Bibliography June 05

1. APARISI L, FARRE A, GOMEZ-CAMBRONERO L, MARTINEZ J, DE LAS HG, CORTS J, NAVARRO S, MORA J, LOPEZ-HOYOS M, SABATER L, FERRANDEZ A, BAUTISTA D, PEREZ-MATEO M, MERY S, SASTRE J: Antibodies to carbonic anhydrase and IgG4 levels in idiopathic chronic pancreatitis: relevance for diagnosis of autoimmune pancreatitis. Gut 54:5 703-709, 2005
   Organism: Unit of Heptatology, University Clinic Hospital, Valencia, Spain aparisi_lui@gvaesFAU - Aparisi, L
   Abstract: BACKGROUND: Increased serum antibodies against carbonic anhydrase II (CA-II Ab) or IgG4 levels have been reported in cases of autoimmune chronic pancreatitis (ACP). AIM: To assess the relevance of serum CA-II Ab and IgG4 levels for the diagnosis of ACP in idiopathic CP (ICP) versus alcoholic CP and Sjogren's syndrome (SS). SUBJECTS: This was a multicentre study involving 227 subjects divided into four groups: ICP (n = 54), normal controls (n = 54, paired by age and sex with ICP patients), alcoholic CP (n = 86), and SS (n = 33). METHODS: CA-II Ab was measured by ELISA and confirmed by western blotting. A score of easy clinical use with major clinical, morphological, and biochemical parameters for the diagnosis of ACP was applied. RESULTS: The percentage of patients with increased serum CA-II Ab was higher in the ICP group (28%) than in controls (1.9%) and in patients with alcoholic CP (10.5%), but lower than in patients with SS (64%). The proportion with elevated IgG4 levels was higher in the ICP group (15%) compared with controls (1.9%) and SS (0%) but not significantly different from alcoholic CP (8%). Most ICP patients (7/8) with high IgG4 levels exhibited increased CA-II Ab and a compatible ACP score. A definitive diagnosis of ACP by histological analysis was associated with other autoimmune disorders, an increase in both serum IgG4 and CA-II Ab levels, and IgG4 positive plasma cells. CONCLUSIONS: The increase in serum IgG4 levels was strongly associated with elevated CA-II Ab levels, manifestations compatible with ACP, and lymphoplasmacytic infiltration when surgical specimens were available

2. ARKELA-KAUTIAINEN M, HAAPASAARI J, KAUTIAINEN H, VILKKUMAA I, MALKIA E, LEIRISALO-REPO M: Favourable social functioning and health related quality of life of patients with JIA in early adulthood. Annals of the Rheumatic Diseases (United Kingdom ) 64:6 875-880, 2005
   Abstract: Objective: To evaluate the social functioning and health related quality of life (HRQoL) in patients with juvenile idiopathic arthritis (JIA) in early adulthood. Methods: The patient files of the Rheumatism Foundation Hospital were screened to identify patients born in 1976-1980 diagnosed as having JIA. HRQoL was measured by the RAND 36-item health survey 1.0; spousal relationships and educational and employment status were assessed by questionnaire. The patients were invited to a follow up study. Age and sex matched controls from the community were identified in the Finnish population registry. Results: Of 187 patients identified, 123 participated. Spousal relationships, educational level, and employment status were similar to controls. HR QoL in JIA patients was similar to controls except on the physical functioning scale. At follow up 35% of patients were in remission. Patients with active disease had poorer HRQoL in the physical component than those in remission or controls. The extended oligoarthritis group had the lowest physical and mental score in HRQoL compared with the other JIA subgroups. The patient's own evaluation was the explanatory factor in both the physical and mental component of HRQoL. Conclusion: Social functioning and HRQoL were similar in JIA patients and age, sex, and municipality matched controls. However, patients with extended oligoarthritis attained significantly lower scores in the physical and mental component of HRQoL than oligo- or polyarthritis patients. Special attention in everyday care should be paid to those patients who have active disease or the extended oligoarthritis type of disease

3. CARRASCO R, SMITH JA, LOVELL D: Erratum: Biologic agents for the treatment of juvenile rheumatoid arthritis (Pediatric Drugs (2004) 6, 3 (137-146)). Pediatric Drugs (New Zealand ) 7:2 136, 2005

4. CEFLE A: Leflunomide and azathioprine combination in refractory Adult-onset Still's disease. Ann Pharmacother 39:4 764-767, 2005
   Abstract: OBJECTIVE: To present a case of Adult-onset Still's disease (ASD) in a patient who was successfully treated with leflunomide and azathioprine. CASE SUMMARY: A 24-year-old woman with ASD was initially treated with indomethacin, corticosteroids, and hydroxychloroquine; there was no clinical improvement. Methotrexate was added to the regimen, followed by azathioprine. The patient still experienced disease flares with this treatment, and cyclophosphamide was started. However, because of persisting disease activity, leflunomide combined with azathioprine was given. Only on this regimen was complete disease control achieved, with a normal erythrocyte sedimentation rate as well as normal C-reactive protein and ferritin levels. No recurrences or adverse effects attributable to leflunomide or azathioprine were observed at the one-year follow-up. DISCUSSION: Clinical experience concerning leflunomide and azathioprine combination in ASD is limited. This combination may be modifying the clinical expression of ASD through its effects on T lymphocyte clonal expansion and production of proinflammatory cytokines. CONCLUSIONS: Leflunomide combined with azathioprine appears to be an effective and safe treatment of ASD

