Bibliography March 04

1. 13th Annual Congress of the Study Group for Child and Adolescent Rheumatology, Halle an der Saale, Saxony-Anhalt, Germany, November 14-15, 2003. Aktuelle Rheumatologie 28:5 269-286, 2003
   Abstract: This meeting contains abstracts of 58 papers, written in German and English, on child and adolescent rheumatology including genetics, autoimmune disease and diagnostics, biology and new drugs, bone metabolism and growth, scleroderma and collagenosis, juvenile idiopathic arthritis, Chronic Infantile Neurological Cutaneous and Articular (CINCA) syndrome, osteomyelitis, osteoporosis, infliximab, etanercept, mycophenolate mofetil, and stem cell transplantation

2. AGGARWAL A, AGARWAL V, DANDA D, MISRA R: Outcome in Juvenile Rheumatoid Arthritis in India. Indian Pediatrics (India ) 41:2 180-184, 2004
   Abstract: Juvenile rheumatoid arthritis (JRA) leads to significant morbidity due to continued disease activity and drug toxicity. Retrospective analysis of patients with JRA seen at a tertiary care hospital between 1990-2000 was done. Data regarding the type of onset, course of disease, joints involved, treatment received, drug toxicity and outcome at last visit were retrived from case records. There were 214 children (76 oligoarticular, 93 polyarticular and 45 systemic onset) with 135 of them being boys. At last follow up, with median disease duration of 6 years; 128 had active diseases, 58 had stable disease and 28 had inactive disease. Polyarticular group had the worst outcome with only 3 of the 93 having inactive disease (13/76 in oligo articular group and 12-45 in systemic onset disease). Intramuscular gold and D-Penicillamine were associated with significant drug toxicity. Outcome of children with JRA in our country is poorer as compared to developed countries

3. AKPEK EK, THORNE JE, QAZI FA, DO DV, JABS DA: Evaluation of patients with scleritis for systemic disease. Ophthalmology 111:3 501-506, 2004
   Organism: The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Maumenee Building #321, Baltimore, MD 21287-9238, USA esakpek@jhmieduFAU - Akpek, Esen Karamursel
   Abstract: OBJECTIVE: To evaluate the relationship between associated medical conditions and scleritis-particularly, the timing of the diagnosis of these diseases. DESIGN: Retrospective case series. PARTICIPANTS: Patients with scleritis presenting to a single center over an 18-year period. METHODS: Medical records were reviewed for the presence of an associated infectious or rheumatic disease and for the timing of the diagnosis of the systemic disease relative to the presentation for evaluation of the scleritis. MAIN OUTCOME MEASURES: Presence of an associated medical condition and timing of diagnosis relative to that of scleritis. RESULTS: In a series of 243 patients with scleritis, 44.0% had an associated medical condition: 7.0%, an infection, and 37.0%, a rheumatic disease. The most frequent infection was herpes zoster, and the most frequent rheumatic disease was rheumatoid arthritis, present in 4.5% and 15.2% of patients, respectively. Of the 107 patients with an underlying disease, 77.6% had a previously diagnosed disease, 14.0% had their conditions diagnosed as a result of the initial evaluation, and 8.4% developed a systemic disease during follow-up. Systemic vasculitis was less likely to have been previously diagnosed than other rheumatic diseases (59.1% vs. 83.8%, P = 0.015) and more likely to be diagnosed by the initial diagnostic evaluation (27.3% vs. 8.8%, P = 0.027). Ten patients (4.1%) had a positive antineutrophil cytoplasmic antibody (ANCA) test result without clinical evidence of a systemic vasculitis. Four of 5 patients with a positive cytoplasmic ANCA test result but no clinical evidence of systemic vasculitis required immunosuppressive drugs for control of the scleritis, whereas 1 of the 5 patients with a positive perinuclear ANCA test result required immunosuppressive drugs. Among patients with no evident systemic disease after the initial diagnostic evaluation, the rate of occurrence of a rheumatic disease was 4% per person-year. CONCLUSIONS: Although associated systemic diseases are frequent among patients with scleritis, the majority are previously diagnosed. Systemic vasculitis is less likely than other rheumatic diseases to have been previously diagnosed. Because vasculitis is a potentially life-threatening disorder, it should be a focus of the diagnostic evaluation

4. ARMBRUST W, KAMPHUIS SS, WOLFS TW, FISELIER TJ, NIKKELS PG, KUIS W, WULFFRAAT NM: Tuberculosis in a nine-year-old girl treated with infliximab for systemic juvenile idiopathic arthritis. Rheumatology (Oxford) 43:4 527-529, 2004

5. BENGTSSON AA, STURFELT G, GULLSTRAND B, TRUEDSSON L: Induction of apoptosis in monocytes and lymphocytes by serum from patients with systemic lupus erythematosus - an additional mechanism to increased autoantigen load? Clin Exp Immunol 135:3 535-543, 2004
   Organism: Department of Rheumatology, Lund University, Lund, SwedenFAU - Bengtsson, A A
   Abstract: The most likely source of autoantigens in systemic lupus erythematosus (SLE) is apoptotic material. Because increased levels of circulating apoptotic cells are found in SLE we wanted to investigate the capacity of serum from patients with SLE or other autoimmune or infectious diseases and normal healthy donors (NHD) to induce apoptosis in normal monocytes, lymphocytes and corresponding cell lines, in relation to clinical and immunological data. Monocytes and lymphocytes from healthy donors were incubated with sera from 37 SLE patients, 37 sex- and age-matched NHD and sera from patients with rheumatoid arthritis, vasculitis, sepsis and mononucleosis. Sera from SLE patients were sampled at both active and inactive disease. The apoptosis-inducing effect (AIE) of these sera was monitored with flow cytometry using annexin V and propidium iodide (PI) binding. The AIE in monocytes and lymphocytes was significantly higher in sera from SLE patients than in other patient groups and NHD (P < 0.001) and was also higher when cell lines were used. Level of C5a in cell culture supernatant correlated with AIE in monocytes (r = 0.451, P = 0.005), suggesting involvement of complement. Heat-inactivation of sera did not affect the AIE, nor did depletion of IgG by protein G absorption of serum. Kinetic analyses showed a peak in apoptosis induction at 12-16 h, with a delayed PI positivity. AIE was equally high using sera from active and inactive SLE cases, and did not correlate with the SLE Disease Activity Index (SLEDAI). Thus, SLE serum has a strong and apparently disease-specific apoptosis-inducing capacity, which could contribute to a high load of potential autoantigen

