bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of naproxen and acetaminophen in a two‐year study of treatment of osteoarthritis of the knee
Authors: James Williams H. , Ward John R. , Egger Marlene J. , Neuner Rosemarie , Brooks Raye H. , Clegg Daniel O. , Field Elizabeth H. , Skosey John L. , Alarcón Graciela S. , Willkens Robert F. , Paulus Harold E. , Jon Russell I. , Sharp John T. 
Published: February 2007

AbstractObjective. To compare the relative safety and efficacy of naproxen and acetaminophen in the treatment of osteoarthritis (OA) of the knee. The major outcome measures were radiographic progression and withdrawal from the trial due to lack of efficacy.Methods. One hundred seventy‐eight patients with OA of the knee were enrolled in a 2‐year prospective, controlled, double‐blind multicenter trial and were randomly assigned to receive acetaminophen (ACT) or naproxen (NPX) treatment.Results. After 6 weeks of treatment, modest improvement in pain on motion and in physician's global assessment was seen in both the ACT and the NPX groups, and the NPX group also had modest improvement in pain at rest and in 50‐foot walk time. Sixty‐two patients completed the 2‐year study. Among these patients, radiographic progression was similar in the 2 treatment groups. Withdrawal from the trial due to lack of drug efficacy was slightly more frequent among patients in the ACT group (22% versus 16%), but withdrawal due to adverse drug effects was slightly more common in the NPX group (23% versus 18%).Conclusion. The efficacy of ACT treatment and NPX treatment was similar, although it was slightly better for NPX. The toxicity rate was slightly lower with ACT. However, the high rate of withdrawal in both treatment groups suggests that neither is satisfactory for the treatment of OA.
The structure of aggrecan fragments in human synovial fluid. evidence that aggrecanase mediates cartilage degradation in inflammatory joint disease, joint injury, and osteoarthritis
Authors: Stefan Lohmander L. , Neame Peter J. , Sandy John D. 
Published: February 2007

AbstractObjective. To determine the proteolytic fragmentation patterns and N‐terminal sequence of aggrecan fragments in human synovial fluid from patients with inflammatory arthritides, joint injury, or osteoarthritis (OA).Methods. Knee synovial fluid was obtained from patients with joint injury, OA, acute pyrophosphate arthritis (pseudogout), reactive arthritis, psoriatic arthritis, or juvenile rheumatoid arthritis. Chondroitin sulfate–substituted aggrecan fragments present in the fluid were purified by cesium chloride gradient centrifugation and enzymatically deglycosylated. Core protein species were determined by N‐terminal analysis and by sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS‐PAGE) with electroblotting and detection with monoclonal antibody 3B3.Results. Samples from patients with joint injury, OA, and inflammatory joint disease all showed a similar 3‐band pattern, with core sizes of approximately 200 kd, 170 kd, and 135 kd. In all samples, diffuse immuno‐reactive products were also seen, with an apparent size of >250 kd. N‐terminal analysis of core preparations of all samples showed a consistent single predominant sequence, beginning at alanine 374 of the human aggrecan core protein.Conclusion. The aggrecan fragments present in joint fluids from patients with various inflammatory arthritides, joint injury, or OA result from a predominant cleavage of the human aggrecan core protein at the glutamate 373–alanine 374 bond within the interglobular domain, between the G1 and G2 domains. The consistent pattern of fragments seen on SDS‐PAGE and the single predominant N‐terminal sequence suggest a common degradative mechanism of aggrecan in these different joint conditions. The identity of the proteolytic agent (aggrecanase), however, remains unknown. These results appear to have important implications with regard to the development of therapies to protect cartilage from degradation in patients with joint disease.
Biased t cell receptor v gene usage in rheumatoid arthritis. oligoclonal expansion of t cells expressing vα2 genes in synovial fluid but not in peripheral blood
Authors: Bröker Barbara M. , Korthäuer Ulf , Heppt Peter , Weseloh Gerd , Camp RÜDiger De La , Kroczek Richard A. , Emmrich Frank 
Published: February 2007