5. FORREST CM, HARMAN G, MCMILLAN RB, STOY N, STONE TW, DARLINGTON LG: Modulation of cytokine release by purine receptors in patients with rheumatoid arthritis. Clin Exp Rheumatol 23:1 89-92, 2005
   Organism: Institute of Biomedical & Life Sciences, University of Glasgow, Glasgow CMForrest@bioglaacukFAU - Forrest, C M
   Abstract: OBJECTIVE: Since adenosine receptors are known to modulate the release of some inflammatory mediators in control subjects, we have examined the effects of the mixed A1 and A2 adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) on basal and lipopolysaccharide (LPS)-induced cytokine release in diluted whole blood cultures from rheumatoid arthritis (RA) patients and healthy volunteers. METHODS: Twenty-eight patients with rheumatoid arthritis aged 18-75 years gave their voluntary consent to participate and give a blood sample. Basal levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) were measured by ELISA, and whole blood cultures were prepared to assess the effects of LPS activation. RESULTS: Following a 40-hour incubation, activation of adenosine receptors by NECA, added to the cell cultures from rheumatoid arthritis patients, was found to suppress both the basal and LPS-induced release of TNF-alpha and IL-1beta, while causing an increase in the release of both basal and LPS-induced IL-6. In healthy volunteers basal cytokines were undetectable, but NECA alone induced the release of all three cytokines. Stimulated levels of TNF-alpha were more than double those in patients. In the control blood cultures, NECA suppressed LPS-induced release of TNF-alpha and IL-1beta, but increased IL-6 release. CONCLUSIONS: Adenosine receptor stimulation has a differential effect on the release of pro-inflammatory cytokines, and may induce cytokine release in normal subjects. Stimulated release of TNF-alpha is substantially lower in patients with rheumatoid arthritis than in control subjects, possibly indicating saturation, exhaustion or down-regulation of the release process

6. GORDON JE, WOLFF A, LUHMANN SJ, ORTMAN MR, DOBBS MB, SCHOENECKER PL: Primary and delayed closure after open irrigation and debridement of septic arthritis in children. J Pediatr Orthop B 14:2 101-104, 2005
   Organism: Department of Orthopaedic Surgery, Washington University School of Medicine, St Louis, Missouri, USA Gordone@msnoteswustleduFAU - Gordon, J Eric
   Abstract: Seventy-one patients with 83 septic joints due to idiopathic septic arthritis were investigated retrospectively. Forty-three joints were closed primarily while 40 underwent delayed primary closure. Two joints in each group failed treatment and had to be reopened after definitive closure. Joints in patients 7 years of age or older had a substantially higher failure rate (12%), with either primary or delayed closure, than joints in patients younger than 7 years (1.7%). Two of 13 patients with a polymorphonuclear leukocyte count in the synovial fluid greater than 100,000 required repeat debridement after final closure. Three of the four patients who required repeat debridement showed evidence of osteomyelitis. The average length of stay was longer in the delayed primary closure group (7.0 days) than in the primary closure group (5.6 days). This study suggests that primary closure is a viable alternative to delayed primary closure with shorter hospital stays and similar outcomes in children with idiopathic septic arthritis. Care should be taken in children aged 7 and older or when concurrent osteomyelitis exists

7. HAJJ-ALI RA, LOWDER C, MANDELL BF: Uveitis in the internist's office: Are a patient's eye symptoms serious? Cleveland Clinic Journal of Medicine 72:4 329-339, /4/5
   Abstract: Uveitis is an inflammatory process that may affect one or several specific areas of the eye. But when a patient presents to an internist with eye symptoms, be it photophobia, "floaters," or red eye, the diagnosis is not always clear. If the diagnosis of uveitis is made, internists must search for an underlying cause, such as infection or an autoimmune disease

8. HARRIS HA, BRUNER-TRAN KL, ZHANG X, OSTEEN KG, LYTTLE CR: A selective estrogen receptor-beta agonist causes lesion regression in an experimentally induced model of endometriosis. Hum Reprod 20:4 936-941, 2005
   Organism: Women's Health Research Institute, Wyeth Research, Collegeville, PA 19426, USA harrish@wyethcomFAU - Harris, Heather A
   Abstract: BACKGROUND: Endometriosis is a common gynaecological problem of uncertain aetiology. It affects primarily young, reproductive-aged women and can result in chronic pelvic pain and infertility. Current approved therapies have significant side-effects and hysterectomy is employed as a final solution. ERB-041 is a selective estrogen receptor-beta (ERbeta) agonist that has anti-inflammatory activity in preclinical models of arthritis and inflammatory bowel disease, but is inactive in many preclinical models of classic estrogen activity. Because endometriosis is now thought to be, at least in part, an inflammatory disease, we evaluated ERB-041's activity in an experimentally induced model of endometriosis. METHODS: Athymic nude mice (ovariectomized or intact) were implanted with tissue fragments of normal human endometrium. After establishment of lesions for 11-14 days, mice were treated with ERB-041 for 15-17 days. Upon euthanasia, the number of lesions, their size and location were noted. Five lesions were recovered for RNA analysis. RESULTS: Across six studies, ERB-041 caused complete lesion regression in 40-75% of the mice studied. The compound appeared to be equally effective in gonad-intact as in ovariectomized mice, and analysed recovered lesions expressed ERalpha but not ERbeta mRNA. CONCLUSIONS: ERB-041 and possibly other ERbeta selective agonists may be a useful new approach to treating endometriosis