6. BIANCHI ML: Bone Problems in Rheumatic Diseases during Childhood and Adolescence. Clinical Reviews in Bone and Mineral Metabolism (United States ) 2:1 63-75, 2004
   Abstract: Metabolic disorders of bone in children and adolescents affected by many chronic rheumatic diseases (most commonly juvenile rheumatoid arthritis, systemic lupus erythematosus, and dermatomyositis) are an important complication as well as a side effect of therapy. In the absence of prevention measures, fragility fractures can occur even at an early age. Glucocorticosteroids, probably the most important drugs in chronic inflammatory diseases with an autoimmune component, have now been proven to constantly induce osteoporosis and increase the rate of fragility fractures even in young patients. Also, they can prevent the acquisition of an optimal peak bone mass and lead to an increased risk of fractures in later life. The daily "stress stimuli," such as walking, running, stair climbing, etc., are critical for skeletal development during childhood and adolescence. Mobility can be significantly reduced in many rheumatologic diseases and disuse osteopenia is frequent. Effective control of the rheumatologic disease is the best first-line approach to preventing osteoporosis. Growth and pubertal delay must be corrected with an appropriate hormonal therapy. Assuring an adequate intake of calcium, phosphate, and protein, as well as maximizing mobility, are especially important in young patients. Very few studies are available on the treatment of low bone mass and bone metabolism derangement in children with rheumatic diseases, treated with glucocorticosteroids or not. Controlled studies are still lacking. Calcium, vitamin D, and 25-hydroxyvitamin D have been studied in pediatric patients with various rheumatic diseases, but their efficacy in reducing or preventing bone loss is uncertain. There are some preliminary data on the efficacy of bisphosphonates in severe osteoporosis or high-risk conditions. Growth hormone has also been used

7. BUCHMANN RF, JARAMILLO D: Imaging of articular disorders in children. Radiol Clin North Am 42:1 151-68, vii, 2004
   Organism: Department of Radiology, Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, MA 02114, USAFAU - Buchmann, Robert F
   Abstract: This article reviews aspects of arthritis imaging that are specific to children. The pediatric skeleton is unique and responds in characteristic ways to articular inflammation. Epiphyseal and physeal cartilage are affected by joint diseases, and disturbances of growth and maturation are sometimes the cardinal manifestations of arthritis. The target joints of pediatric articular diseases differ considerably from those of diseases in adults. Imaging techniques should be tailored to the children being studied

8. DAYER J-M: The process of identifying and understanding cytokines: From basic studies to treating rheumatic diseases. Best Practice and Research in Clinical Rheumatology (United Kingdom ) 18:1 31-45, 2004
   Abstract: This is a historical overview seen from a personal angle. It covers the insights made during the past 20 years into the destructive processes of rheumatoid arthritis (RA) related to cytokines. The biochemical knowledge of the matrix components (i.e. collagen) and enzymology (i.e. collagenase) available in the 1950s led to the identification of cells from synovial tissue producing collagenase (fibroblast-like cells) and their interaction with other immune cells, i.e. monocyte-macrophages (Mphi) and lymphocytes (1976-1979). This insight led to the isolation of soluble factors produced by Mphi, such as interleukin-1 (IL-1) and TNF, the principal cytokines inducing collagenase and PGESUB2 in many target cells (i.e. synovial fibroblasts, chondrocytes, bone-derived cells) (1981-1985). Further advances resulted from observations that, in clinical conditions (i.e. leukaemia, juvenile RA), a remission of fever and inflammation may occur spontaneously and that tissue catabolism may persist despite the absence of systemic inflammation; this gave rise to the concept and identification of endogenous cytokine inhibitors (i.e. IL-1 receptor antagonist and TNF soluble receptor) (1984-1989). The fourth milestone was the observation that the production of IL-1 and TNF by Mphi was induced mainly by direct contact with lymphocytes, prompting studies of the ligands and counter-ligands on Mphi and lymphocytes as well as inhibitors involved in this cell-cell contact, some of these inhibitors being involved in lipid metabolism and acute-phase proteins (HDL-apo A-1 . (c) 2004 Elsevier Ltd. All rights reserved

9. EL SHABRAWI Y, MANGGE H, HERMANN J: Anti-tumour necrosis factor alpha treatment in chronic recurrent inflammation of the anterior segment of the eye in patients resistant to standard immunomodulatory treatment. Annals of the Rheumatic Diseases 62:12 1243-1244, 2003

10. FELDMANN M, BRENNAN FM, PALEOLOG E, COPE A, TAYLOR P, WILLIAMS R, WOODY J, MAINI RN: Anti-TNFalpha therapy of rheumatoid arthritis: what can we learn about chronic disease? Novartis Found Symp 256:53-69; discussion 69-73, 106-11, 266-9.: 53-69, 2004
    Organism: Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College of Science, Technology and Medicine, 1 Aspenlea Road, London W6 8LH, UKFAU - Feldmann, Marc
    Abstract: The importance of tumour necrosis factor (TNF)alpha in rheumatoid arthritis (RA) was initially proposed on the basis of analysis of cytokine gene regulation at the local site of the disease, the synovium. This was then verified in animal models and established in an extensive series of clinical trials, culminating in now 250000 treated patients with either of two approved TNF inhibitors, antibody or fusion protein. The degree and magnitude of clinical benefit has enabled analyses of the mechanism by which anti-TNF benefits, and hence insights into important steps in the disease process. It was found that essentially all aspects of RA were ameliorated, and important mechanisms of benefit involved diminution of multiple pro-inflammatory cytokines, adhesion molecules and chemokines, leading to reduced cell trafficking, reduced angiogenesis and most importantly halting of joint destruction. What of the problems? Safety is better than prior drugs, but there is a small increase in severe infections, smaller than might have been anticipated. Cost is the major drawback limiting greater use. In view of the central pathological processes down-regulated, and their role in many diseases, the early clinical success of anti-TNF in RA led to subsequent successful trials and registration in Crohn's disease and juvenile rheumatoid arthritis, and successful trials in ankylosing spondylitis, psoriasis and psoriatic arthritis. The era of anti-cytokine therapeutics is just dawning

