Bibliography July 2001- BECKER-COHEN R, FRISHBERG Y: Severe reversible renal failure due to naproxen-associated acute interstitial nephritis. European Journal Of Pediatrics 2001, 160:293-295.
Organism:Division of Paediatric Nephrology, Shaare Zedek Medical Centre, Jerusalem, 91031: yaacov@md2.huji.ac.il Israel
Abstract: Acute interstitial nephritis is uncommon in children and has very rarely been described with naproxen treatment. We report the occurrence of severe acute renal failure in a 10-year-old girl with juvenile rheumatoid arthritis after 1 month of naproxen therapy. Renal biopsy showed severe acute interstitial nephritis. The patient recovered completely after discontinuation of naproxen and administration of methylprednisolone. A review of the literature regarding non-steroidal anti-inflammatory drug-associated acute interstitial nephritis is provided. Conclusion: In an era of increasing popularity of non-steroidal anti-inflammatory drugs for use in children, paediatricians should be aware of the potential renal complications of this class of drugs - BLOOM BJ: Development of diabetes mellitus during etanercept therapy in a child with systemic-onset juvenile rheumatoid arthritis. Arthritis & Rheumatism 2000, 43:2606-2608.
Organism:Pediatric Ambulatory Medicine, Hasbro Children's Hospital, 593 Eddy Street, Suite 200, Potter Building, Providence, RI, 02903 USA
Abstract: Although clinical trials of etanercept in adult and juvenile rheumatoid arthritis have generally revealed few adverse events, significant concern has arisen over the potential evolution of secondary autoimmune disease due to modulation of tumor necrosis factor. There have been few reports of such diseases developing, and none in children receiving this therapy. Reported herein is the case of a 7-year-old girl with a 3-year history of systemic-onset juvenile rheumatoid arthritis with a polyarticular course, in whom type 1 diabetes mellitus developed 5 months after the initiation of etanercept therapy - BLOOM BJ, ALARIO AJ, EISENBERG D, NELSON SM: Soluble ICAM-1 and E-selectin as markers of disease activity and endothelial activation in juvenile rheumatoid arthritis. Pediatric Research 2001, 49:14A
Organism:Hasbro Children's Hospital/Brown U., Providence, RI USA - DOLEZ c, TELEKES c, NE c, HOZA J: Nailfold capillaroscopy in paediatric rheumatology. Ceska Revmatologie 2001, 9:78-84.
Organism:Dr. P. Dolez(caron)alova, Klinika de(caron)tskeho, Dorostoveho lekarstvi 1, Ke Karlovu 2, 121 09 Praha 2
Abstract: The study objectives were twofold: 1. To develop a method of direct nailfold capillaroscopy (NFC) applicable to a wide range of paediatric patients. 2. To analyze capillaroscopy images in a representative group of healthy children and rheumatology patients using this method. We examined 157 healthy children aged 7 months to 17 years and 46 children with various diseases: juvenile idiopathic arthritis (JIA: 18), diffuse connective tissue diseases (CTD: 10), systemic lupus erythematosus (SLE: 5), primary vasculitis (Henoch-Schonlein purpura, HSP: 9, other types of vasculitis, VAS: 6) and Raynaud's disease (RS: 3). A stereomicroscope with fibreoptic illumination was used. The following parameters were analysed in the end capillary row: linear density, tortuosity, abnormal loops, avascularity and disarrangement. The mean linear density in healthy children ranged from 7.3 - 8.7 cap/mm, the tortuosity was 20 - 60 % (grade 0.8 - 1.4). In healthy children abnormal capillaries as well as avascularity were present extremely rarely, the degree of disarrangement was also low ranging from 0.7 - 1.4 in a 4-point scale. Children under 4 years of age had lower capillary counts and a higher tortuosity as well as disarrangement degree (p < 0.01). In the whole group tortuosity decreased significantly with age (p < 0.01). Patients with CTD had lower linear density (6.0 cap/mm), higher number of abnormal loops, higher avascularity as well as degree of disarrangement while children in JIA, HSP, VAS and RS groups had normal capillaroscopic findings. The NFC method presented is technically feasible in children of the widest age range. Despite a relatively high interindividual variability of capillaroscopic parameters our NFC modification provides valuable information on the presence and degree of microangiopathy, characteristic for certain rheumatic diseases in childhood. NFC should be performed routinely when diffuse connective tissue disease is suspected even in the presence of isolated Raynaud's phenomenon - DONN RP, BARRETT JH, FARHAN A, STOPFORD A, PEPPER L, SHELLEY E, DAVIES N, OLLIER WER, THOMSON W: Cytokine gene polymorphisms and susceptibility to juvenile idiopathic arthritis. Arthritis & Rheumatism 2001, 44:802-810.
