Bibliography February 2003

1. ADAMEC O, DUNGL P, KASAL T, CHOMIAK J: Knee joint synovectomy in the treatment of juvenile rheumatoid arthritis. Acta Chirurgiae Orthopaedicae et Traumatologiae Cechoslovaca 2002, 69:350-356.
   Organism:Dr. O. Adamec, Ortopedicka Klinika IPVZ a 1. LF UK, FN Na Bulovce, Budinova 2, 180 81 Praha 8
   Abstract: Purpose of the Study. The objective of this study was to assess short-term outcomes of knee joint synovectomy in a group of patients with juvenile rheumatoid arthritis and to present the authors' view on this approach. Material. Between 1990 and 1999, synovectomy of the knee joint was performed in a group of 46 children with juvenile rheumatoid arthritis. This group comprised 19 girls and 27 boys aged 4 to 16 years (mean 9.8 years) with all forms of the disease. A total of 85 synovectomy procedures, including repeat operations, were performed on 58 knee joints. Methods. Arthroscopic synovectomy was used to treat 21 knee joints, open synovectomy from two approaches was indicated, as a primary procedure, in 37 knees. The assessment of subjective and functional conditions of patients was based on a modified rating systems of Lysholm and X-ray films were evaluated by the Larsen classification. The evaluation was carried out at 1 and 2 years after the primary operation. Results. Articular lesions corresponding to mere synovitis were found in 10 knee joints (17.2%), a developing pannus without erosion was seen in 16 (27.6%) and erosion of the articular surface in 32 (55.2%) knee joints. At 1 year, the value of Lysholm's score rose from 47.9 to 84.3 points and was followed by a decrease to 73.2 at 2 years. Within 2 years of the primary operation, the condition recurred in 9 out of 21 knees (42.8%) treated by arthroscopic synovectomy and in 12 cases (32.4%) operated on by open synovectomy. The relapse was observed mostly in patients with an overall high inflammatory activity and polyarticular and systemic progression of the disease. Discussion. We do not agree with the view of some authors that surgical intervention is not indicated until erosions are radiologically manifested. In children, erosions usually present at a late stage, as shown by 12 findings of articular surface destruction in our group that were not detected by radiography. For indication purposes, we distinguished between preventive and therapeutic synovectomy. We found a significant association between the overall activity and early recurrence of the disease. In 60.7% of the cases (28) with excellent outcomes, this activity was low at the time of surgery. On the other hand, in 75% of the cases (8) with poor outcomes, the activity of disease was very high and had a lasting tendency to recur. These findings are in agreement with the conclusions of several other authors who consider the presence of systemic disease to be a contraindication for synovectomy. Advantages of arthroscopic synovectomy reported in adult patients seem to be relative in children. A good view of and accessibility to individual aticular components, which are made an advantage of in the adult knee, are rather exceptional in the "tight" child knee. The evaluation of our patients at a short-term follow-up did not give convincing results although the early effect of synovectomy was very good. The poor outcomes seen in our group, which corresponded with observations of other authors, allow us to learn more about the potentials of synovectomy and thus to promote our policy of a thorough consideration of indications for surgery. Conclusions. Indications for surgical treatment in patients with juvenile rheumatoid arthritis are evaluated in cooperation with a rheumatologist after an appropriate conservative therapy administered for at least 6 months. Cases with clear signs of plastic synovitis and skeletal lesions shown by radiography as well as all recurrent conditions are treated by open synovectomy. The state of low disease activity is preferred for surgical intervention. It has to be borne in mind that, from whole range of curative procedures, conservative therapy supervised by a pediatric rheumatologist is the method of choi

2. AGLE LMA, ROSENKRANZ M, LEHMAN TJA: Novel therapies for the treatment of juvenile rheumatoid arthritis (juvenile idiopathic arthritis). Expert Opinion on Investigational Drugs 2003, 12:19-28.
   Organism:Dr. T.J.A. Lehman, Division of Pediatric Rheumatology, Hospital for Special Surgery, Cornell University, 535 East 70th street, New York, NY 10021
   Abstract: The majority of children with juvenile idiopathic arthritis respond well to conventional treatment. However, some children will have a more aggressive disease course and will be resistant to standard management. Over the past 20 years, growth in our understanding of the immunopathogenesis of juvenile idiopathic arthritis and related diseases has facilitated significant therapeutic advances. In this report, recently released antirheumatic drugs, as well as some treatments currently in development, will be discussed. Biological agents, such as antiTNF and other cytokines inhibitors, and unique drugs, such as thalidomide, provide new opportunities to suppress the inflammation found in severe cases of systemic onset juvenile idiopathic arthritis and can obtain a satisfactory outcome
   Internet : goldscout@aol.com

3. ARBEITSGEMEINSCHAFT FUER KINDER UND JUGENDRHEUMATOLOGIE: 12th Annual meeting of the Arbeitsgemeinschaft fuer Kinder- und Jugendrheumatologie, Garmisch-Partenkirchen, Germany, November 14-16, 2002. Aktuelle Rheumatologie 2002, 27:267-281.
   Abstract: This meeting consisted of 53 abstracts, written in German and in English. The meeting dealt with various aspects of diagnosis, therapy, immunology and cell biology of rheumatic diseases in the human infant, child, and adolescent. Major topics under discussion included juvenile idiopathic arthritis, systemic lupus erythematosus, mixed connective tissue disease, drug-induced lupus, Kawasaki syndrome, Behcet's syndrome, central nervous system vasculitis, oligoarthritis, juvenile dermatomyositis, CINCA syndrome, rhabdomyolysis, complex regional pain syndrome, Borrelia burgdorferi, and Epstein-Barr virus

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4. BODEMER C, CRICKX B, ROUJEAU J-C: [Eruptive diseases in the child.]
   <ORIGINAL> Maladies eruptives de l'enfant. Annales de Dermatologie et de Venereologie 2002, 129:2S76-2S82.
   Organism:Necker-Enfants Malades, Paris, France France

