bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonsteroidal antiinflammatory drugs in rheumatoid arthritis and osteoarthritis. Support for the concept of “responders” and “nonresponders”
Authors: Walker Judith S. , Sheather‐Reid Rachel B. , Carmody John J. , Day Richard O. , Vial Janet H.
Published: February 2007

Objective. A range of functional, biochemical, and psychological indicators was used to test the concept of “responders”/“nonresponders” and to seek predictors of response to 2 nonsteroidal antiinflammatory drugs in 9 patients with rheumatoid arthritis (RA) and 11 with osteoarthritis (OA).

Methods. In a balanced, randomized, doubleblind, latin‐square study design that involved four 4‐ week treatment periods, patients received ketoprofen or piroxicam (each for 2 of the 4 periods). Clinical and laboratory responses (pain, tenderness, swelling, patient and physician global assessments, acute‐phase protein levels, and disability) were assessed in the last 2 weeks of each period. Responders were those who showed >30% improvement in at least 5 of 7 measures of disease activity. Mood was also assessed.

Results. At baseline, variables were higher in RA than in OA patients. The drugs produced clear improvements in patients' visual analog scale scores, physicians' overall assessments, and patients' responses to the McGill Pain Questionnaire, as well as plasma prostaglandin concentrations. In patients with either RA or OA, responders could be distinguished from nonresponders; about one‐third of patients were unambiguous responders. In RA, there were responder nonresponder differences in lymphocyte counts, erythrocyte sedimentation rate (ESR), and levels of tumor necrosis factor α, but no differences were seen in OA patients. However, caution in interpretation of the data is necessary because of the small number of patients. Responders had improved mood scores compared with nonresponders in both disease groups. Baseline ESR and white blood cell counts were correlated with responder status in RA patients.

Conclusion. This study provides support for the responder/nonresponder concept. It also indicates that in RA, pretreatment ESR and lymphocyte counts are possibly useful indicators of therapeutic response.
Predictors of total body bone mineral density in non‐corticosteroid‐treated prepubertal children with juvenile rheumatoid arthritis
Authors: Henderson Carol J. , Specker Bonny L. , Sierra Rosa I. , Wilmott Robert W. , Lovell Daniel J. , Cawkwell Gail Dunkel , Campaigne Barbara N.
Published: February 2007

Objective. To determine the extent of significant osteopenia in prepubertal patients with juvenile rheumatoid arthritis (JRA) not treated with corticosteroids and to identify variables that are highly related to bone mineralization in this population.

Methods. In a cross‐sectional study, 48 JRA patients and 25 healthy control subjects ages 4.6–11.0 years were evaluated. Total body bone mineral density (TB BMD) was determined by Hologic dual energy x‐ray absorptiometry. All patients were prepubertal (Tanner stage I or II) and had never taken corticosteroids. For comparison, JRA patients were divided into “low” TB BMD (Z score ⩽−1) or “normal” TB BMD (Z score >‐1).

Results. The overall mean ± SD TB BMD scores did not differ between the JRA subjects (0.75 ± 0.06 gm/cm2) and controls (0.73 ± 0.07 gm/cm2; P > 0.30). However, 29.2% of the JRA patients had low TB BMD, whereas only 16% would be expected to have low TB BMD based on the standard normal distribution (goodness of fit X2 = 4.84, P = 0.01). The mean Z score for the JRA patients with low TB BMD was ‐1.43, and for those with normal TB BMD, it was 0.32. The JRA subjects with low TB BMD were significantly younger, had more active articular disease, greater physical function limitation, higher erythrocyte sedimentation rate, higher joint count severity score, lower body mass index, lower lean body mass, less participation in organized sports, and more protein and vitamin D in their diet compared with JRA patients with normal TB BMD (all P < 0.05). Using logistic regression, a model including age at JRA onset, Juvenile Arthritis Functional Assessment Report (JAFAR) score, triceps skinfold percentiles, percentage US recommended daily allowance for dietary magnesium intake, and serum 1,25‐dihydroxyvitamin D levels was able to accurately segregate 79.6% of the JRA subjects into either the low or normal TB BMD groups (X2 = 20.5, P = 0.001).

Conclusion. This study demonstrated that in a mildly to moderately ill prepubertal JRA population that had never been exposed to corticosteroids, almost 30% had significantly low TB BMD. The patients with low TB BMD had more active and severe articular disease and greater physical function limitation. Disease‐related parameters in JRA appear to exert a negative effect on bone mineralization even in prepubertal children, which can be demonstrated despite the exclusion of corticosteroid‐treated patients.
Development of validated disease activity and damage indices for the juvenile idiopathic inflammatory myopathies. I. Physician, parent, and patient global assessments
Authors: Rider Lisa G. , Miller Frederick W. , Feldman Brian M. , Perez Maria D. , Rennebohm Robert M. , Lindsley Carol B. , Zemel Lawrence S. , Wallace Carol A. , Ballinger Susan H. , Bowyer Suzanne L. , Reed Ann M. , Passo Murray H. , Katona Ildy M. , Lachenbruch Peter A.
Published: February 2007

Objective. To determine the reliability, content validity, and responsiveness of physician global assessments of disease activity and damage in the juvenile idiopathic inflammatory myopathies (IIM), and to investigate concordance among physician, parent, and patient global ratings.

Methods. Sixteen pediatric rheumatologists rated 10 juvenile IIM paper patient cases for global disease activity and damage, and assessed the importance of 51 clinical and laboratory parameters in formulating their global assessments. Then, 117 juvenile IIM patients were enrolled in a protocol to examine the relationship between Likert and visual analog scale global assessments, their sensitivity to change, and the comparability of physician, parent, and patient global ratings.