11. FERENC V: Eye disorders associated with musculoskeletal diseases
    MOZGASSZERVI BETEGSEGEKET KISERO SZEMESZETI ELVALTOZASOK. Lege Artis Medicine (Hungary ) 14:2 125-131, 2004
    Abstract: The diseases of connective tissue and musculoskeletal system frequently associated with typical eye disorders. These can either be mild, recovering fully after treatment or more serious with persisting symptoms and destructive changes resulting in permanent loss of sight Eye symptoms can occur in the following diseases: rheumatoid arthritis, juvenile chronic arthritis, neonatal onset multisystem disease, ankylosing spondylitis, seronegative spondarthrities, Reiter's syndrome, Behc(cedil)et's syndrome, Lyme disease, systemic lupus erythematosus, scleroderma, polyarteritis nodosa, Wegener's granulomatosis, giant cell arteritis, erythema nodosum, relapsing polychondritis, sarcoidosis, Marfan's syndrome, osteogenesis imperfecta

12. FIETTA P: Respiratory system involvement in adult onset Still's disease
    L'INTERESSAMENTO DELL'APPARATO RESPIRATORIO NELLA MALATTIA DI STILL DELL'ADULTO. Progressi in Reumatologia (Italy ) 4:3 271-278, 2003
    Abstract: Adult onset Still's disease (AOSD), the adult variant of the systemic form of juvenile rheumatoid arthritis, is an uncommon systemic inflammatory disorder of unknown origin with a polymorphous and unpredictable clinical course. Its major features are high spicking fever, evanescent maculo-papular skin rash, arthralgia/arthritis, as well as neutrophilic leukocytosis, marked hyperferritinemia, negative rheumatoid factor and antinuclear antibodies. Sore throat, abdominal pain, lymphadenopathies, hepato-splenomegaly, polyserositis, multiple organ dysfunction and disseminated intravascular coagulation may also occur. The pleuro-pulmonary involvement represents an unusual, but often life-threatening manifestation of AOSD. It usually consists of pleural effusion and transient pulmonary infiltrates, or, rarely, of interstitial pneumopathy, diaphragmatic dysfunction, pulmonary hypertension and respiratory distress syndrome. The treatment of such complications is based on high-dose corticosteroids, but a more aggressive approach with immunosuppressive drugs is often required. In this paper the main clinical features and pleuro-pulmonary manifestations of AOSD are reviewed

13. GUDBRANDSDOTTIR S, LARSEN R, SORENSEN LK, NIELSEN S, HANSEN MB, SVENSON M, BENDTZEN K, MULLER K: TNF and LT binding capacities in the plasma of arthritis patients: Effect of etanercept treatment in juvenile idiopathic arthritis. Clinical and Experimental Rheumatology (Italy ) 22:1 118-124, 2004
    Abstract: Background. Etanercept (Enbrel(R)) induces a rapid and sustained decline in disease activity in the majority of patients with refractory juvenile idiopathic arthritis (JIA). For unknown reasons, however, a number of JIA patients fail to respond to this therapy. During this treatment neutralisation of tumour necrosis factor (TNF, previously termed TNFalpha) and lymphotoxin (LT, previously termed TNFbeta) may be mediated by etanercept itself as well as by naturally occurring soluble TNF receptors. In light of this, it was of interest to study the total TNF neutralizing capacity in plasma before and during treatment with etanercept. Results. In initial experiments plasma samples from healthy individuals were incubated with etanercept, and spiked with TNF or LT to a final concentration of 1000 pg/mL. Detection of TNF and LT by ELISA was found to be reduced by approximately 50% and 80% respectively, at a concentration of etanercept of 5-500 ng/mL, which is close to the pharmacological plasma concentrations. Plasma samples (n = 80) were then collected from 12 JIA patients (5 with pauciarticular, 5 with polyarticular and 2 with the systemic onset type) during treatment with etanercept (0.4 mg/kg twice weekly) for a period of 20.8 (15.6-23.9) months (median, range). The plasma samples were spiked with LT, and the inhibition of LT detection in ELISA was measured. In samples obtained 3 months after the start of etanercept, the inhibition of LT detection was augmented [72% (60-85)] compared with pre-treatment samples [16% (0-32)] (p = 0.0039). These findings were confirmed in binding assays using radiolabelled TNF. Among patients who responded insufficiently to therapy, reduced LT binding capacity, coinciding with flares of disease activity, was observed. Conclusion. We have developed an assay by which LT binding capacity, reflecting the level of free, pharmacologically active etanercept, may be monitored in the blood of patients treated with etanercept. This assay may prove to be useful in guiding dose adjustments in patients with an incomplete response to etanercept

14. HARRIS M, HOFMAN PL, CUTFIELD WS: Growth hormone treatment in children: review of safety and efficacy. Paediatr Drugs 6:2 93-106, 2004
    Organism: Department of Paediatrics, University of Auckland, Auckland, New ZealandFAU - Harris, Mark
    Abstract: Since the advent of growth hormone (GH), the pediatric applications of GH therapy have expanded. Children with a wide variety of growth disorders have received GH treatment. The therapeutic effects and safety profile of GH in a number of pediatric conditions are reviewed, including GH deficiency (GHD), Turner syndrome, chronic renal failure, children born small for gestational age, Prader-Willi syndrome, juvenile chronic arthritis, and cystic fibrosis. GH therapy has been clearly shown to improve height velocity during childhood in a variety of pediatric conditions in which growth is compromised. There is now data that confirms GH treatment also improves final height in a number of diagnostic subgroups. Early initiation and individualization of GH treatment has the potential to normalize childhood growth in children with idiopathic GHD and enable them to achieve their genetic target height in a cost-effective manner. In children in whom GHD is not the main factor compromising growth, supra-physiological doses of GH have been shown to increase height velocity during childhood and final height. The development of predictive models for these conditions may allow further improvements in height outcome while maintaining an acceptable safety profile. Survivors of childhood malignancy, particularly those who have had craniospinal irradiation, represent a particularly challenging group. They appear to be less responsive to GH than children with idiopathic GHD and have a tendency to enter puberty at an earlier age. Both of these factors have a negative impact on their final height. Strategies that combine GH treatment with suppression of puberty using a gonadotropin releasing hormone analog may result in improved height outcomes. When children with GHD are treated with standard doses of GH there is a strong safety record. Adverse events during GH therapy are uncommon and often not drug related. Continued surveillance into adult life is crucial however, particularly in children receiving supra-physiological doses of GH or whose underlying condition increases their risk of adverse effects