5. BOWYER SL, ROETTCHER PA, HIGGINS GC, ADAMS B, MYERS LK, WALLACE C, RENNEBOHM R, MOORE TL, PEPMUELLER PH, SPENCER C, WAGNER-WEINER L, RABINOVICH E, PASSO M, LOVELL DJ, MADSON K, MCCURDY D, ZEMEL L, SCHIKLER KN, SZER I, KURTIN P, LINDSLEY C: Health status of patients with juvenile rheumatoid arthritis at 1 and 5 years after diagnosis. Rinsho Ganka 2003, 30:394-400.
   Organism:Dr. S.L. Bowyer, J. W. Riley Hosp. for Children, 702 Barnhill Dr., Indianapolis, IN 46202
   Abstract: Objective. To describe the health and functional status of children with juvenile rheumatoid arthritis (JRA) diagnosed in the early 1990s. Methods. Patients were obtained from the Pediatric Rheumatology Disease Registry, a database of patients seen in pediatric rheumatology centers across the United States. Questionnaires designed to be filled out after retrospective chart review were sent to pediatric rheumatologists caring for children diagnosed with JRA between 1992 and 1997. Results. We studied 703 patients - 376 with pauciarticular onset (pauci), 232 with polyarticular onset (poly), and 95 with systemic onset JRA (systemic). At 1 year after diagnosis, half of the pauci and systemic patients no longer required medication, compared to 78% of the poly patients; 98% of the patients functioned in Steinbrocker classes I and II. Six percent of pauci, 27% of poly, and 11% of systemic patients had limitations in school function. Nearly 1/3 of poly patients already had joint space narrowing on radiograph. By 5 years after diagnosis, all pauci, 88% of poly, and 70% of systemic patients were in Steinbrocker classes I and II; but 6% of pauci, 28% of poly, and 44% of systemic patients had limitations in school function. Nearly 2/3 of poly and systemic patients had joint space narrowing. Conclusion. In these children treated prior to the era of biologic therapy, at 5 years after onset, > 25% of poly and nearly half of systemic patients had functional limitations that required modifications in their school schedule. Radiographically evident joint space damage was seen within a year of onset in poly patients, and by 5 years 2/3 of poly and systemic patients had damage

6. CLEARY AG, MURPHY HD, DAVIDSON JE: Intra-articular corticosteroid injections in juvenile idiopathic arthritis. Arch.Dis.Child 2003, 88:192-196.
   Organism:Royal Liverpool Children's Hospital, Eaton Road, Liverpool L12 2AP, UK gavincleary@talk21com
   Abstract: Therapeutic intervention with intra-articular steroid injections in juvenile idiopathic arthritis (JIA) has evolved from experience with adults with inflammatory joint disease, with the earliest report being published in 1951. The technique has subsequently been introduced into paediatric rheumatology practice, although much of the evidence supporting its use remains anecdotal or based on open, non-controlled studies. This review examines the body of evidence relating to many aspects of treating children with JIA with intra-articular steroids, and is approached from both a medical and a physiotherapy perspective. Where appropriate, important areas for future research are identified and discussed
   Internet : PM:12598375

7. DONG H, STROME SE, MATTESON EL, MODER KG, FLIES DB, ZHU G, TAMURA H, DRISCOLL CL, CHEN L: Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis. J.Clin.Invest 2003, 111:363-370.
   Organism:Department of Immunology, Mayo Medical School and Graduate School, Mayo Clinic, Rochester, Minnesota 55905, USA
   Abstract: A pathogenic hallmark of rheumatoid arthritis (RA) is persistent activation of self-reactive CD4(+) T cells. The cause of this aberrant activity remains elusive. We report here detection of autoantibodies against B7-H1, a recently described member of the B7 family, in 29% of patients with RA versus 4% of healthy donors. High-level expression of cell surface B7-H1 are found on activated human CD4(+), CD8(+), and CD45RO(+) T cells. Immobilized autoantibodies to B7-H1 are capable of costimulating the proliferation of CD4(+) T cells in vitro, and the presence of these autoantibodies correlates with active disease status. Using immobilized B7-H1 mAb's and programmed death 1Ig, we demonstrate that engagement of B7-H1 on CD4(+) T cells costimulates proliferation and secretion of IL-10, and subsequently leads to programmed cell death, accompanied with upregulated expression of TNF-related apoptosis-inducing ligand and activation of caspase-3. Taken together with our previous findings, these data indicate a bidirectional signaling role of B7-H1 in T cell costimulation and apoptosis and implicate B7-H1 autoantibodies as contributing to the progression of RA by inducing aberrant T cell responses
   Internet : PM:12569162

8. EIERMANN TH, VEJBAESYA S, PRESTEL H, ROEPKE A, MUELLER-MYHSOK B, SCHMITT-EGENOLF M: Association and linkage of human leukocyte antigens with psoriasis: Revisited. Infusion Therapy and Transfusion Medicine 2002, 29:326-330.
   Organism:Abteilung fuer Transfusionsmedizin, Universitaetsklinikum Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany Germany^E-Mail: eiermann@uke.uni-hamburg.de
   Abstract: Until recently blood group and HLA antigens have been used extensively to study associations with human disease. Case control studies reproducibly showed significant associations of particular HLA antigens with various human diseases. These were mainly autoimmune diseases such as juvenile diabetes, multiple sklerosis, rheumatoid arthritis, psoriasis and celiac disease, but also others, e.g. narcolepsy and familial hemochromatosis. With restriction fragment length polymorphism (RFLP), short tandem repeats (STR) and recently single nucleotide polymorphism of DNA, many polymorphic markers spread across the entire genome have been available for about 10 years. These markers were successfully applied in family-based linkage studies to localize disease genes. Today we recognize that successful positional cloning with linkage analysis is mainly limited to rare diseases with Mendelian trait. But for most of the common familial diseases (e.g. juvenile diabetes and psoriasis) a simple Mendelian trait seems unlikely. A polygenic model is more appropriate. This complicates the search and definition of susceptibility genes. In addition within the HLA gene region linkage studies are hampered by allelic association between neighboring genes (linkage disequilibrium), effecting disease associations. Case control studies in different ethnic populations may be a solution to this problem

