bluuebunny/crossref_metadata_2025 huggingface dataset:
The contributions of disease activity, sleep patterns, and depression to fatigue in systemic lupus erythematosus
Authors: Mckinley Paula S. , Ouellette Suzanne C. , Winkel Gary H.
Published: February 2007

Objective. This study describes lupus fatigue multidimensionally and introduces a multivariate model: Sleep problems and depression, through reciprocal effects on each other, act as mediators through which lupus disease activity increases fatigue.

Methods. Self‐reported sleep patterns, depression, and fatigue were assessed in 48 women with systemic lupus erythematosus (SLE) and 27 women from the general population. Rheumatologists rated current lupus disease activity.

Results. The SLE group reported greater overall fatigue than did the controls. Temporal and affective dimensions of fatigue were more differentiating than sensory or severity dimensions. The SLE group also reported longer sleep latency and total sleep time, but not higher depression. Using 2‐stage regression, a form of structural equation modeling, the proposed lupus fatigue model was supported.

Conclusion. These preliminary results describe fatigue as a multidimensional phenomenon arising out of several contributing factors. They suggest that fatigue treatment strategies should address mediating processes such as sleep and depression, in addition to disease activity.
The early clinical recognition of juvenile‐onset ankylosing spondylitis and its differentiation from juvenile rheumatoid arthritis
Authors: Burgos‐Vargas Rubén , Zquez‐Mellado Janitzia VÁ
Published: February 2007

Objective. To determine which early clinical data differentiate juvenile‐onset ankylosing spondylitis (AS) from juvenile rheumatoid arthritis (JRA).

Methods. Medical records of 35 patients with juvenile‐onset AS and 75 with JRA (excluding type II pauciarticular JRA), all of whom had disease onset at age ≤16 years, disease duration of ≤2½ years at the initial visit to the rheumatology clinic, and followup of ≥ 10 years, were analyzed retrospectively with regard to features of disease found 6 months, 12 months, and 10 years after onset.

Results. At 6 months, various features appeared more frequently in the juvenile‐onset AS group than in the JRA group, i.e., pauciarthritis (54.3% versus 30.7%; P = 0.03, odds ratio [OR] = 2.7), enthesopathy (82.9% versus 0%; P < 0.0001, OR = 321.4), tarsal disease (71.4% versus 1.3%; P < 0.0001, OR = 185.0), and lumbar/sacroiliac symptoms (11.4% versus 0%; P = 0.02, OR = 11.9). At 12 months, the features found more frequently among juvenile‐onset AS patients than JRA patients were enthesopathy (88.6% versus 4.0%; P < 0.0001, OR = 186.0), tarsal disease (85.7% versus 10.7%; P < 0.0001, OR = 50.3), and knee disease (100.0% versus 82.7%; P = 0.04, OR = 8.0). Involvement of the upper extremities (especially the hands) was found in significantly fewer juvenile‐onset AS patients compared with the JRA group. Definite involvement of the spine and sacroiliitis in juvenile‐onset AS occurred after a mean ± SD of 7.3 ± 2.0 years.

Conclusion. Regardless of axial disease, enthes opathy and tarsal disease in children who have arthritis of the lower, but not of the upper extremities differentiate juvenile‐onset AS from JRA within 1 year of symptoms. The discriminative value of these parameters approaches that of axial disease (the gold standard) throughout the followup period.
Comparative prospective, double‐blind, multicenter study of the efficacy of tiludronate and etidronate in the treatment of paget's disease of bone
Authors: Roux C. , Gennari C. , Farrerons J. , Devogelaer J. P. , Mulder H. , Kruse H. P. , Picot C. , Titeux L. , Reginster J. Y. , Dougados M.
Published: February 2007

Objective. To compare the efficacy and safety of tiludronate and etidronate at the same dosage (400 mg/day) for the treatment of active Paget's disease of bone.

Methods. We studied 234 patients with radiologic lesions characteristic of Paget's disease of bone and serum alkaline phosphatase (AP) concentrations at least twice the upper limit of normal, in a prospective, randomized, double‐blind, multicenter clinical trial lasting 6 months. Patients were randomly allocated into 1 of 3 treatment groups: tiludronate for 3 months followed by placebo for 3 months, tiludronate for 6 months, or etidronate for 6 months. Serum AP levels and urinary hydroxyproline excretion were measured at baseline and after 3 months and 6 months. Patients with a reduction of at least 50% in the serum AP concentration were considered to be responders.

