Bibliography September 05

1. ADDO A, LE J, LI W, AKSENTIJEVICH I, BALOW J, JR., LEE A, GREGERSEN PK, KASTNER DL, REMMERS EF: Analysis of CARD15/NOD2 haplotypes fails to identify common variants associated with rheumatoid arthritis susceptibility. Scand J Rheumatol 34:3 198-203, 2005
   Organism: Genetics and Genomics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892-0908, USAFAU - Addo, A
   Abstract: OBJECTIVES: The CARD15/NOD2 gene product plays an important role in host response to bacterial lipopolysaccharides and bacterial muramyl dipeptide via activation of NF-kappaB in monocytes. Mutations in CARD15 are associated with Crohn's disease (CD), a chronic inflammatory bowel disease. In this study we sought to determine whether CD-associated mutations or any common variants of this gene might contribute to susceptibility to another chronic inflammatory disease, rheumatoid arthritis (RA). METHODS: We genotyped 376 Caucasian RA cases and 376 ethnically matched healthy controls for three CD-associated CARD15 mutations. We also genotyped these 752 individuals for 12 common CARD15 single nucleotide polymorphisms (SNPs), determined the linkage disequilibrium structure of the gene, and compared the frequencies of the common CARD15 haplotypes in the RA cases and controls. RESULTS: None of the CD-associated mutations or the CARD15 SNPs was associated with susceptibility to RA. We also found no significant difference in the frequencies of any of the common haplotypes of the CARD15 gene in RA patients and controls. Our haplotype analysis was consistent with earlier observations that all three CD-associated variants independently arose on the same ancestral haplotype. CONCLUSIONS: These data suggest that CARD15 variants are not associated with RA susceptibility

2. AKAY AP, UNSAL E, OZBEK A, BAYKARA B: Psychosocial aspects of Turkish mothers of children with juvenile idiopathic arthritis. Rheumatol Int :1-2.: 1-2, 2005
   Organism: Department of Child and Adolescent Psychiatry, Dokuz Eylul University Faculty of Medicine, Inciralti, Izmir, Turkey, pekcanlara@yahoocom

3. ARABSHAHI B, DEWITT EM, CAHILL ANNMARIC, KAYE RD, CRON R: Evaluation of corticosteroid injection for TMJ arthritis in children with JIA. Arthritis & Rheumatism 50:12 4084, 2004

4. ARLET JB, THI HUONG DB, POUCHOT J, PIETTE JC: [Current concepts on the physiopathology of adult-onset Still's disease]. Rev Med Interne 26:7 549-556, 2005
   Organism: Service de medecine interne, groupe hospitalier Pitie-Salpetriere, 83, boulevard de l'Hopital, 75651 Paris cedex 13, France jbarlet@libertysurffrFAU - Arlet, J B
   Abstract: PURPOSE: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder of unknown origin. It is characterized by hectic fever, evanescent rash, polyarthralgias or polyarthritis, sore throat, hepatosplenomegaly, lymphadenopathy, polynuclear leukocytosis, liver cytolysis, and high serum level of ferritin with low glycosylated fraction. CURRENT KNOWLEDGE AND KEY POINTS: An increased serum level of ferritin, IL-8, IL-6, IL-18 and TNF-alpha indicates that macrophages are highly activated in AOSD. Interleukin 18 (IL-18) seems to be a key cytokine in the pathogenesis of AOSD. Serum IL-18 levels are increased in AOSD patients compared to other systemic inflammatory diseases such as rheumatoid arthritis and they are well correlated with serum ferritin levels and disease activity. IL-18 could cause acute liver injury and arthritis. Macrophages could be activated by infectious agents such as viruses and by an inadequate control of T cell response secondary to depressed Natural Killer lymphocyte function, similarly to that observed in systemic juvenile idiopathic arthritis. Sustained macrophage activation can lead to the hemophagocytic syndrome, a severe complication of both AOSD and systemic juvenile idiopathic arthritis. FUTURE PROSPECTS: Cytotoxic cell functions should be probably studied in AOSD as they were in the hemophagocytic syndrome and systemic juvenile idiopathic arthritis because AOSD, characterised by a marked macrophage activation may be related to an immunological deficiency

5. AULELEY GR, DELIGNE J, HANTSON C, BLUM-BOISGARD C: [Selective cyclooxygenase-2 inhibitors. A population-based analysis of use in France over a three-year period and comparison with randomised clinical trials]. Presse Med 34:10 703-710, 2005
   Organism: Caisse nationale d'assurance maladie, service medical national, regime AMPI, Centre Paris-Pleyel, Saint-Denis (93) guy-robertauleley@canamfrFAU - Auleley, Guy-Robert
   Abstract: OBJECTIVES: The use of selective cyclooxygenase-2 (COX-2) inhibitors is highly controversial today, mainly because of doubts about cardiovascular tolerance. Few studies have assessed the use of these drugs in daily clinical practice. This study aims to assess the changes in their use in daily practice in France and to compare it with their use in randomized clinical trials. METHODS: The French National Health Insurance Fund AMPI database of self-employed workers in non-agricultural occupations was used to obtain the following information: patients requesting reimbursement for celecoxib and rofecoxib between November 2000 and October 2003, morbidity assessed by enrollment on the lists of chronic diseases for which care is fully (100%) reimbursed, pregnancy (assessed by the payment of physicians' or hospital fees for delivery or by maternity benefits), and concomitant drugs (by claims for reimbursement). We compared these patients with those in randomized clinical trials (RCT) of celecoxib or rofecoxib published in either English or French before November 2003; we focused on their demographic characteristics, morbidity, pregnancy and concomitant drug use. RESULTS: Use of COX-2 inhibitors in France did not vary over the study period, except for patients' mean age (range: 64.2-62.9 years), proportion of women (56.7%-54.7%) and use of gastroprotective drugs (18.2%-28.4%). The mean age of patients in our study was 10 years older than that of RCT patients, and the proportion of women in our study was 15% lower. The percentage of women who took these drugs while pregnant was 0.02% in our study and 0.09% in the RCT. The percentage of patients with long-term chronic disorders overall was higher in our study than in the RCT, and the percentage for all specific long-term diseases except rheumatoid arthritis was also higher (for example, more patients had cardiovascular diseases or diabetes in our study [15%] than in the RCT [6%]). Patients in our study also used concomitant drugs from 9 of the 14 principal Anatomical Therapeutic Chemical classification groups more frequently than RCT patients: for cardiovascular drugs, for example, the figures were 55% and 5%, respectively. CONCLUSION: The demographic characteristics, prevalence of chronic morbidity and use of concomitant drugs among COX-2 inhibitor users in France varied little over the three years after marketing approval. Compared with RCT patients, these users were less often female, were older and more often had cardiovascular diseases. Cardiovascular events occurring among COX-2 inhibitor users in France should be evaluated

6. BECHTOLD S, URSCHEL S, DALLA PR, JANSSON A, BELOHRADSKY B: Reactive arthritis in childhood. Pathogenesis, classification, diagnosis and therapy
   REAKTIVE ARTHRITIS IM KINDESALTER. PATHOGENESE, KLASSIFIKATION, DIAGNOSTIK UND THERAPIE. Monatsschrift fur Kinderheilkunde (Germany ) 150:4 460-469, 2002
   Abstract: Reactive arthritis constitutes a group of inflammatory arthritides 2 to 4 weeks after an extra-articular infection. HLA-B27 is more frequent in reactive arthritis, in 50 to 80% of the patients. The arthritis is painful and oligo- or polyarticular. The duration of illness ranges from several months to a chronic state. The inflammatory manifestation of reactive arthritis requires the administration of non-steroidal anti-inflammatory drugs. In some disease modifying drugs like Sulfasalazin are necessary. Besides medical treatment physical therapy plays an important role. The course of the disease varies: most children experience only a single episode of monarthritis, others suffer from a recurrent or chronic form. In contrast to the juvenile idiopathic arthritis radiological destructive findings less commonly occur. (c) Springer-Verlag 2002

7. BILGINER Y, TOPALOGLU R, BAKKALOGLU AYSIN, ALIKASIFOGLU A, OZEN S, BESBAS N: The role of neuroencocrine immune system in juvenile rheumatoid arthritis. Arthritis & Rheumatism 50:12 4088, 2004

8. BINSTADT BA, LEVINE JC, NIGROVIC PA, GAUVREAU KIMBERLEE, DEDEOGLU F, FUHLBRIGGE RC, WEINDLING S, NEWBURGER JW, SUNDEL RP: Coronary artery dilation among patients presenting with systemic-onset juvenile idiopathic arthritis. Pediatrics 116:1 E89-E93, /7/5
   Abstract: Objective. To evaluate coronary artery diameters among patients presenting with systemic-onset juvenile idiopathic arthritis (SoJIA).Methods. Fifty cases of SoJIA were reviewed. At the time of initial presentation with fever, 12 patients had echocardiograms that included a complete evaluation of the coronary arteries. A single reviewer measured the diameters of the left main, proximal left anterior descending, and proximal right coronary arteries. Body surface area- adjusted z scores were calculated with respect to a no rmative population.Results. Coronary artery dilation (z score: > 2) was observed for 5 of the 12 patients with SoJIA who had echocardiograms performed at the time of presentation with fever. No patient developed a coronary artery aneurysm, and all of the coronary artery z scores normalized within 4 months. Only 2 of the 5 patients with coronary artery z scores of > 2 fulfilled the clinical criteria for Kawasaki disease, the most commonly recognized cause of coronary artery dilation among children.Conclusions. Children presenting with SoJIA may have coronary artery dilation similar to that observed for children with Kawasaki disease. These data suggest that the presence of coronary artery dilation on initial echocardiograms for patients with fever does not exclude the diagnosis of SoJIA

9. BOUTRY N, HACHULLA E, FLIPO RM, CORTET B, COTTEN A: MR imaging findings in hands in early rheumatoid arthritis: comparison with those in systemic lupus erythematosus and primary Sjogren syndrome. Radiology 236:2 593-600, 2005
   Organism: Department of Musculoskeletal Radiology, Unite de Recherche de l'Appareil Locomoteur, Hopital Roger Salengro, Centre Hospitalier Regional Universitaire de Lille, Blvd du Professeur Leclercq, 59037 Lille CEDEX, France nboutry@chru-lillefrFAU - Boutry, Nathalie
   Abstract: PURPOSE: To evaluate prospectively the use of magnetic resonance (MR) imaging for differentiating true rheumatoid arthritis (RA) from systemic lupus erythematosus (SLE) or primary Sjogren syndrome in patients who have inflammatory polyarthralgia of the hands but no radiographic evidence of RA. MATERIALS AND METHODS: This study had institutional review board approval, and patient informed consent was obtained. Twenty-eight patients (16 female and 12 male patients; mean age, 42 years) with early RA and 19 patients (18 female and one male patient; mean age, 46 years) with SLE (n = 14) or primary Sjogren syndrome (n = 5) underwent MR imaging of both hands. All patients had inflammatory polyarthralgia of the hands and no evidence of erosive changes on radiographs. Coronal T2-weighted short inversion time inversion-recovery, transverse T1-weighted spin-echo, transverse fat-suppressed gadolinium-enhanced T1-weighted spin-echo, and transverse gadolinium-enhanced three-dimensional gradient-echo MR images were obtained. The following MR imaging variables were assessed in the wrist and nonthumb metacarpophalangeal joints: synovitis, bone lesions (erosion, defect, and edema), and tenosynovitis. Synovitis and bone lesions were scored with the OMERACT RA-MRI scoring system. Findings in patients with RA and those without RA were compared by means of Mann-Whitney, chi2, and Fisher exact tests. RESULTS: The only significant difference between the two groups in terms of individual scores for synovitis, bone lesions, and tenosynovitis was the more frequent presence of tenosynovitis of the right fourth extensor tendon in patients without RA (P = .04). There were no significant differences between patients with RA and those without RA in terms of global scores for synovitis, bone lesions, and tenosynovitis. However, bone marrow edema in the metacarpophalangeal joints was seen more frequently in patients with RA (P < .001). CONCLUSION: It may be impossible to distinguish between patients with early RA and those without RA (ie, those with SLE or primary Sjogren syndrome) by means of MR imaging

10. BULTMANN C, MEIER M, KRIMMER H: [Mid-term results after proximal row carpectomy and review of the literature]. Handchir Mikrochir Plast Chir 37:2 113-118, 2005
    Organism: Klinik fur Handchirurgie, Bad Neustadt/Saale ChristineBultmann@t-onlinedeFAU - Bultmann, C
    Abstract: PURPOSE: The aim of this study is to evaluate the results after proximal row carpectomy and to compare them with results in the literature. METHOD: Between 1994 and 2001, 37 patients underwent proximal row carpectomy. 30 patients were available for follow-up. In all cases the proximal row carpectomy was performed through a dorsal approach. Clinical parameters were evaluated by using the conventional wrist score (Krimmer score) as well as the DASH-score. RESULTS: Follow-up examination shows a range of motion (ROM) for wrist extension and flexion of 46 % of the contralateral side. ROM for ulnar and radial deviation is 42 % of the other side, ROM for pronation and supination is equal to the other side. Mean grip strength is determined to be 58 % of the contralateral side. 90 % of the patients are satisfied with the result of the operation. The Krimmer score amounts to 58 and the DASH score to 39 points. CONCLUSION: We consider proximal row carpectomy to be a good therapeutic option for lunate necrosis stage IIIB or IV or carpal collapse stage II (SNAC or SLAC wrist) with a concomitant lesion of extrinsic ligaments with ulnar translocation. Another indication is the acute, non-reconstructable or the chronic perilunar luxation with arthrosis

11. CARPENTIER KG, SEVENANTS L, WOUTERS CH, MORREN MA: Pachydermodactyly may mimic juvenile idiopathic arthritis. Clin Exp Rheumatol 23:5 725, 2005