9. HORNEFF G: Use of biologicals for treating juvenile idiopathic arthritis. Consensus statement of the 2004 Seventh Worlitzer Expert Panel for the German Juvenile Rheumatology Association
   EINSATZ VON BIOLOGIKA BEI DER JUVENILEN IDIOPATHISCHEN ARTHRITIS. KONSENSUS-STATEMENT DES 7. WORLITZER EXPERTENGESPRACHES 2004 FUR DIE ARBEITSGEMEINSCHAFT KIND. Monatsschrift fur Kinderheilkunde (Germany ) 153:5 473-479, 2005
   Abstract: The group of biologicals for treatment of rheumatic diseases is continually growing. They have become an important option not only for previously untreatable chronic inflammatory or rheumatic disease, especially juvenile idiopathic arthritis. In addition, the velocity and degree of improvement are incomparabily better than those of conventional therapies. Further, toxicity and risks seem to be lower, with higher compatibility. Albeit the data are scarce, they are widely used. The present study is an update of the recommendation to treat juvenile idiopathic arthritis with biologicals. (c) Springer Medizin Verlag 2005

10. KOTANIEMI K, ARKELA-KAUTIAINEN M, HAAPASAARI J, LEIRISALO-REPO M: Uveitis in young adults with juvenile idiopathic arthritis: A clinical evaluation of 123 patients. Annals of the Rheumatic Diseases (United Kingdom ) 64:6 871-874, 2005
    Abstract: Objective: To examine the prevalence and characteristics of uveitis in young adults with juvenile idiopathic arthritis (JIA). Methods: The study population consisted of 123 JIA patients born between 1976 and 1980 whose arthritis had been diagnosed and treatment first started at the Rheumatism Foundation Hospital in 1976 to 1995. A clinical re-evaluation was carried out by an ophthalmologist and a paediatric rheumatologist 16 years later on average. Results: The mean age of the patients was 23.5 years, 72% were women, and 63% had oligoarthritis. During the course of the disease, diagnosis of uveitis had been made in 25 patients (20%). Arthritis in the 19 patients with asymptomatic uveitis was more often ongoing than in the 98 patients without uveitis (p = 0.032). Asymptomatic uveitis was persistent in eight of the 19 cases (42%), and arthritis was active in seven of these. Four of the six patients with attacks of symptomatic uveitis had parallel treatment for arthritis. In three of 19 patients with asymptomatic uveitis and in five of six with acute uveitis the eye inflammation had started after the age of 16. At the onset of arthritis the patients with asymptomatic uveitis were younger than those without uveitis (p = 0.002). Complications of uveitis developed in six patients but their sight remained good. Conclusions: Asymptomatic uveitis continued into adulthood in almost half the uveitis patients. Most also had ongoing arthritis. Acute uveitis was often associated with persistent arthritis

11. KRONIG H, RIEDEL M, SCHWARZ MJ, STRASSNIG M, MOLLER HJ, ACKENHEIL M, MULLER N: ICAM G241A polymorphism and soluble ICAM-1 serum levels: evidence for an active immune process in schizophrenia. Neuroimmunomodulation 12:1 54-59, 2005
    Organism: Psychiatric Hospital, Ludwig-Maximilian University Munich, Munich, GermanyFAU - Kronig, Holger
    Abstract: OBJECTIVES: We have previously reported reduced serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) in schizophrenic patients. A single-nucleotide polymorphism (SNP) of the ICAM-1 gene was described at position 241. The G-->A SNP results in a nonsynonymous amino acid exchange of the ICAM-1 protein, and the A allele was shown to be also associated with several immunological disorders like rheumatoid arthritis. METHODS: We investigated 70 schizophrenic patients and 128 unrelated healthy control persons regarding the relationship between the serum levels of sICAM-1 and the ICAM-1 G214A polymorphism. RESULTS: We were able to replicate our previous finding of reduced sICAM-1 levels in schizophrenia. Healthy control persons carrying the polymorphic A allele showed markedly lower sICAM-1 serum levels than carriers of the homozygous GG wild type (p < 0.004). In contrast, no significant difference in the sICAM-1 serum levels were seen regarding the G241A genotype distribution in schizophrenic patients. CONCLUSION: We hypothesize that the biochemical effect of the G241A SNP is masked in schizophrenic patients, indicating a disease-related mechanism leading to reduced levels of sICAM-1 in schizophrenia

12. KUNZMANN S, WARMUTH-METZ M, GIRSCHICK HJ: Cerebral demyelination in association with TNF-inhibition therapy in a 5-year-old girl with aseptic meningitis as the first symptom of Still's disease. Scand J Rheumatol 34:1 76-78, 2005

13. LELIEVELD OTTO THM, TAKKEN T, VAN DER N, VAN WEERT E: Validity of the 6-minute walking test in juvenile idiopathic arthritis. Arthritis & Rheumatism 53:2 304-307, 2005

14. LUMBRERAS B, PASCUAL E, FRASQUET J, GONZALEZ S, RODRIGUEZ E, HERNANDEZ-AGUADO I: Analysis for crystals in synovial fluid: training of the analysts results in high consistency. Annals of the Rheumatic Diseases 64:4 612-615, /4/5
    Abstract: Background: Identification of monosodium urate (MSU) and calcium pyrophosphate dehydrate (CPPD) crystals in synovial fluid samples is diagnostic of gout and CPPD crystal related arthropathy. Various studies have shown poor consistency in results of crystal analysis.Objective: To determine whether training of the analysts increases the consistencyMethods: An expert rheumatologist gave a course on crystal detection and identification. The four trained observers then blindly and independently examined synovial fluid samples previously classified by the expert which had been obtained from patients with both crystal arthropathies and other non-crystal related inflammatory joint conditions.Results: 194 observations were made on 64 synovial fluid samples: 96 without crystals (49.4%), 55 with CPPD crystal (28.4%), and 43 with MSU crystals (22.2%). For crystal detection (presence or absence of crystals), sensitivity was 95.9% and specificity 86.5%. For identification of MSU crystals, sensitivity was 95.3% and specificity 97.2%. For identification of CPPD crystals, sensitivity was 92.7% and specificity 92.1%. The K in dex of agreement with the reference standard between the observers was 0.84 for any crystal detection, 0.93 for MSU crystal sample identification, and 0.79 for CPPD crystal sample identification.Conclusions: For trained observers, the detection and identification of crystals in synovial fluid is a consistent procedure