Organism:EU, ARC, Oxford Road, Stopford Building, Manchester, M13 9PT UK
Abstract: Objective. To investigate the involvement of candidate cytokine genes in the pathogenesis of juvenile idiopathic arthritis (JIA). Methods. Single nucleotide polymorphisms and intragenic microsatellite markers within 8 candidate cytokine genes (interleukin-1alpha (IL-1alpha), IL-2, IL-4, IL-6, IL-10, interferon-alpha1 (IFNA1), interferon-gamma (IFNG), and interferon regulatory factor 1 (IRF-1)) were investigated in 417 Caucasian patients with clinically characterized JIA and a panel of 276 unrelated, healthy Caucasian controls, all from the United Kingdom. Results. A novel 3'-untranslated region (3'UTR) polymorphism in IRF-1 was found to be associated with susceptibility to JIA (corrected P = 0.002). No significant association with IL-1alpha, IL-2, IL-4, IL-6, IL-10, IFNA1, or IFNG was observed. Conclusion. An association between JIA and a previously unreported 3'UTR polymorphism of IRF-1 was observed. This association was not found to be specific to any particular JIA subgroup. This suggests that IRF-1 may contribute to a common pathogenesis shared by all JIA patients, regardless of clinical phenotype. This is most likely to be a genetic contribution to the chronic inflammatory process that underlies JIA pathology - DORIA AS, KISS MHB, LOTITO APN, MOLNAR LJ, DE CASTRO CC, MEDEIROS CC, CERRI GG: Juvenile rheumatoid arthritis of the knee: Evaluation with contrast-enhanced color Doppler ultrasound. Pediatr.Radiol. 2001, 31:524-531.
Organism:A.S. Doria, Department of Diagnostic Imaging, Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ont. M5G 1X8
Abstract: Background. Contrast-enhanced color Doppler ultrasonography is a non-radiation-bearing tool that can be of value for assessment of inflammatory and vascular synovial changes in juvenile rheumatoid arthritis (JRA). Objectives. To evaluate the effect of contrast-enhanced color Doppler ultrasound (US) in the evaluation of synovial changes in the knees of children with JRA. Materials and methods. Sagittal color Doppler sonograms of 31 knees in 22 patients with JRA and of 10 knees in 5 control subjects were obtained before (at baseline) and after (at peak contrast phase) intravenous injection of SHU 508. Images were assessed for overall mean pixel intensity within the synovial tissue and for peak enhancement ratios {[(mean pixel intensity values at maximum contrast enhancement-unenhanced mean pixel intensity values)/unenhanced mean pixel intensity values] x 100}. The joints were classified into three groups by clinical/laboratory criteria: group A (active disease in the knee), n = 9; group B (quiescent disease with serum chemistry levels of active disease), n = 12 and group C (remission disease), n = 10. Results. Mean color pixel intensity values were markedly increased by the use of US contrast agents in groups A (P = 0.004) and B (P = 0.0001), did not reach statistical significance in group C (P = 0.06) and remained essentially unchanged in the control group (P = 0.25). Enhancement ratios for the three groups of JRA patients were not different (P = 0.38) (mean +/- SD, 720% +/- 402 for group A, 731% +/- 703 for group B and 314% +/- 263 for group C). Conclusion. Contrast-enhanced color Doppler imaging holds promise for the detection of active synovial inflammatory disease in subclinical cases of JRA, thereby allowing earlier treatment and improved clinical outcome
Internet : andrea.doria@sickkids.on.ca - FLEDELIUS H, ZAK M, PEDERSEN FK: Refraction in juvenile chronic arthritis: A long-term follow-up study, with emphasis on myopia. Acta Ophthalmologica Scandinavica 2001, 79:237-239.
Organism:Dr. H.C. Fledelius, University Eye Clinic E 2061, Rigshospitalet, Blegdamsvej 9, DK-2100 O Copenhagen
Abstract: Objective: Assessment of refraction anomalies in juvenile chronic arthritis (JCA) on a long-term follow-up basis. Material and Methods: Sixty-five adults, 52 females and 13 males, with a history of active JCA had a complete ophthalmic evaluation including subjective refractioning on average 26.4 years after JCA onset. The age range was 22-49 years. Results: The refraction ranged from -8.12 D to +6.5 D with a mean (SD) of -0.64 (2.16) D. The mean refraction in the JCA group was significantly more towards myopia than that of a coeval adult hospital-based sample used as controls (p=0.008). Twenty-eight out of the 65 (43%) had a negative refractive value of at least 0.37 D. Myopia onset age ranged from 8 to 31 years. In those able to specify their myopia onset by first purchase of spectacles (n=25) the JCA onset had preceded the myopia, with a mean (SD) interval of 10.1 (5.4) years. Conclusion: The elevated myopia figure of 43% among JCA patients suggests an association between myopia and JCA. In lack of more precise indicators and in accordance with older literature, an explanation might be a weakening effect of chronic inflammation on scleral connective tissue
Internet : rh03217@rh.dk - HAMILTON J, CAPELL H: The treatment of juvenile arthritis. Expert Opinion on Pharmacotherapy 2001, 2:1085-1092.
Organism:J. Hamilton, Centre for Rheumatic Diseases, Royal Infirmary, 84 Castle Street, Glasgow G4 0SF
Abstract: Until recently, two different classification systems for juvenile arthritis (JA) were utilised, each with its own terminology and subclassification (Table 1) [1]. It has been recognised that particularly within the polyarticular and pauci-articular groups, many distinct subsets exist each with a different prognosis. As a result, a new classification system for JA has been developed (Table 2) [2]. It is hoped that this will allow more accurate assessment of incidence and aetiology of the various subtypes in future generations and in time will allow therapy to be targeted at those most likely to achieve benefit. Since there is a new classification system for JA, the vast majority of published clinical studies were performed using the old classification system. For the purposes of this review, unless otherwise stated, the American College of Rheumatology classification will be used. This is outlined in Table 1 with clinical features of the major subtypes described in Table 3. This review will cover current best practice and discuss future directions for research using the recent advances in the treatment of rheumatoid arthritis (RA) as a model - HAVELKA S, HALMAN L, PAVELKOVA A, VESELA M: Coincidence of Juvenile Idiopathic Arthritis (JIA) with Diffuse Idiopathic Skeletal Hyperostosis (DISH) and Ankylosing spondylitis (AS). Ceska Revmatologie 2001, 9:26-30.