12. CHOI SW, LIM MK, SHIN DH, PARK JJ, SHIM SC: Diagnostic performances of anti-cyclic citrullinated peptides antibody and antifilaggrin antibody in Korean patients with rheumatoid arthritis. J Korean Med Sci 20:3 473-478, 2005
    Organism: Department of Laboratory Medicine, Eulji University, School of Medicine, Daejeon, KoreaFAU - Choi, Suk Woo
    Abstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease of unknown etiology. We studied the diagnostic performances of anti-cyclic citrullinated peptides antibody (anti-CCP) assay and recombinant anti-citrullinated filaggrin antibody (AFA) assay by enzyme linked immunosorbent assay (ELISA) in patients with RA in Korea. Diagnostic performances of the anti-CCP assay and AFA assay were compared with that of rheumatoid factor (RF) latex fixation test. RF, anti-CCP, and AFA assays were performed in 324 RA patients, 251 control patients, and 286 healthy subjects. The optimal cut off values of each assay were determined at the maximal point of area under the curve by receiver-operator characteristics (ROC) curve. Sensitivity (72.8%) and specificity (92.0%) of anti-CCP were better than those of AFA (70.3%, 70.5%), respectively. The diagnostic performance of RF showed a sensitivity of 80.6% and a specificity of 78.5%. Anti-CCP and AFA showed positivity in 23.8% and 17.3% of seronegative RA patients, respectively. In conclusion, we consider that anti-CCP could be very useful serological assay for the diagnosis of RA, because anti-CCP revealed higher diagnostic specificity than RF and AFA at the optimal cut off values and could be performed by easy, convenient ELISA method

13. DESHMUKH AV, KORIS M, ZURAKOWSKI D, THORNHILL TS: Total shoulder arthroplasty: Long-term survivorship, functional outcome, and quality of life. J Shoulder Elbow Surg 14:5 471-479, 2005
    Organism: Department of Orthopaedics, Kaiser West Los Angeles Medical Center, Los Angeles, CA, USAFAU - Deshmukh, Ashwin V
    Abstract: This study examines long-term outcomes of total shoulder arthroplasty (TSA) via survivorship analysis, patient questionnaires, and minimum 10-year physical examinations. The study group consisted of 320 consecutive TSAs performed in 267 patients between 1974 and 1988. Diagnoses included rheumatoid arthritis (69%), osteoarthritis (22%), and juvenile rheumatoid arthritis (4.7%). Minimum 10-year physical examination follow-up was obtained on a subset of 72 TSAs at a mean (+/- SD) of 14.0 +/- 2.7 years. A Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire was obtained from 80 patients with 103 TSAs at a mean of 15.4 +/- 3.4 years after the index procedure (range, 10.4-23.2 years). Kaplan-Meier survivorship rates with revision as the endpoint at 5, 10, 15, and 20 years were 98%, 93%, 88%, and 85%, respectively. Of the shoulders, 22 (6.9%) required a revision, most commonly for loosening of one or both components (15 shoulders). Dislocation occurred earlier than other causes of revision or complication (P < .05, analysis of variance). Minimum 10-year physical examination follow-up revealed lasting, significant improvements in range of motion and strength. The patients' subjective assessments of TSA were favorable in that 92% felt that their shoulder was "much better" or "better" after TSA. The mean DASH score was 49 +/- 25; no significant differences were found among diagnoses. Long-term analysis of the Neer-type TSA revealed survivorship rates comparable to other joint replacements. The significant improvements in relief of pain, shoulder range of motion, and strength are associated with a high degree of patient satisfaction

14. DEVINE DV, MOLL HD, BAHR RJ: Fracture, luxation, and chronic septic arthritis of the temporomandibular joint in a juvenile horse. J Vet Dent 22:2 96-99, 2005
    Organism: Equine Section, Oklahoma State University, College of Veterinary Medicine, Stillwater 74078, USA devined@okstateeduFAU - Devine, Dustin V
    Abstract: This case report describes chronic sepsis of the right temporomandibular joint in a juvenile horse. Diagnostic work-up included physical examination, radiography, and computed tomography. Humane euthanasia was indicated due to the chronicity of the condition, prognosis, and financial constraints

15. DEWINT P, HOFFMAN IE, ROGGE S, JOOS R, UNION A, DEHOORNE J, DELANGHE J, VEYS EM, DE KEYSER F, ELEWAUT D: Effect of age on prevalence of anticitrullinated protein/peptide antibodies in polyarticular juvenile idiopathic arthritis. Rheumatology (Oxford) .: 2005
    Organism: Departments of Rheumatology, Ghent, Belgium
    Abstract: Objectives. Anticitrullinated protein/peptide antibodies (ACPA) have an excellent diagnostic performance for rheumatoid arthritis (RA). Despite similarities between RA and polyarticular juvenile idiopathic arthritis (JIA), the prevalence of ACPA in polyarticular JIA is low. We wanted to evaluate the influence of age, disease duration and total immunoglobulin G (IgG) concentration on ACPA positivity in this cohort. Methods. Patients with JIA were classified according to age and International League of Associations for Rheumatology classification. Sixty-one JIA patients aged less than 16 yr were included and classified as polyarticular JIA (poly JIA <16; n=23) or non-polyarticular JIA (n=38). In addition, a group of 21 polyarticular JIA patients, aged more than 16 yr (poly JIA >16) and a group of 51 RA patients were included. Antibodies to the synthetic citrullinated peptides pepA and pepB were detected by line immunoassay and antibodies to cyclic citrullinated peptides (CCP2) by enzyme-linked immunosorbent assay. Serum IgG was measured by fixed-time immunonephelometry. Results. No ACPA reactivity was observed in the non-polyarticular group. In poly JIA <16, only 1/23 had anti-CCP2 antibody, whereas in poly JIA >16 patients a significantly higher fraction was detected (6/21). All but one of the anti-CCP2 reactive patients were rheumatoid factor (RF) positive. Assessing anti-CCP2 antibody concentration as a continuous variable, significantly higher titres were found in poly JIA >16 compared with poly JIA <16. No correlation between anti-CCP2 concentration and total IgG was detected. Four patients demonstrated immunoreactivity against pepA and pepB; all of them were anti-CCP2 reactive, poly JIA >16 patients. Conclusions. ACPA are present in low prevalence in polyarticular JIA and are particularly found in the RF-positive subset. With age, a significant increase in anti-CCP2 positivity is observed in polyarticular JIA patients

16. DOSTAL C, PAVELKA K, ZVAROVA J, HANZLICEK P, OLEJAROVA M: Some principles of the development of a clinical database/national register of selected inflammatory rheumatic diseases in the Czech Republic. Int J Med Inform .: 2005
    Organism: Institute of Rheumatology, Na Slupi 2, 128 50 Prague 2, Czech Republic
    Abstract: According to the World Health Organisation, rheumatic diseases are likely to go on occupying a prominent place worldwide. As to US statistics, rheumatic diseases are currently the most frequent chronic disorders and leading cause of disability. The development of functional clinical database or rheumatic diseases represents an essential condition how to acquire necessary epidemiological and other information on disorders under study. In 1999-2003, Institute of Rheumatology in cooperation with EuroMISE have developed clinical database/national register of selected systemic inflammatory rheumatic diseases inclusive of bank of sera and DNA. Aims of this phase of the pilot research have been formulated into following relevant and time borders: to gather clinical, laboratory, genetic but also pharmaco- and socio-economic data in a representative sample of patients with systemic lupus erythematosus, systemic sclerosis, polymyositis/dermatomyositis, mixed connective tissue disease; rheumatoid arthritis, juvenile chronic arthritis, ankylosing spondylitis, psoriatic arthritis and reactive arthritis. The data about patients entering the register are differentiated according to the disease of the patient. However, many diseases have several data in common. Therefore, a simple common data structure for examination of all monitored diseases was chosen. In 2002, the preset number of over 2000 registered patients had been achieved with collaboration of 34 territorial and 20 institutional rheumatologists in the whole covering the majority of the Czech Republic. Some first acquired information inclusive comparison with German database is demonstrated

17. EPPS H, GINNELLY L, UTLEY M, SOUTHWOOD T, GALLIVAN S, SCULPHER M, WOO P: Is hydrotherapy cost-effective? A randomised controlled trial of combined hydrotherapy programmes compared with physiotherapy land techniques in children with juvenile idiopathic arthritis. Health Technol Assess 9:39 1-76, 2005
    Organism: The Children's Trust, Tadworth Court, UKFAU - Epps, H
    Abstract: OBJECTIVES: To compare the effects of combined hydrotherapy and land-based physiotherapy (combined) with land-based physiotherapy only (land) on cost, health-related quality of life (HRQoL) and outcome of disease in children with juvenile idiopathic arthritis (JIA). Also to determine the cost-effectiveness of combined hydrotherapy and land-based physiotherapy in JIA. DESIGN: A multicentre randomised controlled, partially blinded trial was designed with 100 patients in a control arm receiving land-based physiotherapy only (land group) and 100 patients in an intervention arm receiving a combination of hydrotherapy and land-based physiotherapy (combined group). SETTING: Three tertiary centres in the UK. PARTICIPANTS: Patients aged 4-19 years diagnosed more than 3 months with idiopathic arthritides, onset before their 16th birthday, stable on medication with at least one active joint. INTERVENTIONS: Patients in the combined and land groups received 16 1-hour treatment sessions over 2 weeks followed by local physiotherapy attendances for 2 months. MAIN OUTCOME MEASURES: Disease improvement defined as a decrease of 30% in any three of six core set variables without there being a 30% increase in more than one of the remaining three variables was used as the primary outcome measure and assessed at 2 months following completion of intervention. Health services resource use (in- and outpatient care, GP visits, drugs, interventions, and investigations) and productivity costs (parents' time away from paid work) were collected at 6 months follow-up. HRQoL was measured at baseline and 2 and 6 months following intervention using the EQ-5D, and quality-adjusted life-years (QALYs) were calculated. Secondary outcome measures at 2 and 6 months included cardiovascular fitness, pain, isometric muscle strength and patient satisfaction. RESULTS: Seventy-eight patients were recruited into the trial and received treatment. Two months after intervention 47% patients in the combined group and 61% patients in the land group had improved disease with 11 and 5% with worsened disease, respectively. The analysis showed no significant differences in mean costs and QALYs between the two groups. The combined group had slightly lower mean costs (- pound6.91) and lower mean QALYs (-0.0478, 95% confidence interval -0.11294 to 0.0163 based on 1000 bootstrap replications). All secondary measures demonstrated a mean improvement in both groups, with the combined group showing greater improvements in physical aspects of HRQoL and cardiovascular fitness. CONCLUSIONS: JIA is a disease in which a cure is not available. This research demonstrates a beneficial effect from both combined hydrotherapy and land-based physiotherapy treatment and land-based physiotherapy treatment alone in JIA without any exacerbation of disease, indicating that treatments are safe. The caveat to the results of the cost-effectiveness and clinical efficacy analysis is that the restricted sample size could have prevented a true difference being detected between the groups. Nevertheless, there appears to be no evidence to justify the costs of building pools or initiating new services specifically for use in this disease. However, this conclusion may not apply to patients with unremitting active disease who could not be entered into the trial because of specified exclusion criteria. For this group, hydrotherapy or combined treatment may still be the only physiotherapy option. Further research is suggested into: the investigation and development of appropriate and sensitive outcome measures for use in future hydrotherapy and physiotherapy trials of JIA; preliminary studies of methodologies in complex interventions such as physiotherapy and hydrotherapy to improve recruitment and ensure protocol is acceptable to patients and carers; hydrotherapy in the most common paediatric user group, children with neurological dysfunction, ensuring appropriate outcome measures are available and methodologies previously tried; patient satisfaction and compliance in land-based physiotherapy and hydrotherapy and European studies of hydrotherapy in rare disorders such as JIA

18. ESPINOLA ZN, ALEXANDERSON E, SOTO ME, FLORES M, AMIGO MC: [Analysis of the ulsefulnes of contrast echocardiography and nuclear medicine in cardiovascular affection due to autoimmune diseases]. Arch Cardiol Mex 75:1 42-48, 2005
    Organism: Departamento de Ecocardiografia de Consulta Externa, Instituto Nacional de Cardiologia "Ignacio Chavez", (INCICH, Juan Badiano No1, Col Seccion XVI, Tlalpan 14080, Mexico, DF niesza2001@hotmailcomFAU - Espinola Zavaleta, Nilda
    Abstract: A significant correlation between autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and premature or accelerated coronary atherosclerosis was found. The objectives of the study were: a) evaluate myocardial perfusion in patients with rheumatic diseases by means of contrast echocardiography (CE) and to establish its usefulness as compared to the results obtained by nuclear medicine (NM) (reference method). b) evaluate the prevalence of alterations in subclinical myocardial perfusion in autoimmune diseases and to establish a strategy to evaluate the cardiovascular changes in this disease. Myocardial perfusion in 37 outpatients of the rheumatology department was evaluated by CE at rest and with pharmacological stress (dobutamine) and NM. The prevalence of alterations in the myocardial perfusion in autoimmune diseases by CE and NM, when these methods were analyzed independently or when both methods were used was 27%. The positive predictive value (PPV) and negative predictive value (NPV) of both tests was 80% and 93%, respectively, the sensitivity was 80% and the specificity was 93%. The prevalence of alterations of perfusion in the primary antiphospholipid syndrome (PAPS) was of 30%. In this patients it was found that when both diagnostic tests are performed, NM reaches a sensitivity of 100% if the CE is positive and an specificity of 100% when the CE is negative. We can conclude that it is important to determine the presence of subclinic coronary artery disease in patients with autoimmune disease by noninvasive studies such as Sestamibi SPECT and/or CE for assessment of myocardial perfusion in order to plan an adequate treatment and follow-up

19. EVSIKOVA MD, MURAVIEV I: [Unwanted reactions to modifying antirheumatic drugs]. Ter Arkh 77:5 72-74, 2005
    Abstract: AIM: To specify causes of discontinuation of the disease-modifying antirheumatic drugs (DMAD) used in rheumatoid arthritis (RA) by the results of special questionnaire survey. MATERIAL AND METHODS: The study included 298 RA patients treated in the Institute of Rheumatology (34 males and 264 females aged 18-82, mean age 54.6%, duration of the disease 1 to 38 years, mean 10.7 years) who responded to questioning. RESULTS: The following DMAD were used: metotrexate (n = 137), sulfasalasine (n = 49), aminoquinoline drugs (n = 33), chlorbutin (n = 19), azathioprin (n = 13), tauredon (n = 11), cyclophosphamide (n = 5). The drugs were discontinued due to unwanted effects in 50, 10, 46, 9, 4, 3, 3 (methotrexate, sulfasalasin, aminoquinolines, chlorbutin, azathioprin, Ag salts, cyclophosphamide, respectively). Cyclophosphamide and chlorbutin appeared most toxic, while sulfasalasine and aminoquinolines were found least effective. CONCLUSION: DMAD discontinuation rate ranges from 12.1% (aminoquinolines) to 60% (cyclophosphamide), mean 31.1%