15. KASAPCOPUR O, DEMIRLI N, OZDOGAN H, APELYAN M, CALISKAN S, SEVER L, ARISOY N: Evaluation of classification criteria for juvenile-onset spondyloarthropathies. Rheumatol Int .: 1919
    Organism: Department of Pediatrics, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey
    Abstract: OBJECTIVE. The aim of this study was to investigate the adequacy of the following criteria for the classification of juvenile-onset spondyloarthropathies (JSpA): European Spondyloarthropathy Study Group criteria (ESSGCr) and Amor criteria (ACr) (proposed for adult SpA), Garmisch-Partenkirchen (G-PCr), seronegative enthesopathy and arthropathy syndrome (SEACr), and atypical spondyloarthropathies classification criteria (ASpCr) (proposed for JSpA). METHODS. Sixty-two patients with JSpA (48 male and 14 female) and 64 with juvenile idiopathic arthritis (27 male and 37 female) (excluding enthesitis-related and psoriatic arthritis) were enrolled in the study group. Twenty-nine of the patients with JSpA were diagnosed with definite JSpA and the remaining 35 with undifferentiated JSpA. One hundred six patients in the study group were evaluated by one investigator, who was unaware of the diagnosis, according to the following: ESSGCr, ACr, G-PCr, ASpCr, and SEACr. RESULTS. Analysis of the patients diagnosed with JSpA showed 83.9%, 82.3%, 95.2%, 61.3%, and 62.9% sensitivity and 87.5%, 95.3%, 78.1%, 98.4%, and 92.2% specificity for the ESSGCr, ACr, G-PCr, ASpCr, and SEACr sets, respectively. CONCLUSION. None of the criteria evaluated above is sufficient for the classification of JSpA. There is a definite need for a new set of criteria with high specificity and sensitivity for early recognition and classification

16. KIGHT AC, DARDZINSKI BJ, LAOR T, GRAHAM TB: Magnetic Resonance Imaging Evaluation of the Effects of Juvenile Rheumatoid Arthritis on Distal Femoral Weight-Bearing Cartilage. Arthritis and Rheumatism (United States ) 50:3 901-905, 2004
    Abstract: Objective. To examine magnetic resonance imaging-derived T2 relaxation times in the weight-bearing cartilage of the distal femur in healthy children and in children with juvenile rheumatoid arthritis (JRA). Methods. T2 relaxation time maps were created for 39 girls (ages 4.9-10.9 years), 21 of whom were considered healthy and 18 of whom had JRA. The spatial distribution of T2 relaxation times for the distal femoral weight-bearing cartilage (including epiphyseal and articular cartilage) was mapped for each group as a whole. Average data sets for each group were then compared using paired t-tests to detect differences between the 2 populations. Results. The spatial distribution of T2 relaxation time values was nearly identical in the 2 groups, with a concave curve that was highest near the subchondral bone and articular surfaces. The average T2 relaxation times were significantly higher in the girls with JRA than in the group of healthy girls (P < 0.05). Conclusion. The finding of an increased average T2 relaxation time in the children with JRA suggests that T2 relaxation time maps may reflect cartilage microstructure differences that occur in JRA. T2 relaxation time mapping may allow for early detection of cartilage changes and provide an objective, quantitative method of monitoring disease progression, with the long-term potential to guide therapy

17. LARROCHE C, MOUTHON L: Pathogenesis of hemophagocytic syndrome (HPS). Autoimmunity Reviews (Netherlands ) 3:2 69-75, 2004
    Abstract: Hemophagocytic syndrome (HPS) is a clinicopathologic entity characterized by increased proliferation and activation of benign macrophages with hemophagocytosis throughout the reticuloendothelial system. Uncontrolled T-lymphocyte activation is responsible for increased TSUBH1 cytokines secretion such as IFN-gamma, IL-12 and IL-18 that promotes macrophage activation. Genetic defects specific for cytotoxic T lymphocytes (CTL) and natural killer (NK) cells have been identified in patients with primary HPS that are responsible for altered cell death and apoptosis induction or target killing. HPS may be secondary to malignancy, infection or autoimmune disease, and mechanisms involved are poorly understood. However, in adult-onset Still's disease, juvenile chronic arthritis and probably systemic lupus erythematosus, IL-18 might play a role in initiating macrophage activation. (c) 2003 Elsevier B.V. All rights reserved

18. MARIK I, MARIKOVA O, ZEMKOVA D, KUKLIK M, KOZLOWSKI K: Dominantly inherited progressive pseudorheumatoid dysplasia with hypoplastic toes. Skeletal Radiology (Germany ) 33:3 157-164, 2004
    Abstract: Objective: To present four related patients with progressive pseudorheumatoid dysplasia (PPsRD) each with distinctive history, unique phenotype and some peculiar radiographic findings. Results and conclusions: The history was characterised by weather-dependent articular pain. The unique phenotypic features were hypoplasia/dysplasia of one or two toes. Peculiar radiographic findings were hypoplasia of the 3rd and 4th metatarsals, platyspondyly with rectangular shape of the lumbar spinal canal, progressive narrowing of the joint spaces and early synovial chondromatosis. Finally, the condition was inherited as a dominant trait. This constellation of abnormalities constitutes a distinct form of PPsRD. PPsRD must be differentiated from other bone dysplasias, specifically spondyloepiphyseal dysplasias, autosomal dominant spondylarthropathy, juvenile rheumatoid arthritis and osteoarthritis. (c) ISS 2004

19. MCDONAGH JE, SOUTHWOOD TR, SHAW KL: Unmet education and training needs of rheumatology health professionals in adolescent health and transitional care. Rheumatology (Oxford) .: 2004
    Organism: Institute of Child Health, Division of Reproductive and Child Health, University of Birmingham, Birmingham B15 2TT, UK
    Abstract: Objectives. To determine the perceived education and training needs of health professionals involved in transitional care for adolescents with juvenile idiopathic arthritis (JIA). Methods. Two distinct questionnaires to identify transitional issues in JIA were distributed to key health professionals (n = 908) and clinical personnel involved in the implementation of a transitional care programme (n = 22). Results. The first survey was completed by 263 professionals. Education needs were reported by 114 (43%) of health professionals. Transition issues and informational resources were the most frequently reported areas of need. The second survey was completed by 22 clinical personnel who rated 'lack of training', 'lack of teaching materials geared towards adolescents' and 'limited clinic time' as the main barriers to providing developmentally appropriate care to adolescents. Conclusion. Unmet education and training needs of health care professionals exist in key areas of transitional care and provide useful directions for the development of future training programmes