Organism:Prof. S. Havelka, Reumatologicky ustav, Na Slupi 4, 128 50 Praha 2
Abstract: The authors present a report on a quite unique coincidence of three diseases in one female patient. After initial classical juvenile idiopathic arthritis with bilateral ophthalmic triad the patient developed in early adult age ankylosing spondylitis combined with diffuse idiopathic skeletal hyperostosis - JAIN V, SINGH S, SHARMA A: Keratoconjunctivitis sicca is not uncommon in children with juvenile rheumatoid arthritis. Rheumatol.Int. Berlin 2001, 20:159-162.
Organism:Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012: surjitsingh@i91.net.in India
Abstract: Keratoconjunctivitis sicca (KCS), characterised by aqueous tear deficiency, is the most common ocular complication in adult rheumatoid arthritis (RA). In juvenile rheumatoid arthritis (JRA), however, it remains under-reported. For this prospective study, 50 children with JRA were examined clinically and underwent tests for KCS (Schirmer's I and rose bengal tests, fluorescein staining, and tear film breakup time). Six children (12%) with two or more abnormal tests were diagnosed as having definite KCS, while one child with only one abnormal test was labelled with probable KCS. Five of the six (83.3%) with definite KCS were males, and three (50%) had a pauciarticular form of the disease. Two children (33.3%) with definite KCS had no ocular symptoms, five were receiving only nonsteroidal anti-inflammatory drugs, and one was additionally on methotrexate. Keratoconjunctivitis sicca appears to be a common ocular complication and all children with JRA should be screened for it with a comprehensive battery of tests - JAROS c, NE c, VENCOVSKY J: Prognostic indicators of juvenile idiopathic arthritis. Ceska Revmatologie 2001, 9:69-77.
Organism:Dr. K. Jaros(caron)ova, Reumatologicky ustav, Na Slupi 4, 128 50 Praha 2
Abstract: The authors analyze clinical and laboratory data of patients with juvenile idiopathic arthritis (JIA) which could prove useful in early detection of risk patients and could contribute to the classification of JIA. They evaluated retrospectively 185 patients with JIA whose disease lasted for 5-20 years. As to clinical parameters the onset, duration and activity of the disease, radiographic changes, functional impairment and ocular manifestations were evaluated. Some immunological factors were tested. As to genetic factors the authors investigated the polymorphism of the interleukin 1 receptor antagonist gene (IL-1Ra). The results of the investigation confirmed a great heterogeneity of JIA and justification of classification into sub-groups. In two thirds of the patients with JIA the authors confirmed persisting activity of the disease even after many years and in half of the patients slight or medium severe functional affection. The authors found a significantly higher frequency of allele 2 of the gene for IL-1Ra in the whole group with JIA as compared with healthy controls. In the sub-group of oligoarthritis allele 2 was associated with an extended form of oligoarthritis and was thus described as a prognostic indicator of poorer development of the disease. The second prognostic marker for the group of oligoarthritis was the ESR value at the onset of the disease. Chronic uveitis, a serious extraarticular manifestation of JIA, was present most frequently in persisting oligoarthritis and was associated with positive ANA. In 4 out of 16 cases uveitis developed after more than 7 years of JIA duration - JOHNSON JA, ISENBERG DA: Indications for joint replacement and its outcome in a population of patients with SLE. Lupus 2001, 10:S77
Organism:Bloomsbury Rheumatology Unit, University College London Hospitals, London UK - KAUFMANN J, HEIDE K, CLAEYS G, BOSSUYT X: Evaluation of an enzyme immunoassay for the high sensitive detection of C-reactive protein (CRP). Clinical Chemistry 2001, 47:A42
Organism:Roche Diagnostics GmbH, Penzberg Germany - KILIC c, BOSTAN O, IL E: Juvenile rheumatoid arthritis in a patient with common variable immunodeficiency. International Pediatrics 2001, 16:94-95.
Organism:Dr. S. Kilic(cedil), Uludag University Medical Faculty, Department of Paediatrics, Gorukle, Bursa 16059
Abstract: Common variable immunodeficiency (CVID) is an idiopathic state of immune dysregulation that results in impaired antibody synthesis and the development of recurrent bacterial infections. CVID patients have been known to have an increased tendency to develop autoimmune manifestations. A ten-year-old girl who had been followed as juvenile rheumatoid arthritis JRA) since 3-years-old diagnosed CVID is presented. She had recurrent upper respiratory tract infections, splenomegaly and oligoarthritis. Immunologic studies revealed that hypogammaglobulinemia, reversed CD4/CD8 ratio and deficient antibody response to tetanus antigen. CVID was diagnosed and intravenous immunoglobulin treatment (400 mg/kg every 3 weeks) was started. After two months of the therapy, she did not have any complaints and clinical examination was normal except splenomegaly - LABYAK SE, STEIN L, BLOOM B, OWENS J, LUNSFORD V: Sleep in children with juvenile rheumatoid arthritis. Sleep (Rochester) 2001, 24:A15-A16
Organism:University of North Carolina, Chapel Hill, NC USA - LEMANEK KL, KAMPS J, CHUNG NB: Empirically supported treatments in pediatric psychology: Regimen adherence. Journal of pediatric psychology 2001, 26:253-275.