Results. Pediatric rheumatologists demonstrated excellent interrater reliability in their global assessments of juvenile IIM disease activity and damage (97.7% and 94.7% agreement among raters, respectively), and agreed on a core set of clinical parameters in formulating their judgments. Likert scale ratings correlated with those on a visual analog scale, and both were comparable in responsiveness (standardized response means −0.56 for disease activity, 0.02 [Likert] and 0.14 [visual analog] for damage, measured over 8 months). Parent global ratings of disease activity correlated with physician assessments, but were not colinear (Spearman's correlation [r] = 0.41−0.45). Patient global disease activity assessments correlated with those done by parents (r = 0.57−0.84) and physicians (r = 0.37−0.63), but demonstrated less responsiveness (standardized response means −0.21 and −0.12, respectively, over 8 months).

Conclusion. Physician global assessments of juvenile IIM disease activity and damage demonstrated high interrater reliability and were shown to be comprehensive measures. Both physician and parent disease activity assessments should be considered valuable as quantitative measures for evaluating therapeutic responses in juvenile IIM patients.
Mediastinal mass and hilar adenopathy. Rare thoracic manifestations of wegener's granulomatosis
Authors: George Teresa M. , Cash Joseph M. , Farver Carol , van Dyke Carolyn W. , Hoffman Gary S. , Sneller Michael , Derus Charles L.
Published: February 2007

Objective. To assess the frequency and characteristics of hilar and mediastinal involvement in patients with Wegener's granulomatosis (WG).

Methods. A patient with WG presented with the unusual finding of a mediastinal mass, prompting a comprehensive review of 302 patient records from 2 WG registries to obtain evidence of hilar adenopathy or mediastinal masses. Clinic progress notes and findings of chest imaging studies (routine imaging and computed tomography) were reviewed for the presence of hilar lymphadenopathy, mediastinal masses, or mediastinal lymphadenopathy. All radiographs and surgical pathology specimens from these lesions were reviewed.

Results. Six examples of mediastinal or hilar involvement (2.0%) were identified among 302 patients with WG. Three of these 6 patients had mediastinal masses. One patient with a mediastinal mass also had mediastinal lymphadenopathy. Two of the patients with mediastinal masses had lung parenchymal lesions. The remaining 3 patients had enlarged hilar lymph nodes in addition to pulmonary parenchymal lesions. All of the patients were treated with corticosteroids and cytotoxic drugs. Followup information was available on all patients. Two patients died. In the remaining 4 patients, the mediastinal mass or hilar lymphadenopathy decreased in size or resolved after 2 months of immunosuppressive therapy.

Conclusion. In the past, hilar adenopathy and/or mediastinal mass have been considered unlikely features of WG, and their presence has prompted consideration of an alternative diagnosis. Although this caution remains valuable, the present retrospective review of data from 2 large WG registries illustrates that such findings may rarely be a part of the spectrum of WG chest disease. Because these findings are uncommon, they necessitate consideration of a primary or concurrent infection or malignancy in the diagnostic evaluation.
Anticardiolipin IgG subclasses association of IgG2 with arterial and/or venous thrombosis
Authors: Sammaritano Lisa R. , Ng Sonia , Sobel Rachel , Salmon Jane E. , Lo Siu Kong , Simantov Ronit , Silverstein Roy , Furie Richard , Kaell Alan
Published: February 2007

Objective. To determine whether the presence of anticardiolipin antibodies (aCL) of a specific IgG subclass is associated with clinical complications of the antiphospholipid antibody syndrome (APS) and whether polymorphisms of Fc receptors for IgG (FcγR) with differential binding preferences contribute to an increased risk of thrombotic complications.

Methods. In 60 patients with IgG aCL, we assessed clinical complications of the APS, measured the level of antibody activity, and determined the IgG subclass distribution of aCL by a modified enzymelinked immunosorbent assay (ELISA) with murine antihuman IgG subclass monoclonal antibodies. Selective IgG subclass adsorption studies were performed to determine the relative contribution of specific IgG subclasses to overall aCL activity. Fcγ receptor IIA (FcγRIIA) genotypes of aCL patients with thrombosis and of non‐systemic lupus erythematosus controls were determined by polymerase chain reaction amplification of genomic DNA and allele‐specific probes.

Results. IgG2 aCL, detected in 75% of the patients, was the major subclass of aCL. Selective adsorption studies demonstrated that IgG2, in contrast to IgG1, was the predominant subclass responsible for aCL reactivity. IgG2 aCL was the only subclass associated with clinical complications, specifically, arterial and/or venous thrombosis (P < 0.04). The presence of FcγRIIA‐H131, a receptor expressed on platelets, monocytes, and endothelial cells and the only human FcγR which efficiently recognizes IgG2, was associated with thrombosis in aCL patients. Among 45 high‐titer (>40 GPL [IgG phospholipid] units) aCL patients with thrombosis, 40% were homozygous for FcγRIIA‐H131, compared with 25% of disease‐free controls (P = 0.042).

Conclusion. While all 4 IgG subclasses are found in autoimmune aCL, only the presence of IgG2 is significantly associated with thrombotic complications. Reactivity in aCL ELISA is largely due to the presence of IgG2 in high‐titer patients. The presence of IgG2 aCL, particularly in association with FcγRIIA‐H131, may be a useful clinical predictor of increased thrombotic risk in patients with autoimmune IgG aCL. Allelic variants of FcγRIIA with distinct capacities to interact with IgG subclasses provide a mechanism for genetic susceptibility to an autoantibody‐induced prothrombotic state.
Localization of hepatitis C virus in cutaneous vasculitic lesions in patients with type II cryoglobulinemia
Authors: Agnello Vincent , Ábel György
Published: February 2007

Objective. To investigate the role of hepatitis C virus (HCV) in the pathogenesis of the cutaneous vasculitis in patients with type II cryoglobulinemia.

