Bibliography January 05

1. BRUNNER HI, KLEIN-GITELMAN MS, MILLER MJ, BARRON A, BALDWIN N, TROMBLEY M, JOHNSON AL, KRESS A, LOVELL DJ, GIANNINI EH: Minimal clinically important differences of the childhood health assessment questionnaire. J Rheumatol 32:1 150-161, 2005
   Organism: Division of Rheumatology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA herminebrunner@cchmcorgFAU - Brunner, Hermine I
   Abstract: OBJECTIVE: The Childhood Health Assessment Questionnaire (CHAQ) is a commonly used measure of disability and physical function for children with juvenile rheumatoid arthritis (JRA), whose scores range between 0 (no disability) and 3 (very severe disability), with a smallest potential difference in the CHAQ score of individuals at 0.125. We estimated minimal clinically important differences (MCID) of the CHAQ for worsening and improvement that were actually experienced by children with JRA using patient, parent, and clinical perspectives. METHODS: Changes in CHAQ scores were calculated for parent (n = 92) and patient ratings (children age > or = 8 yrs only; n = 67) between subsequent clinic visits. Changes in patient well being and disease activity and the occurrence of flare or important improvement between visits served as external standards for the MCID. MCID were defined as the median changes of the CHAQ scores of individual patients who had a minimal important improvement or worsening between visits. RESULTS: The median change in CHAQ scores of patients who rated themselves or were rated by others as unchanged was often 0. Depending on the external standard used, the MCID for improvement of the CHAQ was -0.188 at most, while the MCID for worsening was at most +0.125. CONCLUSION: The MCID of the CHAQ for both improvement and worsening are often at or close to the level of the smallest potential difference, suggesting that the CHAQ is relatively insensitive to important short term changes in children with JRA. This may warrant a change in the calculation of the global CHAQ score, or the development of more sensitive functional measures

2. BUKULMEZ H, FIFE M, TSORAS M, THOMPSON SD, TWINE NA, WOO P, OLSON JM, ELSTON RC, GLASS DN, COLBERT RA: Tapasin gene polymorphism in systemic onset juvenile rheumatoid arthritis: a family-based case-control study. Arthritis Res Ther 7:2 R285-R290, 2005
   Organism: William S, Rowe Division of Pediatric Rheumatology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio, USA hxb38@caseeduFAU - Bukulmez, Hulya
   Abstract: Juvenile rheumatoid arthritis (JRA) comprises a group of chronic systemic inflammatory disorders that primarily affect joints and can cause long-term disability. JRA is likely to be a complex genetic trait, or a series of such traits, with both genetic and environmental factors contributing to the risk for developing the disease and to its progression. The HLA region on the short arm of chromosome 6 has been intensively evaluated for genetic contributors to JRA, and multiple associations, and more recently linkage, has been detected. Other genes involved in innate and acquired immunity also map to near the HLA cluster on 6p, and it is possible that variation within these genes also confers risk for developing JRA. We examined the TPSN gene, which encodes tapasin, an endoplasmic reticulum chaperone that is involved in antigen processing, to elucidate its involvement, if any, in JRA. We employed both a case-control approach and the transmission disequilibrium test, and found linkage and association between the TPSN allele (Arg260) and the systemic onset subtype of JRA. Two independent JRA cohorts were used, one recruited from the Rheumatology Clinic at Cincinnati Children's Hospital Medical Center (82 simplex families) and one collected by the British Paediatric Rheumatology Group in London, England (74 simplex families). The transmission disequilibrium test for these cohorts combined was statistically significant (chi2 = 4.2, one degree of freedom; P = 0.04). Linkage disequilibrium testing between the HLA alleles that are known to be associated with systemic onset JRA did not reveal linkage disequilibrium with the Arg260 allele, either in the Cincinnati systemic onset JRA cohort or in 113 Caucasian healthy individuals. These results suggest that there is a weak association between systemic onset JRA and the TPSN polymorphism, possibly due to linkage disequilibrium with an as yet unknown susceptibility allele in the centromeric part of chromosome 6

3. DOUGADOS M, EMERY P, LEMMEL EM, ZERBINI CA, BRIN S, VAN RIEL P: When a DMARD fails, should patients switch to sulfasalazine or add sulfasalazine to continuing leflunomide? Ann Rheum Dis 64:1 44-51, 2005
   Organism: Hopital Cochin, Rene Descartes University, 27, Rue du Faubourg Saint-Jacques, 75679 Paris Cedex 14, France maximedougados@cchap-hop-parisfrFAU - Dougados, M
   Abstract: OBJECTIVE: To evaluate the efficacy and safety of adding sulfasalazine to leflunomide treatment compared with switching to sulfasalazine alone in patients with RA with an inadequate response to leflunomide monotherapy. METHODS: Patients with active RA ((DAS28) >3.2) who were enrolled in the first open label phase of the RELIEF study received leflunomide for 24 weeks. Inadequate responders then entered the double blind phase and received a further 24 weeks' treatment with leflunomide (20 mg once daily) plus sulfasalazine (final dose 2 g once daily), or placebo plus sulfasalazine (dose as above). The primary efficacy variable was the DAS28 response rate, and secondary efficacy outcomes were ACR 20%, 50%, and 70% response rates. Adverse events, including standard laboratory tests, were recorded. RESULTS: 106 inadequate responders entered the double blind phase; 56 received leflunomide plus sulfasalazine, and 50 placebo plus sulfasalazine. In the intention to treat population, more patients receiving leflunomide plus sulfasalazine (25/56 (45%)) achieved a DAS28 response than those receiving placebo plus sulfasalazine (17/50 (34%)) (p = 0.179). In week 24 completers, more patients receiving leflunomide plus sulfasalazine (17/56 (30%)) were DAS28 responders than those receiving placebo plus sulfasalazine (10/50 (20%)) (p = 0.081). Comparable numbers in each group were ACR 20% responders; the ACR 50% response rate was significantly higher in the leflunomide plus sulfasalazine group (8.9%) than in the placebo plus sulfasalazine group (0%) (p = 0.038). The safety profiles of both groups were comparable. CONCLUSION: Patient numbers are small and firm conclusions cannot be reached, but a non-significant benefit is indicated for combining leflunomide with sulfasalazine compared with switching to sulfasalazine alone in patients inadequately responding to leflunomide

4. DOUGLAS KM, POTTER T, TREHARNE GJ, OBRENOVIC K, HALE ED, PACE A, MITTON D, ERB N, WHALLETT A, DELAMERE JP, KITAS GD: Rheumatology patient preferences for timing and location of out-patient clinics. Rheumatology (Oxford) 44:1 80-82, 2005
   Organism: Department of Rheumatology, The Guest Hospital, Tipton Road, Dudley, West Midlands DY1 4SE, UK KarenDouglas@dgohnhsukFAU - Douglas, K M J
   Abstract: OBJECTIVES: To determine the preferences of rheumatology patients for the time and location of their out-patient appointments. METHODS: All patients attending the rheumatology out-patient services at Dudley Group of Hospitals NHS Trust over a 2-week period were asked to complete a purpose-designed, scannable, previously piloted, self-administered questionnaire. RESULTS: Four hundred and nineteen patients completed questionnaires (response rate 87%). Age ranged from 16 to 92 yr; 38% of responders were over 65 yr, 72% were female, 57% had an inflammatory arthritis, 20% had a connective tissue disease, 8% had degenerative joint disease and 15% had another diagnosis; 29% were employed, 51% retired and 20% unemployed. Fewer than 1% of patients would like to be seen at community general practice centres (99.3% would prefer a hospital site). Proximity to their home was the main determinant of hospital choice. Monday was the most popular day for appointments, and days from Tuesday to Friday received equal rankings. Only 0.5% of patients would choose a weekend clinic. Fifty-eight per cent of patients would prefer morning appointments, 24% afternoon appointments and 2% evening appointments; 16% did not mind. Only being employed predicted out-of-hours preference. CONCLUSIONS: In this predominantly suburban, industrialized area, rheumatology out-patients prefer to be seen in the hospital rather than primary care environment, ideally close to their home, with appointments in the morning and on a weekday. These results may be generalizable to other districts and other chronic disease states, but we suggest that similar surveys become part of routine service provision and inform current and future planning