Organism:Dr. K.L. Lemanek, Department of Psychology, Children's Hospital, 700 Children's Drive, Columbus, OH 43205
Abstract: Objective: To review empirical studies of psychological interventions for nonadherence to medical regimens for three chronic illnesses: asthma, juvenile rheumatoid arthritis (JRA), and type 1 diabetes. Methods: The Chambless criteria for "promising," "probably efficacious," or "well-established" were applied to 8 intervention studies on asthma, 4 on JRA, and 11 on type 1 diabetes. Results: For asthma, organizational strategies appear probably efficacious in promoting adherence, whereas educational and behavioral strategies appear promising. For JRA, behavioral strategies appear probably efficacious in improving adherence. For type 1 diabetes, multicomponent packages and operant learning procedures appear probably efficacious, whereas cognitive-behavioral strategies appear promising. No interventions were identified as "well-established." Conclusions: Future studies will need to develop adequate definitions of adherence, accurate methods of assessing adherence, and appropriate designs to evaluate multicomponent treatment programs to advance interventions to the "well-established" category
Internet : lemanekk@chi.osu.edu - LEVINSON RD, SMITH JR, HOLLAND GN, JABS DA, ROBINSON MR, WHITCUP SM, ROSENBAUM JT: Differential efficacy of tumor necrosis factor inhibition in the management of ocular inflammatory disease and associated rheumatic disease. IOVS 2001, 42:S708
Organism:Jules Stein Eye Institute, University of California, Los Angeles, CA USA - MANUEL JC: Risk and resistance factors in the adaptation in mothers of children with juvenile rheumatoid arthritis. Journal of pediatric psychology 2001, 26:237-246.
Organism:Dr. J.C. Manuel, Wake Forest Univ. School of Medicine, Department of Public Health Sciences, PHS Hawthorne, Medical Center Blvd., Winston-Salem, NC 27157
Abstract: Objective: To examine the importance of illness severity, child functional status, psychosocial stress, intrapersonal factors, stress processing, and social-ecological factors in predicting psychological symptoms among mothers of children with juvenile rheumatoid arthritis (JRA). Methods: Mothers of 92 children with JRA completed surveys while waiting with their children for physician appointments or during JRA meeting breaks. Results: Mothers reported higher mean levels of psychological symptoms than a normative group. Higher levels of psychosocial stress predicted increased psychological symptoms after accounting for disease severity and functional status. Maternal appraisal of the illness tended to moderate the relationship between illness stress and psychological symptoms, and maternal education moderated the relationship between daily hassles stress and psychological symptoms. Conclusions: These data indicate that mothers of children with JRA are at risk for psychological distress. Interventions that take into account the buffering effects of maternal education and appraisal may serve to decrease the effects of maternal stress
Internet : jmanuel@wfubmc.edu - MARTIGNETTI JA, AL AQEEL A, AL SEWAIRI W, BOUMAH CE, KAMBOURIS M, AL MAYOUF S, SHETH KV, AL EID W, DOWLING O, HARRIS J, GLUCKSMAN MJ, BAHABRI S, MEYER BF, DESNICK RJ: Mutation of the matrix metalloproteinase 2 gene (MMP2) causes a multicentric osteolysis and arthritis syndrome. Nature Genetics 2001, 28:261-265.
Organism:J.A. Martignetti, Departments of Human Genetics, Mount Sinai School of Medicine, Fifth Avenue at 100th Street, New York, NY
Abstract: The inherited osteolyses or 'vanishing bone' syndromes are a group of rare disorders of unknown etiology characterized by destruction and resorption of affected bones. The multicentric osteolyses are notable for interphalangeal joint erosions that mimic severe juvenile rheumatoid arthritis (OMIMs 166300, 259600, 259610 and 277950). We recently described an autosomal recessive form of multicentric osteolysis with carpal and tarsal resorption, crippling arthritic changes, marked osteoporosis, palmar and plantar subcutaneous nodules and distinctive facies in a number of consanguineous Saudi Arabian families. We localized the disease gene to 16q12-21 by using members of these families for a genome-wide search for homozygous-by-descent microsatellite markers. Haplotype analysis narrowed the critical region to a 1.2-cM region that spans the gene encoding MMP-2 (gelatinase A, collagenase type IV; (ref. 3). We detected no MMP2 enzymatic activity in the serum or fibroblasts of affected family members. We identified two family-specific homoallelic MMP2 mutations: R101H and Y244X. The nonsense mutation effects a deletion of the substrate-binding and catalytic sites and the fibronectin type II-like and hemopexin/TIMP2 binding domains. Based on molecular modeling, the missense mutation disrupts hydrogen bond formation within the highly conserved prodomain adjacent to the catalytic zinc ion
Internet : john.martignetti@mssm.edu - MARTINI G, BACCILIERO U, TREGNAGHI A, MONTESCO MC, ZULIAN F: Isolated temporomandibular synovitis as unique presentation of juvenile idiopathic arthritis. J.Rheumatol. 2001, 28:1689-1692.