15. MAGNI-MANZONI S, CUGNO C, PISTORIO A, GARAY S, TSITSAMI E, GASPARINI C, VIOLA S, RUPERTO N, MARTINI A, RAVELLI A: Responsiveness of clinical measures to flare of disease activity in juvenile idiopathic arthritis. Clin Exp Rheumatol 23:3 421-425, 2005
    Organism: Dipartimento di Pediatria, Universita di Pavia, Istituto di Ricovero e Cura a Carattere Scientifico Policlinico S Matteo, Pavia, ItalyFAU - Magni-Manzoni, S
    Abstract: OBJECTIVE: To compare the responsiveness of clinical measures in the assessment of disease flare in patients with juvenile idiopathic arthritis (JIA). METHODS: The clinical records of all consecutive patients with JIA who were diagnosed between 1995 and 2000 were retrospectively reviewed. In each patient, all visits made during follow-up were analyzed and those meeting the criteria for disease flare were recorded. The definition of flare was based on the therapeutic alterations made by the attending physician. Responsiveness of JIA clinical measures to relevant increase in disease activity (a flare) was evaluated by assessing the score change of each measure from a visit made 6 (+/- 3) months before a flare and the flare visit. Responsiveness statistics included the standardized response mean (SRM) and the effect size (ES). RESULTS: A total of 115 patients, who were followed for 0.5 to 6.2 years (mean 2.8 years), were studied. During follow-up, 51 patients (44%) experienced 1 or more disease flares, with the total number of flares being 75. Strong responsiveness (ES and SRM > or = 0.8) to increase in disease activity was demonstrated by the physician's and parent's global assessments, the global articular severity score, and the morning stiffness. The active, swollen and painful joint counts, the swelling, pain on motion/tenderness and limited range of motion (LROM) scores, and the erythrocyte sedimentation rate revealed moderate responsiveness (ES and SRM > or = 0.5). The poorest performances (ES and/or SRM < 0.5) were provided by the parent's assessment of pain, the functional ability tool, the number of joints with LROM, the LROM score, the C-reactive protein, the white blood cell and platelet count, and the hemoglobin level. CONCLUSION: Our analysis suggests that the swollen or painful joint counts are better suited than the count of joints with LROM for the assessment of disease flare in patients with JIA

16. MAHDAVIANI S, HIGGINS GC, KERR NC: Orbital pseudotumor in a child with juvenile rheumatoid arthritis. J Pediatr Ophthalmol Strabismus 42:3 185-188, 2005
    Organism: Department of Ophthalmology, University of Mississippi, Jackson, Mississippi, USAFAU - Mahdaviani, Sheila
    Abstract: We report a child with persistent fevers, arthritis, and parvoviral infection who subsequently developed unilateral orbital pseudotumor, lytic bone lesions, bilateral anterior uveitis, band keratopathy, and migratory polyarthritis. Our working diagnosis was systemic-onset juvenile rheumatoid arthritis, although pseudotumor of the orbit and lytic bone lesions are not found in this disease

17. MINGELS A, HUDDE T, HEINZ C, HEILIGENHAUS A: Vision-threatening complications in childhood uveitis
    VISUSMINDERNDE KOMPLIKATIONEN BEI UVEITIS IM KINDESALTER. Ophthalmologe (Germany ) 102:5 477-484, 2005
    Abstract: Purpose. We analyzed the epidemiologic data and vision-threatening complications in different forms of childhood uveitis. Methods. This retrospective study included 187 consecutive patients with onset of uveitis before the age of 16 years classified as anterior (AU), intermediate (IU), posterior (PU), and panuveitis (PanU). We analyzed the epidemiologic data as well as visual acuity, uveitic complications and the conservative and surgical therapy. Results. Associated disease was observed in 85 of 187 patients. The most common complications in AU patients were cataract, posterior synechiae, band keratopathy and CME. IU was accompanied by dense vitreous opacities, cataract and CME. Macular scars were the most frequent cause for visual loss in PU. PanU was complicated by dense vitreous opacities, cataract, retinal detachment, CME and phthisis bulbi. Conclusions. Childhood uveitis is frequently associated with systemic immune-mediated diseases. The diverse uveitis types have different but typical complications. (c) Springer Medizin Verlag 2005

