Bibliography March 05

1. ANDRE MARIE R: The juvenile arthritis foot disability index: Development and evaluation of measurement properties. Rinsho Ganka 31:12 2488-2493,
   Abstract: Objective. To develop a new juvenile arthritis foot disability index (JAFI) and to test it for validity and reliability. Methods. Samples of 14 children/adolescents and 30 children/adolescents with juvenile idiopathic arthritis (JIA) and 29 healthy children/adolescents participated. We used a questionnaire derived from the International Classification of Functioning, Disability and Health that included 27 statements divided into the dimensions Impairment, Activity Limitation, and Participation Restriction. Comments. on the contents were invited from parents and adolescents. Convergent and divergent construct validity was examined by comparing the 3 JAFI dimensions to joint impairment scores, the Childhood Health Assessment Questionnaire (CHAQ), and self-rated, foot-related participation restriction. Known groups construct validity was assessed by comparing answers from children with JIA to those from healthy children. Test-retest stability was investigated over one week. Results. One item was added after suggestions from 2 participants. A consistent pattern of increasing JAFI scores was found with increasing joint impairment scores, CHAQ scores, and self-rated foot-related. participation restriction. Foot-related disability as assessed by JAFI was more pronounced in children with JIA than in healthy controls. One statement showing a floor effect was excluded. No internal redundancy (rs > 0.90) between items was found, and internal consistency within each subscale was satisfactory (rs > 0.50) for all items but one. No systematic differences were found between test and retest, and weighted kappa coefficients for the 3 JAFI dimensions were 0.90, 0.85, and 0.88. Conclusion. The JAFI appears to be valid and reliable for assessing foot-related disability among children/adolescents with JIA. Its sensitivity to change remains to be investigated

2. BALDIN B, DOZOL A, SPREUX A, CHICHMANIAN RM: [Tuberculosis and infliximab treatment. National surveillance from January 1, 2000, through June 30, 2003]. Presse Med 34:5 353-357, 2005
   Organism: Centre regional de pharmacovigilance, Hopital Pasteur, 30 avenue de la Voie Romaine, BP 69, 06002 Nice baldinb@chu-nicefrFAU - Baldin, Bernadette
   Abstract: OBJECTIVES: Analysis of the tuberculosis cases reported in France in patients treated with infliximab since its marketing approval, assessment of the effect of changes in the summary of product characteristics and national guidelines. METHODS: Based on tuberculosis reports from the national post-marketing adverse drug reaction databank of the manufacturer from January 1, 2000 through June 30, 2003, and records from the national multicenter retrospective survey on opportunistic infections with anti-TNFalpha, we analyzed all cases of tuberculosis and the impact of the changes made in December 2000 in the summary of product characteristics and the guidelines on the prevention and management of tuberculosis in patients treated with infliximab published in February 2002. RESULTS: 56 cases of tuberculosis were reported: the median interval before diagnosis was 12 weeks with a median of 3 infusions. The presence of Koch bacilli was confirmed in 32 patients; 29 patients had extrapulmonary or disseminated forms of tuberculosis. The tuberculosis rate among patients treated with infliximab was greater than among the general population and differed significantly by period (p < 0.005). CONCLUSION: Tuberculosis can occur within the first 12 weeks of treatment with infliximab. Information for practitioners must be continued, together with surveillance of the tuberculosis cases in France

3. BATTHISH M, SCHNEIDER R, RAMANAN AV, ACHONU C, YOUNG NL, FELDMAN BM: What does 'active disease' mean? patient and parent perceptions of disease activity in the systemic arthritis form of juvenile idiopathic arthritis (SO-JIA). Rheumatology (Oxford) 44:6 796-799, 2005
   Organism: Division of Rheumatology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, Canada BrianFeldman@sickkidscaFAU - Batthish, M
   Abstract: OBJECTIVE: The systemic onset form of juvenile idiopathic arthritis (SO-JIA) is a very serious chronic illness of childhood. At present, there is no specific tool to measure disease activity for SO-JIA. Our long-term goal is to develop a disease activity measure for SO-JIA using a consensus (Delphi) approach. In preparation for the development of this measure, we interviewed both patients and their parents. We sought to elicit specific items reflecting their perceptions of active disease that may be considered for inclusion in a disease activity measure for SO-JIA. METHODS: SO-JIA patients followed at The Hospital for Sick Children and their parents were chosen by purposive sampling. A trained research coordinator interviewed all participants using open-ended questions to elicit aspects of disease activity (defined as reversible manifestations of disease) of relevance to families. A list of these aspects was then generated and organized by categories to allow item reduction. RESULTS: Fourteen patients (eight females) with a mean age of 11.8 yr (mean disease duration 5.2 yr) and their parents were interviewed. A total of 292 items were generated, with an average of 11 items generated per interview. Arthralgia, ambulation difficulties, rash, decreased energy level and fever were the most common items mentioned by patients and their parents. Mood disturbances, decreased activity levels, arthritis severity and decreased school attendance were also common items identified as relevant aspects of disease activity. CONCLUSION: This study has allowed us to include patient and parent perspectives in preparation for developing a disease activity measure for SO-JIA. The resulting items will be added to future physician surveys in the further development and validation of a disease activity measure for SO-JIA

4. BECHTOLD S, RIPPERGER P, BONFIG W, POZZA RD, HAEFNER R, SCHWARZ HP: Growth hormone changes bone geometry and body composition in patients with juvenile idiopathic arthritis requiring glucocorticoid treatment: a controlled study using peripheral quantitative computed tomography. J Clin Endocrinol Metab 90:6 3168-3173, 2005
   Organism: University Children's Hospital, Lindwurmstrasse 4, D-80337 Munich, Germany susannebechtold@meduni-muenchendeFAU - Bechtold, S
   Abstract: Osteopenia and growth retardation have been described in children with chronic arthritis. GH has an impact on both. In the present controlled study, we used peripheral quantitative computed tomography to evaluate forearm bone mass, density, and geometry as well as forearm muscle and fat area in 17 patients with juvenile idiopathic arthritis (JIA) receiving treatment with GH for 3.8 +/- 1.1 yr compared with an untreated age- and sex-matched control group (n = 17). All patients had a mean age of 15.3 +/- 2.5 yr and a mean duration of illness of 8.2 +/- 4.4 yr. Height, weight, body mass index, bone parameters, and muscle area were significantly decreased in both groups compared with those in healthy age-matched children. Compared with untreated JIA patients, GH-treated JIA patients had significant higher bone mineral content as well as total cross-sectional area (CSA), cortical CSA, and muscle CSA. Fat CSA was lower in the GH-treated group. A significant difference between groups for height-corrected cortical and muscle areas was only seen in male patients. Cortical CSA relative to muscle CSA was not different between groups. These findings are compatible with an anabolic effect of GH on muscle and bone development