20. MITERSKI B, DRYNDA S, BOSCHOW G, KLEIN W, OPPERMANN J, KEKOW J, EPPLEN JT: Complex genetic predisposition in adult and juvenile rheumatoid arthritis. BMC Genet 5:1 2, 2004
    Organism: Department of Human Genetics, Ruhr-University Bochum, Germany miterski@eurogende
    Abstract: BACKGROUND: Rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) are complex multifactorial diseases caused by environmental influences and an unknown number of predisposing genes. The present study was undertaken in order to investigate association of polymorphisms in candidate genes with RA and JRA in German subjects. RESULTS: Up to 200 unrelated German RA and JRA patients each and 300-400 healthy controls have been genotyped for HLA-DRB1, TNFa, TNFA -238a/g, TNFA -308a/g, TNFA -857c/t, TNFR1 -609g/t, TNFR1 P12P, TNFR2 del 15bp, IKBL -332a/g, IKBL -132t/a, IKBL C224R, CTLA4 -318c/t, CTLA4 T17A, PTPRC P57P, MIF -173g/c, the MIF and IFNG microsatellites as well as for D17S795, D17S807, D17S1821 by polyacrylamide gel electrophoresis, single-strand conformation polymorphism analysis, restriction fragment length polymorphism analysis or allele specific hybridization. None of the investigated genetic markers is associated with both, RA and JRA, but there are some statistically significant differences between patients and controls that have to be discussed sensibly. CONCLUSIONS: The difficulty in investigating the genetics of complex disorders like RA and JRA may arise from genetic heterogeneity in the clinically defined disease cohorts (and generally limited power of such studies). In addition, several to many genes appear to be involved in the genetic predisposition, each of which exerting only small effects. The number of investigated patients has to be increased to establish the possibility of subdivison of the patients according their clinical symptoms, severity of disease, HLA status and other genetic characteristics

21. OYAMA Y, TRAYNOR AE, CRAIG ROBERT_(REPRINT), BARR W, ROSA R, BURT R: Treatment related mortality (TRM) and overall mortality (OM) in patients undergoing autologous hematopoietic stem cell transplantation (HSCT) for autoimmune diseases, a single center experience. Blood 102:11 986a, 2003
    Abstract: Introduction: TRM and OM from autologous HSCT for severe autoimmune diseases (SAD) have been reported higher than initially anticipated. An EULAR/EBMT multicenter analysis reported a TRM in autologous HSCT for scleroderma, multiple sclerosis (MS), rheumatoid arthritis (RA), juvenile rheumatoid arthritis and systemic lupus erythematosus (SLE) were 12.5%, 6%, 2.4%, 14.2% and 13.0%, respectively, while individual centers have reported mortality as high as 27%, particularly for scleroderma. We report our single center experience in seventy-nine patients treated with autologous HSCT for SAD since 1996 focusing on safety. Material and method: There are 79 autograft patients (34 SLE, 25 MS, 10 Crohn's disease (CD), 4 scleroderma, 3 RA, 1 myasthenia gravis (MG), 1 pemphigus, and 1 relapsing polychondritis (RP)). All patients must have active disease and have failed all available conventional therapies in order to be eligible. Cyclophosphamide (Cy), equine (e) or rabbit (r) anti-thymocyte globulin (ATG), Campath-1H (CH) and total body irradiation (TBI) were used as follows: Cy(120/kg)/TBI(1200cGy) for the first 22 MS patients; Cy(200mg/kg)/CH(20mg) for the last 3 MS patients; Cy(200/kg)/eATG(90/kg) for SLE, CD, RP, and RA; Cy/(200/kg)/rATG(5/kg) for pemphigus; Cy(200/kg)/rATG(7.5/kg) for scleroderma; and Cy(200/kg)/rATG(5.5/kg) for MG. Graft's were all CD34 selected via Isolex 300i (Nexell, Irvine, CA) except scleroderma and the last 3 MS patients that were unmanipulated peripheral blood stem cells. Result: Patients beyond 100-days, one-year and two-year post-transplant were 69, 51 and 35 respectively. No patient who underwent autologous HSCT died due to treatment related toxicity. Only 3 patients have died due to either progressive multiple sclerosis (2 patients both with high pre-transplant disability score) or relapsed SLE (1 patient). Death occurred at 11 months, 24 months and 17 months post-transplant, respectively. After follow up duration from 1 to 78 months, the TRM and OM was 0% and 3.8% (3 out of 79), respectively. Conclusion: These results indicate that with experience in treating these diseases, appropriate patient selection, and designing conditioning regimens, it is possible to achieve very low TRM and OM in patients with SAD undergoing autologous HSCT. Further studies will clarify the role of autologous HSCT in the management of this patient group

22. RAMANAN AV, SCHNEIDER R: Drs. Ramanan and Schnieder reply: Macrophage Activation Syndrome and Etanercept in Children with Systemic Juvenile Rheumatoid Arthritis. J Rheumatol 31:3 623-624, 2004

23. ROVETTA G, MONTEFORTE P, MOLFETTA L: Evaluating pain in osteoarthritis of the hands: the effect of patient information. Int J Clin Pharmacol Res 23:2-3 61-67, 2003
    Organism: Rheumatology Center, Istituto Bruzzone, USL 3, Rheumatology Medical School, Dipartimento Scienze Endocrinologiche e Metaboliche, University of Genoa, Italy bruzzone@unigeitFAU - Rovetta, G
    Abstract: The evaluation of osteoarthritis pain is principally based on a subjective rating scale. Accuracy in recording pain score is obviously important. In the present study we evaluated the effect of better standardization of information given to patients in determining the visual analog scale (VAS) score. Fifty-three consecutive male and female outpatients aged 18-65 years (40 women and 13 men) fulfilling the criteria for osteoarthritis of the hands were included in the study. Eligible patients attended the Rheumatology Center on three occasions: day 1, day 3 and day 6 of the study. Two information cards were prepared. On the first card, given to the patient at the end of the first visit, osteoarthritis of the hands was described as a less dangerous disease than rheumatoid arthritis. On the second card, given to patients at the end of the second visit, greater emphasis was placed on anatomo-pathological description of the destructive lesions. VAS score was recorded on days 1, 3 and 6 of observation. ANOVA for repeated measures demonstrated a significant reduction of VAS score between the first and the second assessment and a significant increase between the second and the third assessment. A further significant difference was found in the comparison between the first and third assessment. These results show that different standards of information given to patients may modify VAS score