Methods. Using in situ hybridization detection of HCV, we studied 6 test patients and various control subjects. Serum HCV was quantitated, cryoglobulins were analyzed by column chromatography at 37°C, and lowdensity lipoprotein (LDL) receptors on keratinocytes were detected using LDL labeled with fluorescent dye.

Results. In the cutaneous vasculitic lesions from test patients, but not control subjects, the HCV virion was found in association with IgM and IgG. HCV alone was detected in some vessel walls, and in skin and ductal epithelium and vascular endothelium in inflamed, but not normal, skin. Cryoglobulins showed HCV, monomeric IgM, and monomeric IgG, with little or no immune complexes. The extent of the lesions correlated with levels of viremia. Up‐regulation of LDL receptors on keratinocytes was detected in inflamed, but not normal, skin.

Conclusion. HCV was present in the cutaneous vasculitic lesions, most likely in complexes with IgM and IgG formed in situ. These findings and the correlation of the severity of the rash with the level of viremia suggest that HCV plays a major role in the pathogenesis of cutaneous vasculitis in these patients and strengthens the rationale for antiviral drug therapy. The presence of HCV in keratinocytes and ductal epithelial and vascular endothelial cells may be the in vivo manifestation of endocytosis of HCV by the LDL receptors that has recently been demonstrated in vitro. The upregulation of LDL receptors on keratinocytes in inflamed skin is consistent with this postulation.
Effects of inflammation and treatment on bone turnover and bone mass in polymyalgia rheumatica
Authors: Dolan A. L. , Moniz C. , Li F. , Mackintosh C. , Todd P. , Dasgupta B. , Corrigall V. , Panayi G. S.
Published: February 2007

Objective. Polymyalgia rheumatica (PMR) has an abrupt onset of inflammatory symptoms, making it a useful model for studying the effects of inflammation in bone. PMR requires corticosteroid treatment, which may itself have a detrimental effect on bone. This study used serially measured biochemical markers of bone turnover and bone density to address the relative contributions of systemic inflammation and corticosteroid therapy to bone loss.

Methods. Fifty untreated patients with PMR were randomized to receive oral prednisolone or intramuscular methylprednisolone. Biochemical bone markers (pyridinoline [PYR], deoxypyridinoline [DPYR], procollagen type I carboxy‐terminal peptide [PICP]) and bone mineral density (BMD) were measured at baseline and at 6, 12, and 24 months.

Results. The median disease duration at presentation was 12 weeks (range 5–32 weeks). Levels of urinary crosslinks were increased in patients with untreated PMR compared with controls (PYR 74.9 ± 30.0 nmole/mmole creatinine, DPYR 14.6 ± 6.4 nmoles/mmole creatinine [mean ± SD]; P = 0.0001); the PICP level was normal (115.0 ± 39.0 μg/liter). With treatment, the crosslinks levels fell and PICP levels rose within 6 months (P = 0.01). Bone resorption (PYR) correlated with untreated disease activity (erythrocyte sedimentation rate [ESR]) (r = 0.5, P = 0.003) and with interleukin‐6 levels (r = 0.48, P = 0.05). There was a significant reduction in BMD of both the hip and the spine after 12 months of treatment (P = 0.0002), with no difference between treatment groups. As the steroid dosage was reduced, bone mass improved. Initial ESR influenced the percent change in BMD at 1 year (r = 0.35, P = 0.05), while cumulative steroid dose, mean ESR, and type of steroid used did not.

Conclusion. Inflammation in PMR increases bone resorption and appears to have a more detrimental effect on bone than does low‐dose corticosteroid. If corticosteroids can be tapered and discontinued, bone loss in PMR can be a transient phenomenon.
Induction of interleukin‐1 and subsequent tissue factor expression by anti‐proteinase 3 antibodies in human umbilical vein endothelial cells
Authors: de Bandt Michel , Ollivier Véronique , Babin‐Chevaye Catherine , Khechaï Fouzi , de Prost Dominique , Hakim Jacques , Pasquier Catherine , Meyer Olivier
Published: February 2007

Objective. To assess the ability of anti‐proteinase 3 (anti‐PR3) classic antineutrophil cytoplasmic antibodies (cANCA) to stimulate endothelial expression of tissue factor (TF), which is the main initiator of the coagulation cascade that can lead to endothelial injury and thrombosis in patients with Wegener's granulomatosis.

Methods. Human umbilical vein endothelial cells (HUVEC) were grown to confluence and stimulated with affinity‐purified anti‐PR3 antibodies, Igs from healthy subjects, and endotoxin (lipopolysaccharide) as positive control.

Results. TF activity was generated in anti‐PR3‐ stimulated cells, as shown by a chromogenic test. This activity was inhibited by specific anti‐TF antibodies. TF messenger RNA (mRNA) was found in anti‐PR3‐ stimulated cells, as detected by reverse transcriptasepolymerase chain reaction, but not in cells stimulated with irrelevant human Igs or Igs from normal control sera. TF expression reached maximum levels 12 hours after exposure to the anti‐PR3 cANCA, and did not require complement. TF mRNA expression was inhibited by cycloheximide, suggesting a requirement for protein synthesis. When added to the incubation medium, interleukin‐1 (IL‐1) receptor antagonist inhibited the induced TF mRNA expression, suggesting that cANCA‐stimulated cells initiate IL‐1 synthesis. Moreover, cANCA induced IL‐lα mRNA before TF mRNA.