5. BUKA RL, CUNNINGHAM BB: Connective tissue disease in children. Pediatr Ann 34:3 225-228, 2005
   Organism: Children's Hospital and Health Center San Diego, University of California San Diego, 8010 Frost Street, Suite 602, San Diego, CA 92123, USA rbuka@mdnorthwesterneduFAU - Buka, Robert L
   Abstract: As our understanding of connective tissue disease expands, so too does our therapeutic armamentarium. We have learned that autoimmunity triggers inflammation through unchecked, proliferative cell-mediated inflammation. By targeting this arm of the cytokine cascade, it may be possible to arrest further progression. Several biologic agents, such as etanercept, alefacept, infliximab, efaluzimab, and, recently, adalimumab, have come to market for adult psoriasis and are now undergoing trials for juvenile SLE, psoriasis, and psoriatic arthritis. Of note, etanercept has been used successfully in juvenile rheumatoid arthritis for more than 10 years. These agents target cell-mediated inflammation through various mechanisms and hold great promise for the treatment of many of the disease states discussed above. Moreover, the biologics carry an improved side-effect profile not seen with traditional agents such as corticosteroids and will be central in the evolution of targeted therapeutics for these complex immunologic diseases

6. CHAPUY-REGAUD S, NOGUEIRA L, CLAVEL C, SEBBAG M, VINCENT C, SERRE G: IgG subclass distribution of the rheumatoid arthritis-specific autoantibodies to citrullinated fibrin. Clin Exp Immunol 139:3 542-550, 2005
   Organism: Laboratory of 'Epidermis Differentiation and Rheumatoid Autoimmunity', UMR 5165 CNRS-Toulouse III University, Toulouse, FranceFAU - Chapuy-Regaud, S
   Abstract: In the rheumatoid synovium, deiminated ('citrullinated') forms of fibrin are the major targets of IgG autoantibodies to citrullinated proteins (ACPA), the most specific serological markers of rheumatoid arthritis (RA). To further the characterization of ACPA, we determined their subclass distribution. From a previously validated highly sensitive and specific enzyme-linked immunosorbent assay (ELISA) onto in vitro deiminated human fibrinogen - antihuman fibrin(ogen) autoantibodies (AhFibA)-ELISA - we derived and calibrated four ELISAs, using monoclonal antibodies to each of the four IgG subclasses, to determine the proportions of AhFibA subclasses in the sera. A series of 186 serum samples from RA patients was analysed. All AhFibA-positive sera contained IgG1-AhFibA, which reached the highest titres and accounted for more than 80% of AhFibA in three-quarters of the sera. One or two other subclasses were associated with IgG1 in 39% of the sera, IgG4-AhFibA being observed much more frequently and at higher titres than IgG3- or IgG2-AhFibA. IgG1 alone or IgG(1 + 4)-AhFibA were the AhFibA subclass profiles found in more than 80% of patients. AhFibA are mainly IgG1 and, to a lesser extent, IgG4. Such IgG subclass profiles may influence the effector phases of the immunological conflict between ACPA and deiminated fibrin that takes place specifically in the rheumatoid synovium and therefore may play a critical role in the self-maintenance of rheumatoid inflammation

7. CUNHA BA, THERMIDOR M, MOHAN S, VALSAMIS AS, JOHNSON DH: Fever of unknown origin: subacute thyroiditis versus typhoid fever. Heart Lung 34:2 147-151, 2005
   Organism: Infectious Disease Division, Winthrop-University Hospital, Mineola, New York 11501, USAFAU - Cunha, Burke A
   Abstract: Fever of unknown origin (FUO) is not infrequently a diagnostic dilemma for clinicians. Common infectious causes include endocarditis and abscesses in adults, and noninfectious causes include neoplasms and certain collagen vascular diseases, for example, polymyalgia rheumatica, various vasculitides, and juvenile rheumatoid arthritis (adult Still's disease). Subacute thyroiditis is a rare cause of FUO. Among the infectious causes of FUO, typhoid fever is relatively uncommon. We present a case of FUO in a traveler returning from India whose initial complaints were that of left-sided neck pain and angle of the jaw pain, which initially suggested the diagnosis of subacute thyroiditis. After an extensive FUO workup, when typhoid fever is a likely diagnostic possibility, an empiric trial of anti- Salmonella therapy has diagnostic and therapeutic significance. The presence of relative bradycardia, and response to quinolone therapy, was the basis of the clinical diagnosis of typhoid fever as the explanation for this patients FUO. This case illustrates the diagnostic difficulties in assessing patients with FUO with few diagnostic findings

8. DASS RASHNA, SINGH SURJIT(REPRINT): Varicella glomerulonephritis mimicking microscopic polyangiitis. Rheumatol Int Berlin 24:6 362-364,
   Abstract: Varicella in childhood is usually a self-limiting illness with few complications. Varicella nephritis is an uncommon entity and seen mostly in immunocompromized individuals. We report a 14-year-old boy with juvenile rheumatoid arthritis who developed varicella nephritis and in whom the renal manifestations preceded the skin lesions by 1 week. This is an extremely unusual occurrence, and only one case has been described before. Such a presentation can mimic the clinical features of microscopic polyanglitis

9. DE BENEDETTI F, MARTINI A: Targeting the interleukin-6 receptor: a new treatment for systemic juvenile idiopathic arthritis? Arthritis Rheum 52:3 687-693, 2005

10. DURKIN SR, CASEY TM: Beware of the unilateral red eye: don't miss blinding uveitis. Med J Aust 182:6 296-297, 2005
    Organism: Department of Ophthalmology, Women's and Children's Hospital, North Adelaide, SA 5006, Australia shane_durkin@yahoocomFAU - Durkin, Shane R

11. FAUTREL B: Tumour necrosis factor alpha blocking agents in refractory adult Still's disease: an observational study of 20 cases. Annals of the Rheumatic Diseases 64:2 262-266,
    Abstract: Background: Consensus is lacking on treatment for corticosteroid resistant adult onset Still's disease (ASD). Objective: To assess anti-TNFalpha efficacy and tolerance in refractory ASD. Methods: All departments of rheumatology and internal medicine in France were contacted by mail to identify cases of refractory ASD for which anti-TNFalpha had been used. Medical information was collected using a standardised questionnaire. Results: Of 20 patients with mean age 40.7 years (range 18-74) at treatment start and mean disease duration 8.5 years (range 2-21), the clinical expression of ASD was predominantly systemic in five patients and polyarticular in 15. Response to corticosteroids and methotrexate had been considered inadequate in all patients. Infliximab was used to treat 15 patients, and etanercept used for 10; five had received both drugs consecutively. Steroids were concurrently used in 18 patients and an immunosuppressant in 17. At a mean (SD) follow up of 13 (14) months, complete remission had occurred in five cases (of 25 treatment sequences): one receiving etanercept and four infliximab. Partial response was observed in 16 cases (seven etanercept and nine infliximab). Treatment failed in four cases (two with each anti-TNFalpha). At the last visit, anti-TNFalpha therapy was discontinued in 17 cases, 11 times because of lack (or loss) of efficacy, four times because of a side effect, and twice for other reasons. Conclusion: Anti-TNFalpha therapy may be helpful for some patients with refractory ASD. However, most patients achieve only partial remission. Additional information is thus needed to evaluate more precisely the risk-benefit ratio of this treatment. RN- 185243-69-0: etanercept; 170277-31-3: infliximab; 59-05-2: methotrexate