9. FLATO B, LIEN G, SMERDEL A, VINJE O, DALE K, JOHNSTON V, SORSKAAR D, MOUM T, PLOSKI R, FORRE O: Prognostic factors in juvenile rheumatoid arthritis: A case-control study revealing early predictors and outcome after 14.9 Years. Rinsho Ganka 2003, 30:386-393.
   Organism:Dr. B. Flato, Center for Rheumatic Diseases, Rikshospitalet University Hospital, 0027 Oslo
   Abstract: Objective. To describe the physical and psychosocial outcome in patients with juvenile rheumatoid arthritis (JRA), compared with subjects in the general population, and to determine patient characteristics, HLA alleles, and disease variables within the first 6 months of disease onset that predict persistent disease, joint erosions, and physical disability. Methods. A cohort of 268 (85%) of 316 patients with JRA first admitted to the hospital between 1980 and 1985 were examined after a median of 14.9 years (range 11.7-25.1) of disease duration. Controls matched for age, sex, and geographic region were randomly selected from the general population. Patients' medical records were retrospectively reviewed. Clinical examinations and radiographs of the hips, ankles, and affected joints were obtained. HLA-DRB1 and DPB1 alleles were determined by genotyping and HLA-B27 by serologic testing. Physical and psychosocial health status was assessed using the Short-Form Health Survey (SF-36) and the Health Assessment Questionnaire (HAQ). Results. At followup, 133 patients with JRA (50%) were in remission, 63 (24%) had developed joint erosions, and 93 (36%) had impaired physical functioning (HAQ > 0.0). Patients had greater disability, more bodily pain, and poorer general health than controls. Comparable levels of education, social function, and mental health were found, but the patients had higher rates of unemployment than controls (19% vs 7%; p < 0.001). Predictors of persistent disease and joint erosions were: young onset age and large numbers of affected joints, long duration of elevated erythrocyte sedimentation rate (ESR), and positive IgM rheumatoid factor (RF) within the first 6 months. Additionally, persistent disease was predicted by the presence of DRB1*08, and joint erosions were predicted by symmetric arthritis and DRB1*08 and HLA-B27 in combination. DRB1*01 was a predictor of joint erosions in the pauciarticular onset type (n = 163). Predictors of physical disability were: female sex, symmetric arthritis, hip joint involvement, long duration of elevated ESR and IgM RF. Conclusion. Compared with healthy controls, patients with JRA had impaired physical health and lower employment rates after more than 11 years of disease duration. Elevated ESR, extensive and symmetric arthritis, positive IgM RF, DRB1*08, DRB1*01, HLA-B27 and DRB1*08 in combination, early onset, and female sex were early risk factors for an unfavorable outcome
   Internet : beritflato@rikshospitalet.no

10. FRENCH SPEAKING SOCIETY FOR PAEDIATRIC RHEUMATOLOGY AND INFLAMMATORY DISEASES: Congress of the French Speaking Society for Paediatric Rhumatology and Inflammatory Diseases (SOFREMIP). Archives De Pediatrie 2002, 9:1107-1111.
    Abstract: This meeting consisted of 13 abstracts, all written in French. The meeting dealt with a variety of aspects of rheumatic and inflammatory diseases in the human infant, child, and adolescent. Major topics under discussion included systemic juvenile idiopathic arthritis, lupus erythematosus, mevalonic aciduria, venous angioma, sarcoidosis, osteomyelitis, and cell biology

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11. FROSCH M, FOELL D, GANSER G, ROTH J: Arthrosonography of hip and knee joints in the follow up of juvenile rheumatoid arthritis. Ann.Rheum.Dis. 2003, 62:242-244.
    Organism:Department of Paediatrics, University of Muenster, Albert-Schweitzer-Str 33, D-48149 Muenster, Germany froschm@uni-muensterde
    Abstract: OBJECTIVE: To evaluate sensitivity of arthrosonography of hip and knee joints for monitoring disease activity in juvenile rheumatoid arthritis (JRA). METHODS: Twenty eight patients with JRA with active disease at entry in 15 hips and 38 knee joints were followed up three times in intervals of 4-6 weeks. Sonographic, clinical, and laboratory findings were documented at the same time in clinically active and inactive disease. As controls of the sonographic variables 10 children without a history of arthritis were examined by ultrasound. RESULTS: In active arthritis of the hip joint 19/31 (61%) examinations showed a pathological widening of the synovial joint space. There was no significant correlation between sonographic and clinical measures of disease activity in coxitis. Marked effusion within the suprapatellar pouch was seen in 87% and thickening of the synovial membrane in 92% of cases of active gonarthritis in patients with JRA. There was a significant difference in the number of patients with joint effusion and in the mean joint effusion between patients with clinically active gonarthritis at entry and inactive arthritis at follow up (p<0.001). In contrast, synovial thickening persisted in about 80% after induction of clinical remission. CONCLUSION: The data confirm the high sensitivity of arthrosonography in imaging changes in hip and knee joints of patients with JRA. Sonographic effusion of the knee provided the highest correlation with measures of clinical disease activity. Further prospective studies should evaluate whether persistent thickening of the synovial membrane detected by ultrasound in clinically inactive arthritis indicates residual inflammatory activity and an increased risk of relapse
    Internet : PM:12594110

12. HORNEFF G, SCHMELING H, CSEKE A, KRENZKE V, SELIGER E: Growth and metabolism in juvenile idiopathic arthritis (JIA) and chronic inflammatory diseases. Journal of Pediatric Endocrinology & Metabolism 2002, 15:1418
    Organism:Department of Pediatrics, University Halle, Halle, Germany Germany

13. LAHDENNE P, VAHASALO P, HONKANEN V: Infliximab or etanercept in the treatment of children with refractory juvenile idiopathic arthritis: an open label study. Ann.Rheum.Dis. 2003, 62:245-247.
    Organism:Department of Paediatric Rheumatology, Hospital for Children and Adolescents, University of Helsinki, 00290 Helsinki, Finland pekkalahdenne@husfi
    Abstract: OBJECTIVE: To study infliximab and etanercept in the treatment of refractory juvenile idiopathic arthritis (JIA). METHODS: In a non-randomised, prospective, open label study, 24 patients (mean age 10.2 years, range 3.3-16.3) with polyarticular JIA were treated with either infliximab (n=14) or etanercept (n=10). The patients had had active polyarthritis for at least one year and standard treatment had failed. Anti-tumour necrosis factor (TNF) treatment was added to the current drug treatment. Infliximab (3-4 mg/kg) was given intravenously at weeks 0, 2, and 6, and thereafter at 4 to 8 week intervals. Etanercept (0.4 mg/kg) was given subcutaneously twice a week. Improvement of the patients was assessed at 3, 6, and 12 months according to established JIA response criteria. RESULTS: In intention to treat analyses, patients in both treatment groups improved significantly. ACR Paediatric 50 was achieved at 3, 6, and 12 months by 9/10 (90%), 8/9 (89%), and 8/9 (89%) patients with etanercept and by 8/12 (67%), 10/12 (83%), and 7/9 (78%) with infliximab, respectively. At 12 months, ACR Paediatric 75 was achieved by 67% of patients in both treatment groups. Five withdrawals due to adverse effects or lack of efficacy occurred in the infliximab group and one due to lack of compliance in the etanercept group. CONCLUSION: In this open label clinical study of active JIA, both infliximab and etanercept provided a significant rapid and sustained reduction in disease activity. Adequately powered randomised controlled trials are needed to elucidate the long term safety and efficacy of TNF modulators in the treatment of JIA
    Internet : PM:12594111