AbstractObjective. To analyze the T cell receptor (TCR) variable (V) region gene usage in the rheumatoid joint.Methods. Monoclonal antibodies (MAb) were used to determine the prevalence of selected V elements on T cells in synovial fluid (SF) from rheumatoid arthritis (RA) patients and in peripheral blood (PB) from RA patients and normal controls. Vα2‐positive PB and SF T cells from 1 patient were cloned by immediated limiting‐dilution and analyzed by restriction mapping.Results. In 9 of 14 RA patients, SF was enriched in at least 1 of the selected V elements, compared with PB. TCR genes of the Vα2 family were the most frequently overrepresented in the SF (4 patients). The expanded Vα2‐positive cells were oligoclonal in SF but heterogeneic in PB.Conclusion. Our data showing biased and clonally restricted TCR elements in the rheumatoid joint indicate major histocompatibility complex–restricted antigen recognition, rather than a “superantigen,” in the pathogenesis of RA.
Reduction of leukocyte and interleukin‐1β concentrations in the synovial fluid of rheumatoid arthritis patients treated with methotrexate
Authors: Thomas Ranjeny , Carroll Graeme J. 
Published: February 2007

AbstractObjective. To examine the effect of methotrexate (MTX) on the numbers of leukocytes in the peripheral blood (PB) and synovial fluid (SF) of patients with active rheumatoid arthritis (RA).Methods. Twelve patients were treated with MTX; 5 patients not taking MTX served as controls. Samples of PB and SF were collected at 0, 1, 4, and 8 weeks of the study. Disease activity was scored, and total leukocytes, neutrophils, lymphocytes, and CD4+, CD8+, DR+, and CD25+ lymphocyte subsets were analyzed in PB and SF. Interleukin‐1β (IL‐1β) concentrations in SF were determined.Results. Patients treated with MTX showed significant clinical improvement. No change in PB leukocytes or lymphocyte subsets was observed in either patient group over the 8‐week study period. In contrast, the number of leukocytes, the number and proportion of neutrophils, and the concentration of IL‐1β in the SF of patients treated with MTX were reduced. In addition, in MTX‐treated patients, there was an appreciable decrease in SF CD8+ lymphocytes, but not CD4+, DR+, or CD25+ lymphocytes.Conclusion. These findings suggest that in RA, MTX acts, at least in part, by reducing the migration of leukocytes into the inflamed synovium. Local reduction of IL‐1β secretion may contribute to this effect.
Identification of mothers at risk for congenital heart block and other neonatal lupus syndromes in their children. comparison of enzyme‐linked immunosorbent assay and immunoblot for measurement of anti–ss‐a/ro and anti–ss‐b/la antibodies
Authors: Buyon Jill P. , Winchester Robert J. , Slade Seth G. , Arnett Frank , Copel Joshua , Friedman Deborah , Lockshin Michael D. 
Published: February 2007

AbstractObjective. To identify the fine specificity patterns of maternal anti–SS‐A/Ro and anti–SS‐B/La antibodies that are associated with the birth of a child with transient or permanent manifestations of neonatal lupus syndromes, and to suggest a predictor algorithm for use in counseling.Methods. Sera were obtained from 4 groups of mothers: 57 whose children had congenital heart block, 12 whose children had transient dermatologic or hepatic manifestations of neonatal lupus but no detectable cardiac involvement, 152 with systemic lupus erythematosus and related autoimmune diseases, who gave birth to healthy infants, and 30 with autoimmune diseases whose pregnancy resulted in miscarriage, fetal death, or early postpartum death unrelated to neonatal lupus. Antibodies to SS‐A/Ro and SS‐B/La were assessed by enzymelinked immunosorbent assay (ELISA) and by sodium dodecyl sulfate (SDS)‐immunoblot.Results. Anti–SS‐A/Ro antibodies were identified by ELISA in 100%, 91%, 47%, and 43% of the mothers of infants with heart block, with transient neonatal lupus, healthy infants, and fetal death, respectively. High titers of anti–SS‐A/Ro antibodies were present more often in mothers of children with cardiac disease or transient neonatal lupus than in either of the other 2 groups. Maternal antibodies to SS‐B/La were detected by ELISA in 76% of the heart block group, 73% of the cutaneous neonatal lupus group, 15% of the group with healthy children, and 7% of the fetal death group. On SDS‐immunoblot, sera from 91% of the heart block group mothers who had antibodies to SS‐A/Ro but not to SS‐B/La recognized at least 1 SS‐A/Ro antigen, with significantly greater reactivity against the 52‐kd component. In contrast, only 62% of the anti–SS‐A/Ro positive, anti–SS‐B/La negative responders in the healthy group recognized the 52‐kd and/or the 60‐kd component. Although there was no profile of anti–SS‐A/Ro response unique to the mothers of children with heart block or cutaneous manifestations of neonatal lupus, only 1% of the healthy infants were born to mothers with antibodies directed to both the 52‐kd SS‐A/Ro and 48‐kd SS‐B/La antigens and not to the 60‐kd SS‐A/Ro antigen.Conclusion. Women with antibodies to both SS‐A/Ro and SS‐B/La have an increased risk of giving birth to children with neonatal lupus, especially if the anti‐SS‐A/ Ro response identifies the 52‐kd component on SDS‐immunoblot. Women whose sera contain only anti‐SS‐A/Ro antibodies in low titer and only recognize determinants that are altered by conditions of SDS‐immunoblot have a low risk for giving birth to a child with neonatal lupus. Specific antibody profiles do not distinguish among the manifestations of the neonatal lupus syndromes.
Changes in the proteins coating monosodium urate crystals during active and subsiding inflammation. immunogold studies of synovial fluid from patients with gout and of fluid obtained using the rat subcutaneous air pouch model
Authors: Ortiz‐Bravo Esteban , Sieck Marie S. , Ralph Schumacher H. 
Published: February 2007