12. FORONCEWICZ B, MUCHA K, PACZEK L, CHMURA A, ROWINSKI W: Efficacy of rapamycin in patient with juvenile rheumatoid arthritis. Transpl Int 18:3 366-368, 2005
    Organism: Department of Immunology, Transplantology and Internal Medicine, Transplantation Institute, Medical University of Warsaw, Nowogrodzka 59, 02-006 Warsaw, Poland b_foronc@yahoocomFAU - Foroncewicz, Bartosz
    Abstract: Juvenile rheumatoid arthritis (JRA) is an immune-mediated disease characterized by articular inflammation and subsequent tissue damage that may result in severe disability. Several combinations of drugs, including immunosuppressive agents have been used to control disease progression. Although there is no information available on rapamycin efficacy in JRA, it has demonstrated a potential to inhibit inflammatory processes observed in adult rheumatoid arthritis (RA). We present a 21 years old renal transplant recipient with JRA, primarily treated with tacrolimus and steroids, who achieved a long-term disease remission after introduction of rapamycin. As long as pathogenesis of JRA and RA is similar, we conclude that rapamycin could be promising immunosuppressant for patients after renal transplantation suffering from both JRA and RA

13. HAJRI R, NASRAOUI R, LAATAR A, CHEKILI S, KASSAB S, ZAKRAOUI L: [Juvenile idiopathic arthritis treated by methotrexate: result of treatment and tolerance]. Tunis Med 83:3 137-142, 2005
    Organism: Service de Rhumatologie, Hopital Mongi Slim, La Marsa, TunisFAU - Hajri, R
    Abstract: The MTX has a place of choice in the treatment of the AJI with good observance and the absence of grave side effects. In a retrospective study, 14 cases of AJI having benefited from a treatment by MTX were included in the study. Answer to the treatment was estimated at the 6-th month on the criteria of RINTO. The group included in the therapeutic evaluation, is formed by 10 boys and by 4 girls. The average age of the beginning of the disease is of 6 years (2 - 11). The shape of the beginning is systematic in 7 cases and polyarticular in 5 cases and oligoarticular in 2 cases.. The average duration of the treatment by MTX is of 36 months (9 - 66). Answer to the MTX in the 6-th month was noted in 7 cases, under a MTX's average dose of 7, 14mg / m2 / week. Unwanted effects were observed in 7 cases and have not in any case led to the stop of the treatment

14. HARAOUI B: Differentiating the efficacy of tumor necrosis factor inhibitors. J Rheumatol Suppl 74:3-7.: 3-7, 2005
    Organism: Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec, Canada paulharaoui@attglobalnetFAU - Haraoui, Boulos
    Abstract: Blockade of tumor necrosis factor (TNF) has emerged as one of the most promising therapies in rheumatoid arthritis (RA). Three agents are currently available as specific TNF antagonists, etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira). Data from noncomparative trials suggest that all 3 agents have comparable therapeutic activity in RA. Etanercept and infliximab have also demonstrated beneficial activity in other inflammatory arthritides [i.e., psoriatic arthritis and ankylosing spondylitis (both agents) and juvenile rheumatoid arthritis (etanercept only)] and inflammatory diseases (i.e., psoriasis and uveitis). Their effects in granulomatous diseases are more variable, with only infliximab demonstrating clear efficacy in the treatment of Crohn's disease, sarcoidosis, and Wegener's vasculitis. In this brief review current efficacy data are summarized and possible explanations for observed clinical differences are explored

15. HUEMER MARTINA R: No evidence for hyperhomocysteinemia or increased prevalence of genetic polymorphisms in the homocysteine pathway in patients with moderate juvenile idiopathic arthritis. Rinsho Ganka 32:1 170-174,
    Abstract: Objective. Elevated plasma total homocysteine (tHcy) concentrations are associated with premature cardiovascular disease. We assessed tHcy, folate, vitamin B12 (Vit B12), vitamin B6 (Vit B6), and genetic polymorphisms potentially enhancing tHcy in patients with juvenile idiopathic arthritis (JIA) and healthy controls. Methods. Open study of 56 consecutive patients with JIA and 62 controls. Results. tHcy concentrations were normal in JIA patients (mean 6.5 +/- 2 pmol/l) and controls (mean 7.5 +/- 2.2 p mol/l). Folate concentrations were significantly higher in JIA patients (40.2 +/- 67.9 ng/ml) compared to controls (13.6 +/- 8.2 ng/ml). The prevalence of genetic polymorphisms coding for key enzymes in the homocysteine pathway did not differ between patients and controls. Erythrocyte sedimentation rate (ESR) showed significant inverse correlations with circulating Vit B6 and tHcy concentrations. Conclusion. No evidence for hyperhomocysteinemia or evidence for a specific genetic predisposition for hyperhomocysteinemia was present in patients with JIA. Elevated ESR is not associated with hyperhomocysteinemia. RN- 59-30-3: folate; 454-29-5Q: homocysteine; 6027-13-0Q: homocysteine; 68-19-9: vitamin B12; 8059-24-3: vitamin B6

16. KONNO K, NAGAMOTO T: Membranous proliferation on the posterior surface of an intraocular lens after Nd:YAG laser capsulotomy. Jpn J Ophthalmol 49:2 173-175, 2005
    Organism: Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan konno@eye-centerorgFAU - Konno, Kimihito
    Abstract: BACKGROUND: We report on three patients who showed a rare complication, centripetal membranous proliferation from the posterior capsulotomy edge onto the posterior surface of an intraocular lens (IOL), 3 to 6 months after neodymium:YAG (Nd:YAG) capsulotomy. CASES: These three patients had juvenile rheumatoid arthritis, retinitis pigmentosa, and sarcoidosis, respectively, prior to cataract surgery. OBSERVATIONS: Elschnig's pearls developed in the eyes of all three patients after cataract surgery, and were treated by Nd:YAG laser. However, membranous proliferation continued, and Nd:YAG laser treatment was required a second time to disrupt the proliferating fibrous membrane and achieve resolution of the patients' symptoms. CONCLUSIONS: Common factors in our cases and cases in the literature were that the IOLs were biconvex and made of polymethyl methacrylate. Ophthalmologists should be aware that after cataract surgery, lens epithelial cells can proliferate onto any surface that provides adequate protein nourishment

17. KUSELER ANNELISE R: A 2 year followup study of enhanced magnetic resonance Imaging and clinical examination of the temporomandibular joint in children with juvenile idiopathic arthritis. Rinsho Ganka 32:1 162-169,
    Abstract: Objective. Involvement of the temporomandibular joint (TMJ) in patients with juvenile idiopathic arthritis (JIA) can cause severe craniofacial growth disturbances if not treated in the initial stage. Magnetic resonance imaging (MRI) is an efficient method for detecting early inflammatory changes of the TMJ. We investigated correlation between findings from the clinical examination with MRI of the TMJ, and describe development of the MR image over time. Methods. Fifteen children with newly diagnosed JIA (mean age 12.0 yrs) were examined clinically and with MRI enhanced with Gd-DTPA 4 times at 6-8 month intervals. Clinical and MRI findings were scored. MRI variables included T1 weighted images before and after administration of GdDTPA with and without fat suppression. Results. A total of 115 joints were examined during the 2 year period: 93% showed enhancement, 71% condylar erosions, 26% pannus, and 23% joint fluid accumulation of the TMJ. In all except one child, one or both TMJ showed enhancement of the synovial membrane during the examination period. Symptoms were rare. All patients showing mild to severe findings by clinical examination also had pathological signs on the enhanced MRI, but not all patients without clinical findings had a nor mal MRI Conclusion. TMJ involvement in patients with JIA is very common, and MRI findings such as synovial enhancement, pannus, and joint fluid fluctuate over time. The clinical examination may be used as a filter, where children showing no clinical signs could be selected for enhanced MRI. RN- 80529-93-7: Gd-DTPA