24. SALLFORS C, HALLBERG L-R, FASTH A: Well-being in children with juvenile chronic arthritis. Clinical and Experimental Rheumatology (Italy ) 22:1 125-130, 2004
    Abstract: Objective. The aim of this study was to describe a model for predicting well-being in children with juvenile chronic arthritis (JCA). Methods. 125 children (43 boys) (median age 14.1 yrs; range 10.3 - 17.8) rated disability and discomfort (Childhood Health Assessment Questionnaire). Pain control, pain reduction and fatigue were evaluated (visual analogue scales). In addition, variation of pain intensity was rated by a pain intensity scale. Analysis by the stepwise regression technique was used to explain the variability in well-being. Eight independent variables were included as possible predictors in the model (p < 0.1). Results. The analyses indicated that well-being in children with JCA is related to three clusters of variables; pain "as it normally is", number of pain-free days and attending physical education classes. The analysis explained a substantial portion of the total variance in the children's well-being (55.1%). Conclusion. Pain is a robust predictor of well-being in children with JCA. This supports the concept of the benefits of reducing chronic joint pain as a major goal in caring of these children

25. SARWAR H, ESPINOZA LR, GEDALLA A, RAMANAN AV, SCHNEIDER R: Macrophage Activation Syndrome and Etanercept in Children with Systemic Juvenile Rheumatoid Arthritis [1] (multiple letters). Journal of Rheumatology (Canada ) 31:3 623-624, 2004

26. SAWYER MG, WHITHAM JN, ROBERTON DM, TAPLIN JE, VARNI JW, BAGHURST PA: The relationship between health-related quality of life, pain and coping strategies in juvenile idiopathic arthritis. Rheumatology (United Kingdom ) 43:3 325-330, 2004
    Abstract: Objectives. To investigate the relationship between health-related quality of life (HRQL), experience of pain and pain coping strategies in children with juvenile idiopathic arthritis (JIA). To compare reports describing these variables obtained from children and their parents. Methods. Participants were 59 children aged 8 to 18 yr with JIA and their parents. Parents and children completed the PedsQL(TM) generic core scales and arthritis module, the visual analogue scale of the Varni-Thompson Pediatric Pain Questionnaire, and the Waldron/Varni Pediatric Pain Coping Inventory. Parents rated children's functional disability using the Childhood Health Assessment Questionnaire. Results. Parents reported significantly lower scores (indicating worse HRQL) than children on five of the eight PedsQL(TM) scales rating children's HRQL. Parents and children reported a significant negative relationship between pain levels and the PedsQL(TM) scores assessing children's physical, emotional and social functioning. They also reported a significant negative relationship between scores on several pain coping scales and scores on the PedsQL(TM) scales. However, the pattern of these relationships varied for reports from parents and children. Conclusions. Pain intensity and pain coping strategies have a significant and independent relationship with several domains that comprise the HRQL of children with JIA. However, parents and children have differing perceptions of the nature of these relationships. The differences emphasize the importance of clinicians obtaining information about children's HRQL, pain levels and pain coping strategies from both parents and children. (c) British Society for Rheumatology 2003; all rights reserved

27. SCHMITT A, SCHUBERT D, SENGLER C, KAMRADT T: Autoantibodies against glucose-6-phosphate isomerase are not a diagnostic marker for juvenile idiopathic arthritis. Ann Rheum Dis 63:4 463, 2004

28. SHAW KL, SOUTHWOOD TR, MCDONAGH JE: Developing a programme of transitional care for adolescents with juvenile idiopathic arthritis: Results of a postal survey. Rheumatology (Oxford) 43:2 211-219, 2004
    Abstract: Objectives: To explore the transitional needs of adolescents with juvenile idiopathic arthritis (JIA), as perceived by a range of professionals, and to examine how these needs may be addressed within a structured programme of transitional care. Methods: Postal surveys (n=1670) were distributed to key professionals employed in health, social support, education and vocation. Results: Surveys were completed by 478 individuals. The majority of respondents (91%) were currently active in the care of adolescents with JIA. Planning for transitional care was perceived to be important for both adolescents and parents and to require multidisciplinary involvement. Respondents rated a wide range of resources to be important in supporting adolescents, including self-medication teaching packages and social skills training. A number of barriers to providing transitional care were identified, including inadequate resources, coordination and training. Conclusion: Transitional care in the context of JIA is perceived as necessary by a wide variety of professionals

29. SHAW KL, SOUTHWOOD TR, MCDONAGH JE: User perspectives of transitional care for adolescents with juvenile idiopathic arthritis. Rheumatology (Oxford) .: 2004
    Organism: Institute of Child Health, University of Birmingham, Birmingham, UK
    Abstract: OBJECTIVES: To gain insight into the transitional needs of adolescents with juvenile idiopathic arthritis (JIA) and to examine how these needs may be addressed within a structured programme of transitional care. METHODS: A qualitative study using focused group discussions was performed. Groups comprised (i) adolescents with JIA aged 12-18 yr, (ii) young adults with JIA aged 19-30 yr, (iii) parents of adolescents with JIA, and (iv) parents of young adults with JIA. RESULTS: Transitional needs included aspects of participants' physical, social, psychological and vocational lives. Participants (n = 55) called for developmentally appropriate care based upon shared decision-making, continuity of health professionals, and wider access to information and community services. Suggestions for improved care included individualized assessment of patient's holistic needs and increased transfer preparation. CONCLUSIONS: These results provide a useful guide to transitional care and suggest an approach that is adolescent-focused and evidence-based