AbstractObjective. In this in vivo study, we investigated changes in the proteins that coat monosodium urate (MSU) crystals in human synovial fluid samples and rat air pouch fluid samples obtained sequentially during periods of active and resolving inflammation, in order to evaluate whether in vivo findings are consistent with hypotheses on roles of protein coating based on in vitro findings.Methods. Crystals from patients with gout were isolated from joint fluids with acute inflammation, and subsequently from the same joints at the time inflammation was resolving. Crystals were also obtained using the rat subcutaneous air pouch model. Immunogold was used to label proteins coating MSU crystals, for light microscopy (LM) and transmission electron microscopy (TEM) studies.Results. Dense immunogold–silver labeling for IgG was observed under LM on crystals from fluid with acute inflammation, whereas other proteins (apolipoproteins [Apo], fibronectin, fibrinogen, albumin) were not labeled significantly. Apo B became strongly positive on crystals as the inflammation subsided, whereas other proteins were only weakly positive and IgG became absent or weakly positive. Quantitative TEM evaluation confirmed the LM observations.Conclusion. This study provides the first in vivo evidence supporting the notion derived from previous in vitro studies that proteins coating MSU crystals change as inflammation evolves. Protein coatings may play an important role in the self‐limited nature of gouty inflammation. IgG coating MSU crystals may enhance the inflammation. As the inflammation subsides, Apo B could displace the IgG by competitively coating sites on crystals and could contribute in part to the resolution of the acute gouty arthritis.
Correlation of interleukin‐6 production and disease activity in polymyalgia rheumatica and giant cell arteritis
Authors: Roche Niall E. , Fulbright James W. , Wagner Annette D. , Hunder Gene G. , Goronzy Jörg J. , Weyand Cornelia M. 
Published: February 2007

AbstractObjective. To explore the role of proinflammatory cytokines in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR), two clinically related syndromes characterized by an intense acute‐phase reaction. In particular, to determine plasma concentrations of interleukin‐6 (IL‐6) and tumor necrosis factor α (TNFα) and to correlate changes in plasma IL‐6 levels with clinical symptoms during corticosteroid therapy.Methods. IL‐6 and TNFα concentrations were determined in plasma samples from patients with untreated PMR or GCA, and plasma IL‐6 levels were monitored in patients receiving long‐term therapy (14 months) with corticosteroids. To identify IL‐6–producing cells, the polymerase chain reaction was used to detect IL‐6 messenger RNA. In vitro production of IL‐6 and IL‐2 by peripheral blood mononuclear cells (PBMC) from treated and untreated patients was quantified using IL‐6– and IL‐2–specific bioassay systems.Results. IL‐6 concentrations were increased in PMR and GCA patients, whereas TNFα concentrations were similar to those in normal donors. Administration of corticosteroids rapidly reduced the levels of circulating IL‐6 but did not correct the underlying mechanism inducing the increased IL‐6 production. In individual patients, changes in plasma IL‐6 levels and clinical manifestations during prolonged therapy were closely correlated. Short‐term withdrawal of corticosteroids, even after several months of treatment, was followed by an immediate increase in plasma IL‐6 concentrations. To identify the cellular source of plasma IL‐6, PBMC from treated and untreated patients with PMR or GCA were analyzed for their ability to secrete IL‐6 and the T cell–specific cytokine IL‐2. Polyclonal T cell stimulation caused a rapid release of IL‐6, which was shown to be derived exclusively from CD14+ cells.Conclusion. Increased production of IL‐6, but not TNFα, is a characteristic finding in patients with PMR or GCA. Corticosteroids rapidly suppress IL‐6 production but do not correct the underlying mechanism inducing the increased IL‐6 production. The close correlation of plasma IL‐6 concentrations with clinical symptoms suggests a direct contribution of this cytokine to the disease manifestations and presents the possibility that monitoring IL‐6 levels would be useful in making decisions on adjustment of corticosteroid dosage in individual patients.
The effect of an interleukin‐1 receptor antagonist protein on type ii collagen–induced arthritis and antigen‐induced arthritis in mice
Authors: Wooley Paul H. , Whalen Janey D. , Chapman Darryl L. , Berger Ann E. , Richard Karen A. , Aspar Danielle G. , Staite Nigel D. 
Published: February 2007