Organism:Department of Pediatrics, University of Padua, Italy
Abstract: Temporomandibular joint (TMJ) involvement is quite frequent in juvenile idiopathic arthritis (JIA). We describe a 15-year-old girl with isolated TMJ arthritis presenting as a unique manifestation of JIA, and its successful treatment. She underwent arthroscopic synovectomy followed by intraarticular steroid injection. Early use of synovectomy and intraarticular steroids in TMJ arthritis may reduce pain, improve jaw function, and prevent irreversible deformities
Internet : PM:11469480 - MODI JR, OSTROV BE, GROH B: Definition and natural history of macrophage activation syndrome in systemic onset JRA. Pediatric Research 2001, 49:15A
Organism:Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, PA USA - PRAHALAD S, RYAN MH, SHEAR ES, THOMPSON SD, GLASS DN, GIANNINI EH: Twins concordant for juvenile rheumatoid arthritis. Arthritis & Rheumatism 2000, 43:2611-2612.
Organism:Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH USA - REIFF A, TAKEI S, SADEGHI S, STOUT A, SHAHAM B, BERNSTEIN B, GALLAGHER K, STOUT T: Etanercept therapy in children with treatment-resistant uveitis. Arthritis And Rheumatism 2001, 44:1411-1415.
Organism:Dr. A. Reiff, Division of Rheumatology, Mailstop 60, Childrens Hospital Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA 90027
Abstract: Objective. To evaluate the safety and efficacy of the tumor necrosis factor fusion protein etanercept in children with treatment-resistant uveitis. Methods. Ten children with chronic active uveitis (7 girls and 3 boys, mean age 7.5 years [range 3-12 years]) were enrolled in this prospective study. In 7 children, uveitis was associated with pauciarticular juvenile rheumatoid arthritis. Five children were antinuclear antibody positive. All patients had failed previous therapy with topical steroids and methotrexate and/or cyclosporine. All were treated with etanercept at a dosage of 0.4 mg/kg twice weekly for the first 3 months, and then, if eyes did not improve, with 25 mg twice weekly (mean 1.1 mg/kg) for at least 3 additional months. Results. At the beginning of the trial, uveitis affected 18 eyes in the 10 children. Within 3 months, 10 of 16 affected eyes (63%; P = 0.017) Showed a rapid decrease in anterior chamber cell density, including remission of uveitis in 4 eyes. In children with visual acuity of less than 20/25, 4 of 10 eyes (40%) improved. An exacerbation of uveitis during etanercept therapy occurred in only 1 child (1 of 14 eyes [7%]). Other Ocular outcome parameters, such as intraocular pressure, synechia formation, and lens clarity, remained unchanged. Following a dosage increase to an average of 1.1 mg/kg after 3 months in 7 children, no further improvement was noted. Conclusion. Our data suggest that etanercept injected subcutaneously twice a week has a beneficial effect on treatment-resistant chronic uveitis in children. Further controlled studies with etanercept in systemic or topical form are necessary to confirm its efficacy and optimal mode of administration - SCOLA MP, IMAGAWA T, BOIVIN GP, GIANNINI EH, GLASS DN, HIRSCH R, GROM AA: Expression of angiogenic factors in juvenile rheumatoid arthritis: Correlation with revascularization of human synovium engrafted into SCID mice. Arthritis & Rheumatism 2001, 44:794-801.
Organism:Division of Rheumatology, Children's Hospital Medical Center, 3333 Burnet Avenue, Pavilion Building, 2-129, Cincinnati, OH, 45229 USA
Abstract: Objective. Although increased vascularity was noted in early histopathologic studies of juvenile rheumatoid arthritis (JRA) synovium, the available data on angiogenesis in JRA are very limited. The main purposes of this study were to assess expression of the key angiogenic factors in JRA synovium, and to evaluate a SCID mouse model of JRA as an approach to study in vivo regulation of the expression of these factors in JRA. Methods. RNase protection assay was used to assess the expression of the key angiogenic factors in fresh JRA synovium and in JRA synovial tissue fragments that had been minced and then implanted into SCID mice. Vascularity of the samples was assessed by immunohistochemical staining for von Willebrand factor. Synovial specimens obtained from patients with osteoarthritis (OA) or other noninflammatory arthropathies were used as controls. Results. Detectable levels of messenger RNA for vascular endothelial growth factor and angiopoietin 1 and their respective receptors, as well as endoglin and thrombin receptors, were present in all JRA tissue specimens studied. The levels of expression of these factors in JRA tissues were significantly higher than those in tissues obtained from patients with OA or other noninflammatory arthropathies. Furthermore, increased expression of the key angiogenic factors in the fresh JRA tissues correlated with the exuberant revascularization of JRA minced tissue fragments implanted into SCID mice. This was in sharp contrast to the poor revascularization of implanted OA tissues. Conclusion. JRA synovium is characterized by high angiogenic activity. SCID mouse-human JRA synovium chimeras may provide a good approach to study the in vivo regulation of angiogenesis in JRA - SHAHIN AA, EL MOFTY SA, EL SHEIKH EA, HAFEZ HA, RAGAB OM: Power Doppler sonography in the evaluation and follow-up of knee involvement in patients with juvenile idiopathic arthritis. Zeitschrift Fur Rheumatologie 2001, 60:148-155.