18. MIYAMAE T, MALEHORN DE, LEMSTER B, MORI M, IMAGAWA T, YOKOTA S, BIGBEE WL, WELSH M, KLARSKOV K, NISHOMOTO N, VALLEJO AN, HIRSCH R: Serum protein profile in systemic-onset juvenile idiopathic arthritis differentiates response versus nonresponse to therapy. Arthritis Res Ther 7:4 R746-R755, 2005
    Organism: Division of Rheumatology, Children's Hospital of Pittsburgh, Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213 Takakomiyamae@chpeduFAU - Miyamae, Takako
    Abstract: ABSTRACT : Systemic-onset juvenile idiopathic arthritis (SJIA) is a disease of unknown etiology with an unpredictable response to treatment. We examined two groups of patients to determine whether there are serum protein profiles reflective of active disease and predictive of response to therapy. The first group (n = 8) responded to conventional therapy. The second group (n = 15) responded to an experimental antibody to the IL-6 receptor (MRA). Paired sera from each patient were analyzed before and after treatment, using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Despite the small number of patients, highly significant and consistent differences were observed before and after response to therapy in all patients. Of 282 spectral peaks identified, 23 had mean signal intensities significantly different (P < 0.001) before treatment and after response to treatment. The majority of these differences were observed regardless of whether patients responded to conventional therapy or to MRA. These peaks represent potential biomarkers of active disease. One such peak was identified as serum amyloid A, a known acute-phase reactant in SJIA, validating the SELDI-TOF MS platform as a useful technology in this context. Finally, profiles from serum samples obtained at the time of active disease were compared between the two patient groups. Nine peaks had mean signal intensities significantly different (P < 0.001) between active disease in patients who responded to conventional therapy and in patients who failed to respond, suggesting a possible profile predictive of response. Collectively, these data demonstrate the presence of serum proteomic profiles in SJIA that are reflective of active disease and suggest the feasibility of using the SELDI-TOF MS platform used as a tool for proteomic profiling and discovery of novel biomarkers in autoimmune diseases

19. MULLER-GODEFFROY E, LEHMANN H, KUSTER RM, THYEN U: Quality of life and psychosocial adaptation in children and adolescents with juvenile idiopathic arthritis and reactive arthritis
    LEBENSQUALITAT UND PSYCHOSOZIALE ANPASSUNG BEI KINDERN UND JUGENDLICHEN MIT JUVENILER IDIOPATHISCHER ARTHRITIS UND REAKTIVEN ARTHRITIDEN. Zeitschrift fur Rheumatologie (Germany ) 64:3 177-187, 2005
    Abstract: We sought to measure self-reported health related quality of life (HRQOL) and psychosocial adaptation in children and adolescents with juvenile idiopathic arthritis (JIA) and reactive arthritis and to determine factors associated with these outcomes. We interviewed 72 children and adolescents with chronic arthritis, age 8-16, about HRQOL (KINDL-R-Questionnaire) and functional ability in activities of daily living (Childhood Health Assessment Questionnaire-CHAQ). Mothers reported behavior problems (Child Behavior Checklist-CBCL). Children and adolescents with juvenile idiopathic arthritis and reactive arthritis reported lower HRQOL compared to normative data in several areas. Children reported lower QOL in the dimensions self-esteem; adolescents reported lower QOL in the dimensions physical well being and total QOL. Almost 20% of the sample appeared to have serious behavior problems, mostly social isolation and depression/anxiety. Functional limitations affected HRQOL and behavior problems. Inpatient children and adolescents and those with shorter disease duration reported lower QOL than outpatient children and adolescents and those with longer disease duration. Best predictors for impaired HRQOL were functional limitations, social isolation and depression/anxiety. Self-reported HRQOL and behavior problems may be relevant outcome measures in children and adolescents with chronic arthritis and useful to monitor psychosocial support in this population. (c) Steinkopff Verlag 2005

20. NAGASHIMA M, SHU G, YAMAMOTO K, YAMAHATSU S, YOSHINO S: The ability of disease modifying antirheumatic drugs to induce and maintain improvement in patients with rheumatoid arthritis. epidemiology of DMARDs treatment in Japan. Clin Exp Rheumatol 23:1 27-35, 2005
    Organism: Department of Joint Disease and Rheumatism, Nippon Medical School, Tokyo, JapanFAU - Nagashima, M
    Abstract: OBJECTIVE: The effectiveness of the disease-modifying antirheumatic drugs (DMARDs) methotrexate (MTX), bucillamine (BUC), salazosulphapyridine (SASP) and gold sodium thiomalate (GST) over two courses of treatment with a follow-up period of at least 12 months was evaluated in 425 patients with rheumatoid arthritis. METHODS: Clinical efficacy was evaluated on the basis of the numbers of painful and swollen joints, morning stiffness, grip strength, erythrocyte sedimentation rate, C-reactive protein and rheumatoid factor levels before and after treatment. Results were evaluated on the basis of the survival rate (Kaplan-Meier method) and the incidence and types of adverse drug reactions (ADR) following single and combined therapies. RESULTS: In the first course of treatment, the survival rates for MTX, GST, BUC and SASP were 52.3%, 40.4%, 33.0% and 24.8%, respectively. The rates of development of ADR were 22.9%, 23.5%, 26.3% and 30.0% for BUC, SASP, GST and MTX, respectively. In the second course, the survival rates for MTX, BUC and SASP were 36.6%, 14.1% and 10%, respectively. CONCLUSION: DMARDs used in the first course of treatment improved the clinical parameters until the 6th month after initiation of treatment. Combination treatments showed some effectiveness, but because of the high incidence of ADR the survival rate was low. DMARDs used in the second course of treatment were not efficacious and there was no improvement in the survival rate compared to the first course of treatment