18. LEEB BF, ANDEL I, LEDER S, LEEB BA, RINTELEN B: The patient's perspective and rheumatoid arthritis disease activity indexes. Rheumatology (Oxford) 44:3 360-365, 2005
    Organism: Second Department of Medicine, Humanisklinikum Lower Austria, Lower Austrian Center for Rheumatology, Stockerau, Austria leebkhstockerau@aonatFAU - Leeb, B F
    Abstract: BACKGROUND: Monitoring disease activity in rheumatoid arthritis (RA) patients by composite indexes is regarded as obligatory when following the recent recommendations for therapy. Whether these recommendations and the patient's perspective are in congruence is a crucial question with respect to the patient's compliance. The aim of the study was to obtain information on the patient's perspective with respect to the disease activity indexes used most often. METHODS: Two hundred and seven RA patients (157 female, 50 male; mean age 59.03 yr, 17-86 yr) were enrolled in this cross-sectional evaluation. The patients' satisfaction [PATSAT (Austrian school mark system) 1 = excellent to 5 = unsatisfactory] and the patients' attitude to therapy (PATATT 1 = reduction, 2 = no change, 3 = increase) were assessed and related to the 28-joint Disease Activity Score (DAS28), the Simplified Disease Activity Index (SDAI) and the Modified Health Assessment Questionnaire (M-HAQ). Statistical evaluation was carried out by applying the Mann-Whitney U test, calculating chi2 and ANOVA. RESULTS: According to the DAS28 and the M-HAQ, patients were at a moderately active disease stage and had low functional deficiency. PATSAT was significantly correlated to the disease activity indexes (all PS < or = 0.002). The mean DAS28 (2.56) at PATSAT 1 was within the remission range, whereas at PATSAT 5 a mean of 5.52 indicated highly active disease. PATATT was found to be related to PATSAT, but did not completely parallel it. Reduction of therapy was intended at a mean DAS28 of 2.87, whereas a request for an increase did not occur before a mean DAS28 of 4.92. CONCLUSION: The patients' therapeutic attitudes are somewhat in line with their satisfaction, which mirrors disease activity to a great extent, though not with the common therapeutic recommendations. The DAS28 proved to be superior to both other indexes taking account of the patient's perspective. These results may provide guidance in patient care and education as well as therapeutic strategies

19. LEHMAN THOMAS JA: Thalidomide for severe systemic onset juvenile rheumatoid arthritis: A multicenter study. Journal of Pediatrics 145:6 856-857,
    Abstract: Thirteen children with difficult systemic onset juvenile rheumatoid arthritis were treated with thalidomide. At 6 months, 11 of the 13 were able to reduce their use of prednisone (P <.002), with a concurrent improvement in erythrocyte sedimentation rate (P <.0001) and an increase in hemoglobin level (P < 0.005). Juvenile rheumatoid arthritis improvement scores gtoreq50% were obtained by 10 of the 13 children. RN- 53-03-2: prednisone; 50-35-1: thalidomide

20. LIEN G, SELVAAG AM, FLATO B, HAUGEN M, VINJE O, SORSKAAR D, DALE K, EGELAND T, FORRE O: A two-year prospective controlled study of bone mass and bone turnover in children with early juvenile idiopathic arthritis. Arthritis Rheum 52:3 833-840, 2005
    Organism: Rikshospitalet University Hospital, Oslo, Norway gunhildlien@chellono <gunhildlien@chellono>FAU - Lien, Gunhild
    Abstract: OBJECTIVE: To explore early changes and predictors of bone mass in children with juvenile idiopathic arthritis (JIA) in order to identify patients who will develop bone mass reductions. METHODS: We conducted a prospective cohort study of 108 children with early JIA (ages 6-18 years; mean disease duration 19.3 months) who were individually matched with 108 healthy children for age, sex, race, and county of residence. Bone mass and changes in total body, spine, femur, and forearm bone mineral density and bone mineral content (BMC), body composition, growth, and biochemical parameters of bone turnover were examined at baseline and at followup a mean of 24 months later. Low bone mass was defined as a Z score >1 SD below the reference population. RESULTS: Of the 200 children evaluated at followup, the 100 healthy children had greater gains in total body BMC (P = 0.035), distal radius BMC (P < 0.001), and total body lean mass (P < 0.001) than did the 100 JIA patients. Low or very low total body BMC was observed in 24% of the patients and 12% of the healthy children. Bone formation, bone resorption, and weight-bearing activities were reduced in the patients compared with the healthy children. Multiple regression analysis showed that in patients with JIA, serum bone-specific alkaline phosphatase, serum C-telopeptide of type I collagen, and weight-bearing activities were independent predictors of changes in total body BMC. Total body BMC was lower in patients with polyarticular onset than in those with oligoarticular disease onset. CONCLUSION: Patients with JIA have moderate reductions in bone mass gains, bone turnover, and total body lean mass early in the disease course

21. MAKAROVA TP: Yuvenile rheumatoid arthritis: current aspects. Kazanskii Meditsinskii Zhurnal 85:4 291-297,

22. MASON T, REED AM, NELSON AM, THOMAS KB: Radiographic progression in children with polyarticular juvenile rheumatoid arthritis: a pilot study. Ann Rheum Dis 64:3 491-493, 2005
    Organism: Division of Rheumatology, Mayo Clinic, Rochester, MN 55905, USA masonthomas@mayoeduFAU - Mason, T
    Abstract: OBJECTIVE: To assess disease progression on hand/wrist x rays from children with polyarticular juvenile rheumatoid arthritis. METHODS: Initial and subsequent films of 13 white children (10 girls) were read blind by a paediatric radiologist for the presence of joint space narrowing (JSN), erosions, and relative carpal length (RCL). RESULTS: One child had subcutaneous nodules; one (of 11) was rheumatoid factor positive; six were ANA positive. Median age at diagnosis was 10.7 years (2.5 to 15.9). Median number of involved joints (swelling, pain, or decreased range of motion) at diagnosis was 16 (6 to 33). Four initial x rays had either erosions or JSN. Subsequent x rays were done at (median) 13.3 (8.3 to 24.9) months after initial x rays. One of 10 subsequent x rays had shortened RCL, and six of 13 were worse than the initial ones. Four of these developed new erosions, one had increased number of erosions, and one developed new JSN. CONCLUSIONS: About half the children with polyarticular juvenile rheumatoid arthritis will have evidence of radiographic progression within two years after diagnosis. Thus newly diagnosed children are at high risk of substantial joint destruction and potential disability, emphasising the need for prompt treatment