Conclusion. This study showed that anti‐PR3 treatment of HUVEC induces sequential expression of IL‐lα mRNA and TF mRNA, as well as their corresponding proteins. Both proteins could have pathogenic roles in the vasculitic process, since TF is the main initiator of the coagulation cascade.
In vitro induction of proinflammatory cytokine secretion by juvenile rheumatoid arthritis synovial fluid immune complexes
Authors: Jarvis James N. , Wang Wenlian , Moore Heide T. , Zhao Lin , Xu Chengsu
Published: February 2007

Objective. To characterize juvenile rheumatoid arthritis synovial fluid (SF) immune complexes and to examine their interaction with leukocytes.

Methods. SF immunoglobulin‐containing fractions were prepared by sequential chromatography on protein A and Sephacryl 300. Fractions were subdivided according to molecular weight, characterized for immunoglobulin and complement content, and incubated with either promonocytic U937 cells or normal human peripheral blood mononuclear cells (PBMC).

Results. High molecular weight SF immunoglobulin‐containing fractions stimulated the release of interleukin‐lβ (IL‐1β) from U937 cells. These same complexes stimulated tumor necrosis factor α (TNFα), IL‐lβ, IL‐6, IL‐8, and granulocytemacrophage colony‐stimulating factor (GM‐CSF) from PBMC. Lower molecular weight material was less efficient in inducing any of the cytokines. TNFα and IL‐1β were the earliest of the messenger RNAs examined to be induced by the high molecular weight complexes. However, the secretion of IL‐6, IL‐8, and GM‐CSF stimulated by the complexes was not completely dependent upon the secretion of IL‐1β. Addition of IL‐1 receptor antagonist to the cell cultures reduced GM‐CSF and IL‐6 production by 40% and IL‐8 production by 25% in PBMC.

Conclusion. SF immunoglobulin fractions contain immune complexes that vary in size, composition, and phlogistic potential. High molecular weight complexes are capable of inducing a spectrum of proinflammatory cytokines, all of which have been implicated in the pathogenesis of rhematic disease.
Osteoarthritic Lesions. Involvement of three different collagenases
Authors: Shlopov Boris V. , Lie Wen‐Rong , Mainardi Carlo L. , Cole Ada A. , Chubinskaya Susan , Hasty Karen A.
Published: February 2007

Objective. To assess the presence of fibroblast collagenase (MMP‐1), neutrophil collagenase (MMP‐8), and collagenase 3 (MMP‐13) in osteoarthritic (OA) cartilage, with particular emphasis on areas of macroscopic cartilage erosion.

Methods. Messenger RNA (mRNA) levels were assessed by reverse transcriptase‐polymerase chain reaction (RT‐PCR), in situ hybridization, and Northern blot analysis.

Results. MMP‐1 and MMP‐13 were expressed at higher levels by OA chondrocytes than by normal chondrocytes. In addition, mRNA for MMP‐8 was present in OA cartilage but not normal cartilage by PCR and Northern blot analyses. Chondrocytes from areas surrounding the OA lesion expressed greater quantities of MMP‐1 and MMP‐13 compared with normal chondrocytes, suggesting local modulation by mechanical and inflammatory factors. Tumor necrosis factor α stimulated the expression of all 3 collagenases. Retinoic acid, an agent which induces autodigestion of cartilage in vitro, stimulated only the expression of MMP‐13.

Conclusion. These findings suggest a key role of MMP‐13 and MMP‐8, as well as MMP‐1 in osteoarthritis.
Molecular diagnosis of ureaplasma urealyticum in an immunocompetent patient with destructive reactive polyarthritis
Authors: Vittecoq Olivier , Favre Sylvie , Daragon Alain , Biga Norman , Cambon‐Michot Chantal , Loët Xavier Le , Schaeverbeke Thierry , Bébéar Christiane
Published: February 2007

Polymerase chain reaction (PCR) amplification, which is a useful method for detecting infectious agents in joints, has potential utility in the molecular diagnosis of venereal‐associated arthritis. Among pathogens detected by this technique, Ureaplasma urealyticum, which is primarily associated with reactive arthritis (ReA), is also implicated in septic arthritis in immunocompromised patients. We report here a case of destructive polyarthritis, initially suggestive of septic arthritis, in an immunocompetent patient whose PCR positivity for U urealyticum DNA in one joint, in conjunction with the disease outcome and histologic findings, led to the diagnosis of destructive ReA.
Modulation of synovial cell function by somatostatin in patients with rheumatoid arthritis
Authors: Takeba Yuko , Suzuki Noboru , Takeno Mitsuhiro , Asai Tomiaki , Tsuboi Seiji , Hoshino Takashi , Sakane Tsuyoshi , Takeba Yuko , Suzuki Noboru , Takeno Mitsuhiro , Hoshino Takashi , Sakane Tsuyoshi , Asai Tomiaki , Tsuboi Seiji
Published: February 2007

Objective. To elucidate the role of neurologic, endocrine, and immune system interactions in the development of pathologic responses in patients with rheumatoid arthritis (RA), we studied somatostatin (SOM) production and somatostatin receptor (SOMR) expression in RA synovium and its function in patients with RA.

Methods. The effects of SOM on proinflammatory cytokine (interleukin‐6 [IL‐6] and IL‐8) and collagenase production by RA synovial cells were estimated by enzyme‐linked immunosorbent assay, and their messenger RNA expression was assessed by reverse transcription‐polymerase chain reaction (RT‐PCR) using limiting dilutions of the complementary DNA. The expression of SOMR by RA synovial cells was also studied by RT‐PCR. Local production of SOM was estimated by RT‐PCR and immunohistochemical staining.