AbstractObjective. To investigate the anti‐arthritic effect of recombinant human interleukin‐1 receptor antagonist protein (IRAP) in two experimental models of arthritis.Methods. Recombinant IRAP was administered daily to mice with type II collagen–induced arthritis (CIA) or with antigen‐induced arthritis (AIA) provoked by methylated bovine serum albumin (mBSA). Disease incidence and severity were assessed by a clinical index and histologic features. Serum antibody to type II collagen, spleen cell proliferation to mBSA, and anti‐IRAP antibodies were measured as indices of immune function.Results. IRAP reduced the incidence and delayed the onset of CIA and suppressed the antibody response to type II collagen. In contrast, IRAP did not affect the pathogenesis of AIA and had no effect on either humoral or cellular immune responses to mBSA in arthritic mice.Conclusion. These observations suggest that interleukin‐1 may play a prominent role in the development of some, but not all, forms of arthritis.
Concomitant development of chronic active hepatitis and antibodies to ribosomal p proteins in a patient with systemic lupus erythematosus
Authors: Koren Eugen , Schnitz William , Reichlin Morris 
Published: February 2007

AbstractWe describe a systemic lupus erythematosus (SLE) patient who for several years had typical SLE features and positive antinuclear antibodies (ANA), including anti–native DNA. Over the course of a year, 4 years after the SLE was diagnosed, the ANA disappeared and antibodies to cytoplasmic component ribosomal P protein (anti‐P) appeared. Associated with the appearance of anti‐P antibodies was the development of biochemical evidence of liver disease, later shown histologically to be chronic active hepatitis. The temporal relationship between the occurrence of anti‐P antibodies and the development of liver disease raises the possibility of a role for anti‐P antibodies in liver disease.
Detection of intraarticular abnormalities in osteoarthritis of the knee
Authors: Ike Robert W. , O'Rourke Kenneth S. 
Published: February 2007

AbstractObjective. To determine whether intraarticular abnormalities in osteoarthritis (OA) of the knee can be detected as well by needle arthroscopy as by standard arthroscopy.Methods. Needle arthroscopy followed by standard arthroscopy was performed on 10 patients with knee OA (diagnosed according to American College of Rheumatology criteria) whose symptoms were not entirely attributable to the OA and were therefore an indication for further evaluation. Each knee was assessed for abnormalities of the menisci, articular cartilage (6 sites), and synovium (6 sites).Results. Evaluation of the 18 menisci visualized with both techniques yielded the same results: 6 abnormal and 12 normal. Among the 54 articular cartilage sites evaluable with both procedures, 16 were judged normal by both needle arthroscopy and standard arthroscopy. Of the 38 cartilage sites judged abnormal by standard arthroscopy, 34 (89%) were abnormal by needle arthroscopy. Both techniques indicated cartilage changes were the same at 42 (78%) of the 54 sites; changes at the other 12 sites were 1 grade higher by standard arthroscopy than by needle arthroscopy. Both needle arthroscopy and standard arthroscopy revealed 51 evaluable sites in the synovium. Of 34 areas judged abnormal by standard arthroscopy, 24 (71%) were also judged abnormal by needle arthroscopy; 17 areas were judged normal by both techniques. The 2 techniques assigned the same macroscopic score in 27 (53%) of 51 areas of the synovium, with a higher grade by standard arthroscopy in all but 1 of the other 16 areas.Conclusion. These pilot data suggest that in knee OA, needle arthroscopy can 1) accurately detect meniscal abnormalities, 2) detect cartilage abnormalities, but may underestimate the severity, and 3) detect most synovial abnormalities, but often underestimates the severity. Needle arthroscopy is a potentially valuable rheumatologic tool for the assessment of OA of the knee.
Radiographic assessment of disease progression in rheumatoid arthritis patients enrolled in the cooperative systematic studies of the rheumatic diseases program randomized clinical trial of methotrexate, auranofin, or a combination of the two
Authors: Méndez Ada López‐ , Daniel William W. , Reading James C. , Ward John R. , Alarcón Graciela S. 
Published: February 2007