Results. After 3 months, the proportion of responders was higher in the tiludronate group (57.4%) than in the etidronate group (13.9%) (P < 0.0001). In the etidronate group, this percentage was lower among patients who had received previous treatment with a bisphosphonate (2.3%) than among those who had not (28.6%) (P < 0.01). Previous bisphosphonate treatment was not associated with response in the tiludronate group. After 6 months, the proportion of responders did not differ between the 2 tiludronate groups (60.3% and 70.1%), but was lower in the etidronate group (25.3%) (P < 0.0001). There was a higher proportion of patients with treatment‐resistant disease ( < 25% reduction of serum AP) in the etidronate group (51.9%) than in the tiludronate 3‐month group (17.9%) or the tiludronate 6‐month group (19.5%) (P < 0.0001). Gastrointestinal disturbances were more common, and occurred earlier, with tiludronate, but they were mostly mild, requiring no treatment.

Conclusion. Tiludronate at 400 mg/day for 3 months or 6 months is more effective than the same dosage of etidronate for 6 months in the treatment of Paget's disease.
Markers of bone metabolism in postmenopausal women with rheumatoid arthritis
Authors: Hall G. M. , Spector T. D. , Delmas P. D.
Published: February 2007

Objective. To investigate bone metabolism in postmenopausal women with rheumatoid arthritis (RA) treated with or not treated with corticosteroids, and the response to hormone replacement therapy (HRT).

Methods. One hundred six RA patients were divided into those taking low‐dose steroids (RA+; n = 35) and those not (RA–; n = 71) and randomly allocated to receive HRT or calcium for 2 years. Bone formation markers included serum osteocalcin (OC) and bone‐specific alkaline phosphatase, and resorption markers included urinary deoxypyridinoline (DPyr) and CrossLaps (XL). Bone mineral density (BMD) was measured annually using dual x‐ray absorptiometry.

Results. OC levels were significantly lower in both the RA+ and RA– groups compared with 112 healthy control subjects (P < 0.01 and P < 0.05, respectively), but were similar in the 2 RA groups. DPyr and XL levels were elevated in the RA+ group compared with the RA– group (P < 0.05) but were similar between the RA– group and controls. OC was negatively correlated with parameters of disease activity (P < 0.05). After HRT, XL excretion decreased significantly in the overall RA group. Three‐month changes in XL correlated with 2‐year changes in spinal BMD (P < 0.01).

Conclusion. Bone metabolism may be uncoupled in chronic RA. Bone formation appears to be reduced, partly reflecting disease activity, whereas resorption increased only in steroid users. HRT reduces resorption in RA irrespective of steroid usage, emphasizing its value in the treatment of postmenopausal women with RA.
Radiographic osteoarthritis of the hip and bone mineral density
Authors: Nevitt Michael C. , Lane Nancy E. , Scott Jean C. , Hochberg Marc C. , Pressman Alice R. , Genant Harry K. , Cummings Steven R.
Published: February 2007

Objective. To examine the cross‐sectional association between radiographic features of hip osteoarthritis (OA) and bone mineral density (BMD) of the hip, spine, and appendicular skeleton among Caucasian women ages 65 and older who were participating in the Study of Osteoporotic Fractures.

Methods. Pelvis radiographs of 4,855 subjects were assessed for individual radiographic features of hip OA: osteophytes, joint space narrowing, subchondral sclerosis, cysts, and femoral head deformity. Hips were graded on a summary scale of 0 (no OA) to 4 (severe OA) based on the number of radiographic features present. Appendicular BMD was measured in all subjects, and hip and spine BMD in 84% of the group. We used linear regression to examine the association of BMD with hip OA, and to adjust for age, weight, and other determinants of bone mass.

Results. Three hundred fifty‐one women (7.2%) had mild (grade 2) and 228 (4.7%) had moderate to severe (grade 3–4) radiographic evidence of hip OA. Women with grade 3–4 hip OA had a higher age‐adjusted BMD at the femoral neck and Ward's triangle (9–10%; P < 0.0001), trochanter (4%; P < 0.01), lumbar spine (8%; P < 0.0001), and distal radius and calcaneus (5%; P < 0.0001 [for each comparison]) compared with those with grade 0–1 OA in the worse hip. Elevations in BMD were greatest in the femoral neck of hips with OA, in women with bilateral hip OA, and in women with hip osteophytes. These findings were essentially unchanged by adjustment for determinants of bone mass.