Organism:Dr. A.A. Shahin, 453 Al-Ahram Street, Al-Ahram Giza
Abstract: Introduction: This study was undertaken to evaluate the role of ultrasound (US), con-ventional color (CD) and power Doppler (PD) in the detection and quantification of inflammatory signs of the knee in children with juvenile idiopathic arthritis (JIA) and to correlate these findings with patient history, clinical, laboratory and radiological findings. Patients and methods Thirty patients with JIA who had clinical signs of knee involvement as well as 15 healthy children as a control group where subjected to full clinical examination and laboratory investigations on the same day of US examination. The knee joints were evaluated with plain radiography, US, and color Doppler in 13 patients, while the remaining 17 were assessed with power Doppler. Fourteen patients were subjected to follow-up assessment. Results A highly significant difference in synovial thickening and cartilage thickness detected by US between JIA affected knees and those of controls (p<0.0001). Knee effusion was demonstrated in 93% of patients. Synovial vessles were detected by Doppler in 76.7% of patients. A significant correlation was detected between the degree of vascularity detected by PD and knee score (p<0.05), and JAFAR score (P<0.05). On comparing the findings of the follow-up with those of the initial examination, a significant positive correlation was detected between the differences in the knee score and those in synovial thickness (p<0.05), and with the vascularity scale detected by PD (p<0.05). Conclusion This study suggests the Doppler sonography as a non-invasive, low-cost, and readily available tool for the evaluation and follow-up of articular involvement in knees of JIA patients
Internet : rughe@rusys.eg.net - SHAHIN AA, EL MOFTY SA, EL SHEIKH EA, HAFEZ HA, RAGAB OM: Power Doppler sonography in the evaluation and follow-up of knee involvement in patients with juvenile idiopathic arthritis. Z.Rheumatol. 2001, 60:148-155.
Organism:Department of Rheumatology & Rehabilitation, Faculty of Medicine, Cairo University rughe@rusysegnet
Abstract: INTRODUCTION: This study was undertaken to evaluate the role of ultrasound (US), conventional color (CD) and power Doppler (PD) in the detection and quantification of inflammatory signs of the knee in children with juvenile idiopathic arthritis (JIA) and to correlate these findings with patient history, clinical, laboratory and radiological findings. PATIENTS AND METHODS: Thirty patients with JIA who had clinical signs of knee involvement as well as 15 healthy children as a control group where subjected to full clinical examination and laboratory investigations on the same day of US examination. The knee joints were evaluated with plain radiography, US, and color Doppler in 13 patients, while the remaining 17 were assessed with power Doppler. Fourteen patients were subjected to follow-up assessment. RESULTS: A highly significant difference in synovial thickening and cartilage thickness detected by US between JIA affected knees and those of controls (p < 0.0001). Knee effusion was demonstrated in 93% of patients. Synovial vessels were detected by Doppler in 76.7% of patients. A significant correlation was detected between the degree of vascularity detected by PD and knee score (p < 0.05), and JAFAR score (P < 0.05). On comparing the findings of the follow-up with those of the initial examination, a significant positive correlation was detected between the differences in the knee score and those in synovial thickness (p < 0.05), and with the vascularity scale detected by PD (p < 0.05). CONCLUSION: This study suggests the Doppler sonography as a non-invasive, low-cost, and readily available tool for the evaluation and follow-up of articular involvement in knees of JIA patients
Internet : PM:11475602 - SLOVAK ML, SLATER R, SCHOCH C, POPPLEWELL L, BEDELL V, ARBER DA, ESPINOSA R, WEN M, KARRISON T, ROWLEY JD: Relationship of 21q22-balanced aberrations to prior therapy: A report from international workshop, 21q22 subgroup. Blood 2000, 96:706a
Organism:City of Hope National Medical Center, Duarte, CA USA
Abstract: An International Workshop, on the relationship between balanced chromosomal aberrations (abn) in t-MDS/AML/ALL and prior therapy, identified 83 pts (14.8%) with balanced 21q22 abn among 560 pts collected from 17 centers. Primary diseases were 55% solid tumor, 44% hematologic malignancy & 1% juvenile rheumatoid arthritis, treated by radiation therapy (5 pts), chemotherapy (35 pts), or combined modality (39 pts); 4 incomplete cases were excluded. 52 pts presented with t-AML, 26 with t-MDS, of whom 14 progressed to t-AML, & 1 pt was unclassified. Median age at primary dx was 46.5 yrs; 36M & 43F. Common 21q abn were observed in 81% of cases (t(8;21), t(3;21), t(16;21) in 44, 16, & 4 pts, respectively). 15 other partner chromosomes were identified; AML1 involvement was confirmed in 9, indicating 21q22 is involved with gtoreq 22 different translocations. t-AML at presentation was highest (80%) in t(8;21) and lowest (37.5%) in t(3;21) pts. Dysplastic features were present in all 21q22 cases. Cumulative drug dose scores for alkylating agents (AA) & topoisomerase II inhibitors (topo II), were calculated. No specific drug exposure pattern was identified, although a higher % of t(3;21) pts were more likely to have received mitoxantrone than other 21q22 abn. Among the 6 t-AML groups, 21q22 pts had the highest mean AA score. When compared with 11q23 pts, 21q22 pts had higher AA scores (184 vs 122), lower topo II scores (127 vs 247), and when VP16 & anthracycline scores were calculated separately, both drug scores were notably lower in 21q22 pts. All 5 pts who received RT only, had t(8;21) t-AML. Median latency and overall survival (OS) for 21q22 pts were 36.9 and 14.1 months (mo), compared to 25.9 and 9.0 mo for 11q23 pts, and 32.9 and 10.1 mo for the entire t-AML/MDS cohort. Noticeable differences were observed in median OS between 21q22 pts (n=8) receiving transplant (BMT)(31 mo) compared to 21q22 pts who did not received BMT (13 mo)(p=0.19). However, data analysis of all 560 t-AML/MDS pts revealed those who received BMT did significantly better than those who never received BMT (p=0.0005). These data suggest 21q22 pts have increased exposure to AA and slightly longer latency periods when compared to other t-AML/MDSs with recurring balanced chromosomal rearrangements - SPIEGEL LR, SCHNEIDER R, LANG BA, BIRDI N, SILVERMAN ED, LAXER RM, STEPHENS D, FELDMAN BM: Early predictors of poor functional outcome in systemic-onset juvenile rheumatoid arthritis: A multicenter cohort study. Arthritis & Rheumatism 2000, 43:2402-2409.