20. FELDMANN R, WEGLAGE J, ROTH J, FOELL D, FROSCH M: Systemic juvenile rheumatoid arthritis: Cognitive function and social adjustment. Ann Neurol 58:4 605-609, 2005
    Organism: Department of Pediatrics, University Hospital of Munster, Munster, GermanyFAU - Feldmann, Reinhold
    Abstract: In contrast with other systemic rheumatic diseases in childhood, no systematic studies exist that focus on possible long-term risks for central nervous system involvement in systemic juvenile rheumatoid arthritis (SJRA). We investigated 31 children and adolescents with SJRA, aged 6 to 24 years (mean, 12.5 years; standard deviation, 4.3 years), with mean disease duration of 6.2 years (standard deviation, 3.5 years; range, 0.6-14 years) for their cognitive and fine motor abilities. We also examined 31 matched healthy control subjects. In addition, parents assessed social activities and social and emotional problems in their children. Patients and control subjects performed within normal limits of intelligence quotient, memory and learning, attention, and fine motor scores. Less social activities were reported for patients. Patients and control subjects, however, had normal social and emotional problem scores. SJRA, although a burdensome chronic disease, is not associated with cognitive impairment or increased social and emotional problems. Cognitive performance and social adjustment of young patients with SJRA are not affected by disease activity and duration. Ann Neurol 2005;58:605-609

21. FELICI E, NOVARINI C, MAGNI-MANZONI S, PISTORIO A, MAGNANI A, BOZZOLA E, BUONCOMPAGNI A, MARTINI A, RAVELLI A: Course of joint disease in patients with antinuclear antibody-positive juvenile idiopathic arthritis. J Rheumatol 32:9 1805-1810, 2005
    Organism: Dipartimento di Pediatria, Universita di Genova, Unita Operativa Pediatria II, Istituto di Ricovero e Cura a Carattere Scientifico G Gaslini, Genova, ItalyFAU - Felici, Enrico
    Abstract: OBJECTIVE: To describe the patterns and time course of arthritis in patients with antinuclear antibody (ANA)-positive juvenile idiopathic arthritis (JIA). METHODS: We identified patients followed during a 16-year period who had JIA by ILAR criteria, were ANA-positive (i.e., had >or= 2 positive ANA test results at titer >or= 1:160), and had a disease duration >or= 2 years. Demographic and clinical features, including ILAR category and cumulative number and type of joints affected over time, were recorded. RESULTS: A total of 195 patients were studied. The ILAR category was oligoarthritis in 159 patients and rheumatoid factor-negative polyarthritis in 36 patients. The cumulative rate of polyarticular extension in patients with oligoarticular onset was 26%, 38%, 45%, 49%, and 51% at 1, 2, 3, 4, and 5 years, respectively. At disease onset, most patients had monoarthritis and 95% had <or= 4 joints affected. The knee was the most frequently involved of all joints, followed by the ankle and proximal interphalangeal joints. Among patients with oligoarticular onset, the presence of ankle (in case of monoarticular disease) and/or wrist involvement in the first 6 months was more common in those who progressed to polyarthritis. CONCLUSION: The majority of our ANA-positive patients, including most of those who later developed polyarthritis, had monoarthritis at disease onset. Among patients with oligoarticular onset, polyarticular extension occurred in around 50% of cases within the first 3-4 years after disease onset, and tended to be less likely thereafter. The early occurrence of ankle and/or wrist disease may indicate a higher likelihood of arthritis progression

22. FOELDVARI I, WIERK A: Healthy children have a significantly increased skin score assessed with the modified Rodnan skin score. Rheumatology (Oxford) .: 2005
    Organism: Pediatric Rheumatologic Clinic, Allgemeines Krankenhaus Eilbek, Hamburg, Germany
    Abstract: Objectives. The modified Rodnan skin score (MRSS) is used as a primary outcome measure in most therapeutic trials in systemic sclerosis (SSc) in adults. Before we can apply this outcome measure in trials in juvenile patients with SSc, we need to evaluate this assessment method in children without sclerodermatous skin changes, to establish values for the normal paediatric population. Methods. To determine the MRSS in healthy paediatric population, patients of the paediatric rheumatology out-patient clinic with mechanical pain or with juvenile idiopathic arthritis at the age of 16 yr or under were assessed between 1 January and 31 March 2004. Patients with any sign of connective tissue disease or skin disorders, such as psoriasis or ectopic dermatitis, were excluded. The MRSS was determined at a standardized location and with a standardized pinching method. Results. Two hundred and seventeen patients, including 100 females, were assessed. The mean age of the patients was 10.5 yr (2.9-16), the mean body mass index (BMI) was 18.3 (9.3-35.7), and the mean MRSS was 13.92 (range 4-25). The MRSS score showed a difference between males and females at every Tanner stage. There was a linear correlation between MRSS and body mass index independently of age and Tanner stage. Conclusion. The mean MRSS in healthy children is 13.92 units and this range would be expected in a patient with a diffuse form of SSc. The MRSS score in children correlates with the body mass index and the Tanner stage, so it should be corrected to these parameters, according to this pilot study

23. GIBBONS LJ, THOMSON W, ZEGGINI E, WORTHINGTON J, BARTON A, EYRE S, DONN R, HINKS A: The type 1 diabetes susceptibility gene SUMO4 at IDDM5 is not associated with susceptibility to rheumatoid arthritis or juvenile idiopathic arthritis. Rheumatology (Oxford) .: 2005
    Organism: Arthritis Research Campaign Epidemiology Unit, University of Manchester, Manchester
    Abstract: Objectives. Linkage and association of rheumatoid arthritis (RA) and rheumatoid factor (RF)-negative juvenile idiopathic arthritis (JIA) has previously been demonstrated to the type 1 diabetes (T1D) locus, IDDM5, on chromosome 6q25. An association of a methionine-to-valine polymorphism (rs237025, 163A --> G, M55V) in the SUMO4 gene within IDDM5 has recently been described in T1D. The objective of this study was to test the hypothesis that SUMO4 is a general autoimmune susceptibility gene by investigating whether the SUMO4 polymorphism is associated with RA and/or JIA. Methods. The SUMO4 SNP was genotyped in 875 RA patients, 668 JIA patients and 484 healthy controls using a TaqMan(R) allelic discrimination assay. Allele and genotype frequencies were compared between cases and controls using the chi(2) test. Analyses were also carried out with RA patients stratified by gender, age at onset, RF status, the presence of erosive disease and shared epitope status, while JIA patients were stratified by their International League of Associations for Rheumatology (ILAR) subgroup. Results. No deviation from Hardy-Weinberg equilibrium was detected in either set of cases or controls. No association was observed between rs237025 and RA (chi(2)=0.17, P=0.93), or with any RA subset. Similarly, there was no association between this SNP and JIA (chi(2)=0.21, P=0.90), or with any ILAR subgroup. Conclusions. The M55V substitution in the SUMO4 gene is not associated with susceptibility to RA or JIA in the UK population studied. However, other candidate genes mapping within IDDM5 remain to be investigated

24. GOLDMAN RD, BENSELER SM, SCHNEIDER R: Intra-articular calcifications in a child with juvenile rheumatoid arthritis. Arch Dis Child 90:10 1038, 2005
    Organism: Pediatric Research in Emergency Therapeutics (PRETx) Program, The Hospital for Sick Children, Department of Pediatrics, University of Toronto, Ontario, Canada rangoldman@sickkidscaFAU - Goldman, R D

25. GRAHAM TB, LAOR T, DARDZINSKI BJ: Quantitative magnetic resonance imaging of the hands and wrists of children with juvenile rheumatoid arthritis. J Rheumatol 32:9 1811-1820, 2005
    Organism: Department of Pediatrics, Division of Rheumatology, Imaging Research Center, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA brentgraham@cchmcorgFAU - Graham, T Brent
    Abstract: OBJECTIVE: To assess feasibility of measuring synovial volume in the hand and wrist in patients with polyarticular course juvenile rheumatoid arthritis (JRA) by magnetic resonance imaging (MRI). As well, to compare clinical variables with synovial volume calculated from MRI in patients receiving disease modifying or biologic therapy. METHODS: Ten patients with polyarticular course JRA starting methotrexate (n = 3) or etanercept (n = 7) therapy had MRI with intravenous contrast performed of one hand and wrist at baseline and after 6 weeks and 3 months of pharmacotherapy. Synovial volume was determined for the entire hand and wrist and also for regions. Patients were assessed clinically by the core set of outcome variables for JRA and total hand swelling score, and assessed for clinical improvement based upon change in these variables. RESULTS: Increased synovial volume was observed at entry by MRI in all patients (range 2.4-12.5 cc, median 3.7 cc). Correlation of total synovial volume from MRI with total hand swelling score at each timepoint was good (r = 0.52-0.68). Correlation with other clinical variables was not consistently strong. Patients who improved clinically did not differ from patients who did not improve clinically with respect to change in synovial volume. CONCLUSION: Determining synovial volume in the hand and wrist in patients with JRA by MRI is feasible and correlates with total hand swelling assessed on physical examination. Inconsistent or poor correlation with other clinical variables and the clinical definition of improvement requires further study

26. GRANADOS D, LEFRANC A, REITER R, GREMY I, SPIRA A: [Disability-adjusted life years: an instrument for defining public health priorities?]. Rev Epidemiol Sante Publique 53:2 111-125, 2005
    Organism: Service de Sante publique et d'Epidemiologie, Atelier Parisien de Sante Publique, CHU Bicetre, 78, rue du General-Leclerc, 94275 Le Kremlin-Bicetre CedexFAU - Granados, D
    Abstract: BACKGROUND: The objective of this paper is the study of a health indicator allowing surveillance and evaluation of the overall health of the Paris population, and providing information to help prioritize possible choices among preventive and curative actions. Moreover, comparison between results obtained for Paris with a global health indicator, "Disability-adjusted life years" (DALYs) and available bibliographical data will enable clarifying some points about summary measures of health. METHODS: The method used is that of the Global Burden of Disease. It allows a ranking of diseases using an indicator called DALYs. This indicator integrates mortality and morbidity components by summing expected years of life lost due to premature mortality and calculated years of healthy life lost. DALYs were calculated using local mortality data and published regional disabilities tables from the World Health Organisation (WHO). RESULTS: There were a total of 242 061 DALYs for Paris for the year 1999. The six leading specific causes are: alcoholic psychosis and dependence (accounting for 6.5% of the total), lung cancers (5.7%), ischaemic hearth disease (4.8%), depression (4.4%), dementias (4.2%), and arthritis (3.9%). Men contributed the majority of DALYs for the first three. For four of the six leading causes, the majority of DALYs came from years lived with disability, rather than mortality. Only for lung cancer and ischaemic hearth disease was the majority of DALYs from years of life lost by mortality. CONCLUSION: The results for Paris are used to illustrate how DALYs can illuminate debates about public health priorities. Such data can inform the population about health condition and provide decision makers with global health indicators. The next step will be to estimate the DALYs from local morbidity data when available, and compare these results to those based on the World Health Organisation tables, which are not sensitive to local results other than those due to mortality. Future steps include further evaluation and development of this method for surveillance, assessment and evaluation of public health actions. However, some of the results obtained with this indicator underline the limits of this kind of analysis

27. HAEFNER R, MICHELS H: Transition of young adults with juvenile rheumatoid diseases at the example of Garmisch-Partenkirchen
    <ORIGINAL> Ubergangsstrategien (transition) fur junge erwachsene mit juvenilen rheumatischen erkrankungen am beispiel Garmisch-Partenkirchen. Aktuelle Rheumatologie 30:3 172-175, /6/5
    Abstract: juvenile rheumatic diseases can often become quiescence during childhood or adolescence. The small number of adult rheumatic patients requiring rheumatologic care needs their own program for transition, which must consider the course of juvenile rheumatic diseases as well as the social situation of young rheumatic patients. Apart from an adequate medical and physiotherapeutic treatment, we require an experienced psychosocial staff that helps with vocational integration and guide the patients towards their new life style. Transition begins in pediatric and adolescent rheumatology and ideally integrates the adult rheumatologist. In addition to our established program for transition, we will concentrate the care for young adult patients on own ward and expand our cooperation with the adult Rheumatology Center in Oberammergau

28. HEUBNER G, GROSCHE M, GAHR M: Therapy of juvenile idiopathic arthritis
    THERAPIE DER JUVENILEN IDIOPATHISCHEN ARTHRITIS. Monatsschrift fur Kinderheilkunde (Germany ) 150:4 445-451, 2002
    Abstract: Drugs are the mainstay of the therapy for juvenile idiopathic arthritis. After the nonsteroidal antiinflammatory drugs methotrexate is the most used agent. Corticosteroids, though very effective, are limited for the use in special situations. Of the drugs recently developed only etanercept, a TNF-inhibitor, has been shown to be effective in the treatment of juvenile idiopathic arthritis. Other therapeutic tools are physiotherapy, ergotherapy and psychological giudance of the patients and their parents. (c) Springer-Verlag 2002

29. HOFF AL, PALERMO TM, SCHLUCHTER M, ZEBRACKI K, DROTAR D: Original Research Article: Longitudinal Relationships of Depressive Symptoms to Pain Intensity and Functional Disability Among Children with Disease-Related Pain. J Pediatr Psychol .: 2005
    Organism: Rainbow Babies and Children's Hospital, Case Western Reserve University
    Abstract: Objective To examine the longitudinal relationship between depressive symptoms at study entry (T1) on pain intensity (PI) and functional disability over a 1-year period among children with either sickle cell disease (SCD) or juvenile idiopathic arthritis (JIA). Methods 119 children, ages 8-17 years, completed measures of depression at T1 as well as pain and functional disability at T1, 6-month (T2), and 12-month (T3) follow-ups. Caregivers also rated their child's pain and disability at each time point. General linear mixed modeling was employed to examine longitudinal relationships between study variables. Results For children with JIA, T1 pain significantly moderated the effects of T1-depressive symptoms on T2 and T3 pain where T1-depressive symptoms predicted future child-reported pain only when T1 pain was relatively mild. Similarly, T1-depressive symptoms predicted future child-reported disability only when initial reports of disability were relatively low. Only family income significantly predicted T2 and T3 pain in children with SCD. Conclusions Study findings suggest that T1-depressive symptoms play a role in the longitudinal course of pain symptoms in children with JIA but not in children with SCD