21. NEUDORF U, HEILIGENHAUS A: Uveitis in juvenile idiopathic arthritis: Management of patients - Consensus statement of the Working Group for Children and Adolescents with Rheumatic Diseases in Germany and the German Uveitis Centers
    UVEITIS BEI JUVENILER IDIOPATHISCHER ARTHRITIS: BETREUUNG VON PATIENTEN - KONSENSUSSTATEMENT DER ARBEITSGEMEINSCHAFT KIND. Monatsschrift fur Kinderheilkunde (Germany ) 152:11 1240-1248, 2004
    Abstract: Uveitis adds to the problems in children and adolescents with juvenile idiopathic arthritis (JIA), influencing the prognosis substantially and in ways that are quite independent of the arthritis itself. The Working Group for Children and Adolescents with Rheumatic Diseases in Germany (AGKJR)-and especially the branch group in North Rhine-Westphalia-and the German Uveitis Centers have initiated the formulation of an evidence-based strategy for the management of uveitis in JIA. This gives recommendations on the content and frequency of ophthalmological examinations and also a treatment concept. The aim is to improve the clinical management of these patients and to create a platform for further scientific approaches with uniform strategies. (c) Springer-Verlag 2004

22. NISHINO M, IKEGAMI H, FUJISAWA T, KAWAGUCHI Y, KAWABATA Y, SHINTANI M, ONO M, OGIHARA T: Functional polymorphism in Z-DNA-forming motif of promoter of SLC11A1 gene and type 1 diabetes in Japanese subjects: association study and meta-analysis. Metabolism 54:5 628-633, 2005
    Organism: Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, JapanFAU - Nishino, Masanori
    Abstract: The association of the polymorphism of the Z-DNA-forming repeats in the promoter region of SLC11A1 (solute carrier family 11 member 1), formerly designated NRAMP1 (natural resistance associated macrophage protein 1), with type 1 diabetes was studied in a total of 244 Japanese subjects. Three alleles were detected in Japanese subjects. In diabetic patients, allele 2 was less frequent and allele 3 was more frequent, albeit not significantly, than in control subjects. Allele 2 was significantly ( P < .024) less frequent whereas allele 3 was more, albeit not significantly, frequent in the younger onset group than in the control subjects. In patients with a susceptible HLA allele, DRB1*0405 or DRB1*0901 , the frequency of allele 2 was significantly ( P < .013) lower and that of allele 3 tended to be higher than that in patients without either DRB1*0405 or DRB1*0901 . The protective effect of allele 2 against type 1 diabetes and other autoimmune diseases was confirmed by meta-analysis (summary odds ratio, 0.71, 95% confidence interval, 0.53-0.96). Because allele 2 was shown to be associated with low expression of SLC11A1 and protection against another autoimmune disease, rheumatoid arthritis, the negative association of allele 2 with autoimmune type 1 diabetes in the present study suggests that a less active immune system in subjects with allele 2 may protect individuals from autoimmune diseases

23. OSTENSEN M, FORGER F, NELSON JL, SCHUHMACHER A, HEBISCH G, VILLIGER PM: Pregnancy in patients with rheumatic disease: Anti-inflammatory cytokines increase in pregnancy and decrease post partum. Annals of the Rheumatic Diseases (United Kingdom ) 64:6 839-844, 2005
    Abstract: Objective: To investigate changes in the levels of circulating cytokines with a focus on the Th1/Th2 balance during and after pregnancy in patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), and ankylosing spondylitis (AS). Methods: Plasma and serum samples of 34 pregnant patients, 19 with RA, 6 with JIA, and 9 with AS, and of 30 healthy pregnant women, 20 non-pregnant patients, and 10 non-pregnant healthy women were analysed for levels of interferon gamma(IFNgamma), interleukin (IL) 1beta, IL10, IL1 receptor antagonist (IL1Ra), soluble tumour necrosis factor receptor (sTNFR), and soluble CD30 (sCD30) by ELISA. Clinical assessment and blood sampling in pregnant women was done once in each trimester and 6, 12, and 24 weeks post partum. Disease activity in the patients was evaluated by validated clinical instruments and correlated with circulating levels of cytokines. Results: Low levels of IL10 were found sporadically, whereas IFNgamma and IL1beta were below detection level in the samples tested. Significantly higher concentrations of sTNFR and IL1Ra were measured in pregnant than in non-pregnant subjects. An increase of IL1Ra from the second to the third trimester correlated with improvement of disease activity in patients with RA and AS. Compared with non-pregnant patients and the other pregnant women, patients with RA showed markedly raised levels of sCD30 during pregnancy. Conclusions: IFNgamma and IL10, markers of a Th1 and Th2 response, respectively, were either low or undetectable in the cohorts analysed. The increase of cytokine inhibitors IL1Ra and sTNFR was related to pregnancy and was independent of an underlying disease. These anti-inflammatory mediators seem to affect disease activity

24. PAAP E, VAN DER NJ, HELDERS PJM, TAKKEN T: Physiologic response of the six-minute walk test in children with juvenile idiopathic arthritis. Arthritis Care and Research (United States ) 53:3 351-356, 2005
    Abstract: Objective. To determine the physiologic response of the 6-minute walk test (6-mwt) in children with juvenile idiopathic arthritis (JIA). Methods. Eighteen children with JIA (age 7-17 years; 6 boys, 12 girls) performed a 6-mwt and a maximal exercise test. Results. The physiologic response of the 6-mwt was on average between 80% and 85% of the peak values of heart rate and oxygen uptake (VoSUB2peak) during the maximal exercise test, except for the minute ventilation, which had a mean percentage of 68.5%. Backward regression analysis showed that height and distance walked were the best predictors of Vo SUB2peak during cycling (RSUP2 = 0.883, P < 0.001). During the 6-mwt, the difference between the first and second minute was significant in every variable, except for heart rate. The range of walking distance of children with JIA was comparable with that of healthy elderly people. Conclusion. The physiologic response of the 6-mwt is at a submaximal, intense level of exercise. The course of the responses during the 6-mwt was normal. The 6-mwt can be regarded as a good test for measuring functional exercise capacity. (c) 2005, American College of Rheumatology