14. LAIHO K, SOINI I, KAUTIAINEN H, KAUPPI M: Can we rely on magnetic resonance imaging when evaluating unstable atlantoaxial subluxation? Ann.Rheum.Dis. 2003, 62:254-256.
    Organism:Rheumatism Foundation Hospital, Heinola, Finland karilaiho@reumafi
    Abstract: OBJECTIVES: To examine whether functional radiography and functional magnetic resonance imaging (MRI) are equally efficient in detecting the extent of unstable anterior atlantoaxial subluxation (aAAS) in rheumatic patients. METHODS: 23 patients with unstable aAAS (diagnosed by functional radiography) were examined by functional MRI because of a neck symptom. Twenty two patients had rheumatoid arthritis and one had juvenile idiopathic arthritis. aAAS was diagnosed if the anterior atlantoaxial diameter (AAD) was >3 mm and was considered unstable if the AAD differed by >2 mm between flexion and extension radiographs. The AAD was measured from radiographs (flexion and extension) and MRI images (flexion and neutral). RESULTS: The extent of aAAS during flexion measured by radiography was greater than that found by MRI in all 23 patients (mean difference 3 mm (95% confidence interval 2 to 4)). In four (17%) patients flexion MRI could not demonstrate aAAS detected by radiography. The difference between the AAD measurements during flexion by these two methods was substantial (that is, >or=4 mm) in nine (39%) cases. Severe aAAS (>or=9 mm) was seen in 15 (65%) patients by functional radiography and in four (17%) by functional MRI. CONCLUSIONS: The magnitude of aAAS was often substantially smaller when measured by functional MRI rather than by functional radiography. Thus one cannot rely on the result of functional MRI alone; functional radiographs are needed to show the size of unstable aAAS. The maximal extent of the subluxation must be taken into account when the possible compression of neural structures is evaluated by MRI
    Internet : PM:12594114

15. LISTERNICK R: A 2-year-old boy with fever and a limp. Pediatr.Ann. 2003, 32:11-14.
    Organism:Feinberg School of Medicine, Northwestern University, Division of General Academic Pediatrics, Children's Memorial Hospital, Chicago, Illinois, USA
    Internet : PM:12600133

16. OESTERREICHISCHE GESELLSCHAFT FUER KLINISCHE CHEMIE, OESTERREICHISCHE GfL: Congress for laboratory diagnostics and molecular medicine. First joint annual meeting of the Oesterreichische Gesellschaft fuer Klinische Chemie and the Oesterreichische Gesellschaft fuer Laboratoriumsmedizin, Salzburg, Austria, September 26-28, 2002. Wiener Klinische Wochenschrift 2002, 114:1-34.
    Abstract: This meeting contains 2 papers and 65 abstracts of papers, written in German and English, on topics of laboratory diagnostics and molecular medicine in the human and in animal models. Main topics under discussion included ischemic stroke, atherosclerosis, obesity, heme oxygenase-1, hyperhomocysteinemia, stem cells, thrombosis, cerebrovascular disease, cardiovascular disease, diabetes mellitus, anorexia nervosa, mutation, Chlamydia pneumoniae, Chlamydophila pneumoniae, Pseudoxanthoma elasticum, HIV, human papilloma virus, hepatitis, cancer, and juvenile rheumatoid arthritis

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17. PIGNATTI P, CIAPPONI L, GALLE P, HANSEN MB, MASSA M, MEAZZA C, PAONESSA G, NOVICK D, CILIBERTO G, MARTINI A, DE BENEDETTI F: High circulating levels of biologically inactive IL-6/SIL-6 receptor complexes in systemic juvenile idiopathic arthritis: evidence for serum factors interfering with the binding to gp130. Clin.Exp.Immunol. 2003, 131:355-363.
    Organism:Paediatria Generale e Reumatologia, IRCCS Policlinico San Matteo, Pavia, Italy
    Abstract: We previously demonstrated that high levels of IL-6/sIL-6R complexes are present in sera of patients with systemic juvenile idiopathic arthritis (s-JIA) and that the amount of IL-6 estimated in the IL-6/sIL-6R complexes is markedly higher than that measured by the B9 assay. Here, we show that two additional bioassays, employing human myeloma XG-1 cells and human hepatoma Hep3B cells, detected serum IL-6 levels similar to those measured by the B9 assay and approximately 10-fold lower than the IL-6 levels estimated to be present in the IL-6/sIL-6R complex. Using an assay for the measurement of the amount of circulating IL-6 complexed with the sIL-6R and available for binding to gp130 (gp130 binding activity), we show that the IL-6/gp130 binding activity is similar to that detected by the bioassays and again significantly lower than that estimated to be present in the IL-6/sIL-6R complex. Addition of recombinant human IL-6 (rhIL-6) to sera of patients or controls results in a markedly lower increase in the gp130 binding activity in patients than in controls. Moreover, sera from s-JIA patients inhibited in a dose dependent manner the gp130 binding activity assay. These results show that sera from patients with s-JIA contain a factor, or factors, that inhibit(s) the binding of the IL-6/sIL-6R complex to gp130. This inhibitory activity does not appear to be due to soluble gp130, C-reactive protein or autoantibodies to IL-6
    Internet : PM:12562400