23. MERINO R, DE INOCENCIO J, GARCIA-CONSUEGRA J: Evaluation of revised International League of Associations for Rheumatology classification criteria for juvenile idiopathic arthritis in Spanish children (Edmonton 2001). J Rheumatol 32:3 559-561, 2005
    Organism: Unit of Pediatric Rheumatology, University Hospital La Paz, and CS Estrecho de Corea, Imsalud Area 4, Po de la Castellana 265, 28046 Madrid, SpainFAU - Merino, Rosa
    Abstract: OBJECTIVE: To evaluate the revised (Edmonton 2001) International League of Associations for Rheumatology (ILAR) classification criteria for Juvenile Idiopathic Arthritis (JIA) in a cohort of Spanish children. METHODS: One hundred twenty-five patients with chronic arthritis categorized according to traditional criteria and to the first revision of ILAR JIA criteria (Durban 1997) were reclassified according to the second JIA criteria revision (Edmonton 2001). RESULTS: Edmonton criteria allocated 92% of the patients classified by traditional criteria in their corresponding ILAR categories. Most patients with systemic (94%), pauciarticular (91%) and polyarticular (88%) juvenile chronic arthritis as well as those with juvenile spondyloarthropathy (94%) were reclassified in the corresponding ILAR categories. Two children with probable psoriatic arthritis (PsA) were reclassified in the rheumatoid factor-negative (RF-) polyarthritis category, whereas only one of 2 children with definite PsA could be allocated to the ILAR PsA class. Ten patients (8%) constituted the undifferentiated arthritis group, 8 because of psoriasis in a first-degree relative, one because of the presence of RF in a girl with oligoarthritis, and another because of psoriasis in a boy who was HLA-B27-positive. In comparison with the Durban JIA criteria the Edmonton revision decreased the number of patients whose arthritis fulfilled criteria in no category or in 2 or more categories (from 19 to 10), and delineated better the population included in the RF- polyarthritis category. CONCLUSION: The Edmonton criteria made the ILAR classification more transparent and easy to apply. Family history of psoriasis was responsible for most allocations to the undifferentiated arthritis category (8/10)

24. ORTIZ-ALVAREZ OLIVA, MORISHITA KIMBERLY, AVERY GLENDA, GREEN JAYNE, PETTY ROSS E, TUCKER LORI: Guidelines for blood test monitoring of methotrexate toxicity in juvenile idiopathic arthritis. Rinsho Ganka 31:12 2501-2506,
    Abstract: Objective. To assess the utility of the American College of Rheumatology guidelines for monitoring methotrexate (MTX)-related toxicity in a cohort of children with juvenile idiopathic arthritis (JIA). Methods. Eighty-nine patients with JIA treated with MTX were monitored prospectively: aspartate aminotransferase (AST), alanine aminotransferase (ALT), complete blood count (CBC), and differential blood count were measured prior to starting MTX, and then monthly. Significantly abnormal blood tests (SABT) were prospectively defined as (1) significantly elevated liver enzymes (SELE) greater than twice the upper limit of normal; (2) granulocyte count 1.5 x 109/l; (3) lymphocyte count 0.9 x 109/l; or (4) hemoglobin decreased by > 2 g/l from previous level. Clinical interventions, current and cumulative MTX dose, duration of treatment, comorbidity, and concurrent medications at the time of the first SABT identification were recorded. Independent t tests and chi-squared tests were used for comparisons, and the probability of developing a SABT was calculated by Kaplan-Meier survival analysis. Results. Forty percent of patients had a SABT: 26% had hematological abnormalities and 14% bad SELE. Ninety-five percent of patients with SABT had symptoms consistent with a viral infection when the SABT was drawn and MTX dose was withheld until results had normalized on repeat testing. SABT persisting beyond one month occurred in only, 2 patients, and their abnormalities resolved by 6 months with no specific identified cause; they resumed MTX at a later time without recurrence of SABT. There were no differences between patients with and without SABT with respect to current or cumulative MTX dose, duration of treatment, and concurrent medications at the time of the SABT. The probability of developing a SABT was estimated to be 11% at 3 months, compared to 10% probability of having an abnormal blood test by chance alone. Conclusion. Routine blood tests every 4 to 8 weeks in children with JIA are unnecessarily frequent. RN- 9000-86-6: alanine aminotransferase; 9000-97-9: aspartate aminotransferase; 59-05-2: methotrexate EC- EC 2.6.1.2: alanine aminotransferase; EC 2.6.1.1: aspartate aminotransferase

25. OSTENDORF B, IKING-KONERT C, COHNEN M, SCHNEIDER M: Finger joint swellings in a teenager: juvenile rheumatoid arthritis or a psychiatric disorder? Ann Rheum Dis 64:3 501-502, 2005

26. PAGNOUX C, MAHR A, COHEN P, GUILLEVIN L: Presentation and outcome of gastrointestinal involvement in systemic necrotizing vasculitides: analysis of 62 patients with polyarteritis nodosa, microscopic polyangiitis, Wegener granulomatosis, Churg-Strauss syndrome, or rheumatoid arthritis-associated vasculitis. Medicine (Baltimore) 84:2 115-128, 2005
    Organism: Hopital Cochin, Service de Medecine Interne, 27, rue du faubourg Saint-Jacques, Paris Cedex 14, France cpagnoux@msncomFAU - Pagnoux, Christian
    Abstract: We reviewed the medical records of 62 patients with systemic small and medium-sized vessel vasculitides and gastrointestinal tract involvement followed at our institution between 1981 and 2002. This group included 46 men and 16 women (male:female ratio, 2.9), with a mean age of 48 +/- 18 years. Vasculitides were distributed as follows: 38 polyarteritis nodosa (21 related to hepatitis B virus), 11 Churg-Strauss syndrome, 6 Wegener granulomatosis, 4 microscopic polyangiitis, and 3 rheumatoid arthritis-associated vasculitis. Gastrointestinal manifestations were present at or occurred within 3 months of diagnosis in 50 (81%) patients and were mainly abdominal pain in 61 (97%), nausea or vomiting in 21 (34%), diarrhea in 17 (27%), hematochezia or melena in 10 (16%), and hematemesis in 4 (6%). Gastroduodenal ulcerations were detected endoscopically in 17 (27 %) patients, esophageal in 7 (11%), and colorectal in 6 (10%), but histologic signs of vasculitis were found in only 3 colon biopsies. Twenty-one (34%) patients had a surgical abdomen; 11 (18%) developed peritonitis, 9 (15%) had bowel perforations, 10 (16%) bowel ischemia/infarction, 4 (6%) intestinal occlusion, 6 (10%) acute appendicitis, 5 (8%) cholecystitis, and 3 (5%) acute pancreatitis. (Some patients had more than 1 condition.) Sixteen (26%) patients died.The respective 10-month and 5-year survival rates were 71% (95% confidence interval [CI], 52-90) and 56% (95% CI, 35-77) for the 21 surgical patients; and 94% (95% CI, 87-101) and 82% (95% CI, 70-94) for the 41 patients without surgical abdomen (p = 0.08). Peritonitis (hazard ratio [HR] = 4.3, p < 0.01), bowel perforations (HR = 5.7, p < 0.01), gastrointestinal ischemia or infarctions (HR = 4.1, p < 0.01), and intestinal occlusion (HR = 5.5, p < 0.01) were the only gastrointestinal manifestations significantly associated with increased mortality in multivariate analysis. For this subgroup of 15 patients, 6-month and 5-year survival rates were 60% (95% CI, 35-85) and 46% (95% CI, 19-73), respectively (p = 0.003). None of the other gastrointestinal or extraintestinal vasculitis-related symptoms, or angiographic abnormalities (seen in 67% of the 39 patients who underwent angiography), was predictive of surgical complications or poor outcome. However, prognosis has dramatically improved during the past 30 years, probably owing to better management of these more severely ill patients, with prompt surgical intervention when indicated, and the combined use of steroids and immunosuppressants