AbstractObjective. To determine the radiographic progression of disease in rheumatoid arthritis (RA) patients from the Cooperative Systematic Studies of the Rheumatic Diseases clinical trial of auranofin (AUR) versus methotrexate (MTX) versus a combination of the two.Methods. Baseline (week‐0) and study‐end (week‐48) hand/wrist radiographs in 200 of the 211 patients who completed this multicenter trial (95%) were scored blindly by 2 readers for the presence of erosions and joint space narrowing (JSN). Both intraobserver reliability and interobserver reliability were 0.80 for erosions (P ≤ 0.001); intraobserver reliability and interobserver reliability were both 0.75 for JSN (P ≤ 0.001).Results. Worsening erosion and JSN scores occurred in all 3 treatment groups, but the difference from baseline reached significance only in the AUR group.Conclusion. Clinical improvement has been clearly documented in all 3 treatment groups in this trial. Radiographic deterioration occurs in RA even when clinical features improve, but progression of disease as determined radiographically may be slowed by treatment with MTX.
Effects of methotrexate on radiologic progression in juvenile rheumatoid arthritis
Authors: Harel Liora , Wagner‐Weiner Linda , Poznanski Andrew K. , Spencer Charles H. , Ekwo Edem , Magilavy Daniel B. 
Published: February 2007

AbstractObjective. To assess the effects of methotrexate (MTX) therapy on radiologic progression in juvenile rheumatoid arthritis (JRA).Methods. We evaluated serial wrist radiographs for carpal length in 23 JRA patients with bilateral wrist involvement, before and during MTX treatment. These carpal length measurements were compared with established norms for carpal length in a healthy pediatric population.Results. Both clinical responders to MTX (17 of 23 patients) and nonresponders (6 of 23) had decreasing carpal length prior to initiation of the treatment. Eleven of the 17 clinical responders had improved carpal length after a mean of 2.5 years of MTX treatment. All 6 clinical nonresponders had progressive loss of carpal length.Conclusion. MTX treatment resulted in radiologic improvement, as measured by carpal length, in the majority of children with JRA who had a clinical response to MTX.
Chimeric cd4 monoclonal antibody cm‐t412 as a therapeutic approach to rheumatoid arthritis
Authors: Lubbe Peter A. VanDer , Reiter Christian , Breedveld Ferdinand C. , Kr¨︁ger Klaus , Schattenkirchner Manfred , Sanders Martin E. , Riethm¨︁ller Gert 
Published: February 2007

AbstractObjective. To investigate the effects of chimeric CD4 monoclonal antibody cM‐T412 treatment in patients with rheumatoid arthritis (RA).Methods. Thirty‐two RA patients received daily doses of 10, 50, or 100 mg of cM‐T412 intravenously for 7 days.Results. There was a sustained decrease in the number of CD4+ T lymphocytes in all patients. Those who received 50 mg and 100 mg of the antibody experienced significant reductions in disease activity.Conclusion. Treatment with cM‐T412 appears to have a dose‐dependent beneficial effect in RA patients. The clinical effects of cM‐T412 are independent of the depressed numbers of circulating CD4+ T cells.
Hla‐linked susceptibility to rheumatoid arthritis
Authors: Taneja Veena , Mehra N. K. , Anand C. , Malaviya A. N. 
Published: February 2007

AbstractObjective. To analyze segregation of rheumatoid arthritis (RA) with HLA–DR4 and/or other alleles in multicase RA families and to compare the segregation patterns among affected and unaffected sibs.Methods. Forty‐one multicase families (22 multiplex and 19 simplex) of northern Indian origin were studied for HLA haplotype segregation.Results. HLA haplotype sharing among affected sibs was observed more often than expected in families in which both parents were healthy (P < 0.05). RA cosegregated with a DR4 haplotype among offspring only in multiplex families in which both parents were unaffected (P < 0.05), while in simplex families, the disease segregated with DR4 only when the allele was from the affected DR4‐heterozygous parent. In DR4‐negative affected sib pairs, DR1, DR6, and DR10 were inherited from healthy parents more often than expected.Conclusion. Dissimilar modes of inheritance are seen among multiplex and simplex RA families. The results of segregation analysis are compatible with the hypothesis that an epitope, rather than an individual DR antigen(s), is responsible for increased risk for development of RA.