30. HORNEFF G: [Importance of the new biologicals and cytokine antagonists in the treatment of juvenile idiopathic arthritis (JIA)]. Z Rheumatol 64:5 317-326, 2005
    Organism: Asklepios Klinik fur Kinder- und Jugendmedizin Sankt-Augustin, 53757 Sankt Augustin ghorneff@asklepioscomFAU - Horneff, G
    Abstract: Juvenile idiopathic arthritis is group of diseases of unknown aetiology characterised by the occurrence of chronic arthritis during childhood. Compared to adult onset rheumatoid arthritis, its course is more variable. Increasing knowledge of the inflammatory process as well as in molecular genetics and biotechnology has enable the production of new drugs, the biologicals. These are able to specifically block mechanisms of immune activation and thereby interfere with the inflammatory process. An increasing number of biologicals have been tried in clinical studies in adults suffering from rheumatoid arthritis, psoriasis or psoriasis arthritis and a couple of them were already licensed for treatment.Treatment of juvenile idiopathic arthritis by blockade of tumournecrosis-factor (TNF) using the soluble receptor Etanercept or the monoclonal antibodies Infliximab and Adalimumab showed comparable clinical efficacy. Blockade of TNF therefore already reached a certain place in the therapeutic algorythm for treatment of juvenile idiopathic arthritis. Currently, only Etanercept is licensed for treatment of active juvenile polyarthritis refractory to methotrexate. Studies using Infliximab and Adalimumab will be completed in the near future. However, antibodies blocking TNF may already be used in patients suffering from active uncontrolled chronic uveitis in whom visual impairment is threatening. TNF blockers may also be indicated in juvenile ankylosing spondylitis.The use of further biologicals, the interleukin-1 receptor antagonist Anakinra, Atlizumab (MRA) blocking the receptor for interleukin-6 or Abatacept, an inhibitory ligand of the co-stimulatory T cell membrane molecule CD28, remain experimental and should be preserved for clinical studies

31. HOSHINO-YOSHIO N, WATANABE D, ADACHI Y, NISHIMOTO N: The blocked of interleukin-6 receptor as a therapeutic strategy for chronic inflammatory diseases. Therapy (United Kingdom ) 1:2 267-275, 2004
    Abstract: Interleukin (IL)-6 is an inflammatory cytokine which plays a pathological role in chronic inflammatory disease such as Castleman's disease, rheumatoid arthritis, juvenile idiopathic arthritis and Crohn's disease. A new therapeutic strategy blocking the IL-6 signal utilizing humanized anti-IL-6 receptor antibody has been introduced for these diseases. In this review, shall describe the involvement of IL-6 in those diseases and the present state of clinical development of anti-IL-6 receptor antibody therapy. (c) 2004 Future Drugs Ltd

32. HOWARTH PH, BABU KS, ARSHAD HS, LAU LC, BUCKLEY MG, MCCONNELL W, BECKETT P, ALI MA, CHAUHAN A, WILSON SJ, REYNOLDS A, DAVIES DE, HOLGATE ST: Tumour Necrosis Factor (TNF{alpha}) as a novel therapeutic target in symptomatic corticosteroid-dependent asthma. Thorax .: 2005
    Organism: University of Southampton, United Kingdom
    Abstract: TNFalpha is a major therapeutic target in a range of chronic inflammatory disorders including rheumatoid arthritis, juvenile arthritis, ankylosing spondylitis, Crohns disease, psoriasis, glomerulonephritis, sarcoidosis and Behcets disease. These diseases are characterised by a Th1-type immune response in which TNFalpha is generated in excess. By contrast, asthma is regarded as a Th2 type disorder, especially when associated with atopy. However as asthma becomes more severe and chronic, it adopts additional characteristics including corticosteroid refractoriness and involvement of neutrophils suggestive of an altered inflammatory profile towards a Th1-type response, incriminating cytokines such as TNFalpha. We now provide substantial evidence, at mRNA and protein levels, that TNFalpha production is increased in severe corticosteroid-dependent asthma. At a functional level, its significance has been suggested by showing improvements in clinical and physiological measures of asthma following 12 weeks treatment with the soluble TNFalpha receptor-IgG1Fc fusion protein, etanercept (Enbrel(R)) in an open label uncontrolled clinical study. Etanercept treatment was associated with improvement in asthma symptoms, lung function and bronchial hyperresponsiveness. Since severe asthma makes up a substantial portion of the health costs for this disease, we believe these novel observations may be of clinical significance in identifying TNFalpha as a new therapeutic target. The effects of anti-TNF therapy in severe asthma now require confirmation in placebo controlled studies

33. HUPPERTZ H-I: Oligoarthritis in children and adolescents
    OLIGOARTHRITIS IM KIND. Monatsschrift fur Kinderheilkunde (Germany ) 150:4 437-444, 2002
    Abstract: Early onset pauciarticular juvenile arthritis is the most frequent cause of chronic arthritis in childhood. It affects mostly girls shortly after they started to learn to walk. Diagnosis is by clinical means and laboratory values may be completely normal. Treatment consists of counseling, physiotherapy and pharmacotherapy. After non-steroidal antirheumatic drugs intraarticular steroids are important drugs. Prognosis is favourable, if treatment is given continuously and if the disease does not become polyarticular or chr onic iridocyclitis develops. Treatment of chronic arthritis has changed during the last 10 years: patients and their parents are justified to expect a better outcome and health care providers need to be highly qualified to meet these expectations. The early onset pauciarticular juvenile arthritis is part of the group of diseases called juvenile idiopathic arthritis. Patients are 16 years or younger at the onset of arthritis and had uninterrupted arthritis for at least 6 weeks. Oligoarthritis, arthritis in 4 or less joints, can also be found in other diseases including psoriatic arthritis and juvenile spondyloarthropathy. Classification of chronic arthritis in childhood is contradictory and alterations are to be expected. (c) Springer-Verlag 2002

34. JAIN V, MAHESHWARI A, GULATI S, KABRA M, KALRA V: Juvenile rheumatoid arthritis with myelofibrosis with myeloid metaplasia. Indian J Pediatr 72:9 789-791, 2005
    Organism: Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, IndiaFAU - Jain, Vandana
    Abstract: Myelofibrosis with myeloid metaplasia is defined as a myeloproliferative disorder characterized by leukoerythroblastosis, tear drop erythrocytes, extramedullary hematopoesis and varying degree of myelofibrosis. It may be idiopathic or secondary to a large number of conditions. Here is a rare case of myelofibrosis occurring in a patient with juvenile rheumatoid arthritis

35. JARVIS JN: Diagnostic and prognostic potential of gene microarrays in rheumatoid arthritis. Expert Rev Mol Diagn 5:5 655-659, 2005
    Organism: University of Oklahoma College of Medicine, Department of Pediatrics, Rheumatology Section, Oklahoma City, OK 73104, USA james-jarvis@ouhsceduFAU - Jarvis, James N
    Abstract: Rheumatoid arthritis and juvenile rheumatoid arthritis are histopathologically similar diseases characterized by chronic inflammation of the synovium. The pathogenesis of these diseases is unknown, but the emergence of gene expression profiling provides considerable promise that some of the complex, interconnected immunopathologic events underlying these diseases will soon be better understood. This review will summarize the potential use of gene expression profiling as a diagnostic or prognostic modality, and the potential benefits or limits of such uses. It will conclude with a short discussion of the potential for using gene expression profiling to identify novel targets of therapy in rheumatoid arthritis and related diseases

36. KALLINICH T, HOFFMAN HM, ROTH J, KEITZER R: The clinical course of a child with CINCA/NOMID syndrome improved during and after treatment with thalidomide. Scand J Rheumatol 34:3 246-249, 2005
    Organism: Department of Paediatrics, Pulmonology and Immunology, Charite University Hospital, Augustenburger Platz 1, 13353 Berlin, Germany tilmannkallinich@charitedeFAU - Kallinich, T
    Abstract: Chronic, infantile, neurological, cutaneous, and articular (CINCA) syndrome, also known as neonatal-onset multisystem inflammatory disease (NOMID), is a rare autosomal dominant inherited disease. It is characterized by a persistent rash with onset during the neonatal period, neurological and ocular manifestations, and articular involvement with abnormal ossification. Mutations within the CIAS1 gene are found in up to 60% of CINCA cases, but the exact underlying pathogenetic mechanisms causing this disorder are still unclear. Although the interleukin-1 (IL-1) receptor antagonist anakinra (rHuIL-1Ra) has recently been reported to be effective, no formal recommended treatment protocols exist thus far. Herein, we describe a 17-year-old girl with CINCA for whom numerous medication trials had been unsuccessful. After the introduction of thalidomide, the symptoms of arthropathy improved dramatically even months after the medication was discontinued by the patient. We propose that thalidomide can be beneficial in select patients with CINCA syndrome

37. KRENN V, MORAWIETZ L, BURMESTER GR, HAUPL T: [Synovialitis score: histopathological grading system for chronic rheumatic and non-rheumatic synovialitis]. Z Rheumatol 64:5 334-342, 2005
    Organism: Institut fur Pathologie, Charite Universitatsmedizin Berlin, Schumannstrasse 20/21, 10117 Berlin, Germany veitkrenn@charitedeFAU - Krenn, V
    Abstract: Standardization of the histopathological assessment of synovial membrane specimens might facilitate the diagnosis of chronic rheumatic and non-rheumatic joint diseases. We would like to propose a histological graduation scheme ("synovialitis score"), which is applicable to all forms of synovitis, irrespective of its etiology. This score evaluates the three compartments of chronic synovialitis [enlargement of lining cell layer, activation of synovial stroma (i. e. resident cells), leukocytic infiltrate] semiquantitatively (from 0=absent to 3=strong). Each compartment is graded separately, and the sum resembles the synovialitis score, which is interpreted as follows: 0-1: no synovialitis, 2- 3: slight synovialitis, 4-6: moderate synovialitis, 7-9: strong synovialitis (for sample photos see also www.charite.de/ch/patho/Webpage/pages/forschung/arbeitsgruppen/ag-krenn/in dex.htm). A total of 483 synovial specimens (resections n=462, biopsies n=21) were graded by two independent observers. Clinical diagnoses were osteoarthrosis (OA; n=153), posttraumatic arthritis (PtA; n=31), rheumatoid arthritis (RA; n=239), psoriatic arthritis (PsA; n=32), reactive arthritis (ReA; n=7), and controls (Co, n=21) from necropsies of patients without joint damage. The correlation between two observers was high (p<0.001). The correlation coefficient between the different samples from the same joint in n=112 cases was between 0.86 and 0.95. Median synovialitis scores when correlated with clinical diagnoses were: Co 0.5, OA 2, PtA 3, PsA 3, ReA 4, RA 5. The differences in scores between Co and all other groups were highly significant (p<0.001). A synovialitis score of 4 points and more was strongly associated with rheumatic joint diseases (sensitivity 73%, specificity 86%). Validation of the synovialitis score by gene expression data showed good correlations for the lining cell enlargement with MMP1 (0.685), for the leukocytic infiltrate with CD3 (0.754) and CD138 (0.744) and for the stroma activation with CD14 (0.744). The proposed synovialitis score is based on well definable histopathologic criteria and contributes to the diagnosis of rheumatic and non-rheumatic joint diseases

38. KUZMANOVA SI: The macrophage activation syndrome: a new entity, a potentially fatal complication of rheumatic disorders. Folia Med (Plovdiv) 47:1 21-25, 2005
    Organism: Department of Rheumatology, Medical University--Plovdiv; 15A Vassil Aprilov St, 4002 Plovdiv, BulgariaFAU - Kuzmanova, Stefka Iv
    Abstract: AIM: To review the precipitating events, clinical feature, treatment and outcome of macrophage activation syndrome (MAS). Activation of macrophages resulting from the secondary hemophagocytic syndrome is a rarely reported complication. It was first described in rheumatic diseases in children. The available reliable information on this rare, poorly understood and potentially fatal entity shows MAS to be a complication of the systemic onset juvenile idiopathic arthritis, of systemic lupus erythematosus (SLE) and some other rheumatic diseases. The disruption of the macrophage-lymphocyte interactions leads to uncontrolled proliferation of highly activated macrophages. This secondary reactive hemophagocytic syndrome, referred to as MAS in the current medical terminology, can be a complication either of the rheumatic disease associated syndrome (RAHS), or of the infection associated form (IAHS) and malignancy associated form (MAHS). These three forms are clinically almost identical. High grade fever, hepatosplenomegaly, lymphadenopathy, rash due to refractory thrombocytopenia, mild disseminated intravascular coagulation are the common clinical features in this disorder. Bone marrow studies shows high percentage of non-malignant mature histiocytes which have phagocytized erythrocytes, as well as leukocytes and thrombocytes. Mortality rate of MAS is very high. Early treatment with glucocorticoids, cyclosporin, anti-TNF agents, ATG may induce a prolonged remission. Allogenic bone marrow transplantation leads to a definitive cure

39. LEVY-CLARKE GA, NUSSENBLATT RB, SMITH JA: Management of chronic pediatric uveitis. Curr Opin Ophthalmol 16:5 281-288, 2005
    Organism: aLaboratory of Immunology and bDivision of Clinical Research and Epidemiology, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USAFAU - Levy-Clarke, Grace A
    Abstract: PURPOSE OF REVIEW: The diagnosis and management of chronic pediatric uveitis can be particularly challenging, with an estimated 25-33% of childhood uveitis cases resulting in severe, life-long visual disability. This paper reviews the recent literature on the management of chronic pediatric uveitis. RECENT FINDINGS: This review highlights recent advances in the diagnosis and medical and surgical management of pediatric uveitis. Several systemic diseases associated with chronic uveitis in children are highlighted, including juvenile idiopathic arthritis, sarcoidosis and Behcet's disease. The treatment of primary ocular diseases associated with chronic pediatric uveitis such as intermediate uveitis and Fuchs' heterochromic iridocyclitis is discussed. The management of infectious causes of pediatric uveitis is not covered in this review. SUMMARY: Knowledge of the ocular complications of chronic pediatric uveitis can help to customize efficacious therapeutic regimens for each patient, maximize the visual potential and minimize complications of these diseases. In addition a close relation should be fostered between pediatricians, pediatric rheumatologists and ophthalmologists to effectively monitor these patients who have multiple medical, surgical and refractive needs. Finally, surgical intervention must be appropriately timed with expert perioperative management of immunosuppressive medications with pediatric concerns in mind