27. PALERMO TM, KISKA R: Subjective sleep disturbances in adolescents with chronic pain: relationship to daily functioning and quality of life. J Pain 6:3 201-207, 2005
    Organism: Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA palermot@ohsueduFAU - Palermo, Tonya M
    Abstract: The purpose of this study was to examine the relationship between pain symptoms, daily functioning, health-related quality of life (HRQOL), and subjectively reported sleep disturbances in adolescents with chronic pain. Depressive symptoms were tested as a general risk factor for increased sleep problems. During routine subspecialty clinic visits, 86 adolescents (mean age, 14.75 years; 67% female) diagnosed with chronic headaches, juvenile idiopathic arthritis, or sickle cell disease completed measures to assess pain, sleep disturbances, functional disability, depression, and HRQOL. Across pain diagnoses, adolescents experienced similar sleep patterns and sleep behaviors with the exception of daytime sleepiness, which was higher in adolescents with headache compared to adolescents with sickle cell disease. Bivariate correlations showed low relationships between pain and sleep and moderate to high relationships between depressive symptoms, daily functioning, HRQOL, and sleep. In multivariate analyses, as hypothesized, depressive symptoms were predictive of the severity of sleep disturbances after controlling for the effect of all other demographic, pain, and functional impact variables. Results suggest that a relationship between the experience of recurrent and chronic pain and sleep disturbances exists for adolescents, and these sleep disturbances are linked to mood disturbances and reductions in daily functioning and quality of life. Sleep disturbances have been described in adult patients with chronic pain, but little is known about sleep in adolescents with chronic pain. This study examined the complex interrelationship between sleep, pain, mood, functioning, and HRQOL. Findings suggest that mood is strongly related to sleep and might share common pathophysiologic or behavioral origins in adolescents with chronic pain

28. RAVELLI A, FELICI E, MAGNI-MANZONI S, PISTORIO A, NOVARINI C, BOZZOLA E, VIOLA S, MARTINI A: Patients with antinuclear antibody-positive juvenile idiopathic arthritis constitute a homogeneous subgroup irrespective of the course of joint disease. Arthritis Rheum 52:3 826-832, 2005
    Organism: IRCCS G Gaslini, Genoa, Italy angeloravelli@ospedale-gaslinigeit <angeloravelli@ospedale-gaslinigeit>FAU - Ravelli, Angelo
    Abstract: OBJECTIVE: We recently hypothesized that in the International League of Associations for Rheumatology (ILAR) classification of juvenile idiopathic arthritis (JIA), the presumably homogeneous patient group characterized by early onset of disease, a female predilection, the presence of antinuclear antibodies (ANA), asymmetric arthritis, and the risk for iridocyclitis is classified into different categories. We sought to investigate whether ANA-positive patients belonging to the ILAR categories of oligoarthritis and rheumatoid factor (RF)-negative polyarthritis share homogeneous features and to compare these features with those of ANA-negative patients with JIA in the same categories. METHODS: We identified patients who were followed up during a 15-year period. All patients had JIA according to the ILAR criteria, with oligoarticular or polyarticular onset. ANA positivity was defined as 2 or more positive results at a titer of >or=1:160. Demographic and clinical features, including the number of joints involved over time and measures of JIA severity at the last followup visit, were recorded retrospectively. RESULTS: A total of 256 patients were included: 190 were ANA positive (109 had persistent oligoarthritis, 48 had extended oligoarthritis, and 33 had RF-negative polyarthritis), and 66 were ANA negative (35 had RF-negative polyarthritis, and 31 had oligoarthritis). All patients who were positive for ANA were similar in terms of age at disease presentation, female-to-male ratio, and frequency of symmetric arthritis and iridocyclitis. Compared with ANA-positive patients with polyarticular disease, ANA-negative patients with polyarticular arthritis were older at disease presentation and had a lower frequency of iridocyclitis, a higher frequency of symmetric arthritis, a greater cumulative number of joints affected over time, and a different pattern of joint disease, with a greater frequency of shoulder and hip involvement. The strong relationship between the presence of ANA and younger age at disease presentation, asymmetric arthritis, and development of iridocyclitis was confirmed by multivariate regression analysis. CONCLUSION: Our results support the hypothesis that patients with similar characteristics are currently classified into different JIA categories. The value of ANA positivity as a possible modifier of the current classification system deserves consideration

29. ROVENSKA E(REPRINT): Conspicuous synovial lymphatic capillaries in juvenile idiopathic arthritis synovitis with rice bodies. Annals of the Rheumatic Diseases 64:2 328-329,

30. SCHEEL AK, HERMANN KG, KAHLER E, PASEWALDT D, FRITZ J, HAMM B, BRUNNER E, MULLER GA, BURMESTER GR, BACKHAUS M: A novel ultrasonographic synovitis scoring system suitable for analyzing finger joint inflammation in rheumatoid arthritis. Arthritis Rheum 52:3 733-743, 2005
    Organism: Georg-August-University Gottingen, Germany ascheel@gwdgde <ascheel@gwdgde>FAU - Scheel, Alexander K
    Abstract: OBJECTIVE: To develop an ultrasonographic (US) synovitis scoring system suitable for evaluation of finger joint inflammation in patients with active rheumatoid arthritis (RA) and to compare semiquantitative US scoring with quantitative US measurements. METHODS: US was performed at the palmar and dorsal sides of the second through fifth metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints in 10 healthy subjects and in the clinically more affected hand in 46 RA patients. Ten patients additionally underwent magnetic resonance imaging (MRI). Synovitis was measured, standardized, and scored according to a semiquantitative method. The 2 methods (semiquantitative US scoring, quantitative US) were compared and statistical cutoffs were identified using receiver operating characteristic (ROC) curve analysis. MRI results were compared with semiquantitative US scoring and quantitative US results. The optimal US scoring method from 6 joint combinations was identified (ROC curve analysis). RESULTS: Synovitis was most frequently detected in the palmar proximal area (86% of affected joints). We found no significant differences between individual PIP joints or between individual MCP joints, indicating that all fingers within each of these joint groups should be treated equally for statistical calculations, although each joint group as a whole should be treated separately. The optimal cutoff point to distinguish between "health" and "pathology" was 0.6 mm both for MCP joints (sensitivity 94%, specificity 89%) and for PIP joints (sensitivity 90%, specificity 88%). There was no significant difference between semiquantitative US scores and quantitative US measurements. The best results for joint combinations were achieved using the "sum of 4 fingers" (second through fifth MCP and PIP joints) and "sum of 3 fingers" (second through fourth MCP and PIP joints) methods. Comparison of MRI results with semiquantitative US scores revealed high concordance. CONCLUSION: US evaluation of finger joint synovitis can be considerably simplified by focusing on the palmar side and by applying semiquantitative grading instead of quantitative measurements. For evaluation of treatment efficacy based on synovitis in RA patients, we recommend using the "sum of 3 fingers" method in longitudinal trials