Results. Physiologic concentrations (≈ 10−10M) of SOM inhibited proliferation of RA synovial cells. The production of proinflammatory cytokines and matrix metalloproteinases by RA synovial cells was also modulated by SOM. SOMR subtypes 1 and 2 were expressed on fibroblast‐like synovial cells, and the expression of SOMR‐2 was up‐regulated by proinflammatory cytokine treatment of the synovial cells from patients with RA. RA fibroblast‐like cells synthesized SOM by themselves, suggesting that SOM acts as an autocrine regulator of synovial cell function in patients with RA.

Conclusion. SOM inhibited aberrant synovial cell function in patients with RA, suggesting possible clinical applications of this neuropeptide.
Effects of recombinant human osteogenic protein 1 on the production of proteoglycan, prostaglandin E2, and interleukin‐1 receptor antagonist by human articular chondrocytes cultured in the presence of interleukin‐1β
Authors: Huch Klaus , Flechtenmacher Johannes , Wilbrink Berry , Koepp Holger E. , Mollenhauer Juergen , Thonar Eugene J.‐M. A. , Aydelotte Margaret B. , Kuettner Klaus E. , Sampath T. Kuber
Published: February 2007

Objective. Recombinant human osteogenic protein 1 (OP‐1) is an effective stimulator of human cartilage 35S‐proteoglycan synthesis. The present study was conducted to determine whether stimulation of human articular chondrocytes with OP‐1 can help overcome interleukin‐1β (IL‐1β)‐induced suppression of 35S‐proteoglycan synthesis.

Methods. Human articular chondrocytes in alginate beads were maintained for 3 days in the absence (control) or presence of IL‐1β at 0.1–100 pg/ml with or without OP‐1 at 50 ng/ml, in medium containing 10% fetal bovine serum (FBS). Incorporation of 35S‐sulfate into proteoglycans was quantified during the last 4 hours of culture and reported as counts per minute per μg DNA. Release of interleukin‐1 receptor antagonist (IL‐1Ra) and prostaglandin E2 into the medium was monitored by immunoassay.

Results. IL‐1β at 10 pg/ml caused a 60% decrease in 35S‐proteoglycan synthesis. This could be blocked by including 500 ng/ml IL‐1Ra in the medium. The presence of 50 ng/ml OP‐1 in the IL‐1β‐containing medium was effective in restoring 35S‐proteoglycan synthesis to the level of that found in cultures not treated with IL‐1β. The restorative effects of OP‐1 and IL‐1Ra were cumulative. The rate of release of prostaglandin E2 and IL‐1Ra into the medium was not affected by the presence of OP‐1.

Conclusion. Treatment of human articular chondrocytes with OP‐1 cultured in the presence of FBS is effective in overcoming the down‐regulation of proteoglycan synthesis induced by low doses of IL‐1β.
Histone‐specific Th0 and Th1 clones derived from systemic lupus erythematosus patients induce double‐stranded DNA antibody production
Authors: Voll Reinhard E. , Roth Edith A. , Girkontaite Irute , Fehr Holger , Herrmann Martin , Lorenz Hanns‐Martin , Kalden Joachim R.
Published: February 2007

Objective. To investigate whether histone‐specific T helper (Th) cells that are able to induce anti‐doublestranded DNA (anti‐dsDNA) antibodies can be isolated from patients with systemic lupus erythematosus (SLE) and to characterize the cytokine secretion pattern of such Th clones.

Methods. Peripheral blood mononuclear cells from SLE patients and healthy donors were stimulated with autologous apoptotic cell material or purified histones, expanded with interleukin‐2 (IL‐2), and cloned by limiting dilution. Histone reactivity of clones was examined by histone‐specific proliferation and cytokine release. Cytokines were determined by enzyme‐linked immunosorbent assay (ELISA) and CTLL‐2 bioassay. Induction of anti‐dsDNA antibodies was measured in cocultures of autologous B cells and Th clones by ELISA.

Results. Numerous histone‐specific T cell receptor (TCR) α/β+ Th clones were established from 2 of 3 patients with active SLE and from 1 of 2 healthy individuals. Most Th clones secreted IL‐2, interferon‐γ (IFNγ), and IL‐4, whereas some produced predominantly IL‐2 and lFNγ. Th clones that could stimulate the production of anti‐dsDNA antibodies were derived from SLE patients and from a healthy individual.

Conclusion. Th cells specific for histones may play an important role in the pathogenesis of SLE by inducing autoantibodies to dsDNA. Both Th1 and Th2 cytokines may be involved in the pathogenesis of SLE. The presence of histone‐specific Th cells in a healthy individual indicates the importance of peripheral tolerance for preventing autoimmunity to nuclear antigens.
A prospective, multicenter, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of generalized wegener's granulomatosis
Authors: Guillevin Loïc , Cordier Jean‐François , Lhote Franïois , Cohen Pascal , Jarrousse Bernard , Royer Isabelle , Lesavre Philippe , Jacquot Christian , Bindi Pascal , Bielefeld Philippe , Desson Jean‐Franïois , Détrée Frédérick , Dubois Alain , Hachulla Eric , Hoen Bruno , Jacomy Dominique , Seigneuric Christian , Lauque Dominique , Stern Marc , Longy‐Boursier Maité
Published: February 2007

Objective. To investigate the effectiveness and side effects of oral versus pulse cyclophosphamide (CYC) in combination with corticosteroids (CS) in the treatment of systemic Wegener's granulomatosis (WG).