25. REGAYA F, KHELIFA R, ZOUARI R, KCHIR M, KAROUI M, ESSID R: [Research on Parvovirus B19 infections and chronic articular manifestations in a Tunisian hospital]. Arch Inst Pasteur Tunis 80:1-4 9-15, 2003
    Organism: Banque du sang, Hopital Charles Nicolle a TunisFAU - Regaya, F
    Abstract: Parvovirus B19 infection is often associated with acute and chronic joint diseases thus suggesting an etiologic role for the virus in these pathologies. In this work, we looked for a possible correlation between Parvovirus B19 infection and certain types of chronic inflammatory rheumatisms. We therefore, screened a population of 100 patients with different chronic inflammatory rheumatismal affections for serological markers of Parvovirus B19 infection. All patients were Tunisians of both sexes, who presented at the service of Rheumatology of the Charles Nicolle Hospital, Tunis. One hundred blood donors were taken as controls. Specific Immunoenzyme Assays of the ELISA type (Biotrin International, France) were used to detect anti-Parvovirus IgG and IgM. On the other hand, viral DNA was sought by nested PCR in synovial fluid from 14 patients. The data obtained indicate that specific anti-Parvovirus B19 IgG was detectable in the sera of 80.7% of patients and 43% of controls. In contrast, none of the sera was found positive for specific IgM antibodies. Synovial fluid samples could be collected from 14 anti-Parvovirus B19 seropositive patients and were tested for the presence of viral DNA. None of the samples was found positive. The results of our serological study reinforce the hypothesis that Parvovirus B19 infection is associated with rheumatismal joint affections. However, the lack of detectable viral DNA in synovial fluid of the tested seropositive patients points to an indirect role of the virus in these joint disorders

26. SENGLER C, KEITZER R, PLEYER U: Uveitis in conjunction with rheumatological diseases in childhood
    UVEITIS BEI RHEUMATOLOGISCHEN ERKRANKUNGEN IM KINDESALTER. Ophthalmologe (Germany ) 102:5 463-476, 2005
    Abstract: Children with juvenile chronic arthritis are at risk to develop intraocular inflammation depending on the type of arthritis. The pathogenic mechanisms are unclear; however, an association with antinuclear antibodies is well known. In particular young girls with oligoarticular onset of arthritis are affected most often. Regular ophthalmologic examinations should allow early diagnosis and effective therapy. Complications such as synechiae, cataract, or macula edema are seen especially in uveitis patients with late diagnosis and insufficient anti-inflammatory therapy. Better therapeutic regimens have led to a better overall prognosis of intraocular inflammation in recent years. (c) Springer Medizin Verlag 2005

27. SHAYAN K, HO M, EDWARDS V, LAXER R, THORNER PS: Synovial pathology in camptodactyly-arthropathy-coxa vara-pericarditis syndrome. Pediatr Dev Pathol 8:1 26-33, 2005
    Organism: Division of Pathology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8, CanadaFAU - Shayan, Katayoon
    Abstract: At least 25 families with camptodactyly-arthropathy-coxa vara-pericarditis (CACP syndrome) have been reported, with descriptions of a distinctive synovial pathology based largely on light microscopy. Although described as "proliferative," with numerous multinucleated giant cells, the natures of proliferating cells and giant cells have not been determined. To clarify the pathogenesis of this disorder, we studied 3 patients who had CACP syndrome and underwent synovial biopsy. Cells in the biopsies were studied by immunohistochemistry and electron microscopy. Giant cells were identified as macrophage in origin based on CD68 expression and electron microscopic features of macrophages. Most cells in the synovium were CD68 positive, in keeping with macrophages. The degree of proliferation in synovial biopsies was estimated by MIB1 immunostaining, which showed that up to 30% of cells were cycling compared with fewer than 10% in control synovial biopsies. None of the giant cells was cycling. By double immunostaining, proliferating cells were determined to be fibroblastic synoviocytes rather than macrophages. Thus the proliferative synovitis in this CACP syndrome can be more accurately thought of as hypercellularity by infiltrating macrophages with a contribution by proliferating fibroblastic synoviocytes. The synoviocyte proliferation is likely a response to the underlying genetic mutations involving the proteoglycan-4 (or CACP) gene. The encoded protein normally acts as a lubricant and possibly controls cell proliferation. Loss of one or another of these functions may be a possible mechanism that leads to synoviocyte proliferation in this disease, but the exact pathophysiology leading to this change requires further study

28. SJAKSTE T, POUDZIUNAS I, RUMBA I, SJAKSTE N: Association of the proteasomal protein PSMA6 gene SNP polymorphism with juvenile rheumatoid arthritis in the Latvian population. Tissue Antigens 64:4 409, 2004