18. RAMANAN AV, WHITWORTH P, BAILDAM EM: Use of methotrexate in juvenile idiopathic arthritis. Arch.Dis.Child 2003, 88:197-200.
    Organism:Department of Paediatric Rheumatology, Royal Manchester Children's Hospitals, Charlestown Road, Manchester, UK avramanan@hotmailcom
    Abstract: Methotrexate (MTX) has transformed the outlook for children with juvenile idiopathic arthritis (JIA). Most of the evidence from uncontrolled clinical trials suggests that MTX is an effective agent for treating active JIA. Data from controlled clinical trials suggests that MTX has statistically significant effects on patient centred disability measures in JIA patients with active arthritis. Although we would like a much larger study directed evidence base for our use of the drug, the studies that have been done are sound and have been followed by a change in clinical expectations and advice that speak of qualitative evidence from clinical practice, confirming the scientifically acquired data. Randomised controlled multicentre trials using sufficient numbers of patients, including functional assessment and quality of life measures, are needed to confirm the long term efficacy and safety of MTX in JIA
    Internet : PM:12598376

19. RAMANAN AV, SCHNEIDER R: Macrophage activation syndrome following initiation of etanercept in a child with systemic onset juvenile rheumatoid arthritis. Rinsho Ganka 2003, 30:401-403.
    Organism:Dr. R. Schneider, Hospital for Sick Children, Department of Pediatrics, University of Toronto, 555 University Avenue, Toronto, Ont. M5G 1X8
    Abstract: Systemic onset juvenile rheumatoid arthritis (JRA) accounts for 10-15% of all JRA. Macrophage activation syndrome (MAS), which can also be considered as secondary hemophagocytic lymphohistiocytosis, is a potentially life-threatening complication of systemic onset JRA. We describe a child with systemic onset JRA who developed MAS after initiation of etanercept therapy

20. REIMOLD AM: New indications for treatment of chronic inflammation by TNF-alpha blockade. Am.J.Med.Sci. 2003, 325:75-92.
    Organism:Rheumatic Diseases Division, University of Texas Southwestern Medical Center, Dallas 75390, USA andreasreimold@utsouthwesternedu
    Abstract: The impressive anti-inflammatory effects of the tumor necrosis factor (TNF)alpha blockers etanercept and infliximab have led to their use in multiple inflammatory diseases besides their original indication, rheumatoid arthritis (RA). The well-studied clinical effects of both agents in RA are the reduction of signs and symptoms of joint inflammation as well as the arrest of bone destruction. Infliximab has also been Food and Drug Administration-approved in the treatment of Crohn disease; etanercept is now FDA-approved for juvenile chronic arthritis and psoriatic arthritis. Favorable initial clinical trials have been reported in other rheumatic diseases, including ankylosing spondylitis and adult Still disease. In addition, TNF alpha blockade is being studied in the treatment of uveitis, myelodysplastic syndromes, and graft-versus-host disease. Studies in sepsis and septic shock have identified small subsets of patients that may benefit from TNF alpha blockade, but broader use in septic patients has not improved survival. The TNF alpha blockers have had relatively infrequent serious side effects, especially compared with the immunosuppressive and cytotoxic agents otherwise employed to treat these diseases. Further studies of optimal dosing, combination with other therapies, and long-term benefits and side effects will emerge from future trials
    Internet : PM:12589232

21. SAMBORSKI W: Sandimmun neoral in the treatment of rheumatic diseases. Reumatologia 2002, 40:307-314.
    Organism:Wl(stroke). Samborski, Klin. Reumatol./Immunol. Klinicznej, AM im. K. Marcinkowskiego, ul. Winogrady 144, 61-626 Poznan
    Abstract: Clinical trials conducted over last 10 years have demonstrated that cyclosporin A (CsA), administrated as commersially available Sandimmun soft gelatin capsules, is effective in improving subjective and objective clinical parameters in patients with severe active and refractory rheumatoid arthritis (RA) in advanced stages of disease. Recently a new formulation of CsA called Sandimmun Neoral was developed, which is based on microemulsion technology. The principal mechanism by which CsA exerts its immunosuppressive action is by inhibiting the transcription of a group of T-cell cytokine genes. Although the inhibition of interleukin-2 (IL-2) has been documented most extensively, these agents also inhibit IL-3, IL-4. IL-15, tumor necrosing factor alpha (TNFalpha), and interferon gamma (IF-gamma). CsA is the most extensively investigated of the immunomodulatory drugs. Significant efficacy of CsA as monotherapy as well as in combination with methotrexate for treatment of early and established RA has been demonstrated in studies world-wide. It is also effective in other autoimmune diseases, such as systemic lupus erythematosus, polymyosits, Behcet disease, juvenile chronic arthritis or psoriatic arthritis. CsA is characterized by efficacy as well as by safety and tolerability

22. SLIFMAN NR, GERSHON SK, LEE JH, EDWARDS ET, BRAUN MM: Listeria monocytogenes infection as a complication of treatment with tumor necrosis factor alpha-neutralizing agents. Arthritis Rheum. 2003, 48:319-324.
    Organism:Center for Biologics Evaluation and Research, FDA, Rockville, Maryland, USA
    Abstract: OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) has been implicated in the pathogenesis of certain inflammatory diseases. Two TNFalpha-neutralizing agents are licensed in the US. Infliximab is licensed for the treatment of Crohn's disease (CD) and, when used with methotrexate, for the treatment of rheumatoid arthritis (RA). Etanercept is licensed for the treatment of RA, including juvenile RA, and, more recently, was licensed for the treatment of psoriatic arthritis. Because of the potential for decreased host resistance to infectious agents due to treatment with anti-TNFalpha agents, we sought to evaluate postlicensure cases of opportunistic infection, including Listeria monocytogenes, in patients treated with these products. METHODS: The FDA Adverse Event Reporting System, a passive monitoring system, was reviewed to identify all reports of adverse events (through December 2001) associated with L monocytogenes infection in patients treated with infliximab or etanercept. RESULTS: Fifteen cases of L monocytogenes infection associated with infliximab or etanercept treatment were identified. In 14 of these cases, patients had received infliximab. The median age of all patients was 69.5 years (range 17-80 years); 53% were female. Six deaths were reported. Among patients for whom an indication for use was reported, there were 9 patients (64%) with RA and 5 patients (36%) with CD (information was not reported for 1 patient). All patients for whom information was reported were receiving concurrent immunosuppressant drugs. CONCLUSION: Postlicensure surveillance suggests that L monocytogenes infection may be a serious complication of treatment with TNFalpha-neutralizing agents, particularly infliximab
    Internet : PM:12571839