40. LIEVENSE A, BIERMA-ZEINSTRA S, SCHOUTEN B, BOHNEN A, VERHAAR J, KOES B: Prognosis of trochanteric pain in primary care. Br J Gen Pract 55:512 199-204, 2005
    Organism: Department of General Practice, Erasmus Medical Centre, Room WK-131, PO Box 1738, 3000 DR Rotterdam, The Netherlands alievense@erasmusmcnlFAU - Lievense, Annet
    Abstract: BACKGROUND: Trochanteric pain is the second most important diagnosis of hip problems presenting in primary care, but its incidence and prognosis in this context is largely unknown. AIM: To determine the 1- and 5-year prognoses of trochanteric pain and the predictive variables for consistent complaints. DESIGN OF THE STUDY: Retrospective cohort study. SETTING: One hundred and sixty-four patients (mean age = 55 years, 80% female) with incidental trochanteric pain in the years 1996 or 2000 were asked in 2001 for past and present symptoms of trochanteric pain. Therapeutic interventions, demographic factors and comorbidity were also investigated. METHOD: The databases of 39 GPs were screened in order to identify all incident cases with a suspicion of trochanteric pain in the years 1996 or 2000. These cases were sent a questionnaire. RESULTS: The incidence of trochanteric pain in primary care is 1.8 patients per 1000 per year. After 1 year at least 36% still suffered from trochanteric pain, and after 5 years this was 29%. Patients with osteoarthritis (OA) in the lower limbs had a 4.8-fold risk of persistent symptoms after 1 year, as compared to patients without OA. Patients who had received a corticosteroid injection had a 2.7-fold chance of recovery after 5 years, as compared with patients who had not received an injection. CONCLUSION: Trochanteric pain is shown to be a chronic disease in a substantial number of patients. The disorder is associated with much impairment when conducting daily activities

41. LIPINSKA J, SMOLEWSKA E, BROZIK H, WYKA K, STANCZYK J: Diagnostic value of selected immunological markers in children with JIA
    PRZYDATNOSC OCENY WYBRANYCH MARKEROW IMMUNOLOGICZNYCH W DIAGNOSTYCE Ml(stroke)ODZIENCZEGO IDIOPATYCZNEGO ZAPALENIA STAWOW. Alergia Astma Immunologia (Poland ) 10:2 75-82, 2005
    Abstract: Aim of the study. To assess the diagnostic value of anti-CCP, AKA, ANA and IgM, IgG and IgA rheumatoid factors (RF) in a cohort of patients with juvenile idiopathic arthritis (JIA). Material and methods. In 79 sera and 17 synovial fluid samples from patients with JIA taken at different time of disease course the following parameters analyzed: CCP, IgM-RF, IgG-RF, IgA-RF ELISA and for AKA and ANA. All autoantibodies were also tested in sera of 22 sex-, and age-matched healthy children. Correlations between anti-CCP, other autoantibodies and disease characteristics were determined. Results. At a cut-off value of 203 RU for anti-CCP, sensitivity was 56% and specificity - 100%. Anti-CCP were present in IgM-RF positive, as well as, negative sera, in all 3 subtypes of JIA and in 67% children with early stadium of JIA. IgG-RF had a slightly higher sensitivity (57%), and lower specificity (95,5%) - it was present in 4,5% healthy children. The sensitivity and specificity of IgM- and IgA-RF, AKA and ANA was low. We found a positive correlation of anti-CCP and IgG-RF with disease activity. In synovial fluid the most frequently found marker was RF-IgG. Conclusions. With their excellent specificity, anti-CCP antibodies followed by RF-IgG can be useful in establishing the diagnosis of JIA even in early stadium of the disease. Moreover, anti-CCP and IgG-RF are good markers of disease activity. IgM-RF, IgA-RF, AKA and ANA presented only additional diagnostic value. In difficult diagnostic cases it could be useful to assay all those autoantibodies simultaneously

42. LOVELL DJ, RUPERTO N, CUTTICA RUBEN, WILKINSON N, ESPADA G, WOUTERS C, SILVERMAN E, BALOGH ZSOLT, HENRICKSON M, LAHDENNE P, PRIEUR A, GERLONI V, FASTH A, SAURENMANN RK, BAILDAM E, MARIA T, WOO P, MARTINI A, BEUTLER A, CLARK J, CHUANG EMIL, GIANNINI E: Randomized trial of infliximab (IFX) plus methotrexate (MTX) for the treatment of polyarticular juvenile rheumatoid arthritis (JRA). Arthritis & Rheumatism 50:12 4097-4098, 2004

43. LUMLEY MA, RADCLIFFE AM, MACKLEM DJ, MOSLEY-WILLIAMS A, LEISEN JC, HUFFMAN JL, D'SOUZA PJ, GILLIS ME, MEYER TM, KRAFT CA, RAPPORT LJ: Alexithymia and pain in three chronic pain samples: comparing Caucasians and African Americans. Pain Med 6:3 251-261, 2005
    Organism: Department of Psychology, Wayne State University, Detroit, Michigan 48202, USA mlumley@sunsciencewayneeduFAU - Lumley, Mark A
    Abstract: OBJECTIVE: African Americans often report greater pain than do Caucasians, but the factors responsible for this discrepancy are not known. We examined whether alexithymia-the trait of difficulty identifying and describing one's feelings and lacking introspection-may contribute to this ethnic group difference. We tested whether the mean level of alexithymia is higher, and whether alexithymia and pain are more highly correlated, among African Americans than among Caucasians in patients with chronic pain disorders. DESIGN: Three cross-sectional, correlational studies were conducted on three separate samples of patients with chronic pain. Analyses examined the full sample and then Caucasians and African Americans separately. SETTING AND PATIENTS: Patients were recruited primarily from treatment settings. Samples were patients with rheumatoid arthritis (N = 155), migraine headaches (N = 160), or systemic lupus erythematosus (N = 123), and each sample included only Caucasians or African Americans. MEASURES: The Toronto Alexithymia Scale-20 assessed global alexithymia and three alexithymia facets. Pain severity, functional disability, or symptoms were also measured on each sample. RESULTS: Similar findings occurred across all three samples. African Americans had only slightly higher mean alexithymia levels than did Caucasians, and this was partly accounted for by socioeconomic differences between groups. More importantly, alexithymia correlated only weakly with pain or symptom severity for each full sample, but the two ethnic groups showed different patterns. Alexithymia correlated positively with pain severity among African Americans, but was uncorrelated with pain among Caucasians, even after covarying for various socioeconomic variables. CONCLUSIONS: Alexithymia is more correlated with pain severity among African Americans with chronic pain disorders than among Caucasians, potentially contributing to the higher pain reports among African Americans

44. MACRAE VE, FARQUHARSON C, AHMED SF: The pathophysiology of the growth plate in juvenile idiopathic arthritis. Rheumatology (Oxford) .: 2005
    Organism: Bone Biology Group, Division of Gene Function and Development, Roslin Institute, Edinburgh, UK; Bone and Endocrine Research Group, Royal Hospital for Sick Children, Glasgow, UK
    Abstract: Children with chronic inflammatory diseases, such as juvenile idiopathic arthritis (JIA), suffer from a variety of growth disorders. These range from general growth retardation to local acceleration of growth in the affected limb. These disorders are associated with the increased production of proinflammatory cytokines, which may influence growth through a local effect in the growth plates of long bones and/or systemic effects throughout the whole body. In this article we review these aspects and also discuss the evidence for interaction between the inflammatory cytokine and growth-signalling pathways

45. MAISCH B, RICHTER A, SANDMOLLER A, PORTIG I, PANKUWEIT S: Inflammatory Dilated Cardiomyopathy (DCMI). Herz 30:6 535-544, 2005
    Organism: Department of Internal Medicine-Cardiology, Philipps University Marburg, Baldingerstrasse, 35043, Marburg, Germany, maisch@meduni-marburgde
    Abstract: Cardiomyopathies are heart muscle diseases, which have been defined by their central hemodynamics and macropathology and divided in five major forms: dilated (DCM), hypertrophic (HCM), restrictive (RCM), right ventricular (RVCM), and nonclassifiable cardiomyopathies (NCCM). Furthermore, the most recent WHO/WHF definition also comprises, among the specific cardiomyopathies, inflammatory cardiomyopathy as a distinct entity, defined as myocarditis in association with cardiac dysfunction. Idiopathic, autoimmune, and infectious forms of inflammatory cardiomyopathy were recognized. Viral cardiomyopathy has been defined as viral persistence in a dilated heart. It may be accompanied by myocardial inflammation and then termed inflammatory viral cardiomyopathy (or viral myocarditis with cardiomegaly). If no inflammation is observed in the biopsy of a dilated heart (< 14 lymphocytes and macrophages/mm(2)), the term viral cardiomyopathy or viral persistence in DCM should be applied according to the WHF Task Force recommendations.Within the German heart failure net it is the authors' working hypothesis, that DCM shares genetic risk factors with other diseases of presumed autoimmune etiology and, therefore, the same multiple genes in combination with environmental factors lead to numerous different autoimmune diseases including DCM. Therefore, the authors' primary goal is to acquire epidemiologic data of patients with DCM regarding an infectious and inflammatory etiology of the disease. Circumstantial evidence points to a major role of viral myocarditis in the etiology of DCM. The common presence of viral genetic material in the myocardium of patients with DCM provides the most compelling evidence, but proof of causality is still lacking. In addition, autoimmune reactions have been described in many studies, indicating them as an important etiologic factor. Nevertheless, data on the proportion of patients, in whom both mechanisms play a role are still missing.A pivotal role for autoimmunity in a substantial proportion of patients with DCM is supported by the presence of organ-specific autoantibodies, inflammatory infiltrates and pro-inflammatory cytotoxic cytokines. Furthermore, familial occurrence of DCM has been described in about 20-30% of cases, with the presence of autoantibodies and abnormal cytokine profiles in first-degree relatives with asymptomatic left ventricular enlargement. This suggests the involvement of a disrupted humoral and cellular immunity early in the development of the disease. A similar pattern of humoral and cellular immune dysregulation has been described in other autoimmune diseases. There is considerable evidence that genetic factors play an important role in the pathogenesis of DCM, either as contributors to the susceptibility to environmental factors or as determinants of functional and structural changes that characterize the phenotypic expression of the disease.Yet, it is not known whether the susceptibility to immunologically mediated myocardial damage reflects the presence of genetic risk factors shared by other autoimmune diseases. Preliminary investigations suggest, that this is the case, because the frequency of autoimmune disorders other than DCM was higher in first-degree relatives of the subjects with DCM including juvenile diabetes, rheumatoid arthritis, thyroiditis, psoriasis, and asthma.The nature of the genetic risk is undetermined and probably involves genes in the major histocompatibility (MHC) locus as well as other susceptibility loci. Therefore, the authors started their investigation with the search for MHC class 2 DQ polymorphisms in the peripheral blood of patients with DCM in parallel to the search for new interesting susceptibility loci by the use of the microarray analysis regarding genes responsible for inflammatory and autoimmune diseases. By this approach a new insight in the familial clustering of other autoimmune diseases in patients with DCM and in genetic predisposition can be expected

46. MARCIANO R, GIACOPELLI F, DIVIZIA MT, GATTORNO M, FELICI E, PISTORIO A, MARTINI A, RAVAZZOLO R, PICCO P: A polymorphic variant inside the Osteopontin gene shows association with disease course in Oligoarticular Juvenile Idiopathic Arthritis. Ann Rheum Dis .: 2005
    Organism: G Gaslini Institute, Italy
    Abstract: OBJECTIVE: Oligoarticular-onset juvenile idiopathic arthritis (o- JIA) is a rather homogeneous disease entity with a variable disease course. In some patients the disease remains confined to a few joints (persistent oligoarticular) while in others it extends to affect more joints (oligoarticular extended). Osteopontin (OPN) is thought to play a relevant role in the pathogenesis of inflammatory arthritis. We have investigated whether a polymorphic variant in the human OPN gene, which is in linkage disequilibrium with recently characterized promoter variants, is associated with disease course in o-JIA. METHODS: Genotyping of the 2 bp insertion/deletion variant at +245 in the first intron was performed by polymerase chain reaction amplification of DNA fragments, using a fluorescently labeled primer, followed by allele detection after rapid separation of PCR products on an ABI automated DNA sequencer. RESULTS: Allele 2 of the polymorphic variant in the OPN first intron was found significantly associated with the persistent oligoarticular form in comparison with the extended form. This was verified at the level of genotype and allele frequencies. CONCLUSIONS: Our study suggests that an OPN gene polymorphism is associated to disease course in oligoarticular JIA and might therefore represent an useful genetic marker available to characterize patients with o-JIA who are at risk for a worse outcome

47. MARGETIC S, TOPIC E, RUZIC DF, KVATERNIK M: Soluble transferrin receptor and transferrin receptor-ferritin index in iron deficiency anemia and anemia in rheumatoid arthritis. Clin Chem Lab Med 43:3 326-331, 2005
    Organism: Clinical Institute of Chemistry, Sestre milosrdnice University Hospital, Zagreb, CroatiaFAU - Margetic, Sandra
    Abstract: The aim of the study was to evaluate the clinical efficiency of soluble transferrin receptor and transferrin receptor-ferritin index (sTfR/logF) in the diagnosis of iron deficiency anemia, as well as the differential diagnosis of iron deficiency anemia and anemia in rheumatoid arthritis. The study included 96 patients with anemia and 61 healthy volunteers as a control group. In healthy subjects there were no significant sex and age differences in the parameters tested. The study results showed these parameters to be reliable in the diagnosis of iron deficiency anemia, as well as in the differential diagnosis of iron deficiency anemia and anemia of chronic disease. The results indicate that sTfR/logF could be used to help differentiate coexisting iron deficiency in patients with anemia of chronic disease. Receiver operating characteristic analysis showed a higher discriminating power of transferrin receptor-ferritin index vs. soluble transferrin receptor in the diagnosis of iron deficiency anemia, as well as in the differential diagnosis between iron deficiency anemia and anemia of chronic disease. In patients with anemia in rheumatoid arthritis, the parameters tested showed no significant differences with respect to C-reactive protein concentration. These results suggested that the parameters tested are not affected by acute or chronic inflammatory disease

48. MICHELS H: Rheumatic uveitis in childhood
    DIE RHEUMATISCHE UVEITIS IM KINDESALTER. Monatsschrift fur Kinderheilkunde (Germany ) 150:4 470-476, 2002
    Abstract: Uveitis in childhood is frequently associated with underlying rheumatic diseases, especially with juvenile idiopathic arthritis (JIA). Chronic iridocyclitis (uveitis anterior), which is observed together with JIA-oligoarthritis, JIA-rheumatic factor-negative polyarthritis, JIA-psoriatic arthritis or sarcoidosis, is often followed by irreversible, sight-threatening iridocyclitis complications. Acute iridocyclitis, which is typical for JIA-enthesit is-associated arthritis, for juvenile spondarthritis or juvenile reactive arthritis including Reiter's syndrome, on the other hand, has a more favourable prognosis. Most important for a favourable prognosis of such cases of uveitis are the early diagnosis, that is to say a diagnosis before irreversible eye complications have appeared, and the early onset of a competent treatment. This is made possible by the use of prophylactic slit-lamp examinations which, depending on the risk of developing uveitis complications, are to be performed routinely once every 4 weeks to once every 6 months. It is the paediatrician's responsibility to identify the children at risk, to initiate the mandatory diagnostic measures and to monitor the follow-up. (c) Springer-Verlag 2002