Conclusion. Elderly Caucasian women with moderate to severe radiographic hip OA had higher BMD in the hip, spine, and appendicular skeleton than did women without hip OA. Our findings are consistent with a role of elevated BMD in the pathogenesis of hip OA.
Compartment‐directed physical examination of the knee can predict articular cartilage abnormalities disclosed by needle arthroscopy
Authors: Ike Robert W. , O'Rourke Kenneth S.
Published: February 2007

Objective. To determine whether physical examination maneuvers that focus on each knee compartment and assess crepitus at several distinct sites can specifically disclose articular cartilage abnormalities in the compartment being assessed.

Methods. Twenty patients with knee pain were examined before needle arthroscopy. Crepitus was sought from the patellofemoral compartment, medial tibiofemoral compartment, and lateral tibiofemoral compartment. Any crepitus felt in the distal tibia during a tibiofemoral stress maneuver was recorded as transmitted bony crepitus (TBC). Needle arthroscopy assessed articular cartilage (5 sites) and both menisci in each knee.

Results. Crepitus by conventional assessment revealed patellar cartilage disruption (69% sensitive, 50% specific) and abnormalities of tibiofemoral cartilage (67% sensitive, 40% specific) but could not indicate their location. Tibiofemoral crepitus found cartilage disruption in the compartment at a sensitivity of 22% and a specificity of 100%, and with added tibiofemoral stress, a sensitivity of 65% and a specificity of 94% (the one “false positive” had bare bone in the other compartment). TBC was detected in 7 compartments, all of which had focal bare bone on tibial and femoral surfaces; 6 other compartments had tibial bare bone without TBC. Thus, TBC was 54% sensitive and 100% specific for tibial bare bone, and 88% sensitive and 100% specific for bone‐on‐bone.

Conclusion. Compartment‐directed physical examination of the painful knee can locate and assess the severity of certain articular cartilage abnormalities that are not reliably found by conventional methods. Transmitted bony crepitus is a specific finding for bone‐on‐bone in the compartment being assessed.
Elevated levels of eosinophil major basic protein in the sera of patients with systemic sclerosis
Authors: Cox Darrin , Earle Linda , Jimenez Sergio A. , Leiferman Kristin M. , Gleich Gerald J. , Varga John
Published: February 2007

Objective. To examine eosinophil activation, as reflected by evidence of eosinophil degranulation in the blood and affected tissues, in patients with diffuse and limited cutaneous forms of systemic sclerosis (SSc).

Methods. Levels of the eosinophil‐derived major basic protein (MBP), a marker of eosinophil degranulation, were determined in sera from 46 SSc patients, from patients with rheumatoid arthritis and giant cell arteritis, and from healthy volunteers, and in bronchoalveolar lavage fluid from 4 SSc patients. Extracellular tissue deposition of MBP was evaluated in biopsy specimens from affected skin or lung of 11 SSc patients.

Results. Patients with diffuse cutaneous SSc (dcSSc) had elevated serum MBP levels compared with normal individuals (mean ± SD 762 ± 271 ng/ml versus 534 ± 144 ng/ml; P = 0.0004). MBP levels were positively correlated with the extent of cutaneous involvement, and negatively correlated with pulmonary function and duration of disease (r = –0.20). By immunohistochemical analysis, modest extracellular MBP deposition could be demonstrated in involved skin in 7 of 10 biopsy specimens, and MBP staining was prominent in affected lung tissues in 2 patients.

Conclusion. Eosinophil degranulation appears to be increased in some patients with dcSSc, as indicated by elevated serum levels of MBP and extracellular accumulation of MBP in the lung. Eosinophil granule proteins may contribute to the development of cutaneous and pulmonary fibrosis in SSc.
Changes in glycosaminoglycan epitope levels in knee joint fluid following injury
Authors: Hazell Paula K. , Dent Colin , Fairclough John A. , Bayliss Michael T. , Hardingham Tim E.
Published: February 2007

Objective. To measure the levels of epitopes on the chondroitin sulfate (CS) and keratan sulfate (KS) chains of proteoglycan fragments in synovial fluids from injured and contralateral uninjured knees of patients with traumatic cruciate ligament and/or meniscus damage.

Methods. Enzyme‐linked immunosorbent assays were used to determine the levels of monoclonal antibody epitopes 3‐B‐3 and 7‐D‐4 (CS), and 5‐D‐4 (KS), in paired joint fluids from the injured and uninjured knees of trauma patients.