Methods. Patients with newly diagnosed systemic WG were enrolled in a prospective, randomized trial. At the time of diagnosis, prior to randomization, every patient received a daily injection of methylprednisolone for 3 days, followed by daily oral prednisone (1 mg/kg/day) and a 0.7‐gm/m2 pulse of CYC. Patients were then randomly assigned to receive either prednisone plus intravenous pulse CYC (group A) or prednisone plus oral CYC (group B) as first‐line treatment. CYC was given for at least 1 year and was then progressively tapered and discontinued.

Results. Fifty patients were included in the study: 27 in group A and 23 in group B. At 6 months, 24 group A patients (88.9%) were in remission, versus 18 group B patients (78.3%). At the end of the trial, 18 group A patients (66.7%) and 13 group B patients (56.5%) were in remission. In group A, 66.7% of the patients experienced side effects, versus 69.6% in group B. Infectious side effects were significantly more frequent in group B (69.6%) than in group A (40.7%) (P < 0.05). The incidence of Pneumocystis carinii pneumonia was higher in oral CYC‐treated patients (30.4%) than in pulse CYC‐treated patients (11.1%). Nine group A patients (33.3%) and 10 group B patients (43.5%) died. Actuarial curves showed that relapses were significantly more frequent in group A (59.2%) than in group B (13%) (P = 0.02).

Conclusion. Our results indicate that pulse CYC is as effective as oral CYC in achieving initial remission of WG and is associated with fewer side effects and lower mortality. However, in the long term, treatment with pulse CYC does not maintain remission or prevent relapses as well as oral CYC.
Risk factors for early work disability in systemic lupus erythematosus. Results from a Multicenter Study
Authors: Partridge Alison J. , Fossel Anne H. , Karlson Elizabeth W. , Lew Robert A. , Wright Elizabeth A. , Daltroy Lawren H. , Liang Matthew H. , Straaton Karin V. , Stern Steven H. , Kavanaugh Arthur F. , Roberts W. Neal
Published: February 2007

Objective. To study the risk factors for early work disability in systemic lupus erythematosus (SLE).

Methods. A sample of 159 SLE patients who had been employed at some time since diagnosis was drawn from a multicenter study of outcome in SLE. Disease activity, organ damage, education, income, source of health insurance, and work‐related factors were measured in a standardized interview. Work disability was defined by patient self‐report of not working because of SLE. The outcome measure was current work status. Seven patients were excluded from the analysis because their choice not to work was unrelated to SLE.

Results. An average of 3.4 years after diagnosis, 40% had quit work completely, and job modification was substantial. Univariate analysis (chi‐square and t‐test) showed that significant predictors of early work disability included having a high school education or less, receiving Medicaid or having no health insurance, having a job which required more physical strength, having an income below poverty level, and having greater disease activity at diagnosis. In multivariate models, significant predictors were education level (P = 0.0004), higher physical demands of the job (P = 0.0028), and higher disease activity at diagnosis (P = 0.0078). Race, sex, cumulative organ damage at diagnosis, and disease duration were not significant.

Conclusion. Early work disability in SLE is strongly associated with some sociodemographic factors that might be amenable to intervention.
The long‐term effect of methotrexate therapy on the liver in patients with juvenile rheumatoid arthritis
Authors: Hashkes Philip J. , Balistreri William F. , Bove Kevin E. , Ballard Edgar T. , Passo Murray H.
Published: February 2007

Objective. To determine if the long‐term use of methotrexate (MTX) in juvenile rheumatoid arthritis (JRA) is associated with the development of significant liver fibrosis, and to describe the presence of risk factors for liver fibrosis in patients with JRA.

Methods. Needle biopsies of the liver were performed on a cross‐section cohort of 14 patients with JRA who had received a total cumulative dose of MTX that was either >3,000 mg or >4,000 mg/1.73 m2 of body surface area. Biopsy samples were independently graded according to the Roenigk Classification Scale by 2 pathologists. The presence of risk factors for MTX hepatotoxicity, especially biochemical abnormalities reflective of liver injury and alcohol consumption, were assessed.

Results. Thirteen biopsy samples (93%) were classified as grade I, and 1 (7%) as grade II; none demonstrated significant fibrosis. However, histologic abnormalities were found in 13 biopsy samples (93%). Only 2 patients (14%) consumed more than 1 alcoholic drink per month. Thirteen patients (93%) had biochemical abnormalities while being treated with MTX, but only 5 patients (36%) had at least 1 determination in which the aspartate or alanine aminotransferase elevation was >3 times the upper limit of normal.

Conclusion. Long‐term use of MTX for JRA does not appear to be associated with the development of significant liver fibrosis. Although nearly all patients had minor histologic changes, no significant clinical consequences were apparent. A prospective study of a larger population will more accurately define the incidence of MTX‐related liver fibrosis and appropriate monitoring guidelines in JRA.
Psychosocial outcomes and health status of adults who have had juvenile rheumatoid arthritis. A controlled, population‐based study
Authors: Peterson Lynne S. , Mason Tom , Nelson Audrey M. , O'Fallon W. Michael , Gabriel Sherine E.
Published: February 2007

Objective. The goal of this study was to evaluate the physical and psychosocial impact of juvenile rheumatoid arthritis (JRA) among a population‐based cohort of adults who had the disease during childhood, compared with a control cohort of subjects with no history of JRA.

Methods. The Rochester Epidemiology Project database was used to identify all cases of JRA (based on the American College of Rheumatology [formerly, the American Rheumatism Association] 1977 criteria) among Rochester, Minnesota residents first diagnosed between January 1, 1960 and December 31, 1993. Controls were age‐ and sex‐matched to the cases as of the date of diagnosis of JRA. A pretested postal survey was mailed to all adult cases (whose date of birth was before December 31, 1975) and matched controls from the same population, to obtain information on socioeconomic issues and functional status (using the Health Assessment Questionnaire and the Health Status Questionnaire). The complete medical records of all cases and controls were reviewed to obtain information on demographics and clinical manifestations of JRA.