49. MINDEN K, NIEWERTH M, ZINK A, GANSER G: [Transition clinic--it is not always a simple segue in rheumatology for adults]. Z Rheumatol 64:5 327-333, 2005
    Organism: HELIOS-Kliniken, Klinikum Berlin-Buch, II Klinik fur Kinderheilkunde und Jugendmedizin und Deutsches Rheumaforschungszentrum Berlin, Forschungsbereich Epidemiologie, Schumannstr 21/22, 10117 Berlin, Germany Minden@drfzdeFAU - Minden, K
    Abstract: Chronic inflammatory rheumatic diseases with onset in childhood often persist into adulthood and result in a considerable number of patients in impairments of body functions and structures, activities at the individual level and participation in society. Continuation of health care beyond adolescence is, therefore, necessary. Its provision should be of high quality, coordinated, uninterrupted, patient-centred and developmentally appropriate to ensure smooth transitions between children's and adult services and positive outcomes of transition for the young people themselves. Existing research is very persuasive on the need to improve transitions for young people with rheumatic diseases. To achieve effective transition, not only disease specific, but also aspects of growth and development have to be taken into account. Paediatric and adult rheumatologists should establish close cooperation and implement specific transition programs to meet the special health care needs of these patients

50. MIRKINSON LJ, CERUTI R, KATONA IM: Klinefelter's syndrome and juvenile chronic arthritis. Clin Rheumatol .: 2005
    Organism: Center for Hospital-Based Specialties, Children's National Medical Center, George Washington University School of Medicine, 111 Michigan Avenue NW, Washington, DC, 20010, USA

51. MYERS A, KAY LJ, LYNCH SA, WALKER DJ: Recurrence risk for psoriasis and psoriatic arthritis within sibships. Rheumatology (Oxford) 44:6 773-776, 2005
    Organism: Department of Rheumatology, University of Newcastle upon Tyne, Newcastle upon Tyne, UK andreamyers@nclacukFAU - Myers, A
    Abstract: OBJECTIVE: To quantify the frequency of siblings of patients with psoriatic arthritis (PsA) having psoriasis and/or inflammatory arthritis. To describe the similarity or otherwise of patterns of arthritis in siblings. METHODS: Available and consenting index cases with PsA and one or more siblings living locally were assessed. Mean sibling concordance rates and Weinberg's segregation analysis were calculated. Heritability was also estimated. To assess whether the same type of arthritis occurred within the same sibship, the dually affected sibships were then classified for type of arthritis according to methods suggested by Moll, Helliwell, Veale and McGonagle. RESULTS: Eighty index cases and 112 siblings were assessed. The median age of index cases was 49 yr (range 24-80 yr) and for siblings 46 yr (range 18-79 yr). The concordance rate for all types of PsA was 14% (9% if enthesitis is excluded) and for psoriasis 21%. There was no difference in the two methods used to calculate concordance rates. Sixteen dually affected sib pairs were found. Four of the 16 sibships (25%) had the same pattern of joint involvement (Moll and Wright classification). The most frequent pattern seen was joint involvement identical to rheumatoid arthritis (3/5). The most common symptom in affected siblings was enthesitis (approximately 5%). When the dually affected sibships were analysed using the other classifications, the simpler the classification the greater the concordance for joint pattern. CONCLUSION: The concordance for psoriasis is greater than for PsA, but the concordance rate for PsA was similar to that in HLA identical siblings with rheumatoid arthritis. There was discordance in pattern of arthritis for most sib pairs. There is no support for the use of more complex classifications of PsA

52. NIKLES CJ, CLAVARINO AM, DEL MAR CB: Using n-of-1 trials as a clinical tool to improve prescribing. Br J Gen Pract 55:512 175-180, 2005
    Organism: Discipline of General Practice, University of Queensland Medical School, Herston, Queensland 4006, Australia jnikles@uqeduauFAU - Nikles, C Jane
    Abstract: BACKGROUND: N-of-1 trials are within-patient, randomised, double-blind, placebo-controlled cross-over comparisons of two drugs for chronic illnesses. We have investigated the use of these, offered to doctors as individualised medication effectiveness tests (IMETs), as a tool to improve drug prescribing. AIM: To examine patient perspectives and experiences of n-of-1 trials. DESIGN OF STUDY: We provided n-of-1 trials for osteoarthritis (OA), comparing paracetamol and ibuprofen; and attention deficit hyperactivity disorder (ADHD), comparing dexamphetamine or methylphenidate and placebo. Patients or their carers were surveyed before and after the trials by questionnaire, and after the trial by semistructured interview with thematic analysis. SETTING: Australian community-based patients and practitioners. METHOD: Forty-two patients with OA and 21 carers of patients with ADHD, for whom the effectiveness of proposed or existing medication was uncertain, completed the questionnaires, and 25 patients/carers (11 with OA and 14 with ADHD) participated in semi-structured interviews. RESULTS: Patients in this purposive sample were generally very satisfied with the n-of-1 trial process. Their participation led to increased knowledge, awareness and understanding of their condition, their bodies' response to it, and its management. Some of this arose specifically from use of daily symptom diaries. This led to a sense of empowerment and control as well as improved individually-focused care. CONCLUSIONS: N-of-1 trials appeared to empower these patients as a result of both collecting information about their responses to different treatment options, and participating actively in subsequent therapeutic decisions. They are a patient-centred intervention that may improve medication management in suitable chronic diseases

53. PASCUAL V, ALLANTAZ F, ARCE EDSEL, STICHWEH D, CONNOLLY J, PUNARO M, BANCHEREAU JACQUES: Dramatic clinical response to IL-1 blockade in systemic onset juvenile idiopathic arthritis. Arthritis & Rheumatism 50:12 4099-4100, 2004

54. PEAKE NJ, FOSTER HE, KHAWAJA K, CAWSTON TE, ROWAN AD: Assessment of the clinical significance of gelatinase activity in Juvenile Idiopathic Arthritis patients using quantitative protein substrate zymography. Ann Rheum Dis .: 2005
    Organism: University of Newcastle, United Kingdom
    Abstract: OBJECTIVE: To measure gelatinase activities in paired synovial fluid (SF) and serum of patients with Juvenile Idiopathic Arthritis (JIA), and to assess how these activities relate to clinical and laboratory parameters of disease activity. METHODS: A quantitative protein substrate zymography method was adapted and validated for use with serum and SF. Bands of activity were quantitated by densitometry and correlated to standard laboratory indicators of inflammation; erythrocyte sedimentation rate and platelet count. RESULTS: Gelatinase activity was found consistently in JIA patients, with reproducible, quantified bands of activity corresponding to pro-matrix metalloproteinase-9 (pro-MMP-9) including the neutrophil-associated lipocalin complex, and pro- and active forms of MMP-2. Both active MMP-2 and pro-MMP-9 were higher in JIA serum compared to controls, though no differences were observed between patients grouped according to age, disease duration or JIA sub-type. However, SF MMP-9 correlated significantly with the laboratory indicators of inflammation, as did the relative level of active MMP- 2. CONCLUSIONS: Both MMP-2 and MMP-9 gelatinolytic activities can be found elevated during active JIA and associate with inflammatory activity regardless of age and disease duration, supporting a role for MMPs in the breakdown of joint components from early in disease. These MMPs may be specific markers of active joint destruction linked to inflammatory JIA, MMP-9 as a product of infiltrating cells, and the activation of MMP-2 produced within the joint

55. PETRIC I, LONCAR VL, VATAVUK Z, IVEKOVIC R, SESAR I, MANDIC Z: Cataract surgery and intraocular lens implantation in children with juvenile rheumatoid arthritis associated uveitis. Coll Antropol 29 Suppl 1:59-62.: 59-62, 2005
    Organism: University Department of Ophthalmology, Clinical Hospital, Systers of Mercy, Zagreb, Croatia ivankapetric@hotmailcomFAU - Petric, Ivanka
    Abstract: Clinical records of 6 children (7 eyes) with juvenile rheumatoid arthritis (JRA) who underwent cataract surgery with IOL implantation between January 1998 and December 2002 were reviewed. The median age at the time of cataract surgery was 8 years (range 5-14 years). The median follow up was 48 months (range 26 to 60 months). Five of six children (6 eyes) were on systemic immunosuppressive or anti-inflammatory therapy. Glaucoma was present in three eyes before surgery, and all three eyes underwent combined cataract surgery and trabeculectomy with mitomycin C. A final best corrected visual acuity of 0.5 or better was achieved in all eyes Postoperative complications included posterior capsule opacification (n = 5), glaucoma (n = 1), and cystoid macular edema (n = 1). Intraocular lens implantation in children with control of preoperative and postoperative ocular inflammation could lead to favorable visual results

56. PETROV AV: [Clinical value of morphologic and functional parameters of blood mononuclear leukocytes in patients with rheumatoid arthritis]. Lik Sprava4 16-24, 2005
    Abstract: The immunologic study of 412 patient with rheumatoid arthritis (RA) and 52 person of control group has been carried out. The correlation was established between activity of RA and increase in morphologic and functional activity of CD4+-, CD8+- and CD19+-lymphocytes, enhancement of proliferate response and ability to Fas-induced apoptosis of T-cells (r - from 0,5 to 0,81) and between the development of severe systemic complication and increase in percentage of CD8+-lymphocytes with large homogenous nucleoli (r=+0,71+/-0,08), mean diameter of CD8+-lymphocytes nucleus (r=+0,61+/-0,08) and mononuclear leukocytes proliferate response to FGA (r=+0,56+/-0,07). The step based system of assessment of cell immunity disturbances and the criteria of the evaluation of risks of the development of systemic complication in patients with RA were established on the above mentioned parameters development prognosis based on their immune parameters

57. PRESCOTT NJ, FISHER SA, ONNIE C, PATTNI R, STEER S, SANDERSON J, FORBES A, LEWIS CM, MATHEW CG: A general autoimmunity gene (PTPN22) is not associated with inflammatory bowel disease in a British population. Tissue Antigens 66:4 318-320, 2005
    Organism: Department of Medical and Molecular Genetics, Division of Genetics and Molecular Medicine, GKT School of Medicine, King's College London, London, UKFAU - Prescott, N J
    Abstract: Abstract A single-nucleotide polymorphism (C1858T) causing an amino acid substitution (R620W) in the lymphoid protein tyrosine phosphatase gene PTPN22 has been implicated in type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, juvenile idiopathic arthritis and Hashimoto's thyroiditis, thus revealing a general role for this gene in autoimmune disease. We investigated the association of the C1858T variant in an additional autoimmune disease population by performing a case-control study of 514 British individuals with inflammatory bowel disease (IBD) [294 with Crohn's disease (CD) and 220 with ulcerative colitis (UC)] and 374 normal controls. No significant differences in genotype or allele frequencies were observed between IBD, CD or UC and controls, indicating that PTPN22 does not influence risk of IBD

58. RAMANAN AV, SCHNEIDER R, BATTHISH M, ACHONU C, OTA S, MCLIMONT M, YOUNG NL, FELDMAN M: Developing a disease activity tool for systemic-onset juvenile idiopathic arthritis by international consensus using the Delphi approach. Rheumatology (Oxford) .: 2005
    Organism: Department of Pediatrics, Division of Rheumatology, Hospital for Sick Children, University of Toronto, Ontario, Canada
    Abstract: Objectives. The systemic form of juvenile idiopathic arthritis may present with many diverse symptoms, signs and laboratory abnormalities. Our aim was to elicit and pool items useful for developing a consensus disease activity measure for systemic arthritis in children, using an international pool of respondents. Methods. We used a Delphi survey process in two steps. First we surveyed 187 paediatric rheumatologists and allied health professionals. We elicited 2607 items that, when combined with previously elicited items from parents/patients, could be pooled into 107 independent items. We then surveyed the paediatric rheumatologists to determine the frequency and importance of the 107 items. Results. Our response rate was 83% to both surveys. We identified 29 items as being the most important and most frequently seen indicators of active disease. The most highly rated of these items were: presence of fever, presence of rash, elevated ESR, elevated CRP, requirement for increasing medications, abnormal physician global evaluation and presence of joints with active arthritis. Conclusions. Twenty-nine items are thought by medical practitioners to be most relevant in determining disease activity in systemic arthritis. As a next step, the measurement properties of these items will be tested to help develop a disease activity tool

59. RICHARDS JC, TAY-KEARNEY ML, MURRAY K, MANNERS P: Infliximab for juvenile idiopathic arthritis-associated uveitis. Clin Experiment Ophthalmol 33:5 461-468, 2005
    Organism: Department of Ophthalmology, Royal Perth Hospital, Perth, AustraliaFAU - Richards, Josephine C
    Abstract: Abstract Background: Infliximab is a murine-human recombinant antitumour necrosis factor monoclonal antibody recently introduced for the treatment of autoimmune diseases in which tumour necrosis factor is thought to be a key mediator. Its role in the treatment of juvenile idiopathic arthritis-associated uveitis is as yet undefined. Methods: Six children with juvenile idiopathic arthritis-associated uveitis, inadequately controlled on currently available therapy, were treated with infliximab between September 2002 and November 2004. All children were required to remain on low-dose immunomodulatory treatment in conjunction with the infliximab. A retrospective review of two electronic databases containing details of ophthalmology and rheumatology visits was conducted. Results: In all six children, institution of infliximab therapy was associated with increased ease of management. Ocular inflammation and intraocular pressure control improved in all. It was also possible to reduce the dose or withdraw some glaucoma, steroid and other immunomodulatory drugs. Two children underwent intraocular surgery without noticeable flare of intraocular inflammation. No patient developed any serious systemic complications attributable to infliximab. Conclusion: Infliximab may be a useful adjunct to the management of refractory juvenile idiopathic arthritis-associated uveitis. In our series it was associated with improved uveitis control and simplification of drug use as well as possibly improving safety of surgical intervention. This study suggests that its role is likely to be in conjunction with maintenance immunomodulatory treatment to provide more optimal disease control. Controlled studies are required to confirm its efficacy and safety, and the potential breadth of its use in uveitis and related disorders