Organism:Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario, M5G 1X8 Canada
Abstract: Objective. To examine the ability of a previously described set of criteria to predict poor functional outcome in a large, multicenter cohort of children with systemic-onset juvenile rheumatoid arthritis (JRA). Methods. All children who were diagnosed with systemic-onset JRA since 1980 at the Hospital for Sick Children (Toronto), since 1983 at the Isaac Walton Killam Hospital for Children (Halifax), and since 1981 at the Children's Hospital of Eastern Ontario (Ottawa) were evaluated. Patients were included in the study if they had been evaluated clinically within 6 months of diagnosis and had been followed up for at least 2 years. Patients were divided into 4 cohorts according to their length of followup: 2-4 years, 4-7 years, 7-10 years, and >10 years. Using previously described criteria for destructive arthritis in children with systemic-onset JRA, the patients were classified as either high risk or low risk for poor functional outcome based on the data from their 6-month visit. High-risk patients had active systemic disease (persistent fever or corticosteroid requirement for control of systemic disease) and a platelet count gtoreq600 X 109/liter. Poor outcome was defined as moderate or severe disability (defined as a score of gtoreq0.75 on the Childhood Health Assessment Questionnaire) or disease-associated death. Results. Among 122 eligible patients with systemic-onset JRA, we were able to contact 111 (91%) for outcome data. The mean followup period was 7.7 years (SD 3.7). The mean age at outcome assessment was 13.5 years (SD 5.3). There were 51 boys and 60 girls. Twenty-four patients (22%) had moderate-to-severe disability and 2 patients died; these 26 patients were considered to have had a poor outcome. We could determine risk classification for 104 patients. Twenty-four patients (23%) met the criteria for high risk at the 6-month visit. Overall, the risk of a poor functional outcome was significantly higher in the high-risk group (relative risk 3.3, 95% confidence interval (95% CI) 1.73-6.43, P = 0.0004). This risk was most marked in the cohort with >10 years of followup (relative risk 4.3, 95% CI 1.82-10.29, P = 0.006). Conclusion. The presence of active systemic disease at 6 months, as characterized by fever or the need for corticosteroids, and thrombocytosis strongly predicted the development of a poor functional outcome in these patients. This was especially apparent with long-term followup. Our study validates the previously developed prognostic criteria for systemic-onset JRA - TAKEI S, GROH D, BERNSTEIN B, SHAHAM B, GALLAGHER K, REIFF A: Safety and efficacy of high dose etanercept in treatment of juvenile rheumatoid arthritis. J.Rheumatol. 2001, 28:1677-1680.
Organism:Department of Pediatrics, Keck School of Medicine, University of Southern California, Children's Hospital Los Angeles, USA syuji@m2kufmkagoshima-uacjp
Abstract: OBJECTIVE: To evaluate safety and efficacy of high dose etanercept (> 0.8 mg/kg, maximum 25 mg subcutaneously twice weekly) (Enbrel) in children with juvenile rheumatoid arthritis (JRA) and inadequate prior response to standard dose etanercept. METHODS: Retrospective chart review of 8 children (6 girls, 2 boys, mean age 8.4 yrs, range 5-16 yrs). Five children had systemic onset, polyarticular course JRA; 2 had polyarticular onset; and one had pauciarticular onset, polyarticular course JRA. All children had failed at least 3 mo (mean 9 mo) treatment with standard dose etanercept (0.4 mg/kg SC twice a week). All 8 children had increase in the etanercept dose to at least 0.8 mg/kg (mean 1.1 mg/kg, maximum 25 mg SC twice weekly) for a mean of 7 mo (range 3-10 mo). Efficacy of high dose etanercept was evaluated by changes in joint count, laboratory data, and ability to decrease concomitant medication. RESULTS: Improvements in the joint count and laboratory findings (erythrocyte sedimentation rate, hemoglobin and platelet count) were observed in 2 of 8 (25%) children. In these 2, concomitant prednisone was reduced or discontinued. In contrast, no changes in disease activity or laboratory findings were observed in the other 6 children. Overall, high dose etanercept was well tolerated. No laboratory abnormalities were detected and no child withdrew because of adverse events. CONCLUSION: High dose etanercept is safe and well tolerated in children, but efficacy seems limited. In children with unsatisfactory response to standard dose etanercept, an increased dose or treatment prolongation may not offer any additional benefit
Internet : PM:11469478 - TUCKER LB, ASMUSSEN L, OLSON L, PASSO M, NOCTON JJ, LINDSLEY C, RABINOVICH CE, JUNG D, MILNER RA, SCHALLER JG: Health-related quality of life (HRQOL) in children with juvenile rheumatoid arthritis (JRA). Pediatric Research 2001, 49:13A
Organism:Rheumatology, BC Children's Hospital, Vancouver, BC Canada - TYNDALL A, PASSWEG J, GRATWOHL A: Haemopoietic stem cell transplantation in the treatment of severe autoimmune diseases 2000. Annals of the Rheumatic Diseases 2001, 60:702-707.