23. SOCIETE D'ANTHROPOLOGIE DE PARIS: 1828th Scientific meeting of the Societe d'Anthropologie de Paris, Paris, France, January 16-19, 2003. Bulletins et Memoires de la Societe d'Anthropologie de Paris 2002, 14:196-234.
    Abstract: This meeting contains abstracts of 54 papers, written in French and English, about the history of populations and other issues in anthropology. Main topics under discussion included dentography, anatomy, military mass grave, paleogenetics, paleoanthropology, hunter-gatherers, diet adaptation, DNA variability, migration, human leukocyte antigen, Still's disease, taxonomic probabilistic diagnosis, NeHIR paleoanthropological database, burial methods, ecosystem, patronymics, polymorphism, body mass index, language development, marriage, Homo erectus, Australopithecus boisei, Neanderthal man, and the genera Pan and Gorilla

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24. SOKKA T, PINCUS T: Eligibility of patients in routine care for major clinical trials of anti-tumor necrosis factor alpha agents in rheumatoid arthritis. Arthritis Rheum. 2003, 48:313-318.
    Organism:Jyvaskyla Central Hospital, Jyvaskyla, Finland
    Abstract: OBJECTIVE: To identify the proportion of patients with rheumatoid arthritis (RA) in 2 cohorts from Nashville, Tennessee, who met basic criteria for inclusion in 2 important recent clinical trials of anti-tumor necrosis factor alpha (anti-TNFalpha) agents, the early RA (ERA) trial of etanercept versus methotrexate, and the anti-TNFalpha trial in RA with concomitant therapy (ATTRACT) study of infliximab plus methotrexate versus methotrexate. METHODS: Two cohorts of patients, all of whom had met the American College of Rheumatology criteria for RA at some time, were studied. Cohort E (early) comprised 232 patients who were under the care of 5 private practice rheumatologists, whose duration of RA was fewer than 3 years, and who were reviewed for basic inclusion criteria for the ERA clinical trial. Cohort L (long-term) comprised 152 consecutive patients who had been under care at a weekly academic rheumatology clinic for a mean of 4.5 years, and were reviewed for basic inclusion criteria for the ATTRACT study. RESULTS: In cohort E, basic inclusion criteria for the ERA trial were met by 11 of 36 patients (31%) who had not taken methotrexate, 8 of 19 patients (42%) who were at their first visit and had not taken methotrexate, and 37 of all 232 patients (16%). In cohort L, 5% of patients met the basic inclusion criteria for the ATTRACT study. CONCLUSION: Most patients who were seen in routine care in these 2 cohorts did not meet the criteria for inclusion in these 2 important recent clinical trials. The conclusion that anti-TNFalpha therapy has greater efficacy than methotrexate may be valid only in a limited number of patients with the most severe RA. Anti-TNFalpha therapy may be desirable in most patients with RA, but this possibility has not been studied formally. Criteria for inclusion in RA clinical trials might be modified for greater generalizability of results
    Internet : PM:12571838

25. TOLUSSO B, FABRIS M, DI POI E, ASSALONI R, TOMIETTO P, FERRACCIOLI GF: Response of mononuclear cells to lipopolysaccharide and CpG oligonucleotide stimulation: possible additive effect in rheumatoid inflammation. Ann.Rheum.Dis. 2003, 62:284-285.
    Internet : PM:12594130

26. TSUKAHARA M: Cat scratch disease in Japan. Journal of Infection and Chemotherapy 2002, 8:321-325.
    Organism:Faculty of Health Sciences, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi, 755-8554, Japan Japan^E-Mail: masato@yamaguchi-u.ac.jp

27. TUSZKIEWICZ-MISZTAL E, OPOKA-WINIARSKA V, POSTEPSKI J, KOROBOWICZ A: Infection involvement in the etiopathogenesis of rheumatoid arthritis and juvenile idiopathic arthritis. Reumatologia 2002, 40:293-298.
    Organism:E. Tuszkiewicz-Misztal, Klinika Chorob Pluc i Reumatologii, AM, Dziecie(cedil)cy Szpital Kliniczny, ul. Chodzki 2, 20-093 Lublin
    Abstract: Research confirms that both rheumatoid arthritis and juvenile idiopathic arthritis are autoimmune diseases whose causes include genetic predisposition and a necessary environmental factors. For an autoimmune reaction to occur, the threshold of self-tolerance must be broken. Various microorganisms of different mechanisms of activity partake in the process. Although a causal relationships between bacterial or viral infection and arthritis has been confirmed only in some cases, it is possible that in the pathogenesis of rheumatic diseases infections factors play a more significant role

28. UCHIDA T, FUKAWA A, UCHIDA M, FUJITA K, SAITO K: Application of a novel protein biochip technology for detection and identification of rheumatoid arthritis biomarkers in synovial fluid. Journal of Proteome Research 2002, 1:495-499.
    Organism:Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University, 4-1 Seiryo, Aoba, Sendai, Miyagi, 980-8575, Japan Japan^E-Mail: uchidat@idac.tohoku.ac.jp
    Abstract: We compared protein profiles of the synovial fluid of patients with rheumatoid arthritis and osteoarthritis by using surface-enhanced laser desorption/ionization mass spectrometry technology. With this approach, we identified a protein expressed specifically in the synovial fluid of the patients with rheumatoid arthritis. During the investigation, we found several reproducible and discriminatory biomarker candidates for distinction between rheumatoid arthritis and osteoarthritis. Among these candidates, a 10 850 Da protein peak was the clearest example of a single signal found specifically in the rheumatoid arthritis samples. This candidate was purified using a size-exclusion spin column followed by gel electrophoresis and subsequently identified by peptide mapping and post-source decay (PSD) analysis. The results clearly indicate that the protein is myeloid-related protein 8, which was verified by the enzyme immunoassay. It is known that the myeloid-related protein 8 level in serum and synovial fluid is related to disease activity in juvenile rheumatoid arthritis. The results suggest that the ProteinChip platform is useful to detect and identify protein biomarkers expressed specifically in diseases or in some stage of diseases