60. ROUSSEAU JC, SANDELL LJ, DELMAS PD, GARNERO P: Development and clinical application in arthritis of a new immunoassay for serum type IIA procollagen NH2 propeptide. Methods Mol Med 101:25-37.: 25-37, 2004
    Organism: INSERM Unit 403, Hopital E Herriot, Lyon, FranceFAU - Rousseau, Jean-Charles
    Abstract: Type II collagen, the most abundant protein of cartilage matrix, is synthesized as a procollagen molecule including the N-(PIINP) and C-(PIICP) propeptides at each end. Type II procollagen is produced in two forms as the result of alternative RNA splicing. One form (IIA) includes and the other form (IIB) excludes a 69-amino acid cysteine-rich globular domain encoded by exon 2 in PIINP. During the process of synthesis, these N-propeptides are removed by specific proteases and released in the circulation, and their levels are believed to reflect type II collagen synthesis. In this chapter we describe the development of a specific enzyme-linked immunosorbent assay (ELISA) for the measurement of the IIA form of PIINP (PIIANP) in serum based on a polyclonal antibody raised against recombinant human exon 2 fusion protein of type II procollagen. We show that this ELISA is highly specific for circulating PIIANP and has adequate technical precision. In patients with knee osteoarthritis and rheumatoid arthritis, serum PIIANP was decreased by 53% (p < 0.0001) and 35% (p < 0.001), respectively, suggesting that type IIA collagen synthesis is altered in these arthritic diseases. The measurement of serum PIIANP may be useful for the clinical investigation of patients with joint diseases

61. RUDGE S, HAILWOOD S, HORNE A, LUCAS J, WU F, CUNDY T: Effects of once-weekly oral alendronate on bone in children on glucocorticoid treatment. Rheumatology (Oxford) 44:6 813-818, 2005
    Organism: Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland 1, New ZealandFAU - Rudge, S
    Abstract: OBJECTIVES: To determine the effects of once-weekly oral alendronate on indices of bone size, density and resorption in children with chronic illness being treated with glucocorticoids. METHODS: Twenty-two children with chronic illness treated with prednisone were randomized to receive 1 year's treatment with either once-weekly oral placebo or alendronate (1-2 mg/kg body weight) in a double-blind study. The main outcome measures were changes in lumbar spine and femoral shaft size and volumetric density (measured by dual energy X-ray absorptiometry) and N-telopeptide excretion (a marker of bone resorption). RESULTS: Once-weekly alendronate was well tolerated, and there were no major adverse events. In both groups bone size and bone mineral content increased through growth. Volumetric bone density of the lumbar spine increased significantly in the alendronate group (P = 0.013), but not in the placebo group. There were no differences between the groups in growth in the cortical width of the femoral shaft, but the cross-sectional moment of inertia per unit length-a derived estimate of mechanical strength-increased significantly in the alendronate group (P = 0.014) but not in the placebo group. Urine N-telopeptide excretion was suppressed significantly in the alendronate group (P = 0.007) but not in the placebo group. Height velocity was positively correlated with changes in both lumbar spine area and the total width of the femoral shaft (P = 0.015, P = 0.026, respectively). CONCLUSION: Once-weekly oral alendronate is well tolerated, suppresses bone resorption and may improve volumetric bone density at the lumbar spine and mechanical strength of the femoral shaft in children with chronic illness taking glucocorticoids. It does not affect bone growth. Larger controlled studies are needed to determine if these changes translate into reduced fracture incidence or greater peak bone mass. This study highlights the importance of differentiating between changes in bone size and changes in volumetric bone density in assessing bone in children, and also having control subjects in intervention studies

62. SCHMELING H, BIBER D, HEINS S, HORNEFF G: Influence of methylenetetrahydrofolate reductase polymorphisms on efficacy and toxicity of methotrexate in patients with juvenile idiopathic arthritis. J Rheumatol 32:9 1832-1836, 2005
    Organism: Department of Pediatrics, Martin-Luther University Halle-Wittenberg, Halle, Germany heinrikeschmeling@medizinuni-halledeFAU - Schmeling, Heinrike
    Abstract: OBJECTIVE: To study the relationship of C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene to toxicity and efficacy of methotrexate (MTX) in patients with juvenile idiopathic arthritis (JIA). METHODS: Single nucleotide polymorphisms of the MTHFR gene were investigated by polymerase chain reaction and restriction enzyme analysis of DNA extracted from peripheral blood cells. The fasting plasma homocysteine concentration was analyzed by enzyme immunoassay. Clinical data of 58 patients with JIA treated with MTX were analyzed retrospectively. RESULTS: The 1298A/A genotype was present in 31 patients, 1298C/C in 4 patients, and 21 patients were heterozygous. The 677C/C genotype was present in 29 patients, 677 T/T in 3 patients, and 26 patients were heterozygous. In patients who presented the C allele of the A1298C polymorphism, improvement with respect to the number of swollen joints, the number of tender joints, and a decrease in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels occurred more frequently than in 1298 A/A homozygous patients (p < 0.05 for ESR, p < 0.01 for CRP, chi-square test). There was no relationship between the C677T polymorphism and the efficacy of MTX treatment. Forty-two adverse events were noted in 26 patients; gastrointestinal symptoms were most common (n = 20), followed by elevated serum levels of transaminases (n = 19) and hair loss (n = 3). There was no cytopenia. Patients with the heterozygous genotype 677C/T exhibited adverse events more frequently than patients with the homozygous C/C genotype (65% vs 31%; p < 0.05, chi-square test). The A1298C polymorphism, however, was not associated with occurrence of adverse events. Plasma homocysteine was elevated in 6 patients with up to 16.9 mmol/l. No association was found to a specific genotype or to adverse events. CONCLUSION: These preliminary data suggest an association of the MTHFR 677C/C polymorphism to a higher tolerability of MTX, and of the 1298A/A to lower clinical efficacy of MTX therapy in JIA

63. SCHWARZ-EYWILL M, FRIEDBERG R, STOSSLEIN F, UNGER L, NUSSLEIN H: [Rheumatoid arthritis at the cervical spine -- an underestimated problem]. Dtsch Med Wochenschr 130:33 1866-1870, 1919
    Organism: I Medizinische Klinik, Schwerpunkt Rheumatologie/Klinische Immunologie, Klinikum Dresden-Friedrichstadt, DresdenFAU - Schwarz-Eywill, M
    Abstract: BACKGROUND AND OBJECTIVE: The involvement of the cervical spine in rheumatoid arthritis can be essential regarding prognosis and mortality. The cervical myelopathy due to pannus formation and/or subluxation can be fatal. Aim of this study was to demonstrate the possible changes seen by MRI, and to establish a risk-profile for the individual patient. PATIENTS AND METHOD: Within a period of 24 months 214 patients with active RA were included. Clinical and laboratory data were obtained and plain radiographs of the cervical spine were taken. In patients with pathological findings on X-ray an MRI was performed (36 patients). RESULTS: Within the group of 214 patients 36 were identified to get an cervical spine MRI. In all cases the MRI showed significant changes: in 7 (19.5 %) pannus surrounded the dens, with additional erosions in one patient (2.7 %). In 25 (69.5 %) atlanto-axial-subluxation was present, 7 (19.5 %) showed a spondylodiscitis below C2. In 10 (27.8 %) a cervical myelopathy due to pannus or subluxation was present. There was no correlation of the MRI-results with symptoms and findings by examination. The patients with cervical spine disease were in all stages of RA. The majority was rheumatoid-factor positive. 5 out of 10 patients with cervical myelopathy showed neurological deficits: 3 patients died in consequence of neural compression, 2 patients underwent surgery successfully. CONCLUSION: The early detection of a cervical spine involvement in RA is essential to avoid possibly fatal complications. The only reliable method to achieve this goal has to include radiographic diagnostic including MRI of the cervical spine. Only this approach can answer the question of the right time-point for surgery. In daily clinical practice the cervical-spine involvement in RA is still underestimated

64. SEELIGER S, NIEHUES T, HARMS E, FROSCH M, ROTH J: Methotrexate in the treatment of juvenile idiopathic arthritis
    METHOTREXAT IN DER BEHANDLUNG DER JUVENILEN IDIOPATHISCHEN ARTHRITIS. Monatsschrift fur Kinderheilkunde (Germany ) 150:4 452-459, 2002
    Abstract: Low-dose methotrexate (MTX) is an established disease-modifying antirheumatic drug (DMARD) for the treatment of both juvenile idiopathic arthritis (JIA) and rheumatoid arthritis of adults (RA). However, in common clinical praxis, indication and application of MTX-treatmentas well as monitoring of the respective side effects are differently managed. At the end of the eighties MTX was prescribed only to children, who were refractory to traditional slow-acting agents. In different clinical studies it has been found that MTX is a very safe and effective drug for treatment of JIA and that it is well tolerated in children. The common dosages of MTX in pediatric rheumatology ranges from 5-15 once a week, max. 250 mg/mSUP2/week (0,2-0,8 mg/kg/week).The dosages given to children can be much higher than this given to RA patients (7.5-15 mg/week). This difference in dosage may be due to a different pharmakokinetic in children. Frequent side effects of MTX-treatment in children are gastrointestinal symptoms, like nausea and vomiting besides elevated liver enzymes and stomatitis. Thus, the weekly low dose MTX presents compared to other diseases-modifying antirheumatic drugs a beneficial efficie ncy-toxicity ratio in the treatment of juvenile idiopathic arthritis. (c) Springer-Verlag 2002

65. SHIN YS, CHOI JH, NAHM DH, PARK HS, CHO JH, SUH CH: Rheumatoid factor is a marker of disease severity in Korean rheumatoid arthritis. Yonsei Med J 46:4 464-470, 2005
    Organism: Department of Allergy-Rheumatology, Ajou University School of Medicine, San 5 Woncheon-dong, Youngtong-gu, Suwon 442-721, KoreaFAU - Shin, Yoo Seob
    Abstract: Serum rheumatoid factor (RF) is important in the diagnosis and prognosis of rheumatoid arthritis (RA). The purpose of this study is to compare the clinical characteristics and treatment patterns of RA according to the presence of RF in Korean patients. A retrospective analysis was performed on the records of 109 patients who were followed for at least 2 years, among 230 RA patients who visited at the rheumatology clinic in Ajou University Hospital and who fulfilled the 1987 revised American College of Rheumatology criteria for RA. Sixty-four patients were RF positive (58.7%) and 91 patients were female (83.5%). There was no significant difference in demographic characteristics, joint involvements, or percentage of morning stiffness between seropositive and seronegative groups. Antinuclear antibody was detected more frequently in the seropositive group (p < 0.05). At initial diagnosis, the seropositive group had higher white blood cell and platelet counts than the seronegative group (p < 0.01). However, the difference was disappeared at the last follow-up. Inflammatory markers such as ESR and CRP were also higher at diagnosis in the seropositive group (p < 0.01). These inflammatory markers were still greater than the seronegative group at the last follow-up (p < 0.01). There was no significant difference in the use of disease modifying antirheumatic drug (DMARD) and steroid dosage between groups. However, DMARD combination therapy was more commonly used in the seropositive group (p < 0.05), especially triple DMARD combination. These results suggest that disease activity is more severe in the seropositive than the seronegative group, and more aggressive treatments are needed in the seropositive group

66. SICAT J, SUTKOWSKI N, HUBER BT: Expression of human endogenous retrovirus HERV-K18 superantigen is elevated in juvenile rheumatoid arthritis. J Rheumatol 32:9 1821-1831, 2005
    Organism: Department of Rheumatology, Tufts-New England Medical Center, Boston, Massachusetts, USAFAU - Sicat, Jocelyn
    Abstract: OBJECTIVE: To investigate the presence of a host-encoded superantigen as possible etiologic factor in pediatric rheumatic disease. We measured the expression and the ability of interferon-alpha (IFN-alpha) to induce the human endogenous retrovirus HERV-K18 superantigen in juvenile rheumatoid arthritis (JRA) and pediatric systemic lupus erythematosus (SLE). METHODS: Expression levels of HERV-K18 were measured in peripheral blood or synovial fluid mononuclear cells (SFMC) from 13 patients with JRA, 11 pediatric SLE patients, and 24 healthy controls, by semiquantitative reverse transcription-polymerase chain reaction, comparing 18S ribosomal transcripts as endogenous standard. IFN-alpha induction was tested by pretreatment of samples with 2000 U/ml. RESULTS: HERV-K18 expression was significantly elevated in peripheral blood from patients with JRA (mean ratio of HERV-K18 to 18S ribosomal transcripts 2.456, SD 2.122; p = 0.014), but not patients with SLE (mean 0.997, SD 0.579; p = 0.258), compared to controls (mean 0.749, SD 0.598). HERV-K18 transcripts were detected in SFMC of 7/7 JRA patients. IFN-alpha induced HERV-K18 strongly in JRA (mean fold induction = 8.934, SD 15.556) and controls (mean 8.270, SD 6.609), but weakly in SLE (mean 2.432, SD 2.219; p = 0.009). HERV-K18 levels were found to be independent of previously determined modifiers of expression, including Epstein-Barr virus infection, IFN-alpha levels, or the percentage of B cells in peripheral blood. CONCLUSION: HERV-K18 superantigen levels were elevated in JRA patients, but not pediatric patients with SLE, suggesting a possible mechanism for autoimmunity in the former group by superantigen stimulation of autoreactive T cells

67. SOROA VE, DEL H, V, GIANNONE C, CAVIGLIA H, GALATROS G, FERNANDEZ D, MENDEZ M, NASWETTER GG, NICOLINI JO: Effects of radiosynovectomy with p-32 colloid therapy in hemophilia and rheumatoid arthritis. Cancer Biother Radiopharm 20:3 344-348, 2005
    Organism: Centro de Medicina Nuclear, Comision Nacional de Energia Atomica Argentina, Buenos Aires, IAEA, Argentina soroa@cneagovarFAU - Soroa, Victoria Ester
    Abstract: AIM: The aim of this study was to assess the effects of treatment with our locally produced P-32 colloidal suspension on knee synovitic inflammations of hemophilic and rheumatoid arthritis (RA) patients, as well as to compare results with chemical synovectomy or corticoid intra-articular injections and evaluate the cost-benefit ratio. MATERIALS AND METHODS: Thirty-six hemophilic male patients, 4-28 years of age and sent by the Hemophilic Foundation (Buenos Aires, Argentina), were enrolled for knee radiosynovectomy (RS) with P-32 colloid (26 patients), or the antibiotic rifampicin with the cooperation of orthopaedists (10 patients). Parents' informed consent was obtained. The following procedures were performed: routine blood tests, X-ray, ultrasound, a 3-phase bone scan, plus monthly methylene diphosphonate (MDP) controls. Patients were included in this study only if several knee episodes had occurred. Exclusion criteria included bone destruction and big Baker's cyst. Twelve RA patients were included, with similar selection criteria: 6 RA patients received P-32 therapy, and the other 6 patients intra-articular corticoids. Clinical, blind evaluation (state of joint involvement, pain, motility, requirements of antihemophilic factors, corticoids, or analgesics) was registered in follow-up charts. If required, joint aspiration was carried out. Intra-articular instillation of saline plus flushing was done before the needle was withdrawn. P- 32 Bremsstrahlung emission was used in the gamma camera for early and late imaging to confirm the absence of leakage. For intra-articular chemical injections therapy, 4 MBq of Tc-99m MAA (macroaggregates) was used. Immobilization and relative rest for 72 hours followed the procedures. RESULTS: There were neither local or systemic effects, nor leakage during P-32 treatment. Intra-articular rifampicin and corticoids procedures required frequent injections. Comparison of regions of interest (ROIs) in treated knees during soft-tissue scintigraphies in pre- and post-third MDP control showed knee improvement. The follow-up evaluation demonstrated an increase in joint motion, diminished volume, and less requirement and frequency of the use of antihemophilic factors (AHF) in 80% of the radiosynovectomies (21 of 26), thus lowering health costs. Five female RA patients (5 of 6) had decreased joint swelling and pains, resulting in increased joint motion. CONCLUSIONS: Radiosynovectomy in RA showed a 3-month pain palliative effect. One intra-articular knee radiosynoviorthesis in haemophilic patients provides a more than 3- month relief of symptoms after treatment with locally produced P-32 (11 patients). This turned out to be a safe, economic alternative procedure in emerging nations where the availability of AHF is difficult and expensive