31. SHAW KL, SOUTHWOOD TR, MCDONAGH JE: Growing up and moving on in rheumatology: a multicentre cohort of adolescents with juvenile idiopathic arthritis. Rheumatology (Oxford) 44:6 806-812, 2005
    Organism: ARC Senior Lecturer in Paediatric and Adolescent Rheumatology, Institute of Child Health, Diana, Princess of Wales Children's Hospital, Steelhouse Lane, Birmingham B4 6NH, UK jemcdonagh@bhamacukFAU - Shaw, K L
    Abstract: OBJECTIVES: To define the transitional care workload of a multicentre cohort of adolescents with juvenile idiopathic arthritis (JIA) including disease, self-advocacy and vocational issues prior to the implementation of a transitional care programme. METHODS: Data were collected using questionnaires completed by senior clinicians, patients and parents in 10 UK paediatric rheumatology centres. Entry criteria for patients included a confirmed diagnosis of JIA for at least 6 months and an age of 11, 14 or 17 yr. RESULTS: Of 359 families invited to participate, 308 (85.79%) adolescents with JIA and 303 parents/guardians accepted. Of these, 19.5% had persistent oligoarthritis. Despite their imminent transfer to adult care, ongoing transitional issues were identified in the 17-yr-old cohort: 55.8% were still seeing the rheumatologists with their parent, 20% were not self-medicating, 68.5% had not had intra-articular injections under local anaesthetic and 14% had received no careers counselling. This age group also had significant disease-related issues; 54.6% had moderate to severe functional disability, 67.5% were still on disease-modifying anti-rheumatic drugs and, as a group, they had significantly greater pain than younger patients. CONCLUSIONS: This study has objectively identified the transitional care workload facing paediatric and adult rheumatologists in terms of disease-related, self-advocacy and vocational issues. Outcome data following the implementation of a coordinated transitional care programme are awaited

32. SIMONINI G, GIANI T, STAGI S, DE MARTINO M, FALCINI F: Bone status over 1 yr of etanercept treatment in juvenile idiopathic arthritis. Rheumatology (Oxford) 44:6 777-780, 2005
    Organism: Department of Pediatrics-Rheumatology Unit, Via Pico della Mirandola 24, 50132 Firenze, Italy gabrielesimonini@unifiitFAU - Simonini, G
    Abstract: OBJECTIVE: To evaluate bone mineral status over 1 yr of etanercept treatment in juvenile idiopathic arthritis (JIA). METHODS: Twenty children (13 female, 7 male) aged 5.2-11.4 yr, with active polyarticular JIA were prospectively enrolled to receive etanercept (0.4 mg/kg, twice weekly). Responders were defined according to the American College of Rheumatology Pediatric 50 definition of improvement. Broadband ultrasound attenuation (BUA) by bone was determined at the left calcaneus to assess bone status at baseline and at 1-yr follow-up. RESULTS: After 12 months of treatment, 15 (75%) patients were considered as responders. At baseline, responders and non-responders did not differ with regard to age, disease duration, core-set variables or BUA and Z-score values (patient's value - age specific normal value/normal group's s.d.). At 6-month and 1-yr follow-up in the whole group, BUA and Z-score values were not significantly different compared with baseline. At 1-yr follow-up, but not at 6 months, all 15 responders, differently from non-responders, showed a significant increase in both BUA and Z-score values: BUA at 1 yr 55.2 +/- 3.3 vs baseline 43.5 +/- 3.2 dB/MHz, P<0.001; Z score at 1 yr -0.3 +/- 0.2 vs baseline 1.5 +/- 0.4, P<0.002. CONCLUSION: For the first time in childhood rheumatic disease this pilot prospective study, although in a small group, shows evidence that 1 yr of etanercept therapy by controlling the underlying disease activity induces a sustained benefit on JIA bone loss. Prospective studies in larger patient samples are needed to confirm these data

33. SKYTTA E, SAVOLAINEN A, KAUTIAINEN H, BELT EA: Stapling of knees with valgus deformity in children with juvenile chronic arthritis. Clin Exp Rheumatol 23:2 270-272, 2005
    Organism: Surgical Department, Paijat-Hame Central Hospital, Lahti, Finland eerikskytta@reumafiFAU - Skytta, E
    Abstract: OBJECTIVE: Leg length discrepancy and excessive knee valgus are potential complications of juvenile chronic arthritis of the knee. The aim of the present study was to evaluate retrospectively the safety and efficacy of temporary stapling of the knee epiphyses in management of valgus deformities of the knee in children with JCA. METHODS: Medical data of the patients with temporary epiphyseodesis due to knee valgus deformity (KVD) were studied. 177 knees in 112 patients were found with sufficient data for evaluation. Patient documents and radiographs of these patients were evaluated. RESULTS: Mean age at the time of operation was 8 years (range: 2 - 17) in 19 males and 93 females. The patients are predominantly affected by aggressive polyarticular disease. Preoperative mean valgus angle was 11 degrees (IQR: 9, 14) and at staple removal 4 degrees (IQR: 2, 5). In 120 of 177 knees (68% [95% CI: 61 - 74], p < 0.001) the physiological angle (3-8 degrees) was reached. Median time of stapling was 10 months (IQR: 8, 13). Five reversible and one irreversible (3% [95% CI: 2 to 7]) major complications were documented among the 177 stapled knees. CONCLUSION: Temporary epiphyseal stapling enables flexible correction of KVD in children with JCA. Low complication rate encourages the use of the method. Prompt follow-up is, however, important in avoing excess over-correction to varus

34. SMOLEWSKA ELZBIETA R: Safety and efficacy of methylprednisolone pulse therapy in children with systemic inflammatory connective tissue diseases
    <ORIGINAL> Bezpieczenstwo i skutecznosc stosowania pulsow z metylprednizolonu w ukladowych zapalnych chorobach tkanki lacznej u dzieci. Reumatologia (Warsaw) 42:4 515-524,
    Abstract: The aim of this study was to evaluate the safety and efficacy of methylprednisolone pulse therapy (MPT) in children with systemic inflammatory connective tissue diseases. 22 children (18 girls and 4 boys) in the age from 4 to 18 with juvenile idiopathic arthritis (15), systemic lupus erythematosus (4), periarteritis nodosa (1). dermatomyositis (1) and erythema nodosum (1) were treated with methylprednisolone (20 mg/kg max. 1 g) in 3 hour intravenous infusion. Hemoglobin, red blood cells count, white blood cells and platelet count. ESR and CRP were measured on admission and before discharging. the level of serum electrolytes and glucose were measured prior and after the pulse. Hotter ECG monitoring during the infusion and standard ECG before and after that were performed in every patient. Blood pressure was measured before, during and 6 hours after methylprednisolone infusion. 21 of 22 children responded to the therapy with clinical and laboratory improvement. A statistically significant reduction of ESR and CRP (p 0.05) was obtained. Mild increase of glucose (p 0.05) level was observed on the next day after the pulse. All adverse effects of the therapy were benign and transient. In 3 cases mild hypertension was observed during and on the next day after infusion which required short treatment with hypotensive drugs. Arrhythmias registered during Hotter monitoring were not life-threatening, mostly supra- and ventricular extrasystolies, and short episodes of brady- and tachycardia. The results of our study revealed high efficacy of MPT. Such therapy seems to be safe but the possibility of severe adverse effects can not be fully excluded. RN- 50-99-7Q: glucose; 58367-01-4Q: glucose; 83-43-2: methylprednisolone