5. FALCONE A, CASSONE R, ROSSI E, PISTORIO A, MARTINI A, RAVELLI A: Inter-observer agreement of the physician's global assessment of disease activity in children with juvenile idiopathic arthritis. Clin Exp Rheumatol 23:1 113-116, 2005
   Organism: Dipartimento di Pediatria, Universita di Genova, Pediatria II, Istituto di Ricovero e Cura a Carattere Scientifico G Gaslini, Genova, ItalyFAU - Falcone, A
   Abstract: OBJECTIVE: To assess the inter-observer agreement in the physician's global assessment of overall disease activity (MD global) in a cohort of patients with juvenile idiopathic arthritis (JIA). METHODS: Forty consecutive patients with JIA, who were representative of a wide spectrum of disease activity and severity, were examined simultaneously by 4 observers. Observer 1 (who was the most experienced rheumatologist) carried out a routine rheumatologic examination of each patient including a complete articular assessment, and subsequently calculated in secrecy the MD global score on an anchored horizontal 10-cm VAS. Observers 2, 3 and 4 were present during the examination; afterwards they also scored in secrecy the MD global score for the patient. Agreement was measured by the intra-class correlation coefficient (ICC), using the score of Observer 1 as the gold standard. An ICC below 0.75 was considered unsatisfactory. RESULTS: The mean (SD) MD global scores for Observers 1, 2, 3, and 4 were 5.2 (3.4), 6.7 (3.9), 5.9 (3.5), and 5.6 (3.7), respectively. The level of agreement with Observer 1 in scoring was 0.83 for Observer 2, 0.88 for Observer 3, and 0.90 for Observer 4, indicating good agreement for all observers. CONCLUSIONS: Our study shows a good inter-observer agreement in the physician's global assessment of overall disease activity in patients with JIA. Analyses involving investigators from different countries are needed to determine whether these results can be generalized

6. FASCE F, BRANCATO R: Incomplete extrusion of an acrylic punctum plug in a case of severe dry eye syndrome. Eur J Ophthalmol 15:1 132-134, 2005
   Organism: Department of Ophthalmology and Visual Sciences, University Hospital San Raffaele, Milano - ItalyFAU - Fasce, F
   Abstract: PURPOSE: To report a case of extrusion of a new soft punctum plug with thermoexpansion property (Medennium SmartPLUG). METHODS: A soft punctum plug was implanted in a 32-year-old woman with a severe dry eye syndrome in juvenile arthritis. RESULTS: One week after implant the plug partially extruded outside the punctum. Despite this adverse event, all subjective dry eye symptoms improved. CONCLUSIONS: The peculiarity of this case is the persistence of clinical efficacy of the soft punctum plug even if partially extruded. The patient experienced relief of symptoms that can be compared to the benefits usually obtained with a successfully implanted silicon plug

7. FELDMAN BM: Treating children with arthritis: towards an evidence-based culture. J Rheumatol Suppl 72:33-5.: 33-35, 2005
   Organism: Department of Pediatrics, Health Policy Management and Evaluation Unit, Public Health Sciences, University of Toronto, Canada brianfeldmdan@sickkidscaFAU - Feldman, Brian M
   Abstract: We live in a culture of evidence-based medicine. Many areas of medicine have embraced this culture. However, for unusual diseases, like the childhood arthritides, there is little evidence. To provide this evidence a culture change must occur in pediatric rheumatology. The most convincing reason to make this change comes from the field of childhood oncology. Through successive clinical trials, collaborative oncology study groups have discovered cures for many childhood cancers. The most convincing studies are randomized trials; however, these are difficult to do. Collaborative trial groups and innovative designs are needed for an acceptable culture change in childhood arthritis. Recently a number of collaborations have been developed to help further the study of pediatric rheumatology. The best known are the Pediatric Rheumatology Collaborative Study Group in North America, and the Paediatric Rheumatology International Trials Organization in Europe, South America, and Asia. A new North American collaborative study group has formed--the Childhood Arthritis and Rheumatology Research Alliance (CARRA)--to undertake investigator-initiated clinical trials. These groups might potentially lead the way to a new evidence-based culture for childhood arthritis

8. FERUCCI ED, MAJKA DS, PARRISH LA, MOROLDO MB, RYAN M, PASSO M, THOMPSON SD, DEANE KD, REWERS M, AREND WP, GLASS DN, NORRIS JM, HOLERS VM: Antibodies against cyclic citrullinated peptide are associated with HLA-DR4 in simplex and multiplex polyarticular-onset juvenile rheumatoid arthritis. Arthritis Rheum 52:1 239-246, 2005
   Organism: Division of Rheumatology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USAFAU - Ferucci, Elizabeth D
   Abstract: OBJECTIVE: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been detected in patients with juvenile rheumatoid arthritis (JRA), particularly in those with polyarticular, rheumatoid factor (RF)-positive JRA. Our objectives were to determine whether anti-CCP antibodies are associated with HLA-DR4 in children with polyarticular JRA, whether anti-CCP antibodies are associated with clinical features of disease, and whether affected sibling pairs (ASPs) with JRA are concordant for this antibody. METHODS: Stored serum samples obtained from 230 HLA-typed patients with JRA (77 with polyarticular-onset disease and 153 with pauciarticular- or systemic-onset disease), 100 JRA ASPs, and 688 healthy children were tested for anti-CCP antibodies and RF. RESULTS: Thirteen percent of the patients with polyarticular-onset JRA and 2% of the other JRA patients exhibited anti-CCP antibodies, compared with only 0.6% of the controls. Fifty-seven percent of RF-positive patients with polyarticular-onset JRA had anti-CCP antibodies. HLA-DR4-positive patients with polyarticular-onset JRA were more likely to have anti-CCP antibodies than were those without HLA-DR4 alleles (odds ratio [OR] 5.20, 95% confidence interval [95% CI] 1.30-20.9). Anti-CCP antibodies were associated with polyarticular onset (OR 7.46, 95% CI 1.99-28.0), a polyarticular disease course (OR 9.78, 95% CI 1.25-76.7), and erosive disease (OR 14.3, 95% CI 3.01-67.9). Concordance rates for anti-CCP antibodies among ASPs were statistically significant. CONCLUSION: These data demonstrate increased anti-CCP antibody formation in HLA-DR4-positive patients with polyarticular-onset JRA. The overall prevalence of anti-CCP antibodies in JRA is low, but a substantial proportion of RF-positive patients with polyarticular-onset JRA have these antibodies. Anti-CCP antibodies in JRA are associated with polyarticular onset, a polyarticular course, and erosive disease

9. GATTORNO M, PRIGIONE I, MORANDI F, GREGORIO A, CHIESA S, FERLITO F, FAVRE A, UCCELLI A, GAMBINI C, MARTINI A, PISTOIA V: Phenotypic and functional characterisation of CCR7+ and CCR7- CD4+ memory T cells homing to the joints in juvenile idiopathic arthritis. Arthritis Res Ther 7:2 R256-R267, 2005
   Organism: II Division of Pediatrics, University of Genoa, Genoa, Italy marcogattorno@ospedale-gaslinigeitFAU - Gattorno, Marco
   Abstract: The aim of the study was to characterise CCR7+ and CCR7- memory T cells infiltrating the inflamed joints of patients with juvenile idiopathic arthritis (JIA) and to investigate the functional and anatomical heterogeneity of these cell subsets in relation to the expression of the inflammatory chemokine receptors CXCR3 and CCR5. Memory T cells freshly isolated from the peripheral blood and synovial fluid (SF) of 25 patients with JIA were tested for the expression of CCR7, CCR5, CXCR3 and interferon-gamma by flow cytometry. The chemotactic activity of CD4 SF memory T cells from eight patients with JIA to inflammatory (CXCL11 and CCL3) and homeostatic (CCL19, CCL21) chemokines was also evaluated. Paired serum and SF samples from 28 patients with JIA were tested for CCL21 concentrations. CCR7, CXCR3, CCR5 and CCL21 expression in synovial tissue from six patients with JIA was investigated by immunohistochemistry. Enrichment of CD4+, CCR7- memory T cells was demonstrated in SF in comparison with paired blood from patients with JIA. SF CD4+CCR7- memory T cells were enriched for CCR5+ and interferon-gamma+ cells, whereas CD4+CCR7+ memory T cells showed higher coexpression of CXCR3. Expression of CCL21 was detected in both SF and synovial membranes. SF CD4+ memory T cells displayed significant migration to both inflammatory and homeostatic chemokines. CCR7+ T cells were detected in the synovial tissue in either diffuse perivascular lymphocytic infiltrates or organised lymphoid aggregates. In synovial tissue, a large fraction of CCR7+ cells co-localised with CXCR3, especially inside lymphoid aggregates, whereas CCR5+ cells were enriched in the sublining of the superficial subintima. In conclusion, CCR7 may have a role in the synovial recruitment of memory T cells in JIA, irrespective of the pattern of lymphoid organisation. Moreover, discrete patterns of chemokine receptor expression are detected in the synovial tissue