Organism:Prof. A. Tyndall, Department of Rheumatology, F. P. Spital Burgfelderstrasses 101, 4012 Basel
Abstract: An international meeting took place in Basel, Switzerland from 5 to 7 October 2000 involving 180 participants from 30 countries, with the aim of assessing the existing data on autologous haemopoietic stem cell transplantation (HSCT) in the treatment of severe autoimmune disease, and to decide on future trial planning. Data on 390 patients were presented: 260 from the EBMT/EULAR Basel European/Asian database, 87 from North America (55 from the IBMTR), 39 from Australia, and 4 others. The major disease categories and number of patients receiving transplant were: multiple sclerosis (MS) 127, systemic sclerosis (SSc) 72, rheumatoid arthritis (RA) 70, juvenile idiopathic arthritis (JIA) 36, systemic lupus erythematosus (SLE) 34, dermatomyositis/polymyositis (DM/PM) 5, idiopathic thrombocytopenic purpura (ITP) 7. Single or several cases of other autoimmune diseases were reported. Clinically significant responses were seen in two thirds of all the cases and in all disease categories, with a more accentuated trend towards relapse in JIA and RA. Treatment was associated with a significant morbidity and mortality. In the EULAR/EBMT database (71 centres in 22 countries), a mobilisation associated mortality of 1.5% and an overall procedure related mortality (actuarially adjusted at 12 months) of 9% (confidence interval 6 to 12%) were found, with significant variation between diseases. The North American data showed similar results. Higher mortalities were seen in SSc and systemic JIA, with only one death reported in RA. After presentation of the data and workshop discussion a consensus was reached on several aspects: prospective randomised phase III trials are now appropriate in SSc, MS, and RA. A protocol is ready for SSc (ASTIS Trial), concepts are clear for MS and RA. Further phase I and II data are required in SLE, JIA, and vasculitis. The need for continuing collection of all cases after mobilisation by the standardised EBMT and IBMTR data forms was emphasised
Internet : alan.tyndall@fps-basel.ch - ZELTSER R, VALLE L, TANCK C, HOLYST MM, RITCHLIN C, GASPARI AA: Clinical, histological, and immunophenotypic characteristics of injection site reactions associated with etanercept: A recombinant tumor necrosis factor alpha receptor: Fc fusion protein. Arch.Dermatol. 2001, 137:893-899.
Organism:Dr. A.A. Gaspari, Campus Box 697, 601 Elmwood Ave, Rochester, NY 14642
Abstract: Objective: To study injection site reactions (ISRs) associated with etanercept therapy. Design: Retrospective chart review, along with prospective analysis of selected patients experiencing ISRs associated with etanercept therapy. Setting: Academic rheumatology/immunology unit and dermatology clinic. Subjects: Patients with rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory seronegative arthritis, psoriatic arthritis, psoriasis, or inflammatory bowel disease. Interventions: Skin biopsy specimens were taken from selected patients experiencing ISRs. Main Outcome Measures: Incidence of IRSs and histological and immunophenotypic analysis of ISRs in 3 patients undergoing prospective study. Results: Twenty-one (20%) of 103 of all patients receiving etanercept reported ISRs, all within the first 2 months of inception of therapy. The reactions occurred 1 to 2 days after the last injection and resolved within a few days. Moreover, eventual waning of reactions was observed, with none proving to be dose limiting. Histological examination of all biopsy specimens showed an inflammatory infiltrate composed of predominantly lymphoid cells and some eosinophils, in a perivascular cuffing pattern, without evidence of leukocytoclastic vasculitis. The infiltrating lymphoid cells were predominantly activated mature (HLA-DRSUP+/CD3SUP+/CD4SUP-/CD8SUP+) cytotoxic T lymphocytes, with a small number of CD4SUP+ cells. A biopsy specimen from a recall ISR showed strong HLA-DR expression by epidermal keratinocytes. Conclusions: Injection site reactions associated with etanercept therapy are common, and may be an example of a T-lymphocyte-mediated delayed-type hypersensitivity reaction, with waning over time due to eventual induction of tolerance
Internet : anthony_gaspari@urmc.rochester.edu