30. SIMONINI G, AZZARI C, GELLI AM, GIANI T, CALABRI GB, LEONCINI G, DEL ROSSO A, GENERINI S, CIMAZ R, CERINIC MM, FALCINI F: Neprilysin levels in plasma and synovial fluid of juvenile idiopathic arthritis patients. Rheumatol Int .: 2004
    Organism: Rheumatology Unit, Department of Pediatrics, University of Florence, Via Pico della Mirandola 24, 50132, Florence, Italy
    Abstract: OBJECTIVE. Neprilysin (neutral endopeptidase, 3:4:24:11, CD10) (NEP) is a Zn metallopeptidase linked to controlling inflammation through the degradation of neuropeptides involved in neurogenic inflammation of chronic rheumatic diseases. The aim of our study was to evaluate circulating activity and cellular expression of NEP in the plasma of 58 children with juvenile idiopathic arthritis (JIA) and 52 controls. In 20 subjects requiring local steroid injection, NEP was measured in synovial fluid. METHODS. Plasma and synovial NEP were evaluated using a fluorimetric technique. Neprilysin, expressed as the antigen CD10, was determined on circulating and synovial fluid cells as mean fluorescence intensity (MFI) and as percentage of positive cells by two-color immunofluorescence. RESULTS. Circulating NEP levels were lower in JIA patients than in controls (42.0+/-16.6 vs 76.5+/-24 pmol/ml per min, P<0.001), while synovial fluid NEP values were higher than circulating levels (241.4+/-86.2 vs 40+/-15.3 pmol/ml per min, P<0.001). In monocytes, the percentage of CD10-positive circulating cells and the MFI in JIA were lower than in controls (11.6+/-5.2% vs 41.4+/-13%, P<0.001 and 18.1+/-7.5 vs 31.2+/-5.4, P<0.05, respectively). On synovial monocytes, the percentage of CD10-positive cells and the MFI were higher than on circulating monocytes (35.2+/-14.6% vs 9.1+/-2.4%, P<0.001 and 66.4+/-5.4 vs 22.8+/-14.7, P<0.001, respectively). CONCLUSIONS. The downregulation of CD10 expression in monocytes and the reduction in NEP activity may be linked to the enzyme's role in the control of peptides involved in the inflammation. The increased levels of NEP, MFI, and CD10-positive monocytes in synovial fluid, even though in plasma, might reflect a reactive effort to control synovial proliferation

31. SINHA AK, AGARWAL A, LAKHEY M, ANSARI J, RANI S: Pure red cell aplasia - Report of 11 cases from eastern Nepal. Indian Journal of Pathology and Microbiology (India ) 46:3 405-408, 2003
    Abstract: There were eleven cases of pure red cell aplasia diagnosed over a period of 2 years (January 2000-December 2001). All the patients had anemia with pallor and weakness being the presenting complaints. Hematological profile depicted normocytic normochromic anemia, reticulocytopenia and marked paucity of eythroid precursors on bone marrow aspiration and biopsy studies. In the present study, one case was of congenital pure red cell aplasia, in one other case of pyrexia of unknown origin, no definitive diagnosis could be made. Other associated diseases seen with pure red cell aplasia were thymoma, septicemia, protein energy malnutrition, non-hodgkin's lymphoma, juvenile rheumatoid arthritis, acute myeloid leukemia, tuberculosis and hepatitis C. The association of pure red cell aplasia with haematologic malignancies is rare. There are very few case reports on pure red cell aplasia with hepatitis C

32. SMOLEWSKA E, BROZIK H, SMOLEWSKI P, DARZYNKIEWICZ Z, STANCZYK J: Regulation of peripheral blood and synovial fluid lymphocyte apoptosis in juvenile idiopathic arthritis. Scandinavian Journal of Rheumatology (Norway ) 33:1 7-12, 2004
    Abstract: Objective: Complex regulatory mechanisms are involved in the induction of apoptosis. Their impairment may play a role in the pathogenesis of several autoimmune diseases. Recently, we have described higher incidences of spontaneous apoptosis of peripheral blood (PB) lymphocytes in children with juvenile idiopathic arthritis (JIA). This study aimed to evaluate the regulatory mechanisms that may be responsible for this phenomenon. Methods: Thirty-four JIA children were examined and compared with 20 healthy children of similar ages. Expression of regulatory proteins p53, Bax and Bcl-2 in lymphocytes isolated from PB and synovial fluid (SF) was assessed. Serum and SF levels of interleukin-15 (IL-15) were also evaluated. Results: The study showed significantly decreased Bcl-2 expression in JIA PB lymphocytes, compared to both healthy control (p=0.03) and JIA SF lymphocytes (p=0.005). There were no significant differences found in Bax expression between groups or compartments examined. However, the Bax/Bcl-2 ratio was nearly two-fold higher in PB lymphocytes than in SF of JIA patients (p=0.001). p53 expression in PB lymphocytes from both JIA and control children did not statistically differ. In JIA, however, p53 was significantly higher in PB than SF lymphocytes (p=0.016). IL-15 levels were about 20-fold higher in JIA SF than in serum from either JIA or healthy children (p<0.0001). Conclusion: The results suggest that a higher incidence of apoptosis of PB lymphocytes observed in JIA may be associated with down-regulation of Bcl-2, rather than with changes in expression of Bax and p53. In contrast, the low p53 expression and elevated IL-15 appear to provide mechanisms responsible for suppression of apoptosis in SF cells from JIA patients

33. STEERE AC, GLICKSTEIN L: Elucidation of Lyme arthritis. Nature Reviews Immunology (United Kingdom ) 4:2 143-152, 2004
    Abstract: Before the first description of Lyme arthritis in 1976, patients with this disease were often thought to have juvenile or adult rheumatoid arthritis. It is now known that Lyme arthritis is caused by a tick-borne spirochete that disseminates to joints, where it induces marked pro-inflammatory responses. In most patients, the arthritis resolves with antibiotic treatment. However, in the United States, about 10% of patients with Lyme arthritis develop persistent synovitis, which lasts for months or even several years after the apparent eradication of the spirochete from the joint with antibiotic therapy. The elucidation of Lyme arthritis, from acute infection to chronic synovitis, might help in our understanding not only of this entity, but also of other forms of chronic inflammatory arthritis, including rheumatoid arthritis