29. VAN LAAR JM, TYNDALL A: Intense immunosuppression and stem-cell transplantation for patients with severe rheumatic autoimmune disease: a review. Cancer Control 2003, 10:57-65.
    Organism:Department of Rheumatology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands jmvan_laar@lumcnl
    Abstract: BACKGROUND: Intense immunosuppression plus stem-cell transplantation (SCT) has emerged as a new treatment modality for patients with refractory, severe rheumatic autoimmune disease. Its rationale is based on eliminating autoaggressive lymphocytes by ly
    Internet : PM:12598856

30. VAN ROSSUM MA, ZWINDERMAN AH, BOERS M, DIJKMANS BA, VAN SOESBERGEN RM, FISELIER TJ, FRANSSEN MJ, TEN CATE R, SUIJLEKOM-SMIT LW, WULFFRAAT NM, KUIS W, VAN LUIJK WH, OOSTVEEN JC, DIJKSTRA PF: Radiologic features in juvenile idiopathic arthritis: a first step in the development of a standardized assessment method. Arthritis Rheum. 2003, 48:507-515.
    Organism:Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands mvan_rossum@lumcnl
    Abstract: OBJECTIVE: To describe radiologic features of patients with juvenile idiopathic arthritis (JIA) in a standardized manner, to test the reliability and feasibility of this description, and to correlate these features with clinical signs as a first step in the development of a standardized assessment method. METHODS: The placebo-controlled study of sulfasalazine in patients with oligoarticular, extended oligoarticular, and polyarticular JIA performed by the Dutch Juvenile Idiopathic Arthritis Study Group yielded the data for this study. All trial entry radiographs (clinically involved joints and contralateral joints) were scored (in consensus by a skeletal radiologist and pediatric rheumatologist) for the presence of swelling, osteopenia, joint space narrowing, growth abnormalities, subchondral bone cysts, erosions, and malalignment. RESULTS: Data on 67 of 69 patients were analyzed. The mean age was 9.1 years (range 2.5-17.6 years), and the median disease duration was 24 months (range 5-176 months). Thirteen percent of the patients were IgM rheumatoid factor (IgM-RF) positive, and 16% were HLA-B27 positive. All 68 clinically evaluated joints were included in the maximum of 19 radiographed joints (or joint groups) per patient. The mean number of radiographed joints per patient was 7 (range 2-15); knees, hands, ankles, and feet were most frequently affected. Fifty-eight patients (87%) had radiologic abnormalities in at least one joint (soft-tissue swelling in 63% of patients, growth disturbances in 48%, joint space narrowing in 28%, and erosions in 15%). In total, half of the radiographs of the clinically involved joints showed radiologic abnormalities, including two-thirds of the radiographs of the clinically affected hands and knees. Univariate analysis revealed a good correlation between the overall articular (clinical) severity and the presence of radiologic abnormalities (odds ratio [OR] 1.38, P < 0.0001). Multivariate analysis showed increased ORs for the presence of radiologic abnormalities and IgM-RF positivity (OR 4.6, P = 0.005) or HLA-B27 positivity (OR 3.0, P = 0.004). In general, reproducibility of the radiologic scoring method was good (mean kappa coefficient of 0.74 [range 0.40-0.86]), although there were scoring discrepancies for swelling, osteopenia, and growth disturbances. The scoring took 10-20 minutes per patient. CONCLUSION: Our model of describing and scoring radiologic abnormalities of radiographed joints in JIA was feasible, mostly reproducible, correlated well with the overall articular severity score, and added substantial new information not available on clinical examination
    Internet : PM:12571861

31. WAKAMATSU H, SEKINE I: Alterations of 20S proteasome subunits in long-term cultured B lymphoblastoid cell lines. Boei Ika Daigakko Zasshi 2002, 27:148-156.
    Organism:Department of Pediatrics, Japan Central Hospital, Setagaya, Tokyo, 154-8532, Japan Japan
    Abstract: The levels and composition of ten major proteasome subunits from 33 B lymphoblastoid cell lines (BLCLs), 19 of which were established from Ebstein-Barr (EBV)-seronegative patients and infected in vitro with EBV (EBV-infected BLCLs), and 14 of which were established with long-term culture from seropositive patients for EBV (spontanous BLCLs), were analyzed by HPLC. The total amount of 20S proteasome did not differ significantly among the cell lines, regardless of p53 protein, levels of EBV status. The levels of subunit 2 (C2) of 20S proteasome were significantly increased in the EBV-infected BLCLs (p=0.0155). Significant elevations in the amount of the C2 were also seen in cells in which cytoplasm was stained positively with anti-20S proteasome antibody (p=0.0497), as well as in denucleated cells that stained positively with anti-20S proteasome antibody (p=0.0001). Subunit 10 (C10) levels were significantly increased in cell lines having nuclei that were predominantly stained with anti-20S proteasome antibody (p=0.0132). These data suggest that changes in the intracellular composition of the proteasome subunits may reflect the activity of such cytological events as programmed cell death, immortalization, and benign or malignant transformation in these BLCLs

32. WEDDERBURN LR, ABINUN M, PALMER P, FOSTER HE: Autologous haematopoietic stem cell transplantation in juvenile idiopathic arthritis. Arch.Dis.Child 2003, 88:201-205.
    Organism:Rheumatology Unit, Institute of Child Health, UCL and Great Ormond Street Hospital NHS Trust, London, UK lwedderburn@ichuclacuk
    Internet : PM:12598377

33. WILKINSON N, JACKSON G, GARDNER-MEDWIN J: Biologic therapies for juvenile arthritis. Arch.Dis.Child 2003, 88:186-191.
    Organism:Department of Rheumatology, Great Ormond Street Hospital, London, UK petherton@claracouk
    Abstract: A group of therapies with exciting potential has emerged for children and young people with severe juvenile idiopathic arthritis (JIA) uncontrolled by conventional disease modifying drugs. Theoretical understanding from molecular biologic research has identified specific targets within pathophysiological pathways that control rheumatoid arthritis (RA) and JIA. This review identifies the pathways of autoimmunity to begin to show how biologic agents have been produced to replicate, mimic, or block culpable molecules and so promote or inhibit cellular activity or proliferation. Of these agents, cytokine antagonists have shown greatest promise, and early clinical studies of tumour necrosis factor (TNF) blockade have identified dramatic clinical benefit in many children with JIA. However, as will also be discussed, overlap of pathways within a complex immune system makes clinical response unpredictable and raises additional ethical and administrative concerns
    Internet : PM:12598373