10. GONCALVES M, TERRERI MT, BARBOSA CM, LEN CA, LEE L, HILARIO MO: Diagnosis of malignancies in children with musculoskeletal complaints. Sao Paulo Med J 123:1 21-23, 2005
    Organism: Department of Pediatrics, Universidade Federal de Sao Paulo, Escola Paulista de Medicina, Sao Paulo, BrazilFAU - Goncalves, Marcela
    Abstract: CONTEXT: Musculoskeletal complaints may be associated with neoplasias as an initial manifestation of the disease. When these symptoms predominate at the onset of the disease, the differential diagnosis includes several rheumatic diseases. OBJECTIVE: To assess the frequency, clinical features and types of cancer manifested in children presenting with musculoskeletal complaints over a seven-year period. TYPE OF STUDY: Retrospective. SETTING: Discipline of Allergy, Clinical Immunology and Rheumatology, Universidade Federal de Sao Paulo-Escola Paulista de Medicina. METHODS: The medical records of patients with musculoskeletal complaints and final diagnosis of malignant disease were reviewed. The data collected were: age when symptoms initially presented, age at diagnosis, clinical features presented, laboratory findings, and the initial and final diagnoses. RESULTS: A final diagnosis of cancer was found in nine out of 3,528 patients (0.25%) whose initial symptom was musculoskeletal pain. The mean time between disease onset and final diagnosis was five months. The most common features presented were pauciarticular arthritis or arthralgia involving the large joints. Juvenile rheumatoid arthritis was the most frequent initial diagnosis, in four out of nine patients. Anemia was the most frequent initial hematological change. Six out of eight patients had an increased erythrocyte sedimentation rate. The lactate dehydrogenase level was raised in five out of eight patients. The malignancies found included acute lymphocytic leukemia, acute myeloid leukemia, lymphoma, neuroblastoma and Ewing's sarcoma. DISCUSSION: The frequency of neoplasia in patients with musculoskeletal pain resembled reports in the literature. Consumptive symptoms were not the warning signal in most of our patients. In subsidiary tests, progressive anemia was the most common finding, although the peripheral blood cell count may continue to be normal for weeks or months after symptom onset. CONCLUSION: Malignancy always needs to be ruled out in cases of children with musculoskeletal complaints. Uncharacteristic clinical manifestations and nonspecific laboratory tests may cause difficulty in the final diagnosis, and rigorous investigation should be performed

11. HUANG J-L, YAO T-C, SEE L-C: Prevalence of pediatric systemic lupus erythematosus and juvenile chronic arthritis in a Chinese population: A nation-wide prospective population-based study in Taiwan. Clinical and Experimental Rheumatology (Italy ) 22:6 776-780, 2004
    Abstract: Objective. To estimate the national prevalence of systemic lupus erythematosus (SLE) and juvenile chronic arthritis (JCA) in Chinese children in Taiwan. Methods. A nationwide prospective population based epidemiologic study for the prevalence of pediatric SLE and JCA was undertaken in Taiwan (23 million inhabitants). The population at risk was identified as children under the age of 16 living in Taiwan (5.78 million). All citizens have been obligated to participate in Taiwan's National Health Insurance program since 1995. This gave us access to nationwide case data from the Major Illness/Injury registry and enabled us to calculate population prevalence. The population data were derived from the 1999 Taiwan census. Results. Three hundred six ty-five and 218 prevalent cases of pediatric SLE and JCA were identified, respectively. The prevalence of pediatric SLE was 6.3 per 100,000 (95% CI: 5.7-7.0). The prevalence in girls (11.2 per 100,000, 95% CI: 10.0-12.5) was 6.2 times higher than that in boys (1.8 per 100,000, 95% CI: 1.4-2.4). The prevalence of SLE substantially increased in children over the age of seven, especially in girls. The prevalence of JCA was 3.8 per 100,000 (95% CI: 3.3-4.3). The figures were similar for boys (3.5 per 100,000, 95% CI: 2.9-4.2) and girls (4.1 per 100,000, 95% CI: 3.3-4.9). Conclusion. In this first population based epidemiologic survey of pediatric SLE and JCA in Taiwan, we provided a good starting point in our understanding of the epidemiology of these serious conditions in the Chinese population. The discrepancies between our prevalence figures and those reported from Western countries are possibly the results from true differences pertaining to ethnicity, geography or both. Future studies are necessary to elucidate the implications suggested by these data. (c) Copyright Clinical and Experimental Rheumatology 2004

12. HUEMER M, HUEMER C, ULMER H, CRONE J, FODINGER M, FALGER J, SAILER-HOCK M: No evidence for hyperhomocysteinemia or increased prevalence of genetic polymorphisms in the homocysteine pathway in patients with moderate juvenile idiopathic arthritis. J Rheumatol 32:1 170-174, 2005
    Organism: Department of Pediatrics, Landeskrankenhaus Feldkirch, Feldkirch, Austria m333huemer@aonatFAU - Huemer, Martina
    Abstract: OBJECTIVE: Elevated plasma total homocysteine (tHcy) concentrations are associated with premature cardiovascular disease. We assessed tHcy, folate, vitamin B12 (Vit B12), vitamin B6 (Vit B6), and genetic polymorphisms potentially enhancing tHcy in patients with juvenile idiopathic arthritis (JIA) and healthy controls. METHODS: Open study of 56 consecutive patients with JIA and 62 controls. RESULTS: tHcy concentrations were normal in JIA patients (mean 6.5 +/- 2 micromol/l) and controls (mean 7.5 +/- 2.2 micromol/l). Folate concentrations were significantly higher in JIA patients (40.2 +/- 67.9 ng/ml) compared to controls (13.6 +/- 8.2 ng/ml). The prevalence of genetic polymorphisms coding for key enzymes in the homocysteine pathway did not differ between patients and controls. Erythrocyte sedimentation rate (ESR) showed significant inverse correlations with circulating Vit B6 and tHcy concentrations. CONCLUSION: No evidence for hyperhomocysteinemia or evidence for a specific genetic predisposition for hyperhomocysteinemia was present in patients with JIA. Elevated ESR is not associated with hyperhomocysteinemia

13. JAAKKOLA JJ, GISSLER M: Maternal smoking in pregnancy as a determinant of rheumatoid arthritis and other inflammatory polyarthropathies during the first 7 years of life. Int J Epidemiol 34:3 664-671, 2005
    Organism: Institute of Occupational and Environmental Medicine, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UKFAU - Jaakkola, Jouni Jk
    Abstract: OBJECTIVES: Personal smoking and gender are determinants of adult rheumatoid arthritis. We assessed the independent and joint effects of maternal smoking in pregnancy and gender on the development of rheumatoid arthritis and other inflammatory polyarthropathies (RA&IP, ICD-9 code 714) in particular juvenile rheumatoid arthritis (JRA, ICD-9 code 714.3) in the first 7 years of life in a cohort of Finnish children born in 1987. METHODS: We identified 58 841 singleton births from the Finnish Medical Birth Registry and followed-up on them through other nationwide registries for 7 years. The birth registry provided categorical information on the mother's smoking during pregnancy: no smoking as a reference, low exposure (<10 cigarettes per day) and high exposure (>10 cigarettes per day). RESULTS: There were 75 cases of RA&IP yielding an incidence rate of 18.5 per 100 000 person-years. Of these, 31 were classified as JRA with an incidence rate of 7.6 per 100 000 person-years. In logistic regression, both the risks of RA&IP (adjusted odds ratio (OR) 2.10; 95% confidence interval (CI) 1.30-3.40) and JRA (3.03; 1.36-6.76) were increased in girls. High exposure to tobacco smoke increased the risks of RA&IP (2.57; 1.13-5.89) and JRA (2.98; 0.95-8.78) in girls, but not in boys. The adjusted ORs for girls with heavy exposure were 4.64 (1.94-11.07) for RA&IP and 6.76 (2.00-22.9) for JRA compared with unexposed boys. CONCLUSION: This is an original finding of a potential effect of foetal exposure to tobacco smoke on the risks of RA&IP and JRA in girls

14. KAUPPI M, HARTIKAINEN S, KAUTIAINEN H, LAIHO K, SULKAVA R: Capability for daily activities in old people with rheumatoid arthritis: a population based study. Ann Rheum Dis 64:1 56-58, 2005
    Organism: Rheumatism Foundation Hospital, Pikijarventie 1, 18120 Heinola, Finland markkukauppi@reumafiFAU - Kauppi, M
    Abstract: OBJECTIVE: To describe the functional capacity for daily activities in old people with clinical rheumatoid arthritis (including juvenile rheumatoid arthritis (JRA)) in a population based cohort. METHODS: A cohort of 700 people was randomly collected from the population older than 75 years in a Finnish town. Altogether 601 persons (86%) participated. Data were collected from clinical records and by interview, clinical examination, and questionnaire. Ability to carry out activities of daily living (ADL) was assessed by the Barthel index, and the IADL (instrumental activities of daily living) by the Lawton and Brody questionnaire. RESULTS: 16 people had clinical rheumatoid arthritis (one with JRA). The prevalence was 16/601 (2.7% (95% confidence interval, 1.7% to 4.5%)). Eight patients with rheumatoid arthritis (50%) obtained the best possible ADL figures, while three (19%) had very poor results. Seven (44%) could not dress themselves without help. Three (19%) were unable to walk, and five (31%) could not climb stairs. Sex and age adjusted results showed no statistical difference (ADL and IADL) between patients with clinical rheumatoid arthritis and rest of the cohort. Four patients (25%) had dementia, which was associated with the poor functional capacity. CONCLUSIONS: The prevalence of the disease was unexceptional. The ability of old people with rheumatoid arthritis to carry out activities of daily living did not differ from the general population, but the disease may lead to severe disability on an individual level, especially when associated with dementia. It therefore remains a considerable challenge to the health care and social systems