35. STRAUB RH: How psychological stress via hormones and nerve fibers may exacerbate rheumatoid arthritis. Arthritis & Rheumatism 52:1 16-26,

36. THACKER MM, FELDMAN DS, MADAN SS, STRAIGHT JJ, SCHER DM: Hinged distraction of the adolescent arthritic hip. J Pediatr Orthop 25:2 178-182, 2005
    Organism: Pediatric Orthopaedic Surgery, Center for Children, NYU Hospital for Joint Diseases, New York, New York, USAFAU - Thacker, Mihir M
    Abstract: From 1996 to 2000, 11 adolescents with hip joint arthritis secondary to osteonecrosis or idiopathic chondrolysis were treated with articulated hinged distraction arthroplasty. Indications for surgery were severe pain and limited ambulation. Charts and radiographs were reviewed. Clinical status was assessed preoperatively and at latest follow-up (mean 4.8 years after surgery) using criteria of pain, range of motion, and ambulation level. Ten patients showed improved clinical status, with seven having an excellent outcome and three a good outcome. One patient failed distraction. Mean joint space was 2.6 mm before surgery and 4.8 mm at latest follow-up. Average duration of fixator use was 4.4 months. Four patients (36.4%) had complications. Articulated hip distraction was effective in eliminating pain, improving function, and preventing progressive degenerative changes in young patients' hips. It should be considered a salvage procedure for arthritic hips and an alternative to arthrodesis in this difficult-to-treat group of patients

37. WULFFRAAT NM, VASTERT B, TYNDALL A: Treatment of refractory autoimmune diseases with autologous stem cell transplantation: focus on juvenile idiopathic arthritis. Bone Marrow Transplant 35 Suppl 1:S27-9.: S27-S29, 2005
    Organism: Department of Pediatrics, Section Immunology, University Medical Center Utrecht, Utrecht, The Netherlands nwulffraat@wkzazunlFAU - Wulffraat, N M
    Abstract: Autologous stem cell transplantation (ASCT) can be performed in a variety of refractory autoimmune diseases. A retrospective multicenter analysis is presented to evaluate safety and efficacy of ASCT for refractory juvenile idiopathic arthritis. In all, 18 of the 34 patients (53%) with a follow-up of 12 to 60 months achieved a drug-free complete remission. There were three cases (9%) of transplant-related mortality and two cases of disease-related mortality (6%). Infectious complications were seen frequently. We propose adjustments in future protocols to reduce this mortality in this high-risk patient group

38. YIM DS, ZHOU H, BUCKWALTER M, NESTOROV I, PECK CC, LEE H: Population pharmacokinetic analysis and simulation of the time-concentration profile of etanercept in pediatric patients with juvenile rheumatoid arthritis. J Clin Pharmacol 45:3 246-256, 2005
    Organism: Center for Drug Development Science, Department of Pharmacology, Box 571441, Georgetown University School of Medicine, Washington, DC 20057-1441, USAFAU - Yim, Dong-Seok
    Abstract: This study was performed to estimate the population pharmacokinetic (PK) parameters of etanercept in pediatric juvenile rheumatoid arthritis (JRA) patients and to compare the steady-state time-concentration profiles between etanercept 0.8-mg/kg once-weekly and 0.4-mg/kg twice-weekly subcutaneous (SC) regimens by clinical trial simulation. To this end, mixed-effect analysis (NONMEM, Version 5.1) was performed using the etanercept PK database consisting of 69 JRA patients (4-17 years). Based on the population PK parameters obtained herein, a Monte Carlo clinical trial simulation experiment was conducted to compare the PK profiles in 200 virtual JRA patients who randomly received either etanercept 0.4 mg/kg SC twice weekly or 0.8 mg/kg once weekly for 12 weeks. The following population PK model could adequately describe etanercept PK profiles for twice-weekly SC dosing of 0.4 mg/kg: CL/F (L/h)=0.0576 (female) or 0.0772 (male) x (body surface area in m2/1.071)1.41, V/F(L)=7.88 x (body weight in kg/30.8). The means +/- standard deviations of simulated trough concentrations for 0.8-mg/kg once-weekly and 0.4-mg/kg twice-weekly dosing regimens were 1.58 +/- 1.07 mg/L and 1.92 +/- 1.09 mg/L, respectively. Peaks during 0.8-mg/kg once-weekly dosing (2.92 +/- 1.41 mg/L) were only 11% higher than during 0.4 mg/kg twice-weekly dosing (2.62 +/- 1.23 mg/L). In conclusion, the clinical trial simulation confirmed that 0.8-mg/kg once-weekly and 0.4-mg/kg twice-weekly SC regimens of etanercept are expected to yield overlapping steady-state time-concentration profiles, leading to equivalent clinical outcomes. This has been the basis of the recent Food and Drug Administration approval of the 0.8-mg/kg once-weekly regimen in pediatric patients with JRA

39. YOKOTA S, MIYAMAE T, IMAGAWA T, IWATA N, KATAKURA S, MORI M, WOO P, NISHIMOTO N, YOSHIZAKI K, KISHIMOTO T: Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 52:3 818-825, 2005
    Organism: Yokohama City University School of Medicine, Kanagawa, Japan syokota@medyokohama-cuacjp <syokota@medyokohama-cuacjp>FAU - Yokota, Shumpei
    Abstract: OBJECTIVE: To investigate the safety and efficacy of a recombinant human anti-interleukin-6 (anti-IL-6) receptor monoclonal antibody (MRA) that indirectly inhibits the effects of IL-6 in children with systemic-onset juvenile idiopathic arthritis (JIA) refractory to high-dose, long-term corticosteroids. METHODS: An individual escalating-dose trial was conducted in 11 children with active systemic-onset JIA who met the inclusion criteria. All were first administered an intravenous dose of 2 mg/kg MRA. Each child without active inflammation was given a second identical dose 2 weeks later and a third identical dose 2 weeks after the second dose. Children with disease flares according to laboratory marker values received a 4-mg/kg dose. Those without disease flares at this dose received a second 4-mg/kg dose 2 weeks later and a third 4-mg/kg dose 2 weeks after the second dose, while those with active inflammation received an additional 3 doses of 8 mg/kg MRA. Efficacy was evaluated every 2 weeks according to responses on the JIA core set of improvement criteria and the results of laboratory tests. RESULTS: MRA abruptly reduced disease activity in 10 of the 11 children, as assessed by the occurrence of febrile episodes, active arthritis, scores on the Childhood Health Assessment Questionnaire, and levels of acute-phase reactants. However, levels of inflammatory reactants fluctuated until the proper MRA dose for each child was reached. Two weeks after the third fixed dose of MRA, 90.9% of all patients had a 30% improvement response, 90.9% had a 50% improvement response, and 63.6% had a 70% improvement response. CONCLUSION: MRA treatment of children with active systemic disease results in clinical improvement and in normalized levels of acute-phase reactants. MRA was safe and well tolerated and provided greater clinical benefit than conventional corticosteroids, considering the ill effects of IL-6 and adverse events