34. WULFFRAAT NM, RIJKERS GT, ELST E, BROOIMANS R, KUIS W: Reduced perforin expression in systemic juvenile idiopathic arthritis is restored by autologous stem-cell transplantation. Rheumatology (Oxford) 2003, 42:375-379.
    Organism:Department of Paediatric Immunology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, PO Box 85090, 3508 AB Utrecht, The Netherlands
    Abstract: OBJECTIVES: Familial haemophagocytic lymphohistiocytosis (FHL) is a disorder characterized by deficient cytotoxic T-cell function and activated macrophages, owing to a defect in the perforin gene and absent perforin expression. Because symptoms of patients with systemic juvenile idiopathic arthritis (sJIA) are sometimes clinically very similar to those with FHL, we studied whether perforin expression in sJIA patients would be reduced also. METHODS: We determined the perforin expression levels on two subsets of CD8(+) cells (CD8(+)CD28(-)CD45RA(-) and CD8(+)CD28(-)CD45RA(+)) and natural killer (NK) cells from patients with sJIA under conventional treatment as well as before and after autologous stem-cell transplantation (ASCT). RESULTS: CD45RA(-) cytotoxic effector cells of sJIA patients (n=13) express significantly lower levels of perforin than polyarticular juvenile idiopathic arthritis (pJIA, n=9) patients [sJIA mean fluorescence intensity (MFI) 34.6; pJIA MFI 98.0] or control donors (MFI 124.6, n=5). A similar pattern was seen in the CD45RA(+) subset. Also NK cells from sJIA patients expressed significantly less intracellular perforin (sJIA MFI 398.4; controls MFI 972.4). In four patients with sJIA who were treated with ASCT, a clear increase in perforin expression was found at 12 months after ASCT in both cytotoxic effector cell subsets (CD45RA(-) subset before ASCT MFI 13.2; 12 months after ASCT MFI 172.3). CONCLUSION: We conclude that perforin expression can be severely reduced in sJIA. This finding may implicate defective cytotoxicity and haemophagocytosis and could thus explain why sJIA may be complicated by macrophage activation syndrome. ASCT leads to a reconstitution of the (T cell) immune system with a normal expression of perforin
    Internet : PM:12595640

35. WULFFRAAT NM, HAAS PJ, FROSCH M, DE KLEER IM, VOGL T, BRINKMAN DM, QUARTIER P, ROTH J, KUIS W: Myeloid related protein 8 and 14 secretion reflects phagocyte activation and correlates with disease activity in juvenile idiopathic arthritis treated with autologous stem cell transplantation. Ann.Rheum.Dis. 2003, 62:236-241.
    Organism:Department of Paediatric Immunology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, The Netherlands NWulffraat@wkzazunl
    Abstract: OBJECTIVES: To determine whether myeloid related proteins (MRP8/MRP14), a complex of two S100 proteins related to neutrophil and monocyte activation, might be used as a marker for disease activity, and as an early indicator of relapse in juvenile idiopathic arthritis. PATIENTS AND METHODS: A group of 12 patients who underwent an autologous haematopoietic stem cell transplantation (ASCT) for refractory juvenile idiopathic arthritis (JIA) were studied. MRP8/MRP14 serum concentrations were determined by a sandwich enzyme linked immunosorbent assay (ELISA) as described. Improvement from baseline was described by a definition of improvement employing a core set of criteria as detailed previously by Giannini. RESULTS: After ASCT, MRP8/MRP14 serum concentrations in JIA showed a positive correlation with the Child Health Assessment Questionnaire (CHAQ; r=0.80) and erythrocyte sedimentation rate (r=0.45), but not with the total leucocyte count (r=0.26). Mean MRP8/MRP14 serum concentrations dropped markedly in the first three months after ASCT (p=0.0039) and clinical parameters of disease activity such as CHAQ markedly improved (p=0.0039). During a transient relapse there was an increase in MRP8/MRP14. CONCLUSIONS: MRP8/MRP14 serum concentration can be used as a marker for disease activity in patients who receive an ASCT for refractory JIA. This indicates a role of macrophage activation in the pathogenesis of JIA. The occurrence of MAS in three patients in this study was not preceded by significant changes in MRP8/MRP14 concentration
    Internet : PM:12594109

36. ZABEK J, BIERNACKA E, GUTOWSKA-GRZEGORCZYK G, MICHALAK-WIEJAK H: Antibodies to cytokeratin (AKA) in sera and synovial fluids of patients with juvenile idiopathic arthritis (JIA). Reumatologia 2002, 40:222-228.
    Organism:J. Za(cedil)bek, Zakad Mikrobiologii i Serologii, Instytut Reumatologiczny, ul. Spartanska 1, 02-637 Warszawa
    Abstract: RA is the most frequent chronic inflammatory autoimmune disease with still unknown etiology. Between autoantibodies occuring in RA the most useful is so called classical rheumatoid factor (IgM class). But unfortunately RF-IgM is present only in about 75% of RA cases and in early RA (6 to 12 months duration) only in 25-30% of cases. In JIA (Juvenile idiopathic arthritis) the frequencies of RF-IgM are much lower than in adults - ranging about 30%. The most promising group of the autoantibodies is group of so called anti-keratin antibodies (AKA), but there is a lot of controverses concerning the frequency, sensitivity, specificity and also the "marker" meaning of these antibodies. The aim of the presented study was to compare all (above mentioned) parameters, especially the frequencies of AKA-s in the cohort of 18 patients (11 female and 7 male) with established JIA. The AKA was tested by IIF - method (acc. to Young) and also by immunoperoxidase staining method. In both methods air-dried cryostat-sections of the rat oesophageus were used. For the final confirmation Western-blott and ELISA method have been used. In 33% of 18 JIA pts. sera and 11% of synovial fluids have been found to be AKA-positive and none in the sera of healthy blood donors. What is more important, in this same group RF-IgM only in 11% of the sera and 16.5% of synovial fluid is present. These preliminary data showed that AKA-antibodies are a very promising "marker" of RF-IgM seronegative, early and active RA, and we intend to confirm these data in the large groups of children with undifferentiated connective tissue diseases