Results. Of the 50 eligible cases, 44 (88%) responded to the survey. There were 102 age‐ and sexmatched controls (2–3 per case) who responded to the survey. Seventy‐three percent of the cases had pauciarticular‐onset JRA, 16% had polyarticular‐onset JRA, and 11% had systemic‐onset JRA. Average followup was 24.7 years and 24.5 years after the index date for cases and controls, respectively. Greater disability (P = 0.0002), more bodily pain (P = 0.0002), increased fatigue (P = 0.0112), poorer health perception (P = 0.0004), and decreased physical functioning (P = 0.0002) were reported by the cases compared with the controls. JRA cases reported significantly lower rates of employment (P = 0.015) and lower levels of exercise (P = 0.0002) than did controls. Level of educational achievement, annual income, health insurance status, and rate of pregnancy and childbirth were similar for both cases and controls.

Conclusion. Adults who have had JRA during childhood experience long‐term physical and psychosocial impairment.
Risk for periodontal disease in patients with longstanding rheumatoid arthritis
Authors: Käber Ulrich R. , Michel Alexander , Bolten Wolfgang W. , Gleissner Christiane , Dehne Florian , Willershausen‐Zönnchen Brita
Published: February 2007

Objective. To quantify periodontal disease in rheumatoid arthritis (RA) patients and controls, and to correlate the degree of destruction from periodontal disease and from RA

Methods. Fifty RA patients were matched for age, sex, smoking status, and oral hygiene with 101 controls. Correlations between indices of chronic destruction in periodontal disease (gingival attachment loss) and in RA (Larsen radiographic score) were determined.

Results. Patients with longstanding active RA (mean ± SD 13 ± 8 years) who were receiving treatment with disease‐modifying antirheumatic drugs (n = 46), corticosteroids (n = 38), or nonsteroidal antiinflammatory drugs (n = 43) had a higher rate of gingival bleeding (increased by 50%), greater probing depth (increased by 26%), greater attachment loss (increased by 173%), and higher number of missing teeth (increased by 29%) compared with controls. No correlation was found between the Larsen radiographic score and gingival attachment.

Conclusion. Patients with longstanding active RA have a substantially increased frequency of periodontal disease, including loss of teeth, compared with controls. Antiinflammatory treatment interferes with periodontal disease and might have masked a possible correlation between the indices of chronic destruction in RA and periodontal disease.
Effect of age and osteoarthritis on knee proprioception
Authors: Pai Yi‐Chung , Rymer W. Zev , Chang Rowland W. , Sharma Leena
Published: February 2007

Objective. To test the hypotheses that 1) knee position sense declines with age; 2) patients with osteoarthritis (OA) have worse knee position sense than elderly controls; and 3) knee position sense is correlated with functional status.

Methods. The threshold for detection of knee joint displacement was measured in 30 patients with bilateral knee OA (Kellgren/Lawrence grade ⩾2 in both knees), 29 elderly controls (who met clinical and radiographic criteria for exclusion of OA), and 25 young controls. Range of motion, laxity, radiographic severity, and functional status were also assessed.

Results. A moderate correlation was found between joint displacement detection threshold and age (r = 0.598 and r = 0.501 for the right knee and the left knee, respectively). The threshold was substantially and significantly different between the OA patients and the elderly controls. Proprioceptive impairment was associated with worse disease‐specific functional status.

Conclusion. Proprioception declines with age, and is further impaired in elderly patients with knee OA. Poor proprioception may contribute to functional impairment in knee OA.
Improving medication compliance for juvenile rheumatoid arthritis and its effect on clinical outcome: A single‐subject analysis
Authors: Rapoff Michael A. , Purviance Mark R. , Lindsley Carol B.
Published: February 2007

Compliance with regimens for chronic childhood diseases such as juvenile rheumatoid arthritis (JRA) is often less than optimal. This study examined the effectiveness of strategies designed to improve the medication compliance of a 14‐year‐old patient with JRA. A withdrawal (single‐subject) design with repeated measures of compliance and clinical outcome was used to evaluate the compliance‐improvement strategies. Positive reinforcement behavioral strategies were most effective in improving compliance when compared with baseline and a simplified regimen condition. Compliance changes were maintained during a nine‐month follow‐up period. Although clinical outcome results were not as straight forward, there seemed to be a trend toward improvement in symptoms, which was associated with higher compliance levels.
Social environment in families of children with juvenile arthritis
Authors: Myones Barry L. , Williams Gordon F. , Billings Andrew , Miller John J.
Published: February 2007

The Family Environment Scale (FES) was used to study 50 families of children with juvenile arthritis (JA). The FES was administered to all family members over age 10. Interpersonal relationships among family members were evaluated by the cohesion, expressiveness, and conflict subscales of the FES, and personal development was indexed by the FES independence subscale. The family scores in each subscale were compared with normative data from 1,125 families from the San Francisco Bay Area comparable with study families in age, education, number of children, and socio‐economic status.

