumatologic conditions, and preliminary quality measures for juvenile idiopathic arthritis, and cites examples of quality improvement in progress in the pediatric rheumatology

22. RUSU TE, MURGU A, MORARU E, FLOREA MM, IONIUC I, ALEXOAIE M, RUGINA Aet GOTIA S: [Osteopenia in children with juvenile idiopathic arthritis], Rev.Med.Chir Soc.Med.Nat.Iasi., Vol. 112(1), 88-93., 2008
    Organism:Universitatea de Medicina si Farmacie GrT Popa" Iasi, Facultatea de Medicina, Clinica a IIa PediatrieFAU - Rusu, Tania-Elena
    Abstract:The aim of the study was to evaluate the presence and ethiopathogenesis of osteopenia in 41 children with Juvenile Idiopathic Arthritis (JIA). METHODS: Bone status was evaluated by quantitative ultrasound using a Sunlight Omnisense 7000s Ultrasound Bone Sonometer. Measurements were performed at the distal radius and midshaft tibia. Results were obtained as Speed of sound (SOS) and Z-score. We used standardised clinical evaluation (modified Giannini's criteria, CHAQ). ESR, Fibrinogen, serum calcium, magnesium, alkaline phosphatase, protein electrophoresis, 25-OH vitamin D (RIA) and urinary Hydroxiproline were obtained in all patients. Osteopenia was present in 15 (36.5%) patients. Statistical analysis was performed with SPSS 13.0. RESULTS: Age, sex, age at onset, disease duration, life standards and duration of corticotherapy and methotrexat treatment were not related to osteopenia in our study. The disease activity, evaluated by clinical criteria, ESR and Fibrinogen, was strongly associated with osteopenia (p<0.001). Nutritional status was an independent risk factor for osteopenia (p<0.001). Low serum calcium (p=0.034), magnesium (p=0.010), 25-OH vitamin D (p=0.091) and alkaline phosphatase (p=0.31) were more frequent in patients with osteopenia. Hydroxiproline was increased in all patients with osteopenia (p<0.001). CONCLUSIONS: Osteopenia was a frequent (36.5%) complication of JIA in our study. The disease activity and nutritional status were the most important risk factors for osteopenia. The increase of bone reabsorption was the main pathogenic mechanism of osteopenia in our study. Calcium and magnesium deficits were related to osteopenia. Decrease of bone synthesis was not associated with osteopenia in the present study

23. SMOLEWSKA E, CEBULA B, BROZIK Het STANCZYK J: Relationship between impaired apoptosis of lymphocytes and distribution of dendritic cells in peripheral blood and synovial fluid of children with juvenile idiopathic arthritis, Arch.Immunol.Ther.Exp.(Warsz.)., Vol. 56(4), 283-289., 2008
    Organism:Department of Pediatric Cardiology, 2nd Chair of Pediatrics and Cardiology, Medical University of Lodz, Sporna 36/50, 91-738, Lodz, Poland, esmolewska@wpplFAU - Smolewska, Elzbieta
    Abstract:INTRODUCTION: The pathogenesis of juvenile idiopathic arthritis (JIA) is not fully understood. Recently the present authors described disturbed apoptosis of JIA lymphocytes in both peripheral blood (PB) and synovial fluid (SF) as well as an abnormal distribution of blood dendritic cells (BDCs) between the PB and SF in this disease. Possible relationships between these events during the development of JIA process are assessed here. MATERIALS AND METHODS: Lymphocyte apoptosis and BDC counts were assessed in the PB and SF of untreated JIA children. Lymphocyte apoptosis was analyzed by the Annexin-V/propydium iodide assay. Total DC (TDC) number was based on the sum of three BDC subpopulations determined using a panel of monoclonal antibodies against BDC antigens (BDCA): myeloid type 1 (mDC1, BDCA-1(+)/HLA-DR(+)/CD19(-)), myeloid type 2 (mDC2, BDCA-3(+)/HLA-DR(+)/CD14(-)), and plasmacytoid (pDC, BDCA-2(+)/HLA-DR(+)/CD123(+)). Cells were enumerated by the flow cytometric "single-platform" method. The concentration of tumor necrosis factor (TNF)-alpha and the distribution of particular lymphocyte subtypes in both PB and SF were also investigated. RESULTS: There was significant positive correlation between apoptosis of PB lymphocytes and SF TDC count (p=0.002) as well as SF TNF-alpha concentration (p=0.007). SF TNF-alpha levels also correlated with SF TDC count (p=0.003). Moreover, JIA SF was distinctly enriched with CD4+ and CD8+ T lymphocytes and included CD4(+)/CD25(high) cells as well. There was significant positive correlation between the number of CD4(+)/CD25(high) cells and SF JIA BDC count (p=0.015). CONCLUSIONS: These data suggest a possible link between impaired apoptosis of PB/SF lymphocytes and increased recruitment of PB BDCs to SF and other elements of the immune system in JIA, including regulatory CD4+/CD25high cells

24. SOFKA CMet BOGNER E: Imaging of juvenile rheumatoid arthritis, HSS.J., Vol. 4(1), 71-73., 2008
    Organism:Department of Radiology and Imaging, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA, sofkac@hsseduFAU - Sofka, Carolyn M
    Abstract:

25. TREBUSAK PK, MILENKOVIC T, ODINK R, CLAAHSEN H, BRATANIC N, HOVNIK Tet BATTELINO T: Detection of a complete AIRE gene deletion and two additional novel mutations in a cohort of patients with atypical phenotypic variants of APS-1, Eur.J.Endocrinol., 2008
    Organism:K Trebusak Podkrajsek, University Children's Hospital, Centre for Medical Genetics, University Medical Centre Ljubljana, Ljubljana, Slovenia
    Abstract:Objective: Autoimmune polyglandular syndrome type 1 (APS-1) is characterised by multiple autoimmune diseases. Detection of AIRE (autoimmune regulator) gene mutations facilitates timely and precise diagnosis. Design: AIRE mutation detection was performed in a cohort of 11 patients. Two did not meet clinical APS-1 criteria and several started with atypical presentation. Methods: Sequencing and TaqMan genotyping were used to identify AIRE mutations. Complete AIRE deletion was confirmed and framed by real-time PCR, long-range amplification and analysis of the microsatellite markers. Results: Seven different mutations were detected, three were novel (c.892G>A in exon 8, silent mutation c.462A>T in exon 3 most likely affecting splicing, a complete deletion of a single AIRE allele (?_68)_(1567-14_?)del). Novel (chronic otitis) and rare (systemic juvenile rheumatoid arthritis, autoimmune bronchiolitis, epilepsy) clinical presentations were observed. Conclusions: AIRE mutation detection was valuable in diagnostics of APS-1 in patients with atypical presentation. Chronic otitis media possibly broadened the cluster of APS-1 manifestations

26. YILDIRIM-TORUNER C, KIMURA Yet RABINOVICH E: Hodgkin's lymphoma and tumor necrosis factor inhibitors in juvenile idiopathic arthritis, J.Rheumatol., Vol. 35(8), 1680-1681., 2008
    Organism: