bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of sulfasalazine and placebo in the treatment of psoriatic arthritis. A department of veterans affairs cooperative study
Authors: Clegg Daniel O. , Reda Domenic J. , Mejias Edwin , Cannon Grant W. , Weisman Michael H. , Taylor Thomas , Budiman‐Mak Elly , Blackburn Warren D. , Vasey Frank B. , Mahowald Maren L. , Cush John J. , Schumacher H. Ralph , Silverman Stuart L. , Alepa F. Paul , Luggen Michael E. , Cohen Miriam R. , Makkena Rama , Haakenson Clair M. , Ward Richard H. , Manaster B. J. , Anderson Robert J. , Ward John R. , Henderson William G.
Published: February 2007

Objective. To determine whether sulfasalazine (SSZ) at a dosage of 2,000 mg/day is effective for the treatment of active psoriatic arthritis (PsA) resistant to nonsteroidal antiinflammatory drug therapy.

Methods. Two hundred twenty‐one patients with PsA were recruited from 15 clinics, randomized (double‐blind) to SSZ or placebo treatment, and followed up for 36 weeks. Treatment response was based on joint pain/tenderness and swelling scores and physician and patient global assessments.

Results. Longitudinal analysis revealed a trend favoring SSZ treatment (P = 0.13). At the end of treatment, response rates were 57.8% for SSZ compared with 44.6% for placebo (P = 0.05). The Westergren erythrocyte sedimentation rate declined more in the PsA patients taking SSZ than in those taking placebo (P < 0.0001). Adverse reactions were fewer than expected and were mainly due to nonspecific gastrointestinal complaints, including dyspepsia, nausea, vomiting, and diarrhea.

Conclusion. SSZ at a dosage of 2,000 mg/day is well tolerated and may be more effective than placebo in the treatment of patients with PsA.
Degradation of type II collagen, but not proteoglycan, correlates with matrix metalloproteinase activity in cartilage explant cultures
Authors: Kozaci L. Didem , Buttle David J. , Hollander Anthony P.
Published: February 2007

Objective. To determine the contribution of certain matrix metalloproteinases (MMPs) to the degradation of proteoglycan and type II collagen in cartilage.

Methods. Bovine nasal and articular cartilage explants were cultured with recombinant human interleukin‐1α (IL‐1α) for up to 4 weeks. Release of proteoglycan and type II collagen into the medium was determined by colorimetric assay and immunoassay, respectively. The activity of MMPs in the medium was assayed using a quenched fluorescent substrate, as well as with a collagen fibril assay, by zymography, and in Western immunoblots. In some experiments, the effects of specific MMP inhibitors on type II collagen degradation were studied.

Results. In cultures of nasal cartilage with IL‐1α, almost all the proteoglycan was released within the first week, whereas there was no detectable release of type II collagen for the first 2 weeks of culture. A rapid period of almost complete dissolution of the collagen occurred in the third or fourth week. MMP activity measured using a quenched fluorescent substrate was negligible during the first 2 weeks of culture but was substantially increased in the third week of culture, at the time of collagen degradation. Similarly, there was a large increase in collagenolytic activity (by collagen fibril assay) and gelatinolytic activity (by zymography) during the third week of culture. Articular cartilage cultured with IL‐1α lost proteoglycan progressively during the 4‐week period; however, there was no loss of type II collagen from the matrix in that time and no significant increase in MMP activity. The loss of type II collagen from nasal cartilage stimulated with IL‐1α was inhibited by BB87, an inhibitor of both collagenases and gelatinases, and by BB3003, a selective inhibitor of gelatinase A. In Western immunoblots, procollagenase and active interstitial collagenase could be readily detected in nasal cartilage cultures. Some procollagenase 3 and active collagenase 3 was also shown to be present.

Conclusion. MMP activity correlates with degradation of type II collagen, but not proteoglycan, in cartilage cultures. Interstitial collagenase, collagenase 3, and gelatinases are all likely to contribute to cleavage and removal of collagen from the cartilage matrix. The proteinase(s) responsible for aggrecan breakdown remains unclear.
Cd8high+ (CD57+) T cells in patients with rheumatoid arthritis
Authors: Wang Eddie C. Y. , Lawson Tom M. , Vedhara Kav , Moss Paul A. H. , Lehner Paul J. , Borysiewicz Leszek K.
Published: February 2007

Objective. To investigate the development and T cell receptor (TCR) usage of CD8+, CD57+ T cells in rheumatoid arthritis (RA) patients.

Methods. Three‐color flow cytometry using monoclonal antibodies (MAb) to CD8, CD57 and different TCR Vβ gene products.

Results. The proportion of CD8+ T cells expressing CD57 (CD57/CD8) was significantly higher in RA patients compared with age‐matched controls. Expanded TCR Vβ populations were more frequent, and were found in both RA patient—derived CD8high+(CD57+) and CD8+, CD57– populations. TCR Vβ5+ and TCR Vβ13+ expansions were present at high frequency (5 of 26 and 7 of 26, respectively). TCR Vβ expansions in CD8high+(CD57+) lymphocytes from RA patients were significantly larger than those in age‐matched controls (expansion index 2.38 ± 0.28, n = 41 and 1.63 ± 0.09, n = 32, respectively), and were stable over time.

Conclusion. RA leads to an increase in the frequency of expanded CD8+ T cell subsets expressing selected TCR, due to expansion of TCR Vβ+ populations in CD8high+(CD57+) T cells. Their restricted TCR usage suggests potential specificity for RA antigens and, therefore, a potential role in the pathogenesis of RA.
Nitric oxide production by superficial and deep articular chondrocytes
Authors: Hayashi Takeshi , Abe Etsuko , Yamate Tomoo , Taguchi Yasuto , Jasin Hugo E.
Published: February 2007

Objective. Chondrocytes have been shown to produce large amounts of nitric oxide (NO) when appropriately stimulated with proinflammatory cytokines or bacterial lipopolysaccharide (LPS). In view of recent observations underscoring profound phenotypic differences between superficial and deep articular chondrocytes, these studies investigated NO production, inducible NO synthase (iNOS) activity, and messenger RNA (mRNA) expression of superficial and deep cartilage explants and cells.

Methods. Superficial and deep bovine and human articular cartilage explants and isolated bovine chondrocytes were cultured in the presence of stimulating cytokines or LPS. NO was measured by the Griess reagent. Inducible NOS activity was quantitated by conversion of L‐14C‐arginine to L‐14C‐citrulline. Inducible NOS mRNA expression was quantitated by reverse transcription‐polymerase chain reaction (RT‐PCR) and in situ hybridization.

Results. Superficial bovine cartilage explants stimulated with interleukin‐1α, LPS, or tumor necrosis factor α for 24 and 48 hours produced significantly more NO than did deep explants with all stimulants and at both times. Similar results were obtained with stimulated isolated superficial and deep cells. NO synthase activity, measured by the conversion of L‐14C‐arginine to L‐14C‐citrulline, paralleled NO production. Comparable results were obtained using explants from a normal human donor. Semiquantitation of iNOS mRNA by RT‐PCR showed significantly larger amounts of PCR products in superficial cells and superficial explants. These results were confirmed by in situ hybridization of explants and isolated cells.

Conclusion. Increased NO production at the cartilage surface‐synovial fluid interface may play an important role in the modulation of cartilage damage in inflammatory arthritis.
Patterns of uveitis as a guide in making rheumatologic and immunologic diagnoses
Authors: Bañares Antonio , Jover Juan A. , Fernández‐Gutiérrez Benjamín , Del Castillo Jose M. Benítez , García Javier , Vargas Emilio , Hernández‐García César
Published: February 2007

Objective. To describe the patterns of clinical presentation in a series of 407 patients with uveitis and to establish the relationship between these patterns and the final diagnosis.

Methods. Patients were referred to the Uveitis Clinic of a tertiary hospital from January 1992 to January 1996. All patients received a complete ophthalmologic examination, and a general clinical history was obtained. The current International Uveitis Study Group classification system was used for anatomic classification. To establish the final diagnosis of the most common entities causing uveitis, current diagnostic criteria were used. A discriminant analysis, with diagnostic grouping as the outcome variable and the clinical presentation features as discriminating variables, was performed.

Results. With our classification system, 66.5% of the cases could be correctly classified according to the clinical pattern and morphologic findings. By diagnostic groups, discriminant analysis showed that 75% of patients with Behçet's disease, 77.1% of those with spondylarthropathy (including inflammatory bowel disease), 33.3% of those with sarcoidosis, 97.9% of those with toxoplasmosis, 85.7% of those with Vogt‐Koyanagi‐Harada syndrome, 100% of those with herpes, and 50.4% of those with idiopathic uveitis were correctly classified. In the miscellaneous group, which included disease entities with fewer than 5 cases, 42.9% were correctly classified.

Conclusion. Rheumatologic evaluation of the patient with uveitis can be more cost‐effective if the referring ophthalmologist follows the classification system described herein, allowing a tailored approach in which only specific and necessary diagnostic tests are used.
Total lymphoid irradiation in rheumatoid arthritis. A ten‐year followup
Authors: Westhovens Rene , Verwilghen Jo , Dequeker Jan
Published: February 2007

Objective. To report the findings of a 10‐year followup of patients enrolled in a randomized trial of total lymphoid irradiation (TLI) versus chemotherapy for rheumatoid arthritis (RA).

Methods. A retrospective analysis of the charts of 19 patients who had been included in a randomized trial comparing TLI and chemotherapy for the treatment of RA.

Results. Ten years after the start of the trial, a higher number of TLI‐treated patients had died (7 of 10), compared with patients who had received chemotherapy (2 of 9). In addition, 3 of the TLI‐treated patients developed B cell—related malignancies, whereas no such malignancies developed in the control group.

Conclusion. TLI was associated with a less‐favorable long‐term outcome than chemotherapy. These data stress the importance of careful long‐term followup in experimental trials of immunosuppressive agents.
Characteristic epitope recognition pattern of autoantibodies against eukaryotic ribosomal protein L7 in systemic autoimmune diseases
Authors: Neu Elli , Hemmerich Peter H. , Peter Hans‐Hartmut , Krawinkel Ulrich , von Mikecz Anna H.
Published: February 2007

Objective. To define the epitope‐recognition pattern and the fine specificity of the autoantibody response to protein L7 in patients with rheumatic diseases.

Methods. The epitope‐recognition pattern was studied by enzyme‐linked immunosorbent assay utilizing overlapping fragments of L7. The fine specificity was examined by binding inhibition and isoelectric focusing.

Results. We observed a disease‐specific epitope‐recognition pattern of anti‐L7 autoantibodies. There was one immunodominant epitope that was recognized by all anti‐L7‐positive sera from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc). Additional recognition of minor epitopes was observed; it arises by intramolecular epitope spreading and was correlated with disease activity in SLE patients. SSc patients differed from SLE and RA patients in that their sera did not recognize certain minor epitopes. The major epitope was recognized by high‐affinity autoantibodies of limited heterogeneity. Minor epitopes were recognized by heterogeneous low‐affinity autoantibodies.

Conclusion. The anti‐L7 autoantibody response is oligoclonal. Additional B cell clones are activated by antigen during active phases of disease.
Risk factors for incident radiographic knee osteoarthritis in the elderly. The framingham study
Authors: Felson David T. , Zhang Yuqing , Hannan Marian T. , Naimark Allan , Weissman Barbara , Aliabadi Piran , Levy Daniel
Published: February 2007

Objective. Knee osteoarthritis (OA) is highly prevalent, especially in the elderly. Preventive strategies require a knowledge of risk factors that precede disease onset. The present study was conducted to determine the longitudinal risk factors for knee OA in an elderly population.

Methods. A longitudinal study of knee OA involving members of the Framingham Study cohort was performed. Weight‐bearing knee radiographs were obtained in 1983–1985 (baseline) and again in 1992–1993. Incident disease was defined as the occurrence of new radiographic OA (Kellgren and Lawrence grade ⩾2 on a 0–4 scale) in those without radiographic OA at baseline. Risk factors assessed at baseline and in the interim were tested in univariate and multivariate equations to evaluate their association with incident knee OA.

Results. Of 598 patients without knee OA at baseline (mean age 70.5 years, 63.7% women), 93 (15.6%) developed OA. After adjustment for multiple risk factors, women had a higher risk of OA than did men (adjusted odds ratio [OR] = 1.8, 95% confidence interval [95% CI] 1.1–3.1). Higher baseline body mass index increased the risk of OA (OR = 1.6 per 5‐unit increase, 95% CI 1.2–2.2), and weight change was directly correlated with the risk of OA (OR = 1.4 per 10‐lb change in weight, 95% CI 1.1–1.8). Physical activity increased the risk of OA (for those in the highest quartile, OR = 3.3, 95% CI 1.4–7.5). Smokers had a lower risk than did nonsmokers (for those who smoked an average of ⩾10 cigarettes/day, OR = 0.4, 95% CI 0.2–0.8). Factors not associated with the risk of OA included chondrocalcinosis and a history of hand OA. Weight‐related factors affected the risk of OA only in women.

Conclusion. Elderly persons at high risk of developing radiographic knee OA included obese persons, nonsmokers, and those who were physically active. The direction of weight change correlated directly with the risk of developing OA.
Cytokine concentrations in bronchoalveolar lavage fluid of patients with systemic sclerosis
Authors: Bolster Marcy B. , Ludwicka Anna , Sutherland Susan E. , Strange Charlie , Silver Richard M.
Published: February 2007

Objective. The pathophysiology of pulmonary fibrosis in patients with systemic sclerosis (SSc) is poorly understood, but a number of recent studies have demonstrated an inflammatory process involving the lower respiratory tract. The objective of the present study was to determine the concentrations of several cytokines in the bronchoalveolar lavage (BAL) fluid of patients with SSc and to assess whether the enhanced expression of certain cytokines is associated with the presence of alveolitis.

Methods. BAL was performed on patients with SSc (with or without alveolitis) and on normal control subjects. Lyophilized BAL fluid samples were assayed by enzyme‐linked immunosorbent assay for tumor necrosis factor α (TNFα), interleukin‐1α (IL‐1α), IL‐4, IL‐6, IL‐8, macrophage inflammatory protein 1α (MIP‐1α), and RANTES.

Results. There were significant differences between groups in the BAL fluid concentrations of TNFα (P = 0.0005, with levels in SSc patients with alveolitis higher than those in normal controls), IL‐8 (P = 0.006, with levels in both SSc groups higher than those in normal controls), MIP‐1α (P = 0.009, with levels in SSc patients with alveolitis higher than those in SSc patients without alveolitis and than those in normal controls), and RANTES (P = 0.03, with levels in SSc patients without alveolitis higher than those in normal controls). With the exception of RANTES, the highest levels were detected in SSc patients with alveolitis.

Conclusion. Each of these cytokines, either alone or in combination, may play an important role in the pathogenesis of pulmonary fibrosis in SSc.
An unusual case of carcinoma polyarthritis with associated vasculitis
Authors: Madiedo Jose M. Acosta , Murthy Anant , Cortese Denis A. , Cohen Marc D.
Published: February 2007

This report describes a patient who presented with an unusual polyarthritis syndrome. After extensive evaluation, squamous cell carcinoma of the lung was diagnosed. During the course of the illness, the patient developed vasculitic features and “rheumatoid‐like” nodules. Two months after the administration of combined‐modality therapy for stage IIIA non‐small cell lung carcinoma, the signs and symptoms of polyarthritis and vasculitis had disappeared completely. Ten months later, the patient remains in clinical remission. This is the first published report of simultaneous vasculitic and polyarticular manifestations in a patient with carcinoma polyarthritis.
The reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index in patients with Systemic Lupus Erythematosus
Authors: Gladman Dafna D. , Urowitz Murray B. , Goldsmith Charles H. , Fortin Paul , Ginzler Ellen , Gordon Caroline , Hanly John G. , Isenberg David A. , Kalunian Kenneth , Nived Ola , Petri Michelle , Sanchez‐Guerrero Jorge , Snaith Michael , Sturfelt Gunnar
Published: February 2007

Objective. To test the reliability of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in the assessment of patients with SLE.

Methods. Ten patients with SLE, representing a spectrum of damage and activity, were included. Each patient was examined by 6 of 10 physicians from 5 countries, representing 10 lupus clinics. The SLICC/ACR Damage Index was used to assess accumulated damage, and the SLEDAI was used to assess disease activity. The order of the patients and physicians was randomized according to a Youden square design.

Results. The SLICC/ACR Damage Index detected differences among patients (P < 0.001). There was no detectable observer difference (P = 0.933), and there was no order effect (P = 0.261). Similar results were obtained with the SLEDAI. There was concordance in the SLICC/ACR Damage Index among observers, despite a wide spectrum of disease activity detected by the SLEDAI.

Conclusion. Physicians from different centers are able to assess patients with SLE in a reproducible way, using the SLEDAI to assess disease activity and the SLICC/ACR Damage Index to assess accumulated damage.
Selective activation of the JNK/AP‐1 pathway in FAS‐mediated apoptosis of rheumatoid arthritis synoviocytes
Authors: Okamoto Kazuyoshi , Fujisawa Koushi , Hasunuma Tomoko , Kobata Tetsuji , Sumida Takayuki , Nishioka Kusuki
Published: February 2007

Objective. To evaluate the Fas‐dependent signaling pathway, we examined the involvement of protein tyrosine phosphorylation and the DNA binding activity of AP‐1 in rheumatoid arthritis (RA) cultured synovial cells.

Methods. The number of dead cells was counted after treatment with anti‐Fas antibody in the presence of protein tyrosine kinase or phosphatase inhibitor. Protein tyrosine phosphorylation in synoviocytes after Fas ligation was examined by immunoblot and immunoprecipitation analyses. The DNA binding activity of AP‐1 was examined by electrophoretic mobility shift assay.

Results. Treatment with the protein tyrosine phosphatase inhibitor, orthovanadate, significantly enhanced the apoptosis of RA synoviocytes after Fas ligation. Ligation of the Fas molecule on RA synoviocytes induced a rapid tyrosine phosphorylation of JNK (c‐Jun amino‐terminal kinase) and formation of the AP‐1 transcription factor.

Conclusion. Our results strongly suggest that the JNK/AP‐1 signaling pathway is activated during the process of Fas‐mediated apoptosis of RA synovial cells.
Enhancement of cartilage matrix protein synthesis in arthritic cartilage
Authors: Okimura Akinobu , Okada Yasunori , Makihira Seicho , Pan Haiou , Yu Li , Tanne Kazuo , Imai Kazushi , Yamada Harumoto , Kawamoto Takeshi , Noshiro Mitsuhide , Yan Weiqun , Kato Yukio
Published: February 2007

Objective. To investigate whether the synthesis of cartilage matrix protein (CMP) is enhanced in arthritic cartilage.

Methods. The content of CMP in human and pig cartilage was determined by immunoblotting, and CMP‐producing chondrocytes in osteoarthritic (OA) and rheumatoid arthritic (RA) joints were immunostained.

Results. CMP was undetectable in the condylar cartilage and disc of pigs, whereas it was abundant in the rib and tracheal cartilage of the same animals. By immunohistochemical analysis, CMP was localized in only a few chondrocytes (5%) in normal human joints, whereas numerous chondrocytes (>60%) were immunostained in RA joints. The number of CMP‐producing cells was also increased in OA cartilage (>40%). Immunoblotting analyses confirmed that the CMP content in the cartilage from OA and RA patients was much higher than that in normal cartilage.

Conclusion. These findings demonstrate that articular chondrocytes can synthesize CMP, although it is suppressed under physiologic conditions. The results also suggest that articular chondrocytes express CMP in response to arthritic stimuli.
Major role of collagen IIB in the elevation of total type II procollagen messenger RNA in the hypertrophic phase of experimental osteoarthritis
Authors: Matyas John R. , Adams Mark E. , Huang Dinqqiu , Sandell Linda J.
Published: February 2007

Objective. To define the relative contributions of procollagen IIA and IIB messenger RNA (mRNA) in the 8‐fold elevation of total (IIA + IIB) type II procollagen mRNA in cartilage from joints with early experimental osteoarthritis (OA).

Methods. Unilateral cruciate ligament transection was performed on skeletally mature animals. Total RNA was extracted from articular cartilage from control joints and from joints with experimental OA. Northern blot hybridization with oligoprobes was used to distinguish between types IIA and IIB mRNA.

Results. Levels of IIA mRNA were similar in control and experimental cartilage. Type IIB mRNA accounted for the increase in total type II mRNA expression in OA joints.

Conclusion. Although OA chondrocytes adapt to making immature forms of aggrecan proteoglycan, they do not revert to the prechondrocyte stage characterized by IIA mRNA expression.
Expansion of unusual CD4+ T cells in severe rheumatoid arthritis
Authors: Martens Peter B. , Goronzy Jörg J. , Schaid Daniel , Weyand Cornelia M.
Published: February 2007

Objective. The repertoire of T cells in patients with rheumatoid arthritis (RA) is characterized by clonal expansion of selected CD4+ T cells, which are autoreactive and lack the expression of the functionally important CD28 molecule. The goal of this study was to determine the contribution of these unusual lymphocytes to the disease process.

Methods. RA patients (n = 108) and normal controls (n = 53) were examined for the expression of CD4+CD28‐ T cells by 2‐color fluorescence‐activated cell sorter analysis. Clinical data were ascertained by retrospective chart review.

Results. The frequencies of CD4+CD28‐ T cells displayed a bimodal distribution, defining carriers and noncarriers in normal subjects and RA patients. In longitudinal studies, the noncarrier and carrier phenotypes were stable over time. Carriers of CD4+CD28‐ T cells accumulated in the RA population (64% versus 45%; P = 0.02). The expansion of CD4+CD28‐ T cells correlated with extraarticular involvement, but not with disease duration, antirheumatic treatment, or severity of joint destruction. The patient subsets with nodular disease (P = 0.02) and rheumatoid organ disease (P = 0.04) had the highest proportion of CD4+CD28‐ T cell carriers. The size of the CD4+CD28‐ compartment correlated with extraarticular progression of RA (P = 0.001 in nodular RA, P = 0.003 in rheumatoid organ disease).

Conclusion. The bimodality of distribution of CD4+CD28‐ T cell frequencies is compatible with genetic control of the generation of these unusual T cells. In RA patients, CD4+CD28‐ T cells are not an epiphenomenon of the disease process, but predispose patients to developing inflammatory lesions in extraarticular tissues.
Differential effects of aging on human chondrocyte responses to transforming growth factor β. Increased pyrophosphate production and decreased cell proliferation
Authors: Rosen Fred , McCabe Greg , Quach Jacqueline , Solan Joell , Terkeltaub Robert , Seegmiller J. Edwin , Lotz Martin
Published: February 2007

Objective. To address the influence of age on inorganic pyrophosphate (PPi) accumulation in human articular chondrocytes.

Methods. Articular cartilage was obtained from men and women in 2 different age groups: ages 15‐55 and 56‐91. The effects of transforming growth factor β1 (TGFβ1) on PPi levels in the media and cell lysates of chondrocytes were investigated. In addition, the effects of TGFβ on PPi accumulation were compared with chondrocyte proliferation.

Results. TGFβ1 increased PPi levels to a greater extent in chondrocytes from subjects in the older age group compared with those obtained from younger subjects. Treatment of chondrocytes with TGFβ1 led to a similar increase in total intracellular protein in both age groups. Although TGFβ increased nucleoside triphosphate pyrophosphohydrolase activity and decreased alkaline phosphatase activity, these effects did not differ between the 2 age groups. Analysis of the same cell preparations showed an age‐related decrease in TGFβ‐induced chondrocyte proliferation, whereas these same cells showed an increased response with respect to PPi elaboration.

Conclusion. These results show that aging differentially affected TGFβ‐induced PPi accumulation versus proliferation in human articular chondrocytes. These differences in TGFβ response are likely to contribute to the development of age‐associated cartilage diseases such as osteoarthritis.
A summary of economic evaluations published in the field of rheumatology and related disciplines
Authors: Ferraz Marcos Bosi , Maetzel Andreas , Bombardier Claire
Published: February 2007

Introduction. The relationship between the effectiveness of health care interventions and their costs is of increasing interest. The goal of the present study was to summarize the economic evaluations (EEs) published in the field of rheumatology and related disciplines, and to focus in particular on methodologic issues.

Methods. MEDLINE was searched in order to identify all relevant EEs published between 1966 and February 1995. Titles and abstracts of 1,435 articles were retrieved and independently reviewed by 2 assessors. Overall, 63 articles were identified by either assessor as being definite or possible full EEs (defined as an analysis comparing 2 or more strategies involving the assessment of both costs and consequences), and were assessed independently.

Results. Thirty‐six articles were determined to be full EEs (33 cost‐effectiveness and 3 cost‐utility analyses). Most were published in the periods 1984–1990 (31%) and 1991–1995 (61%). Main areas covered were methods of prevention (44%), treatment (31%), and treatment‐prevention (22%). Disorders most frequently studied were osteoarthritis (36%), osteoporosis (22%), and rheumatoid arthritis (14%). Direct and indirect costs were measured or estimated in 100% and 28% of the EEs, respectively. The viewpoint of the analysis was stated explicitly in 12 studies (33%). Incremental and sensitivity analyses were presented in 17 (47%) and 23 (64%), respectively. Inadequate use of economic terms was also documented.

Conclusion. The EE articles reviewed adhered partially to basic analytic methods. Economic evaluations in the field of rheumatology need to be improved to comply with current standards for the evaluation of health care interventions.
Association of a new allele of the TAP2 gene, TAP2* Bky2 (Val577), with susceptibility to Sjögren's syndrome
Authors: Kumagai Shunichi , Kanagawa Sugayo , Morinobu Akio , Takada Masami , Nakamura Kishiko , Sugai Susumu , Maruya Etsuko , Saji Hiroh
Published: February 2007

Objective. To investigate the polymorphisms of TAP (transporters associated with antigen processing) genes among patients with primary Sjögren's syndrome (SS) in order to clarify the potential association of the polymorphisms with disease susceptibility.

Methods. Polymorphisms of the TAP1 and TAP2 genes in 108 Japanese SS patients were determined by analyzing TAP genes using the polymerase chain reaction‐single‐stranded conformation polymorphism technique.

Results. The allelic frequency of the TAP1 gene was not significantly different between SS patients and normal subjects. In addition to all known TAP2 alleles, a new allele (Bky2), which had a unique substitution at codon 577 (ATG→GTG: Met→Val), was identified in both groups. The allelic frequency of Bky2 was significantly higher in SS patients (12.0%) than in normal subjects (5.1%) (P < 0.05). Moreover, a significantly greater frequency of SS‐A antibody was found among SS patients with Bky2 (18 of 23; 78%) than among those without Bky2 (33 of 85; 39%) (P = 0.001).

Conclusion. The mutation in TAP2 (Val577) may be involved in SS‐A autoantibody production and could be a genetic factor that determines susceptibility to SS.
Periosteal new bone formation in a canine neuropathic model of osteoarthritis
Authors: Myers Stephen L. , Brandt Kenneth D. , O'Connor Brian , Widmer William R. , Albrecht Marjorie
Published: February 2007

Objective. To characterize, for the first time, periosteal new bone formation in a well‐established canine model of accelerated osteoarthritis (OA) with features of neuropathic arthropathy.

Methods. Seven dogs underwent left L4‐S1 dorsal root ganglionectomy (DRG), followed 3 weeks later by transection of the anterior cruciate ligament of the ipsilateral knee (ACLT). Eight weeks thereafter, a postmortem examination was performed to assess the severity of cartilage changes of OA and the formation of new bone on the distal femur and proximal tibia in the cruciate‐deficient limb.

Results. As described previously, extensive fullthickness ulceration of the articular cartilage was present in the unstable knee of every dog. The femoral shaft immediately proximal to the condyles in the unstable limb was consistently wider (mean ± SD diameter 22.4 ± 2.2 mm) than that in the contralateral limb (19.9 ± 1.3 mm; P = 0.01). Xeroradiography and histologic examination of the distal femur revealed extensive formation of woven bone on the periosteal surfaces of the medial, lateral, and anterior aspects of the femoral shaft in the OA limb of every dog. These bony changes were not seen in radiographs of dogs that underwent DRG with the cruciate ligament left intact (n = 8) or of neurologically intact dogs that underwent ACLT (n = 7) and were examined 24 weeks after surgery.

Conclusion. Formation of new periosteal bone on the distal femur and tibia is a feature of this model of accelerated OA that is not seen in the conventional ACLT model of OA in the neurologically intact dog. This observation suggests that interruption of sensory input from the limb may affect the regulation of osteogenesis in the mechanically unstable joint.
P‐31 Magnetic resonance spectroscopy demonstrates unaltered muscle energy utilization in polymyalgia rheumatica
Authors: Mattei J. P. , Bendahan D. , Erkintalo M. , Harle J. R. , Weiller P. J. , Roux H. , Cozzone P. J.
Published: February 2007

Objective. To characterize muscle metabolic anomalies associated with polymyalgia rheumatica (PMR) using P‐31 magnetic resonance spectroscopy (MRS).

Methods. Seventeen patients with PMR and 9 age‐matched control subjects were investigated. The forearm flexor muscles were examined by P‐31 MRS in a 4.7 T superconducting horizontal magnet (Biospec Bruker 47/30) during a rest‐exercise‐recovery protocol. The intracellular pH and the relative concentrations of phosphocreatine (PCr), inorganic phosphate (Pi), ATP, and phosphomonoesters were measured every minute during the protocol. Based on the PCr and pH timedependent changes during exercise and recovery, the rates of ATP production from PCr hydrolysis, glycogenolysis, and aerobic metabolism were calculated for each minute of exercise.

Results. At rest, the metabolic parameters [PCr]: [Pi], pH, and [PCr]:[ATP] were not significantly different between the PMR patients and the control subjects. During exercise, the energetic cost and the contribution of anaerobic and oxidative pathways to energy supply were similar in the 2 groups, as were the recovery kinetics of the phosphorylated compounds and pH.

Conclusion. Muscle MRS does not confirm the findings of histologic and biochemical studies that suggest an alteration of mitochondrial function in PMR. No other modifications in glycolytic or glycogenolytic pathways or in proton handling were found that could indicate an alteration of muscle energetics in patients with PMR.
Ribozyme‐based gene cleavage approach to chronic arthritis associated with human T cell leukemia virus type I. Induction of apoptosis in synoviocytes by ablation of HTLV‐I tax protein
Authors: Kitajima Isao , Hanyu Naohiro , Kawahara Koichi , Soejima Yasuko , Maruyama Ikuro , Kubo Toshikazu , Yamada Ryo , Kaneda Yasufumi
Published: February 2007

Objective. To develop gene therapy for patients with human T cell leukemia virus type I (HTLV‐I)‐associated arthropathy (HAAP), we investigated the effects of ribozyme‐mediated cleavage of HTLV‐I tax/rex messenger RNA (mRNA) on synovial overgrowth.

Methods. We introduced 2 hammerhead ribozymes targeted against HTLV‐I tax/rex mRNA into synovial cells obtained from patients with HAAP and from patients with HTLV‐I‐negative rheumatoid arthritis (RA) and examined the ribozyme‐mediated ablation of Tax expression. Using standard methods, we also determined the cells' ability to stop proliferating and to undergo apoptosis.

Results. The ribozymes successfully cleaved tax/rex mRNA in HAAP patient synoviocytes. Both tax mRNA expression and Tax protein synthesis were inhibited significantly, resulting in inhibition of synovial cell growth and induction of apoptosis. In contrast, synovial cells from RA patients were not affected.

Conclusion. In vitro results suggest that ribozyme‐mediated gene therapy can inhibit the growth of HTLV‐I‐infected synovial cells, which is maintained by Tax protein, in HTLV‐I‐related diseases including HAAP.
Pain management in rheumatoid arthritis: Cognitive behavior modification and transcutaneous neural stimulation
Authors: Bruce James R. , Riggin Carole S. , Parker Jerry C. , Walker Sara E. , Meyer Andrew A. , Wellman Frank E. , Kunce Joseph
Published: February 2007

In order to assess the combined effects of cognitive‐behavior modification (CBM) and transcutaneous neural stimulation (TNS) on patients with rheumatoid arthritis, a pilot research project was conducted. An interrupted time‐series design was utilized with subjects serving as their own controls. Eight male rheumatoid arthritis patients were randomly assigned, two subjects each, to one of the following treatment conditions: (1) Cognitive Behavior Modification (CBM); (2) Transcutaneous Neural Stimulation (TNS); (3) CBM followed by a CBM/TNS combination; or (4) TNS followed by a CBM/TNS combination. The dependent measures included a visual analogue scale, grip strength, McGill Pain Questionnaire, and joint evaluations by a rheumatologist blind to the treatment conditions. Regarding self‐reported pain, this study found a slight superiority for the combined TNS/CBM treatments, particularly when the TNS procedures were introduced first. Further research on strategies for maximizing nonpharmacological pain management is recommended.
The N of 1 trials design in the rheumatic diseases
Authors: Giannini Edward H.
Published: February 2007

Recently the N of 1, or single case experimental trial design, has increased in popularity among physicians and therapists interested in assessing the usefulness of a therapeutic modality within a single subject [1, 2]. The techniques are not considered new; single case experimental designs have found acceptance and widespread use for many years in the behavioral sciences [3]. Additionally, experimental physiology and medicine have employed these methods extensively over the last few decades, although there is a relative paucity of articles in the clinical literature that report the results of N of 1 trials. There is a variety of design options possible for N of 1 studies, and the interested reader is referred to Reference 3 for a more comprehensive review of the topic. This paper will review a few of the major design options, with particular attention given to the alternating treatment design (ATD). The advantages and drawbacks of the N of 1 technique, with specific reference to the field of rheumatology, will be the main emphasis.
Ethnicity, self‐care, and use of medical care among the elderly with joint symptoms
Authors: Coulton Claudia J. , Milligan Sharon , Chow Julian , Haug Marie
Published: February 2007

Elderly individuals with self‐reported joint symp‐toms representing three ethnic groups (i.e., blacks [n = 105], Hispanics[n = 100], and whites of Eastern European origin [n = 112] answered questions about their use of self‐care and medical care for these symptoms. Ethnic groups differed in both self‐care practices and their use of medical care for joint symptoms. Multiple regression analyses demonstrated that arthritis‐specific and general health status were better predictors than ethnicity of the tendency to rely on self‐care and medical care. There was no evidence that self‐care served as a substitute for medical care.
Rheumatology algorithms for primary care physicians
Authors: Ambrose Richard F. , Kendall Lee G. , Alarcón Graciela S. , Brown Samuel , Lipstate James M. , Wirtschafter David D. , Jackson James R. , Glass Steven , Rossi Kevin , Margolis Carmi Z.
Published: February 2007

Primary care physicians were trained on three rheumatology topics to assess the effectiveness of an educational strategy for continuing medical education. Algorithm training was shown to be at least as effective as that based on standard prose monographs. Both training groups improved their knowledge of patient management skills but there were no statistically significant differences between groups in the amount learned. When algorithms were used to design text materials, the designed texts required less study time than did the annotated clinical algorithms alone. That difference was significant for the shoulder pain materials (P < 0.05) but not for the osteoporosis materials. The ratio of knowledge gained to study time was significantly higher for the algorithm group on the low back pain topic (P < 0.05) but not for the other topics. Taped interview problems tests were studied as a method for assessing patient management skills related to problem‐specific indicator conditions and were found to produce interrater reliability greater than 0.80 on five of the six tests.
Therapeutic ultrasound in the treatment of musculoskeletal conditions
Authors: Falconer Judith , Hayes Karen W. , Chang Rowland W.
Published: February 2007

This paper presents a quantitative synthesis of the literature addressing the effectiveness of ultrasound in selected musculoskeletal conditions. Pain and range of motion appear to improve following ultrasound treatment in acute periarticular inflammatory conditions and osteoarthritis, but not in chronic periarticular inflammatory conditions. Placebo response and experimenter expectancy bias can not be ruled out as explanations for the positive results. The literature concerning the therapeutic efficacy of ultrasound for pain and immobility in musculoskeletal conditions is therefore inconclusive. Well‐designed clinical trials are needed to resolve this question.
Pain management in the older adult with rheumatoid arthritis or osteoarthritis
Authors: Davis Gail C. , Cortez Cynthia , Rubin Bernard R.
Published: February 2007

The study's major purpose was to explore the pain management of the older adult with rheumatic disease. Medication, rest, heat, distraction, exercise, and talking with others were methods most often used by older adults (n = 31). Methods identified by them as most helpful included medication, rest, and heat. When the pain management techniques of those adults 65 and over were compared with those of younger adults (n = 51), several differences were noted. The combined number of methods used by the younger group was significantly greater, and they rated relaxation techniques as being significantly more helpful. Increasing the elderly arthritis patient's repertoire of pain management modalities and measuring the ongoing individual effectiveness of the individual and combined methods used are identified as needs to be addressed in improving pain management.
Reflex sympathetic dystrophy
Authors: Rothschild Bruce
Published: February 2007

Reflex sympathetic dystrophy, causalgia, Sudeck's atrophy, shoulder—hand syndrome, and transient osteoporosis represent a spectrum of sympathetic disturbances which typically present with regional findings. They are often pauciarticular in distribution and uniquely sensitive to timely therapeutic intervention and to preventative measures. Clinical and radiologic appearances are quite characteristic. Thermographic examination provides a valuable tool for monitoring the therapeutic response. The major factor in therapeutic efficacy is aggressive physical therapy. Although therapeusis has been facilitated by a multitude of agents, therapeutic resistance is unfortunately the circumstance, when intervention is delayed.
Counterpoint: Is patient control of treatment always appropriate?
Authors: Moncur Carolee
Published: February 2007

Health care providers often find tension and even conflict between what they consider is important for the patient to do and what the patient wants or decides to do. The current trend among patients is to assume more autonomy and freedom in the process of their care. Yet situations that commonly arise between the provider and the patient prompt the patient to refuse to accept or acquiesce to the provider's wishes or choices that are perceived by the provider to be in the patient's best interest. Under what circumstances should the provider practice beneficence in the form of paternalism at the expense of the patient's autonomy? This article explores justifiable paternalism and beneficence.
School attendance and patterns, special services and special needs in pediatric patients with rheumatic diseases: Results of a multicenter study
Authors: Lovell Daniel J. , Athreya Balu , Emery Helen M. , Gibbas Donna L. , Levinson Joseph E. , Lindsley Carol B. , Spencer Charles H. , White Patience H.
Published: February 2007

This study represents the first multicenter study of school attendance and service needs of children with rheumatic disease. Utilizing a standardized form in seven pediatric rheumatology centers, over 90% of 1135 patients were reported as attending school full time with an average of 3.9 days absent from school for health reasons during a 2‐month period (national average, 1.1 days). At least one‐third of the patients with juvenile rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, spondyloarthropathy, scleroderma, and vasculitis exceeded 1.25 days absent in 2 months (national average, + 2 SEM). Less than one‐half of the eligible school‐aged patients with rheumatic disease are receiving school‐based physical or occupational therapy and adaptive physical education services more than a decade after the passage of P.L. 94–142 (the Education for All Handicapped Children Act of 1975). Only 8% of rheumatic disease patients at least 15 years of age are receiving services by vocational and rehabilitation workers. This study documents both the ongoing need for efforts to increase school services for children with rheumatic disease and the increased frequency of school absence in childhood rheumatic disease. Suggestions are made for improving habilitative and rehabilitative school services.
The efficacy of the back school: An analysis of the literature
Authors: Keijsers Jolanda F. E. M. , Steenbakkers Mieke W. H. L. , Gerards Frans M. , Meertens Ree M.
Published: February 2007

One of the possible treatments for patients suffering from low back pain is the so‐called back school, which is of Swedish origin. Back schools offer an education and skills program in a group setting, directed toward pain management and consisting of elements of education and/or training of skills. The contents and, briefly, the efficacy of all reported and evaluated back schools in a group setting are presented. Based on the different contents of back schools and the necessity of a multidimensional approach to treating low back pain, we designed the Maastricht Back School to be a combination of all those elements about which we consider a back school should give information and/or training.
Reflex sympathetic dystrophy in children A physical therapy approach
Authors: Wesdock Kimberly A. , Stanton Robert P. , Singsen Bernhard H.
Published: February 2007

Children with reflex sympathetic dystrophy (RSD) almost always receive physical therapy as part of a multidisciplinary approach, but there is controversy about the efficacy of many alternative modalities. In a retrospective chart review of 24 females and 12 males with 49 episodes of RSD (mean age at onset, 13.4 years), the average time to correct diagnosis was 9.4 months (median, 4.2 months; range, 1–53 months). Sixteen ankles, 12 knees, eight wrists, two hips, and two shoulders were involved. Psychological assessments revealed significant abnormalities in 25 (83%) of 30 children evaluated. Thirty‐four (94%) of 36 children received physical therapy including a wide variety of nonstandardized approaches. Children with one to two episodes of RSD averaged 4.0 physical therapy modalities; unresolved cases had 8.9 modalities attempted. Time from the first RSD episode to resolution averaged 9.0 months in 69% of children. Incorrect diagnoses prolonged many initial episodes; following correct diagnosis, symptom resolution occurred in 3.1 months. Recurrences are common, and 25% of children still exhibited RSD symptoms at last follow‐up.
Combination of disease‐modifying antirheumatic drugs in the treatment of rheumatoid arthritis A survey of alabama rheumatologists
Authors: Baum Susan K. , Tracy Irene C. , Henderson Ella H. , Alarcón Graciela S.
Published: February 2007

Combinations of disease‐modifying antirheumatic drugs (DMARDs) in the treatment of rheumatoid arthritis (RA) have been recently advocated. Efficacy and toxicity data are scant. We conducted a survey of Alabama rheumatologists to determine actual practice patterns regarding combined DMARD treatment for their patients with RA. No differences were found between academic and nonacademic rheumatologists nor between users and nonusers of combination DMARDs in demographics or practice pattern profiles. The majority did report use of combination DMARD treatment, though only in a small proportion of their patients for whom the pyramid approach had failed. The combination most often employed was gold salts and antimalarials. Users, as compared to nonusers, did favor changing the classic pyramid approach for the treatment of RA, but the differences did not reach statistical significance.
A simple method to measure gait for use in arthritis clinical research
Authors: Falconer Judith , Hayes Ptkaren W.
Published: February 2007

This report describes and discusses a simple, inexpensive method to quantify step length, stride width, cadence (steps per minute), and velocity (centimeters per second) for use as outcome measures in arthritis clinical trials. The method involves footprint recordings taken during gait on pressure‐sensitive paper. Data from 42 adults with osteoarthritis of the knee and a brief review of the literature suggest that gait measurements using this method are reliable, valid, and practical.