15. KINDER AJ, HASSELL AB, BRAND J, BROWNFIELD A, GROVE M, SHADFORTH MF: The treatment of inflammatory arthritis with methotrexate in clinical practice: treatment duration and incidence of adverse drug reactions. Rheumatology (Oxford) 44:1 61-66, 2005
    Organism: Leicester Royal Infirmary, Haywood Hospital, Burslem, Stoke on Trent, UKFAU - Kinder, A J
    Abstract: OBJECTIVE: To identify the proportion of patients with inflammatory arthritis who remain on methotrexate in the medium to long term and the incidence of side-effects in clinical practice. METHOD: The study population comprised all patients with inflammatory arthritis treated with methotrexate and monitored in clinics under the auspices of Staffordshire Rheumatology Centre. Two clinical auditors collected data retrospectively from the computer database used to support monitoring of patients on disease-modifying anti-rheumatic drugs. Information was collected on duration of treatments and reasons for stopping treatment. For patients identified as having potentially serious side-effects or who died whilst taking methotrexate, further information on their outcome was collected from patients' medical notes and where applicable post mortem reports and death registers. RESULTS: Between 1986 and 1999, 673 patients were treated with methotrexate, of whom 551 had a diagnosis of rheumatoid arthritis. From the Kaplan-Meier analysis, the probability of patients remaining on treatment 5 yr after starting methotrexate was 0.74. Three hundred and sixteen patients stopped methotrexate between 1986 and 1999. In 117 patients, the methotrexate was restarted. Seventy-two patients (10.7% of all patients) stopped because of inefficacy or patient choice or situation. Thirty-seven patients (5.5%) stopped methotrexate due to abnormal haematology (usually low neutrophils). Thirty-seven patients (5.5%) stopped methotrexate due to abnormalities in liver function tests. Life-threatening side-effects were identified in 12 patients (1.8%). These included six pneumonitis, five cytopenias and one disseminated varicella zoster. Two of these patients (0.3%) died, one from pneumonitis and one from disseminated varicella zoster. A total of 25 patients (3.7%) died while taking methotrexate and four died (0.6%) within 3 months of stopping methotrexate. One death (0.15%) was directly attributable to methotrexate (methotrexate pneumonitis). CONCLUSION: This study has shown that methotrexate is well tolerated in clinical practice in the medium to long term. It has produced accurate data on the incidence of adverse effects of methotrexate in a local population in a non-research setting. It has identified the incidence of life-threatening side-effects to be 1.7% with one death (0.15%) directly due to methotrexate. This information should prove useful when recommending such treatment to patients with inflammatory arthritis

16. KOUNAMI S, YOSHIYAMA M, NAKAYAMA K, OKUDA M, OKUDA S, AOYAGI N, YOSHIKAWA N: Macrophage activation syndrome in children with systemic-onset juvenile chronic arthritis. Acta Haematol 113:2 124-129, 2005
    Organism: Departmentof Pediatrics, Wakayama Medical University, Kimiidera, Wakayama City, Japan nami@mailwakayama-medacjpFAU - Kounami, Shinji
    Abstract: Macrophage activation syndrome (MAS) is a life-threatening complication in children with rheumatic diseases, particularly systemic-onset juvenile chronic arthritis (SOJCA). Because of the potential fatality of this condition, prompt recognition and immediate therapeutic intervention are important. This study assessed the clinical features of nine MAS events in five children with SOJCA. Nonremitting fever and decreased platelet and white blood cell counts led to a diagnosis of MAS. The urinary beta2-microglobulin (beta2MG) level was a sensitive indicator of MAS. Serum levels of beta2MG and soluble interleukin-2 receptor were also elevated. These biologic markers reflecting hyperactivated cellular immunity are useful indicators of MAS. Four children treated with cyclosporin A (CSP) achieved rapid and complete recovery, but one patient without CSP died due to rapidly progressive respiratory failure. All children treated with CSP responded quickly, and fever abated within 36 h of initiation of treatment. CSP should be added to first-line therapy of MAS

17. KUSELER A, PEDERSEN TK, GELINECK J, HERLIN T: A 2 year followup study of enhanced magnetic resonance imaging and clinical examination of the temporomandibular joint in children with juvenile idiopathic arthritis. J Rheumatol 32:1 162-169, 2005
    Organism: Department of Orthodontics, the Paediatric Rheumatology Clinic, University of Aarhus, Aarhus, DenmarkFAU - Kuseler, Annelise
    Abstract: OBJECTIVE: Involvement of the temporomandibular joint (TMJ) in patients with juvenile idiopathic arthritis (JIA) can cause severe craniofacial growth disturbances if not treated in the initial stage. Magnetic resonance imaging (MRI) is an efficient method for detecting early inflammatory changes of the TMJ. We investigated correlation between findings from the clinical examination with MRI of the TMJ, and describe development of the MR image over time. METHODS: Fifteen children with newly diagnosed JIA (mean age 12.0 yrs) were examined clinically and with MRI enhanced with Gd-DTPA 4 times at 6-8 month intervals. Clinical and MRI findings were scored. MRI variables included T1 weighted images before and after administration of Gd-DTPA with and without fat suppression. RESULTS: A total of 115 joints were examined during the 2 year period: 93% showed enhancement, 71% condylar erosions, 26% pannus, and 23% joint fluid accumulation of the TMJ. In all except one child, one or both TMJ showed enhancement of the synovial membrane during the examination period. Symptoms were rare. All patients showing mild to severe findings by clinical examination also had pathological signs on the enhanced MRI, but not all patients without clinical findings had a normal MRI. CONCLUSION: TMJ involvement in patients with JIA is very common, and MRI findings such as synovial enhancement, pannus, and joint fluid fluctuate over time. The clinical examination may be used as a filter, where children showing no clinical signs could be selected for enhanced MRI

18. LANDAU H, SCHRODER R, ROTH J: Panoramic X-rays. Comprehensive Radiodiagnostics or Radiation Protection at all Costs? J Orofac Orthop 66:1 78-82, 2005
    Organism: Department of Orthodontics and Dentofacial Orthopedics, Charite-University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany
    Abstract: A case report is presented to examine the question of whether a panoramic x-ray in standard projection can be readily replaced by a radiation-reduced projection with shielding of the condylar processes.A female patient with juvenile idiopathic arthritis was examined by a panoramic x-ray and MRI prior to TMJ splinting. The panoramic x-ray in standard projection showed short, atypically-shaped condylar processes with cystic lesions and cortical erosion. The MRI confirmed the TMJ destruction. The condylar processes were shielded on the x-rays taken for a previous orthodontic treatment. Thus TMJ assessment was not done, though it is an integral part of orthodontic radiodiagnostics according to Hirschfelder and other authors.This example of juvenile idiopathic arthritis with TMJ involvement shows that visualization of the condylar processes is indispensable

19. LEBWOHL MG: Use of etanercept in the dermatology setting. A review. Am J Clin Dermatol 6:1 49-59, 2005
    Organism: Mount Sinai Medical Center, New York, NY, USAFAU - Lebwohl, Mark G
    Abstract: As psoriasis and psoriatic arthritis are chronic in nature, ideal treatment should have sustained efficacy, with minimal short- and long-term toxicities to allow lifelong treatment. Traditional therapies used for psoriatic arthritis or psoriasis, including phototherapies and systemic agents, do not satisfy these criteria. Ninety percent of patients surveyed in 1998 by The National Psoriasis Foundation were not satisfied with their treatment options.Several observations have supported the introduction of the tumor necrosis factor (TNF) antagonist etanercept as a treatment for psoriatic disease, including the failure of traditional therapies to meet patient needs, evidence that TNF plays a fundamental role in the inflammatory processes underlying psoriatic arthritis and psoriasis, and the safety and efficacy of this agent in other inflammatory, immune-mediated diseases, such as rheumatoid arthritis (RA). Etanercept prevents initiation of the proinflammatory cascade by competitively binding TNF. First indicated for RA, etanercept is also approved for the treatment of psoriatic arthritis, juvenile RA, ankylosing spondylitis, and most recently psoriasis.Etanercept provides dermatologists with a safe, effective, and convenient treatment option for patients with psoriatic arthritis and psoriasis, which can be used continuously with or without traditional therapies. The self-administered injections provide a distinct advantage over traditional therapies that often require frequent office visits and laboratory monitoring, and other biologic agents that require administration in the doctor's office. Dermatologists should be aware of the ongoing research with etanercept in psoriasis and other dermatologic conditions

20. LOVELL DJ, ZAOUTIS TE, SULLIVAN KATHLEEN_(REPRINT): Immunosuppressants, infection, and inflammation. Clinical Immunology (Orlando) 113:2 137-139, 2004

21. MARTINI G, ZULIAN F, CALABRESE F, BORTOLI M, FACCO M, CABRELLE A, VALENTE M, ZACCHELLO F, AGOSTINI C: CXCR3/CXCL10 expression in the synovium of children with juvenile idiopathic arthritis. Arthritis Res Ther 7:2 R241-R249, 2005
    Organism: Department of Paediatrics, Padua University School of Medicine, Italy martini@pediatriaunipditFAU - Martini, Georgia
    Abstract: The accumulation of T cells in the synovial membrane is the crucial step in the pathophysiology of the inflammatory processes characterizing juvenile idiopathic arthritis (JIA). In this study, we evaluated the expression and the pathogenetic role in oligoarticular JIA of a CXC chemokine involved in the directional migration of activated T cells, i.e. IFNgamma-inducible protein 10 (CXCL10) and its receptor, CXCR3. Immunochemistry with an antihuman CXCL10 showed that synovial macrophages, epithelial cells, and endothelial cells bear the chemokine. By flow cytometry and immunochemistry, it has been shown that CXCR3 is expressed at high density by virtually all T lymphocytes isolated from synovial fluid (SF) and infiltrating the synovial membrane. Particularly strongly stained CXCR3+ T cells can be observed close to the luminal space and in the perivascular area. Furthermore, densitometric analysis has revealed that the mRNA levels for CXCR3 are significantly higher in JIA patients than in controls. T cells purified from SF exhibit a definite migratory capability in response to CXCL10. Furthermore, SF exerts significant chemotactic activity on the CXCR3+ T-cell line, and this activity is inhibited by the addition of an anti-CXCL10 neutralizing antibody. Taken together, these data suggest that CXCR3/CXCL10 interactions are involved in the pathophysiology of JIA-associated inflammatory processes, regulating both the activation of T cells and their recruitment into the inflamed synovium

22. MATSUMOTO M, CHIBA K, NAKAMURA M, OGAWA Y, TOYAMA Y, OGAWA J: Impact of interlaminar graft materials on the fusion status in atlantoaxial transarticular screw fixation. J Neurosurg Spine 2:1 23-26, 2005
    Organism: Department of Orthopaedic Surgery, School of Medicine, Keio University, Tokyo, Japan morio@scitckeioacjoFAU - Matsumoto, Morio
    Abstract: OBJECT: Structural interlaminar graft materials were used for atlantoaxial transarticular screw fixation (TSF), and its impact on the fusion status was investigated. METHODS: Forty-two patients (10 men, 32 women, mean age 51 years, mean follow-up period 45 months; 30 with rheumatoid arthritis, and 12 with os odontoideum) underwent TSF and modified Brooks posterior wiring involving titanium cables. As interlaminar graft materials, autologous bone from posterior iliac crest alone was used in 20 patients (Group A), and a structural spacer (13 ceramic spacers, nine titanium mesh cages) in 22 (Group B). Lateral radiographs were evaluated to determine bone fusion, alignment of the cervical spine, and wire loosening. Solid osseous fusion was obtained in 95% of Group A and 96% of Group B patients. The mean atlantoaxial angle was 19.1+/-9.7 degrees and 16.7+/-10.4 degrees before surgery (p = 0.45), and 27.4+/-7.8 degrees and 22.1+/-5.5 degrees after surgery (p = 0.02) in Groups A and B, respectively. Atlantoaxial hyperlordosis (atlantoaxial angle > or = 30 degrees) was observed in 32% of Group A and 18% of Group B patients (p = 0.26). Postoperative kyphosis occurred in 40% of Group A and 23% of Group B patients (p = 0.28). Loosening of the cable was demonstrated in 50% of Group A and 36% of Group B patients(p = 0.37). In Group B patients maintenance of cervical lordosis was more likely than in those in Group A, although the differences did not reach statistical significance. CONCLUSIONS: These results indicate that structural interlaminar spacers can maintain proper cervical alignment without a decease in the fusion rate; the authors recommend their use in conjunction with TSF

23. MIAN AN, FARNEY AC, MENDLEY SR: Mycoplasma hominis septic arthritis in a pediatric renal transplant recipient: case report and review of the literature. Am J Transplant 5:1 183-188, 2005
    Organism: University of Maryland School of Medicine, Department of Pediatrics, Baltimore, MD, USA amian@pedsumarylandeduFAU - Mian, Ayesa N
    Abstract: Septic arthritis (SA) typically occurs in young children, often from Staphylococcus. With chronic immunosuppression, however, pathogens may be atypical. A 15-year-old African-American female developed Mycoplasma hominis SA in her right hip 2 months following cadaveric renal transplant (Tx). Her presentation was subtle and indolent, without fever or leukocytosis. Although reported in adult Tx recipients, M. hominis infections have not been described in pediatric recipients. Early immunosuppression (basiliximab, prednisone, tacrolimus, mycophenolate mofetil and Thymoglobulin) may have increased her susceptibility to M. hominis. Optimal therapy for M. hominis SA is not well established and relapses occur. This patient underwent joint incision and drainage, treatment for 8 weeks with doxycycline and levofloxacin guided by in vitro sensitivities, and a reduction in immunosuppression. She has been free of ongoing infection for 3 years with stable graft function (Cr 1.1 mg/dL) on moderate immunosuppression with prednisone, tacrolimus and MMF

24. MIRANDA LA, FISCHER RG, SZTAJNBOK FR, JOHANSSON A, FIGUEREDO CM, GUSTAFSSON A: Increased interleukin-18 in patients with juvenile idiopathic arthritis and early attachment loss. J Periodontol 76:1 75-82, 2005
    Organism: Institute of Odontology, Karolinska Institute, Huddinge, SwedenFAU - Miranda, Leticia A
    Abstract: BACKGROUND: Patients with juvenile idiopathic arthritis (JIA) have been shown to have incipient attachment loss (AL) more frequently than systemically healthy individuals. This study investigated neutrophil activity and proinflammatory cytokines in these patients and aged-matched controls. METHODS: Elastase activity, measured with a low molecular weight substrate (S-2484), and interleukin-1beta (IL-1beta), measured with the enzyme-linked immunosorbent assay (ELISA), were analyzed in the gingival fluid of 38 patients with JIA and 29 controls. IL-1beta and interleukin-18 (IL-18) were measured with ELISA in the serum of the same groups. Subgingival plaque was analyzed by DNA probes to detect 12 bacteria. RESULTS: Significantly elevated serum levels of IL-1beta and IL-18 were found in the JIA group. No differences were found in the gingival fluid levels of elastase and IL-1beta between groups, or in the frequency of subjects positive to most of the bacteria analyzed, except F. nucleatum, C. rectus, P. micros, and S. intermedius, which were significantly more frequent in the control group. When the JIA group was subdivided according to the presence/absence of AL, IL-18 was significantly increased in the JIA subgroup with AL compared to those without it. There were no differences in the subgingival microbiota between the subgroups. CONCLUSION: The findings of increased serum IL-18 and IL-1beta in patients with JIA accompanied by a similar subgingival microbiota suggest that the increased frequency of incipient attachment loss observed in these patients might be due to their altered systemic inflammatory response, making them more susceptible to periodontal disease

25. MOK MY, LO Y, LEUNG PY, LAU CS: Pregnancy outcome in patients with adult onset Still's disease. Rinsho Ganka 31:11 2307-2309, 2004
    Abstract: The effect of pregnancy on disease activity and maternal and fetal outcome in patients with adult onset Still's disease (AOSD) has not been well addressed. We describe pregnancies from 3 Chinese patients with AOSD and review the pregnancy outcome of patients satisfying the classification criteria for AOSD1,2 (Table 1) reported in the English literature3-12

26. MURRAY MJ, TANG T, RYDER C, MABIN D, NICHOLSON JC: Lesson of the week - Childhood leukaemia masquerading as juvenile idiopathic arthritis. BMJ 329:7472 959-961, 2004

27. NOBILI V, DEVITO R, COMPARCOLA D, CORTIS E, SARTORELLI MR, MARCELLINI M: Juvenile idiopathic arthritis associated with autoimmune hepatitis type 2. Ann Rheum Dis 64:1 157-158, 2005

28. OLEJAROVA M: Safety and efficacy of vaccination in patients with inflammatory rheumatic diseases
    BEZPECNOST A UCINNOST OCKOVANI NEMOCNYCH SE ZANETLIVYMI REVMATICKYMI CHOROBAMI. Ceska Revmatologie (Czech Republic ) 12:4 157-162, 2004
    Abstract: Introduction. Patients with inflammatory rheumatic disease are in increased risk of infection, which is still leading cause of mortality in rheumatoid arthritis and systemic lupus erythematosus (SLE). Vaccination in these subjects may decrease the risk of severe infectious complications, but also might lead to flare up of the disease. Case report. A female, 24 years old patient developed 3 weeks after vaccination severe SLE with multiorgan involvement (meningoencephalitis, polyserositis, pancytopenia, nephritis, myositi s, secondary antiphospholipid syndrome) and high autoantibodies levels. Despite of intensive intravenous corticosteroids, followed with oral therapy, the condition deteriorated and only plasmapheresis and IV pulse cyclophosphamide (6 pulses) reversed the critical state. Therapy led finally to complete remission of the diseases. After 1 year follow-up the patient has been treated only with maintaining doses of methylprednisolone, azathioprine and warfarin, she complained only for steroid cataract. Respectively, it has been revealed, that the patient was in the age of 9 years treated temporarily for juvenile idiopathic arthritis, which has been long term remitted. Conclusion. A risk of induction of a new autoimmune disease after vaccination in healthy subjects is very low and wide experiences show, that vaccination is safe (excluding alive vaccines) also in patients with inflammatory rheumatic diseases with stabilized disease. Flares cannot be excluded, but they are reported rarely and have not been observed in controlled studies. In patients treated with high doses of immunosupressive drugs the efficacy of vaccination may not be sufficient and a check of induced antibodies titres is recommended

29. PERFETTO F, TARQUINI R, SIMONINI G, BINDI G, MANCUSO F, GUIDUCCI S, MATUCCI-CERINIC M, FALCINI F: Circulating leptin levels in juvenile idiopathic arthritis: a marker of nutritional status? Ann Rheum Dis 64:1 149-152, 2005
    Organism: Department of Internal Medicine, Rheumatology Unit, University of Florence, 50139 Florence, Italy perfetto@unifiitFAU - Perfetto, F
    Abstract: BACKGROUND: Weight loss is common in juvenile idiopathic arthritis (JIA) and has been positively correlated with an increase in the production of proinflammatory cytokines. OBJECTIVE: To assess if plasma leptin is a mediator of cytokine dependent decreased food intake during inflammatory diseases and if it is increased in JIA. METHODS: Leptin levels were determined in 31 patients with polyarticular disease and in 37 with oligoarticular disease; 32 healthy children served as controls. RESULTS: Patients had significantly reduced body mass index (BMI) compared with controls (17.3 (3) v 19.1 (3) kg/m(2); p<0.005). Leptin was significantly lower in patients than controls (8.1 (4.8) v 10.7 (7.3) ng/ml; p = 0.036), but leptin/BMI values were similar. Absolute (8.2 (4.8) v 8 (4.9); p>0.05) and normalised (0.45 (0.24) v 0.47 (0.24); p>0.05) leptin levels were not significantly different between patients with active and inactive disease and between patients with oligoarticular and polyarticular arthritis (7.8 (4.4) v 8.6 (5.3); p>0.05 and 0.45 (0.23) v 0.48 (0.26); p>0.05, respectively). CONCLUSIONS: Leptin production per unit of fat mass is similar in patients and controls. The hypothesis that high levels of proinflammatory cytokines that characterise JIA might induce an increase of adipocytes leptin production is not supported by the results. Leptin may be a marker of nutritional status of JIA

30. RAYEN BS, CHAPMAN A: Monoarthritis; remember to ask the child. Arch Dis Child 90:1 69, 2005
    Organism: Dumfries & Galloway Royal Infirmary, Bankend Road, Dumfries DG1 4AP, UK drrayen@yahoocomFAU - Rayen, B S

31. REID GJ, MCGRATH PJ, LANG BA: Parent-child interactions among children with juvenile fibromyalgia, arthritis, and healthy controls. Pain 113:1-2 201-210, 2005
    Organism: Psychology, IWK Health Centre and Dalhousie University, Halifax, NS, Canada greid@uwocaFAU - Reid, Graham J
    Abstract: Parent-child interactions during pain-inducing exercise tasks among children (11-17 years old) with fibromyalgia, juvenile rheumatoid arthritis, and pain-free controls were examined and the contribution of parent-child interactions to disability was tested. Fifteen children in each of the three diagnostic groups and their parents completed 5-min exercise tasks and completed questionnaire measures of disability (Functional Disability Inventory) and coping (Pain Coping Questionnaire). There were few group differences in parent-child interactions. After controlling for children's ratings of pain evoked by the exercise, group differences in interactions during exercise tasks were no longer significant. Sequential analyses, controlling for group and exercise task, revealed that when parents made statements discouraging coping following children's negative verbalizations about the task or pain, children were less likely to be on task, compared to when parents made statements encouraging coping or when parents made any other statements. Children's general pain coping strategies were not related to parent-child interactions. Parent-child interactions were generally not related to disability. Across the groups, more pain and less time on task during the exercises were related to Functional Disability Inventory scores and more school absences. Parent-child interaction patterns influence children's adaptation to pain during experimental tasks. Parents' discouragement of coping in response to their children's negative statements related to the pain or the pain-evoking task are counter productive to children's ability to maintain activity in a mildly painful situation

32. ROJER DE, GOODMAN SB: Total knee replacement in juvenile rheumatoid arthritis. Orthopedics 28:1 39-45, 2005
    Organism: Dept of Orthopedic Surgery, Stanford University Medical Center 300 Pasteur Dr, Stanford, CA 94305, USAFAU - Rojer, David E
    Abstract: In general, longer operative times and in some cases increased blood requirements can be expected with TKA in patients with juvenile rheumatoid arthritis. Complications also are more frequent. Pain relief is usually good to excellent, and function and deformity are significantly improved. Range of motion after TKA for juvenile rheumatoid arthritis is usually less than that obtained in osteoarthritis, but still allows for dramatic improvements in performing activities of daily living (Figure 3)

33. RUNSTADLER JA, SAILA H, SAVOLAINEN A, LEIRISALO-REPO M, AHO K, TUOMILEHTO-WOLF E, TUOMILEHTO J, SELDIN MF: Association of SLC11A1 (NRAMP1) with persistent oligoarticular and polyarticular rheumatoid factor-negative juvenile idiopathic arthritis in Finnish patients: haplotype analysis in Finnish families. Arthritis Rheum 52:1 247-256, 2005
    Organism: Davis Rowe Program in Human Genetics, University of California-Davis, One Shields Avenue, Davis, CA 95616, USAFAU - Runstadler, Jonathan A
    Abstract: OBJECTIVE: The SLC11A1 (formerly called NRAMP1) gene is important in natural resistance to a variety of intracellular infections mediated by macrophages and has been proposed as a candidate gene for autoimmune disease susceptibility. The aim of this study was to examine susceptibility in Finnish patients with persistent oligoarticular and polyarticular rheumatoid factor (RF)-negative juvenile idiopathic arthritis (JIA) due to the presence of the SLC11A1 locus on chromosome 2. METHODS: A total of 234 Finnish JIA nuclear families and 639 elderly Finnish controls without a history of JIA were evaluated for association with JIA at 3 intragenic single-nucleotide polymorphisms: an intragenic insertion/deletion, a promoter microsatellite (NRAMP1), and a 3' microsatellite (D2S1471). RESULTS: Analysis of marker haplotypes demonstrated a strong association of Finnish JIA with 6-marker, 4-marker, and 2-marker haplotypes. Most impressively, 1 of the 6-marker haplotypes showed an odds ratio (OR) of 4.0 (95% confidence interval [95% CI] 2.6-6.2) in all JIA patients, 3.5 (95% CI 1.9-6.5) in those with persistent oligoarticular JIA, and 4.1 (95% CI 2.5-6.7) in those with polyarticular RF-negative JIA. Stratification of the haplotype data suggested that susceptibility to JIA in the haplotype spanning the SLC11A1 locus is independent (P < 0.01) of an association with a DRB1 JIA shared epitope (DRB1*JIASE) that includes well-characterized strong susceptibility to DRB1*08 and *11 alleles. This SLC11A1 haplotype also had an additive effect with DRB1*JIASE in those with polyarticular, but not those with persistent oligoarticular, disease (P = 0.06, OR 2.9 [95% CI 0.9-9.2] versus P = 0.5, OR 1.6 [95% CI 0.4-6.0]). CONCLUSION: Taken together, these data provide support for the existence of a locus at or near SLC11A1 that is a strong susceptibility factor for JIA in Finnish patients

34. SANCHEZ-BORGES M, CABALLERO-FONSECA F, CAPRILES-HULETT A: Tolerance of nonsteroidal anti-inflammatory drug-sensitive patients to the highly specific cyclooxygenase 2 inhibitors rofecoxib and valdecoxib. Ann Allergy Asthma Immunol 94:1 34-38, 2005
    Organism: Allergy-Immunology Service, Centro Medico-Docente La Trinidad, Caracas, Venezuela malsan@cantvnetFAU - Sanchez-Borges, Mario
    Abstract: BACKGROUND: Selective inhibitors of cyclooxygenase 2 (COX-2) are generally tolerated by patients sensitive to nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit COX-1. Valdecoxib is a new sulfonamide-containing COX-2-specific inhibitor indicated for the treatment of acute pain, osteoarthritis, and rheumatoid arthritis. OBJECTIVE: To compare the clinical tolerance to rofecoxib and valdecoxib in patients who previously developed urticaria and angioedema while taking classic NSAIDs. METHODS: Patients with challenge-proven NSAID cutaneous sensitivity were submitted to single-blinded controlled oral challenges with rofecoxib, 50 mg, and valdecoxib, 40 mg. RESULTS: Twenty-eight patients (19 females and 9 males; mean +/- SD age, 28.6 +/- 15.0 years; age range, 10-61 years) participated in this study. Twenty-two (85%) of 26 patients who underwent skin tests were atopic, as demonstrated by a clinical history of rhinitis and/or asthma plus positive immediate-type skin hypersensitivity test results. A previous exclusive cutaneous reaction pattern (urticaria and/or angioedema) had occurred in 10 patients (36%), whereas a mixed pattern of skin and respiratory symptoms had occurred in 18 patients (64%). Twenty patients (71%) were multiple reactors, and 8 patients (28%) were single reactors. In this current study, 2 patients (7%) taking rofecoxib experienced angioedema, and 1 patient (4%) taking valdecoxib experienced urticaria. CONCLUSIONS: Rofecoxib and valdecoxib can be safely used by most NSAID-sensitive patients with cutaneous reactions. Our findings suggest that isolated cross-reactions may occur in these patients, and for this reason, controlled oral provocation may be prudent when prescribing valdecoxib or rofecoxib for patients who have previously had urticaria or angioedema triggered by NSAIDs

35. SAVAGE MO, BLAIR JC, JORGE AJ, STREET ME, RANKE MB, CAMACHO-HUBNER C: IGFs and IGFBPs in GH insensitivity. Endocr Dev 9:100-6.: 100-106, 2005
    Organism: Department of Endocrinology, St Bartholomew's Hospital, London EC1A 7BE, UK mosavage@qmulacukFAU - Savage, M O
    Abstract: IGF-I, IGFBP-3 and ALS are GH-dependent peptides and their production is disturbed in states of GH insensitivity. This chapter explores the relative degrees of IGF-I, IGFBP-3 and ALS deficiency across the spectrum of GH insensitivity. In classical GH insensitivity syndrome (GHIS), known as Laron syndrome, due to GH receptor (GHR) deficiency, serum IGF-I, IGFBP-3 and ALS are severely reduced with inability to produce these peptides during an IGF-I generation test. Across the spectrum of severity of GHR defects, some patients have short stature and normal facial appearance, so-called partial or non-classical GH insensitivity. In these cases the IGF-I, IGFBP-3 deficiency is less severe. A positive relationship exists between height SDS and IGFBP-3 SDS (r2 = 0.45, p < 0.001) in patients from the European series with GHIS. In a new series of GHIS cases (n = 36) there was a significant difference in IGFBP-3 and ALS (p < 0.05) between classical (n = 25) and non-classical cases (n = 11). IGF-I, IGFBP-3 and ALS were significantly higher (p < 0.05) in pubertal compared with pre-pubertal subjects in the same series. In idiopathic short stature (ISS), heterozygous mutations of the GHR may have a dominant negative effect. ISS patients have lower IGF-I levels than the normal population. In 21 cases, mean IGF-I SDS was -1.39 (-2.4 to -1.16) and IGFBP-3; -0.45 (-1.13 to 0.38). However, IGF-I and IGFBP-3 responses in the IGF-I generation test were generally normal. In acquired GHI due to chronic illness such as Crohn's disease, juvenile arthritis and cystic fibrosis, IGF-I deficiency is present, although IGFBP-3 is usually normal. In summary, assessment of IGF-I, IGFBP-3 and ALS contributes to diagnosis in GH insensitivity states. In our experience, IGF-I is more sensitive to disturbance of GH action that IGFBP-3, however in severe GHIS cases, IGF-I is usually undetectable and measurement of IGFBP-3 is valuable as a guide to the severity of the biological defect

36. SCHNITZER TJ, GITTON X, JAYAWARDENE S, SLOAN VS: Lumiracoxib in the treatment of osteoarthritis, rheumatoid arthritis and acute postoperative dental pain: results of three dose-response studies. Curr Med Res Opin 21:1 151-161, 2005
    Organism: Northwestern University Feinberg School of Medicine, Chicago, IL, USAFAU - Schnitzer, Thomas J
    Abstract: OBJECTIVES: Overview of three dose-response studies demonstrating the efficacy of lumiracoxib, a novel COX-2 selective inhibitor, for chronic pain associated with osteoarthritis (0A), or rheumatoid arthritis (RA) and acute pain following dental extraction. METHODS: OA and RA: 4-week, randomized, placebo- and active-controlled studies of similar design. Patients (OA, n = 583; RA, n = 571) received lumiracoxib 50 mg, 100 mg or 200 mg twice daily (bid), lumiracoxib 400 mg once daily (od), diclofenac 75 mg bid or placebo. Dental: 12-h, single-center, randomized, placebo- and active-controlled study. Patients (n = 202) received single oral doses of lumiracoxib 100 mg or 400 mg, ibuprofen 400 mg or placebo. Main outcome measures: OA: pain intensity (PI) in the target joint (visual analogue scale [VAS]) and WOMAC score at Week 4; RA: overall PI (VAS) and ACR20 response at Week 4; Dental: difference (PID, categorical and VAS) score over 12h post dose, time to onset of analgesia. RESULTS: Throughout the OA study, all lumiracoxib doses provided superior reductions in PI versus placebo and at Week 4, all lumiracoxib doses provided efficacy similar to each other and to diclofenac. In the RA study, lumiracoxib 100 mg bid, 200 mg bid and 400mg od were significantly better than placebo in PI at Weeks 1 and 2 (all p < 0.05) but demonstrated borderline significance at Week 4 (lumiracoxib 400 mg od, p = 0.06). In pain following dental surgery, PID scores for both lumiracoxib doses were superior to placebo from 1.5 h onwards and always comparable, or superior, to ibuprofen. Lumiracoxib 400 mg had the fastest onset of analgesia, measured as median time to confirmed first perceptible pain relief using the two-stopwatch method (37.4 min, superiority versus placebo, p < 0.001). Lumiracoxib was well tolerated in all studies. CONCLUSIONS: These studies provide initial evidence that lumiracoxib is an effective, well-tolerated agent for the treatment of chronic and acute pain

37. SEIDEL P, GRUNDER W: Collagene order of articular cartilage by clinical magnetic resonance images and its age dependency. Z Med Phys 15:1 45-51, 2005
    Organism: Institute of Medical Physics and Biophysics, University of Leipzig, Germany Peter-Seidel@gmxdeFAU - Seidel, Peter
    Abstract: The present paper describes a novel method to obtain information on the degree of order of the collagen network of the knee meniscal cartilage by means of a single clinical MRI. Images were obtained from 34 healthy volunteers aged between 6 and 76 years as well as from one patient with clinically-diagnosed arthrosis at the age of 32 and 37 years. A Siemens Vision (1.5 T) MRT with TR=750 ms, TE=50 ms, FoV=160 mm, and Matrix 512x512 was used for this purpose. The MR signal intensities of the cartilage were read out along slices with constant height above the subchondral bone and plotted versus the actual angle to the external magnetic field. The obtained intensity curves were fitted by a model distribution, and the degree of order of the collagen fibers was calculated. For the knee meniscal cartilage, there was an age-dependency of the degree of order and a significant deviation of the volunteer with arthrosis from the normal curve. The results are discussed in view of the arcade model and of a possible use of non-invasive clinical MRT for the detection of early arthrotic changes of cartilage

38. SHAYA FT, BLUME S: Prescriptions for cyclooxygenase-2 inhibitors and other nonsteroidal anti-inflammatory agents in a medicaid managed care population: African Americans versus Caucasians. Pain Med 6:1 11-17, 2005
    Organism: Center on Drugs and Public Policy, University of Maryland Baltimore-School of Pharmacy, Baltimore, Maryland 21201, USA fshaya@rxumarylandeduFAU - Shaya, Fadia T
    Abstract: OBJECTIVE: To determine whether race is a predictor of a patient's likelihood of being prescribed selective cyclooxygenase-2 inhibitors (COX-2s) versus other nonsteroidal anti-inflammatory agents (NSAIDs) in Medicaid managed care plans (MCO). DESIGN: All medical and prescription claims for Medicaid MCO enrollees receiving at least one prescription for a COX-2 or NSAID between January 2000 and June 2002 were retrieved. Selected for study were adults claiming at least one COX-2 prescription or NSAID prescription with a minimum 30 days of supply after June 2000; having 60 total days of supply or more over the study period was also required for study inclusion. The probability of being prescribed a COX-2 was estimated as a logistic function of patient age, gender, race, city/suburban/rural residence, and history of rheumatoid arthritis, osteoarthritis, chronic back pain, acute pains, gastrointestinal problems, use of anticoagulants or corticosteroids, and comorbidities. RESULTS: Of the 16,868 enrollees meeting the selection criteria, 4,005 (24%) were prescribed a COX-2 and 12,863 another NSAID. Half of those studied were African American, three-quarters were female, and a third were 50-64 years old. After adjusting for confounders, odds of a COX-2 prescription were a third less for African Americans and other races compared to Caucasians (OR, 0.67; 95% confidence intervals, 0.62-0.73). CONCLUSION: Patient race is a significant predictor of COX-2 prescriptions in the Medicaid population, even after adjusting for other demographic and clinical variables. Cost to the patient was not a factor, as the patient copayment was 1 US dollar for any prescription

39. SMITH JR: Management of uveitis. Clinical and Experimental Medicine 4:1 21-29, 2004
    Abstract: Uveitis is a group of inflammatory eye diseases that cause substantial visual disability and present challenges to diagnosis and treatment. Immune-mediated subtypes of uveitis must be distinguished from infections and malignant forms of the disease, and systemic associations of an ocular inflammation must be recognized. Clinical examination, rather than screening by a series of laboratory and radiological investigations, is generally the key to making the correct diagnosis. Treatment of many forms of immune-mediated uveitis involves immunosuppressive agents, which may be administered locally o r systemically. The introduction of biological agents and novel methods for drug delivery are providing further therapeutic options for patients with recalcitrant disease. This review focuses on the common specific forms of uveitis, and describes current and potential future treatment practices