29. SZUMERA M: Parvovirus B19 (PB19) - Is the infection associated with connective tissue diseases in adults and children?
    PARWOWIRUS B19 (PB19) - CZY ZAKAZENIE MOZNA WIAZAC Z CHOROBAMI ZAPALNYMI TKANKI l(stroke)ACZNEJ U DOROSl(stroke)YCH I DZIECI? Reumatologia (Poland ) 43:2 80-84, 2005
    Abstract: Parvovirus B 19 is the cause of erythema infectiosum, aplastic anaemia, neonatal anaemia, thrombocytopenia, leukopenia. The course of infection is biphased, after flulike symptoms arthritis or pancytopenia may occur, more often in women than men and children. Laboratory diagnosis consists of detection of immunoglobulins M and G against capsid proteins VP2, VP1 and NS-1. Serological status and time of infection can be established this way. None the less the most specific is the detection of PB 19 DNA by hybrydization and polymerase chain reaction assays which are positive even in distant time from infection and in immunocompromised patients Protractive arthritis may follow the infection leading to diagnosis of rheumatoid or juvenile idiopathic arthritis. The coincidence of PB 19 infection and joint lesions may suggest its etiology. The irrefutable prove was not assessed, yet seropositive RA and JIA as a result of PB 19 infection were introduced so far. Some authors discussed the problem of other connective tissue diseases following PB 19 infection. As long as the prove will be obtained PB19 should be searched for in arthropathies and all PB 19 positive patients with protracted arthritis should be controlled

30. THACKER NM, DEMER JL: Chorioretinitis as a complication of pauciarticular juvenile rheumatoid arthritis. J Pediatr Ophthalmol Strabismus 42:3 183-184, 2005
    Organism: Department of Ophthalmology, Jules Stein Eye Institute, David Geffin Medical School at UCLA, Los Angeles, California 90095-7002, USAFAU - Thacker, Neepa M
    Abstract: A girl with pauciarticular juvenile rheumatoid arthritis developed bilateral uveitis complicated by cataract and glaucoma. Sequential fundus photography documented development of extensive choroidal scarring and retinal pigment epithelial atrophy in the left macula. Vision was not impaired. This case suggests uveitis in juvenile rheumatoid arthritis can be associated with chorioretinitis

31. VIOLA S, FELICI E, MAGNI-MANZONI S, PISTORIO A, BUONCOMPAGNI A, RUPERTO N, ROSSI F, BARTOLI M, MARTINI A, RAVELLI A: Development and validation of a clinical index for assessment of long-term damage in juvenile idiopathic arthritis. Arthritis Rheum 52:7 2092-2102, 2005
    Organism: Universita di Genova, IRCCS G Gaslini, Genoa, Italy
    Abstract: OBJECTIVE: To develop and validate a clinical measure of articular and extraarticular damage in patients with juvenile idiopathic arthritis (JIA). METHODS: The Juvenile Arthritis Damage Index (JADI), which is derived from physical examination and a brief review of the patient's clinical history, is composed of 2 parts: assessments of articular damage (JADI-A) and extraarticular damage (JADI-E). Instrument validation was accomplished by evaluating 158 JIA patients with disease duration of at least 5 years, seen consecutively over 21 months. The instrument's feasibility, face and content validity, construct and discriminative ability, internal consistency, and interrater reliability were examined. RESULTS: Among the 158 JIA patients, 47% and 37% had articular and extraarticular damage, respectively. The JADI was found to be feasible and to possess both face and content validity. The JADI-A score correlated highly with the number of joints with limited range of motion (Spearman's r [r(S)] = 0.72) and correlated moderately with the Childhood Health Assessment Questionnaire score (r(S) = 0.41), Steinbrocker functional classification (r(S) = 0.50), and Poznanski's score of radiographic damage (r(S) = -0.54), thereby demonstrating good construct validity. Correlations with the JADI-E score were lower, owing to the heterogeneity of its items. The JADI-A discriminated well among different levels of disability. The internal consistency (Chronbach's alpha) of the JADI-A and JADI-E was 0.93 and 0.59, respectively. The intraclass correlation coefficients between pairs of independent observers ranged from 0.85 to 0.97. CONCLUSION: The JADI exhibited good reliability, construct validity, and discriminative ability and is therefore a valid instrument for the assessment of long-term damage in patients with JIA, in the context of both clinical management and research settings

32. WEDDERBURN LR, WOO P, HULL RG: Paediatric rheumatology: a bright future in the UK and Europe. Rheumatology (Oxford) 44:4 423-425, /4/5

33. YOKOTA S, MIYAMAE T, IMAGAWA T, IWATA N, KATAKURA S, MORI M: Inflammatory cytokines and systemic-onset juvenile idiopathic arthritis. Modern Rheumatology (Japan ) 14:1 12-17, 2004
    Abstract: Systemic-onset juvenile idiopathic arthritis (JIA) is a severe and steroid-dependent disease, which sometimes progresses to the fatal disease macrophage activation syndrome. An investigation of inflammatory cytokine levels revealed increases in IL-6 in serum of systemic-onset disease patients. Continuously elevated levels of IL-6 in serum may play a important role in manifesting the clinical symptoms and signs of systemic-onset JIA, including spiking fever, rash, arthritis, and serositis. The characteristic fever spikes parallel IL-6 levels. Long-term exposure to high levels of IL-6 in children results in severe growth impairment, which was strongly suggested by the recent establishment of IL-6 transgenic mice. To avoid disease progression to macrophage activation syndrome and the adverse effects of high-dose corticosteroids, it might be reasonable to inhibit the formation of IL-6/IL-6R complex in order to block the binding to gp130 receptor, a biologically active receptor for IL-6. This review will provide evidence of the relationship between IL-6 homeostasis and systemic-onset JIA, and our recent trials of anti-IL-6R antibody (MRA) for children with acute systemic disease intractable to long-term and high-dose corticosteroid therapy. MRA could be a therapeutic modality for children with systemic-onset JIA intractable to high-dose corticosteroids. (c) Springer-Verlag Tokyo 2004