No significant differences (t tests) were found in family cohesion, expressiveness, conflict, or independence in families of children with JA compared with control families when using the FES. These data do not support the hypothesis that psychosocial distress in families precedes or inevitably results from development of arthritis in a child.
Five‐minute walking test of aerobic fitness for people with arthritis
Authors: Price Linda G. , Hewett John E. , Kay Donald R. , Minor Marian A.
Published: February 2007

To determine if a five‐minute walking field test can be a valid indicator of cardiorespiratory fitness in patients with arthritis, distances walked were examined in relation to directly measured maximum oxygen consumption values. Pre‐ and post‐exercise intervention data were obtained from five arthritis patients taking part in a larger exercise—arthritis research project. Correlations of r =.87 (P = 0.05) for both pre‐ and post‐exercise measures suggest that the 5‐minute walk is a valid field method for assessing relative cardiorespiratory fitness in arthritis patients. Further, compared to the longer traditional field test protocols, a shortened walking time is a safe, more realistic, and appropriate approach for field testing populations with low exercise tolerance such as arthritis patients.
Arthritis appraisal and ways of coping. Scale development
Authors: Regan Catherine A. , Lorig Kate , Thoresen Carl E.
Published: February 2007

An instrument was developeted to measure appraisal and coping in older people with osteoarthritis (OA). Based on the Lazarus‐Folkman model of stress and coping, our Arhtritis Appraisal and Ways of coping scale assessed the primary appraisal (perception of harm/loss) and coping thoughts and actions of OAs in response to specific incidents of pain. Factor analysis of the scores of 151 persons with osteoarthritis produced five coping subscales: dependency, adapting, distancing, anger‐withdrawal, and expanding thoughts and actions. In a sample of 95 OAs, primary appraisal and coping were found to relate significantly to each other, to self‐efficacy, and to health status (pain, depression, and activity level). Use of this instrument to understand better the change processes in sucessful patient education program is discussed.
Patient education in the rheumatic diseases: A research agenda
Authors: Daltroy Lawren H. , Liang Matthew H.
Published: February 2007

Despite the explosion of research in patient education and compliance, little has been specific to rheumatology until the last few years. Many effective educational techniques can be borrowed from research on other chronic diseases. Research should be theory based, but it should also emphasize the testing of various combinations of intervention strategies. Fertile research areas include access to care, patient‐provider interaction, adherence to medical regimens, and diffusion of practical educational skills among caregivers. Common limitations in research methodology are identified and addressed in this paper.
An electromyographic analysis of the hip abductor muscles during a standing work task
Authors: Neumann Donald A. , Sobush Dennis C. , Paschke Sean , Cook Thomas M.
Published: February 2007

Research data strongly suggest that osteoarthritis of the hip occurs statistically more often on the right side. A possible contributing factor to this right‐sided bias in frequency may be that the articular cartilage on the right hip is subjected to relatively higher muscular‐based forces throughout a lifetime. As an initial attempt to study this possibility, this research examined healthy persons to determine the existence of a “dominant” hip similar to that expressed for handedness. Electromyographic (EMG) analysis was used to compare the electrical activity between the right and left hip abductor muscles during a standardized standing work task using 40 right‐handed and 40 left‐handed healthy subjects. Analysis of the data showed that the hip muscle on the side of the subject's handedness produced higher normalized EMG activity than did the opposite hip; however, the differences were not all statistically significant. The trend of this data set, however, warrants further research into a possible association between hip dominance, asymmetrical muscle use, and the development of hip osteoarthritis.
Heat‐moldable shoes for management of forefoot problems in rheumatoid arthritis
Authors: Moncur Carolee , Ward John R.
Published: February 2007

Heat‐moldable shoes (Thermold) were created as an alternative to the regular extra‐depth shoe (Extra Depth) to be used on patients whose painful forefoot conditions can not be easily ameliorated. We report our preliminary experience using this heat‐moldable, extra‐depth shoe for the treatment of painful forefeet in patients with rheumatoid arthritis (RA). Twenty‐five patients with RA, who were classified as American Congress of Rheumatology (ACR) functional classes II and III, were selected to wear heatmoldable, extra‐depth shoes on an experimental basis. All patients had been complaining of being unable to wear normal shoes or extra‐depth shoes because of pain in the forefeet. Patients were interviewed after a period of wearing their shoes (average, 5 months) to determine their level of satisfaction. All patients reported that the heat‐moldable shoes helped relieve the pain in their feet. Eighty percent of the patients reported they walked better. It appears that the heat‐moldable shoe may offer an advantage over other extra‐depth shoes in patients who have moderate to severe involvement of their forefeet with RA.
The beck depression inventory, center for epidemiological studies depression scale (CES‐D), and general well‐being schedule depression subscale in rheumatoid arthritis criterion contamination of responses
Authors: Callahan Leigh F. , Kaplan Mark R. , Pincus Theodore
Published: February 2007

Three widely used depression scales—the Beck Depression Inventory (BDI), Center for Epidemiological Studies Depression scale (CES‐D), and General Well Being Schedule depression subscale (GWB‐D)—were studied in rheumatoid arthritis (RA). Twenty‐three rheumatologists identified 19 of the 45 items on these three questionnaires as likely to differ in patients with RA and control subjects because of the presence of RA, regardless of psychological status. Responses to 13 of these 19 individual scale items, designated as “RA‐related items,” differed significantly in 41 RA patients versus 57 agematched control subjects. Only three of the other 26 items differed significantly in the two groups. These data extend evidence that responses of people with RA on widely used depression scales might be affected by somatic disease regardless of psychological status.
Hand splinting in rheumatoid arthritis. A perspective on current knowledge and directions for research
Authors: Falconer Judith
Published: February 2007

A theoretical rationale for the use of hand splints in rheumatoid arthritis and selected literature relevant to the efficacy of splints in the acutely inflamed or chronic rheumatoid joint are briefly reviewed. The purposes of this review are to provide a broad perspective on nonsurgical hand splinting and to suggest some directions for future research based on this perspective.