34. STEGEMAN M, RIJNBERG WJ, VAN LOON CJ: Biaxial total wrist arthroplasty in rheumatoid arthritis. Satisfactory functional results. Rheumatol Int .: 2004
    Organism: Ziekenhuis Rijnstate, Postbus 9555, 6800 TA, Arnhem, The Netherlands
    Abstract: We reviewed 16 uncemented biaxial total wrist arthroplasties (TWA) in 14 patients with rheumatoid or juvenile arthritis. The mean follow-up was 25 months (range 5-60). According to the Hospital for Special Surgery scoring system (HSS), good-to-excellent results were accomplished in 69%, moderate in 19%, and poor in 12%. The mean pain score was 0.4 on a visual analog scale from 0-10 (0=no pain). The Wrightington activities of daily life assessment chart showed a 63% improvement, and we found a threefold increase in range of motion at follow-up. Four TWAs showed early dislocation, one of which was revised. Biaxial TWA yields good short-term results in rheumatoid patients, although instability is a frequent complication

35. VAN GAALEN FA, LINN-RASKER SP, VAN VENROOIJ WJ, DE JONG BA, BREEDVELD FC, VERWEIJ CL, TOES RE, HUIZINGA TW: Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study. Arthritis Rheum 50:3 709-715, 2004
    Organism: Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands favan_gaalen@lumcnlFAU - van Gaalen, F A
    Abstract: OBJECTIVE: Rheumatoid arthritis (RA) is a common, severe, chronic inflammatory joint disease. Since the disease may initially be indistinguishable from other forms of arthritis, early diagnosis can be difficult. Autoantibodies seen in RA can be detected years before clinical symptoms develop. In an inception cohort of patients with recent-onset arthritis, we undertook this study to assess the predictive value of RA-specific autoantibodies to cyclic citrullinated peptides (CCPs) in patients with undifferentiated arthritis (UA). METHODS: Anti-CCP2 antibody tests were performed at baseline in 936 consecutive, newly referred patients with recent-onset arthritis. Patients who could not be properly classified 2 weeks after inclusion were categorized as having UA. Patients with UA were followed up for 3 years and evaluated for progression of their disease to RA as defined by the American College of Rheumatology (ACR) 1987 revised criteria. RESULTS: Three hundred eighteen of 936 patients with recent-onset arthritis were classified as having UA and were available for analysis. After 3 years of followup, 127 of 318 UA patients (40%) had been classified as having RA. RA had developed in 63 of 249 patients (25%) with a negative anti-CCP test and in 64 of 69 patients (93%) with a positive anti-CCP test (odds ratio 37.8 [95% confidence interval 13.8-111.9]). Multivariate analysis of the presence of anti-CCP antibodies and parameters from the ACR criteria identified polyarthritis, symmetric arthritis, erosions on radiographs, and anti-CCP antibodies as significant predictors of RA. CONCLUSION: Testing for anti-CCP antibodies in UA allows accurate prediction of a substantial number of patients who will fulfill the ACR criteria for RA

36. WAKHLU A, GUPTA D, AGGARWAL A, MISRA R: Low levels of anti-histone antibodies in north Indian children with juvenile rheumatoid arthritis. Indian Journal of Medical Research 118:November 204-207, 2003
    Abstract: Background & objectives: Early onset pauciarticular disease with uveitis is distinctly uncommon in Indian children with juvenile rheumatoid arthritis (JRA). The occurrence of anti-histone antibodies (AHA) in serum is strongly associated with presence of uveitis. There is a paucity of information from India on the levels of AHA in patients of JRA. In this study, an attempt was made to evaluate the levels of IgG and IgM antibodies to histones in children with JRA in north India. Methods: Serum samples of 148 children with JRA (84 boys, 64 girls) were collected. Clinical details including onset, symptoms and course of the disease in each patient were recorded. Detailed eye examination including slit lamp examination was done in all patients at presentation and yearly thereafter to rule out uveitis. The presence of antihistone IgG and IgM antibodies was studied by ELISA. Antinuclear antibodies (ANA) were measured by indirect immunofluorescence using HEP-2 cells as substrate at a screening dilution of 1:40. Results: Of the 148 children, 54 had pauciarticular (12 early onset and 42 late onset), 64 polyarticular and 30 systemic onset disease respectively. ANA were present in two children. AHA were raised in 15 (10%) children, of whom 10 had IgM antibodies, 3 had IgG and 2 had both isotypes. None of the children with early onset pauciarticular disease had uveitis, ANA or AHA. Interpretation & conclusion: The low occurrence of AHA and uveitis in our subset of patients with JRA is in contrast to that reported from Western countries. The low occurrence is unlikely due to technical reasons as the antigen that has been used consistently showed significant binding to serum from patients with systemic lupus erythematosus (SLE). This is in accordance with the rarity of early onset pauciarticular disease and chronic uveitis in these patients. More studies from other parts of the country are required to validate this observation

37. WANCHU A, CHAWLA Y, DHIMAN RK, SUD A, BAMBERY P: Paucity of anti-hepatitis C virus antibodies in the serum of Indian patients with Sjogren's syndrome and inflammatory myositis. Indian J Pathol Microbiol 46:2 191-193, 2003
    Organism: Department of Internal Medicine, Post-Graduate Institute of Medical Education and Research, Chandigarh awanchu@yahoocomFAU - Wanchu, A
    Abstract: Several extrahepatic manifestations have been associated with infection with Hepatitis C virus (HCV) infection. It has been associated with Sjogren's syndrome (SS) and inflammatory myositis (IM). The objective was to look at the prevalence of anti-HCV antibodies in the serum of SS and IM patients of Indian origin. Individuals satisfying the European Economic Community criteria for the diagnosis of SS and those satisfying the criteria of Bohan and Peter for the diagnosis of IM were recruited in the study. Routine evaluation for liver functions was made. Anti-HCV antibodies were tested by a third generation ELISA, using microplate HCV3.0 ELISA. Of the 23 patients with SS studied, 14 had extraglandular features. The commonest were anaemia and arthritis in six each, followed by in lymphopenia in two. One patient each had interstitial lung disease, hypothyroidism and chronic active hepatitis. Twenty-two patients with IM were studied alongside. None of the patients had abnormal liver functions. One patient with primary SS tested positive for anti-HCV antibodies. None of the patients with inflammatory myositis tested positive for anti-HCV antibodies. The presence of anti-HCV antibodies in our cohort of patients with SS and IM is low and more in keeping with the generally low prevalence of the infection in the Indian population

38. YOKOTA S: [Effective application of anti-IL-6-monoclonal antibody for children with systemic-onset juvenile idiopathic arthritis]. Nihon Rinsho Meneki Gakkai Kaishi 27:1 22-27, 2004
    Organism: Department of Pediatrics, Yokohama City University School of MedicineFAU - Yokota, Shumpei