40. TAUBER T, DANIEL D, BARASH J, TURETZ J, MORAD Y: Optic neuritis associated with etanercept therapy in two patients with extended oligoarticular juvenile idiopathic arthritis. Rheumatology (Oxford) 44:3 405, 2005

41. VILLANUEVA J, LEE S, GIANNINI EH, GRAHAM TB, PASSO MH, FILIPOVICH A, GROM AA: Natural killer cell dysfunction is a distinguishing feature of systemic onset juvenile rheumatoid arthritis and macrophage activation syndrome. Arthritis Res Ther 7:1 R30-R37, 2005
    Organism: 1Division of Hematology/Oncology, Children's Hospital Medical Center, Cincinnati, Ohio, USAFAU - Villanueva, Joyce
    Abstract: Macrophage activation syndrome (MAS) has been reported in association with many rheumatic diseases, most commonly in systemic juvenile rheumatoid arthritis (sJRA). Clinically, MAS is similar to hemophagocytic lymphohistiocytosis (HLH), a genetic disorder with absent or depressed natural killer (NK) function. We have previously reported that, as in HLH, patients with MAS have profoundly decreased NK activity, suggesting that this abnormality might be relevant to the pathogenesis of the syndrome. Here we examined the extent of NK dysfunction across the spectrum of diseases that comprise juvenile rheumatoid arthritis (JRA). Peripheral blood mononuclear cells (PBMC) were collected from patients with pauciarticular (n = 4), polyarticular (n = 16), and systemic (n = 20) forms of JRA. NK cytolytic activity was measured after co-incubation of PBMC with the NK-sensitive K562 cell line. NK cells (CD56+/T cell receptor [TCR]-alphabeta-), NK T cells (CD56+/TCR-alphabeta+), and CD8+ T cells were also assessed for perforin and granzyme B expression by flow cytometry. Overall, NK cytolytic activity was significantly lower in patients with sJRA than in other JRA patients and controls. In a subgroup of patients with predominantly sJRA, NK cell activity was profoundly decreased: in 10 of 20 patients with sJRA and in only 1 of 20 patients with other JRA, levels of NK activity were below two standard deviations of pediatric controls (P = 0.002). Some decrease in perforin expression in NK cells and cytotoxic T lymphocytes was seen in patients within each of the JRA groups with no statistically significant differences. There was a profound decrease in the proportion of circulating CD56bright NK cells in three sJRA patients, a pattern similar to that previously observed in MAS and HLH. In conclusion, a subgroup of patients with JRA who have not yet had an episode of MAS showed decreased NK function and an absence of circulating CD56bright population, similar to the abnormalities observed in patients with MAS and HLH. This phenomenon was particularly common in the systemic form of JRA, a clinical entity strongly associated with MAS

42. WORKIE DW, DARDZINSKI BJ, GRAHAM TB, LAOR T, BOMMER WA, O'BRIEN KJ: Quantification of dynamic contrast-enhanced MR imaging of the knee in children with juvenile rheumatoid arthritis based on pharmacokinetic modeling. Magnetic Resonance Imaging (United States ) 22:9 1201-1210, 2004
    Abstract: Improved management of arthritis requires a reliable, quantifiable, noninvasive method to monitor the degree of inflammation and therapeutic response during the early phase of the disease. For this purpose, the uptake of Gd-DTPA in the distal femoral physis and synovium in children with juvenile rheumatoid arthritis (JRA) was evaluated with a two-compartment pharmacokinetic model and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Employing a two-compartment pharmacokinetic model, the theoretical signal enhancement from Gd-DTPA enhanced dynamic 3D gradient-recalled echo (GRE) images was shown to have a simple linear relationship with tissue concentration independent of flip angle. The signal-enhancement patterns for each individual knee were found to be characterized by three pharmacokinetic parameters: k SUBep (minSUP-1), the rate constant; kSUBel (min SUP-1), the elimination rate constant; and ESUBR (min SUP-1), the initial enhancement rate, which is proportional to the transfer constant KSUPtrans (minSUP-1). Characteristic patterns were observed in the image signal intensity-time course. The initial enhancement rate, ESUBR, in regions of interest (ROIs) was found to have a wide range of variation: 5 to 38 minSUP-1 over the distal femoral physis and 1 to 10 minSUP-1 in the synovium. The ESUBR of the synovium was correlated with the ESUBR of the distal femoral physis (P<.05). In addition, the ESUBR of the synovium was correlated to the clinical outcome measures of knee swelling. Further investigation is needed to determine whether wide variations in the pharmacokinetic parameters reflect the degree of disease activity, and whether there are changes in response to therapy. This method can also be applied in adults with rheumatoid arthritis (RA) and other disorders where TSUB1-weighted contrast is used (breast cancer, brain tumors). (c) 2004 Elsevier Inc. All rights reserved

43. YAVASCAN O, AKSU N, KURUN U, BAYOL U, NUR AF: Macrophage activation syndrome due to blood transfusion in a child with systemic onset juvenile chronic arthritis
    SISTEMIK BASLANGICLI JUVENIL KRONIK ARTRITLI BIR HASTADA KAN TRANSFUZYONU SONRASI GELISEN MAKROFAJ AKTIVASYON SENDROMU. Cocuk Sagligi ve Hastaliklari Dergisi (Turkey ) 47:4 287-291, 2004
    Abstract: Macrophage activation syndrome (MAS) is a life-threatening syndrome characterized by persistent fever, hepatosplenomegaly, cytopenia, coagulopathy, hypofibrinogenemia, hyperlipidemia, rapid fall in erythrocyte sedimentation rate, high levels of serum ferritin and liver enzymes and infiltration of vital organs by non-Langerhans histiocytes. This syndrome is rapidly fatal without early diagnosis and institution of therapy. The clinical and laboratory findings that occur suddenly are characteristic. In this article, we describe a three-year-old girl with systemic onset juvenile chronic arthritis who developed MAS after blood transfusion

44. YEH TC, CHIU NC, LI WC, CHI H, LEE YJ, HUANG FY: Characteristics of primary osteomyelitis among children in a medical center in Taipei, 1984-2002. J Formos Med Assoc 104:1 29-33, 2005
    Organism: Department of Pediatrics, Mackay Memorial Hospital, Taipei, TaiwanFAU - Yeh, Ting-Chi
    Abstract: BACKGROUND AND PURPOSE: The presentation and sequelae of osteomyelitis are variable. This study evaluated the clinical manifestations and outcome of osteomyelitis in children in different age groups, and in different periods before and after the implementation of National Health Insurance (NHI). METHODS: The records of pediatric patients with osteomyelitis treated at a medical center in Taipei from 1984 to 2002 were reviewed. Clinical features, pathogens, laboratory and imaging findings, treatment, and outcome were analyzed. The patients were stratified into 3 groups based on age: infants (< or = 3 months of age), young children (between 4 months and 5 years), and older children and adolescents (> 5 years). Based on the date of implementation of the NHI program, the study period was divided into 2 stages: prior to implementation, from January 1984 to February 1995; and after implementation, from March 1995 to December 2002. RESULTS: The records of 209 patients were reviewed, including 45 infants, 77 young children, and 87 older children. The most common presenting findings were local tenderness (79%), local swelling (72%), and fever (57%). The lower limbs were the most commonly involved sites (65%). Staphylococcus aureus (34%), Mycobacterium tuberculosis (10%), Salmonella species (7%), and Pseudomonas aeruginosa (6%) were the most frequently isolated pathogens. At the time of diagnosis, abnormalities were found on radiographs in 83% of patients and on radionuclide bone scans in 86%. Surgical intervention with local debridement and curettage was performed in 102 patients (49%). Sixty five patients (31%) developed complications, including specific bony sequelae in 26 (12%). Sepsis and septic arthritis were more common in infants (p < 0.01). A history of trauma, protracted course of osteomyelitis, and surgical intervention were more common in older children and adolescents (p < 0.01). After the implementation of NHI, a larger proportion of patients had negative cultures (p < 0.01), and the mean duration of antibiotic therapy was shorter (p = 0.01). CONCLUSIONS: The clinical characteristics of osteomyelitis associated with sepsis or septic arthritis, chronic changes, and the need for surgery may differ depending on the age of the child. S. aureus, M. tuberculosis, and salmonellae were the most common pathogens in this Taiwanese series. Implementation of NHI in the more recent decade of the study period was associated with a shorter duration of intravenous antibiotic administration

45. YOKOTA S, UMEBAYASHI H, KATAKURA S, IMAGAWA T, MORI M: [Treatment of juvenile idiopathic arthritis]. Nippon Rinsho 63 Suppl 1:453-8.: 453-458, 2005
    Organism: Department of Pediatrics, Yokohama City University School of MedicineFAU - Yokota, Shunpei