68. SPECKER BL, SCHOENAU E: Quantitative bone analysis in children: Current methods and recommendations. Journal of Pediatrics 146:6 726-731, 2005

69. VAN MARLE S, VAN VLIET A, SOLLIE F, KAMBAYASHI Y, YAMADA-SAWADA T: Safety, tolerability and pharmacokinetics of oral S-3304, a novel matrix metalloproteinase inhibitor, in single and multiple dose escalation studies in healthy volunteers. Int J Clin Pharmacol Ther 43:6 282-293, 2005
    Organism: Pharma Bio-Research Group B V Science Park, Zuidlaren, The NetherlandsFAU - van Marle, S
    Abstract: OBJECTIVE: A novel sulfonamide derivative, S-3304, was discovered as a potent matrix metalloproteinase (MMP) inhibitor. It is a more specific inhibitor to MMP-2 and MMP-9 (in vitro) than to MMP-1, and may therefore lack the musculoskeletal side effects seen with non-specific inhibitors. The aim of the present study was to investigate the safety, tolerability and pharmacokinetics of S-3304 when administered as single and multiple oral doses to healthy male volunteers. MATERIALS AND METHODS: 48 male volunteers received single oral doses ranging from 10 - 800 mg S-3304 or placebo under fasting conditions. At the 200 mg dose level, effects of high-fat diets were studied in a crossover design. In the multiple dose design, 24 male subjects were administered 200 mg, 400 mg or 800 mg S-3304 or placebo b.i.d. after meals for 10 - 17 days. Studies were conducted in a randomized double-blind fashion. Safety assessment was conducted based on blood chemistry, hematology, urinalysis, electrocardiogram and physical examination. Pharmacokinetic parameters were determined for S-3304 and its metabolites. All subjects were enrolled in the studies after obtaining informed consent. RESULTS: Adverse events reported after single dose administration of S-3304 or placebo were all of mild severity. Adverse events reported in the multiple dose treatment with S-3304 or placebo were mostly of mild severity, except for two episodes of moderate headache and two episodes of moderate myalgia. Most commonly reported adverse events in the multiple treatments with S-3304 were headache and somnolence. No clinically significant changes were observed in the clinical laboratory tests, except for reversible elevation of alanine aminotransferase of one subject at 800 mg S-3304 b.i.d. In the single dose administration, Cmax and mean AUC0-infinity linearly increased up to 63,167 ng/ml and 311,960 ng x h/ml at the 800 mg dose level, respectively; tmax and t1/2 ranged from 2 - 3 hours and from 9.5 - 15.5 hours, respectively. High-fat diets reduced Cmax from 21,565 ng/ml to 14,095 ng/ml but did not alter AUC0-infinity. Hydroxylated metabolites were detected in plasma in concentrations less than 1% of S-3304. Less than 1% S-3304 was excreted in urine. The AUC of one dosing interval and Cmax did not change after multiple doses but t1/2 increased from 9.5 - 10.0 hours to 12.5 - 13.5 hours. The 6beta-hydroxycortisol/ cortisol ratio was not changed after multiple doses suggesting no effect on CYP3A4 activity. CONCLUSION: S-3304 demonstrated a good safety profile and good systemic exposure when administered orally up to 800 mg b.i.d. during 10 - 17 days. At the highest dose level of 800 mg b.i.d., it was free of rheumatoid arthritis-like symptoms

70. VAN ROSSUM MA, BOERS M, ZWINDERMAN AH, VAN SOESBERGEN RM, WIERINGA H, FISELIER TJ, FRANSSEN MJ, CATE RT, SUIJLEKOM-SMIT LW, WULFFRAAT NM, VAN LUIJK WH, OOSTVEEN JC, KUIS W, DIJKMANS BA: Development of a standardized method of assessment of radiographs and radiographic change in juvenile idiopathic arthritis: Introduction of the Dijkstra composite score. Arthritis Rheum 52:9 2865-2872, 2005
    Organism: Emma Children's Hospital AMC and Jan van Breemen Instituut, Amsterdam, The NetherlandsFAU - van Rossum, Marion A J
    Abstract: OBJECTIVE: To evaluate the sensitivity to change of a newly developed radiologic assessment tool, the Dijkstra score, and to develop a numeric composite score and progressor classification scheme to apply in juvenile idiopathic arthritis (JIA) trials. METHODS: A placebo-controlled trial of sulfasalazine (SSZ) in patients with oligoarticular- and polyarticular-onset JIA yielded the data for this study. Data were obtained from 418 sets of radiographs of the clinically involved and contralateral joints (at study entry and at 6 months' followup) from 66 JIA patients. The Dijkstra score assesses the presence or absence of swelling, osteopenia, joint space narrowing, growth abnormalities, subchondral bone cysts, erosions, and malalignment. These signs were combined in the Dijkstra composite score, to assess inflammation (DI), growth (DG), and damage (DD). Progression was defined as an increase in either the DG or the DD score. Scores were evaluated among all radiographs, a standard set of films (hand, foot, and knee), and per patient. All scores were used to explore differences between the 2 treatment groups. RESULTS: Over time, 58% of joints remained normal, 23% remained abnormal but stable, 14% showed an increase in signs, and 5% showed a decrease in signs. Of the 66 JIA patients, 12% had normal radiographic findings throughout followup, 27% showed abnormalities at some sites without change, and 61% showed change in at least 1 site. Changes in the DI, DG, and DD scores varied considerably per type of joint and occurred most frequently in joints of the standard set. DI and DG scores changed most often in the knees, while DD scores changed primarily in the hands and feet. The disease course in 8% of joints was classified as progressive. Films of SSZ-treated patients, versus the placebo group, showed less deterioration by the DD scores (P = 0.04), and the disease course was more often classified as nonprogressive in the SSZ group (P = 0.037). When progressors were defined as those who had at least one radiograph showing progression, significantly more placebo-treated patients were considered progressors (P = 0.046). CONCLUSION: In this trial data set, the Dijkstra composite score and the resulting progressor classification system are comprehensive and feasible tools that are sensitive to change and discriminate between clinical situations. They should now be tested by other investigators and in other data sets

71. VANDER CB, HOFFMAN IE, ZMIERCZAK H, VAN DEN BM, KRUITHOF E, DE RYCKE L, MIELANTS H, VEYS EM, BAETEN D, DE KEYSER F: Anti-citrullinated peptide antibodies may occur in patients with psoriatic arthritis. Ann Rheum Dis 64:8 1145-1149, 2005
    Organism: Department of Rheumatology, De Pintelaan 185, Ghent University Hospital, B-9000 Gent, Belgium bertvandercruyssen@ugentbeFAU - Vander Cruyssen, B
    Abstract: BACKGROUND: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are considered highly specific markers of rheumatoid arthritis. Despite the high specificity of the test, anti-CCP antibodies have also been observed in psoriatic arthritis. OBJECTIVE: To determine the frequency of anti-CCP antibodies in psoriatic arthritis and to describe the clinical characteristics of such patients. METHODS: Serum samples from 192 patients with psoriatic arthritis were analysed for anti-CCP antibodies. A previously defined cut off point was applied at a specificity level of > or =98.5% (42 U/ml). Antibodies against pepA and pepB (two synthetic citrullinated peptides) were determined on samples containing anti-CCP antibodies by line immune assay. The swollen joint count and the numbers of affected joints (present or past) were recorded. Clinical features were noted and if available radiographs of hands and feet were scored for erosions. Rheumatoid factor was determined in all samples. RESULTS: Anti-CCP antibodies were found in 15 patients (7.8%); 13 of 15 anti-CCP2 positive samples were also positive for anti-pepA or pepB antibodies. The prevalence of anti-CCP antibodies was higher than expected in view of the highly specific cut off applied in the test. Detailed analysis of the clinical and radiological features makes it improbable that the high prevalence of anti-CCP antibodies resulted solely from concomitant psoriasis and rheumatoid arthritis or from misclassification. CONCLUSIONS: Anti-CCP antibodies may be present in patients with psoriatic arthritis. Although some of the present cohort could have had psoriasis with concomitant rheumatoid arthritis, a proportion at least had the typical characteristics of psoriatic arthritis as the primary diagnosis

72. WELLER F, HUPPERTZ HI: [The treatment of juvenile rheumatism: pharmacotherapy]. Z Rheumatol 64:5 308-316, 2005
    Organism: Prof-Hess-Kinderklinik Zentrum fur Kinderheilkunde und Jugendmedizin am Klinikum Bremen-Mitte, Sankt-Jurgen-Strasse 1, 28205 BremenFAU - Weller, F
    Abstract: The treatment of juvenile idiopathic arthritis has changed a great deal in the last few years. Pharmacomedical treatment, physiotherapy and teaching the patients and parents are the mainstays of successful therapy. Using all available treatment options and thanks to new therapeutic options (TNFalpha-blockade) and due to a better understanding of the pathogenesis, individual therapeutic strategies provide adequate disease control in the large majority of cases. According to the subtype of juvenile idiopathic arthritis, different medications are used in combination with nonsteroidal antiinflammatory drugs (NSAID) which are used initially. Methotrexate (MTX) and steroids in various applications are the drugs of choice for the systemic and polyarticular courses; intraarticular steroids, sulfasalazine and hydroxychloroquine for the oligoarticular subtype. The new option of TNFalpha-blockade (Etanercept, Infliximab, Adalimumab) offers significant clinical benefit in patients with polyarticular involvement, who do not respond to MTX. Further biological agents (Anakinra, Abatacept, Atlizumab) are used in children and adolescents in clinical studies. Rarely azathioprine, cyclosporine A, leflunomide and cyclophosphamide are used. Stem cell transplantation has been tried as a very last resort but interpretation of the results is controversial. Due to the improvement of the therapeutic options, the approaches to the patients and their disease has changed and cautious optimism is justified

73. WESTAWAY MD, HU WY, STRATFORD PW, MAITLAND ME: Intra- and inter-rater reliability of the anterior atlantodental interval measurement from conventional lateral view flexion/extension radiographs. Man Ther 10:3 219-223, 2005
    Organism: Faculty of Kinesiology, University of Calgary, 19 Discovery Valley Cove SW, Calgary, Alb, Canada T3H 5H3 westaway@telusplanetnetFAU - Westaway, Michael D
    Abstract: An investigation of intra- and inter-rater reliability anterior atlantodental interval (AADI) measurements was conducted using flexion/extension plain radiographs. Flexion and extension lateral radiographs of individuals investigated for atlantoaxial instability were measured for AADI on three occasions. Intra-rater intraclass correlation coefficients (ICC) were calculated for both flexion (0.99) and extension (0.96). Inter-rater ICCs were 0.93 and 0.84 for flexion and extension, respectively. The AADI measurement proved to be reproducible with a minimal standard of error, between and within raters

74. XU XY, ZHOU WH, XIAO CS, LI XF, WANG LY: [A clinical study of hyperhomocysteinemia in rheumatological diseases.]. Zhonghua Nei Ke Za Zhi 44:2 111-114, 2005
    Organism: Department of Rheumatology, Zhongda Hospital of Southeast University, Nanjing, Jangsu 210009, China xiaoyanxu111@sohucomFAU - Xu, Xiao-yan
    Abstract: OBJECTIVE: To analysis plasma homocysteine (Hcy) level and some relative factors in some rheumatological diseases. METHODS: 54 cases with systemic lupus erythematosus (SLE), 48 cases with rheumatoid arthritis (RA), 60 cases with ankylosing spondylitis (AS), 30 cases with undifferentiated spondyloarthropathy (uSpA) and 62 controls were recruited to participate the study. Plasma Hcy, vitamin B(12), folate and the MTHFR gene C677T polymorphism were measured in all patients and controls. RESULTS: (1) Plasma Hcy levels were higher significantly in all disease groups than in the controls, the mean plasma Hcy level was (19.04 +/- 6.86) micromol/L for SLE, (19.07 +/- 7.43) micromol/L for RA, (16.47 +/- 6.50) micromol/L for AS, (16.59 +/- 6.72) micromol/L for uSpA and (12.24 +/- 3.58) micromol/L for controls (P < 0.01). (2) Significant inverse correlation was found between plasma Hcy level and vitamin B(12), folate (r = -0.701, -0.443, respectively; P < 0.01). (3) The MTHFR gene mutation make Hcy level dramatically rise, CC genotype (13.41 +/- 5.78) micromol/L, CT genotype (16.81 +/- 4.22) micromol/L, TT genotype (20.88 +/- 6.60) micromol/L (P < 0.05). TT genotype is susceptible for hyperhomocysteinemia and SLE (OR = 84.46, 7.56 respectively; P < 0.05). CONCLUSIONS: (1) Hyperhomocysteinemia is found in most SLE, RA, AS and uSpA patients. (2) There are lots of factors associated with Hcy concentration, such as folate, vitamin B12 and MTHFR gene mutation. (3) TT genotype of MTHFR is susceptible for hyperhomocysteinemia and SLE

75. YIM D, ZHOU H, PECK CC, LEE H: Population pharmacokinetic-pharmacodynamic (PK-PD) modeling of etanercept in patients with juvenile rheumatoid arthritis (JRA) using a dichotomous clinical endpoint. Clinical Pharmacology & Therapeutics 77:2, Suppl. S 92, /2/5