Results. Levels of the CS epitopes were increased in the trauma joint fluids from most patients, with higher levels of 3‐B‐3 epitope in 12 of the 16 patients, but the difference did not achieve significance; however, 7‐D‐4 levels were higher in 15 patients, and the difference was highly significant (P = 0.0005). In contrast, the KS epitope detected by 5‐D‐4 was decreased in 13 of 15 patients, and the difference was significant (P = 0.0074).

Conclusion. The increased level of 7‐D‐4 epitope on proteoglycans in joint fluid from injured knees may reflect the response of the articular cartilage to acute trauma resulting in altered expression of specific CS epitopes on cartilage proteoglycans. The fall in KS epitope levels may reflect the synthesis of proteoglycans that have lower KS content.
Growth factor responsiveness of human articular chondrocytes in aging and development
Authors: Guerne Pierre‐andré , Blanco Francisco , Kaelin André , Desgeorges Alain , Lotz Martin
Published: February 2007

Objective. To examine growth factor responses of human articular chondrocytes in aging and development. We have previously established a growth factor response profile for adult human articular chondrocytes and shown that transforming growth factor β (TGFβ) is the most potent mitogen among a variety of factors tested.

Methods. Chondrocytes were isolated from human articular cartilage obtained from donors ages 11–83 years and tested in primary culture for proliferative responses to serum and recombinant preparations of the major chondrocyte growth factors. Proliferation was measured by 3H‐thymidine incorporation and cell counting. Skeletal maturity of the young donors was determined by radiographic assessment of Risser's index.

Results. Chondrocytes showed a continuous age‐related decline in the proliferative response to serum. Analysis of recombinant growth factors showed that with increasing donor age, there was a decrease in the levels of DNA synthesis in response to all factors tested. In chondrocytes from adult donors, there was no change in the relative potencies of the different growth factors. The decrease in the levels of DNA synthesis as measured by 3H‐thymidine incorporation corresponded to a reduced rate of in vitro cell replication with increasing donor age. In addition to the quantitative changes in the proliferative responses of chondrocytes with increasing age, there was a qualitative change in the pattern of growth factor responses during development. Cells from young donors (ages 10–20) responded better to platelet‐derived growth factor, AA chain homodimer (PDGF‐AA) than to TGFβ1, while the inverse pattern was seen in cells from adult donors. This decrease in the response to PDGF‐AA was significantly correlated with increasing skeletal maturity.

Conclusion. Chondrocyte growth factor responsiveness shows qualitative changes during development, and after skeletal maturity, there is a profound decline in the levels of DNA synthesis and cell replication in response to the known chondrocyte growth factors.
Increased levels of stromelysin‐1 and tissue inhibitor of metalloproteinases–1 in sera from patients with rheumatoid arthritis
Authors: Yoshihara Yasuo , Obata Ken'ichi , Fujimot Noboru , Yamashita Kyoko , Hayakawa Taro , Shimmei Masayuki
Published: February 2007

Objective. To evaluate the efficacy of stromelysin‐1 (matrix metalloproteinase–3 [MMP‐3]) and tissue inhibitor of metalloproteinases–1 (TIMP‐1) in serum as markers for joint inflammation in rheumatoid arthritis (RA).

Methods. Levels of both macromolecules in sera from 97 healthy controls, 109 patients with RA, and 47 patients with osteoarthritis (OA) were measured by respective 1‐step sandwich enzyme immunoassays. In the patients with RA, serum levels of MMP‐3 and TIMP‐1 were investigated in relation to laboratory and clinical measures of disease activity. In addition, the relationships between serum and synovial fluid (SF) levels in paired samples from individual patients were examined.

Results. Serum levels of both MMP‐3 and TIMP‐1 in RA patients were significantly higher than those in OA patients and in healthy controls (P < 0.001), and were shown to correlate with traditional systemic markers of inflammation including the erythrocyte sedimentation rate and C‐reactive protein level, and with the Lansbury articular index. In addition, it was noted that serum levels of MMP‐3 correlated with the corresponding values in paired SF samples obtained concurrently from patients with RA (rs = 0.588, P < 0.001), while such correlations were not found for TIMP‐1 levels.

Conclusion. Our results support the notion that levels of both MMP‐3 and TIMP‐1 in RA patient sera are increased in association with inflammation. Furthermore, the level of MMP‐3 in serum provides a particularly useful marker of inflammatory activity in the joints of patients with RA.
Comparative analysis of cathepsin l, cathepsin d, and collagenase messenger rna expression in synovial tissues of patients with rheumatoid arthritis and osteoarthritis, by in situ hybridization
Authors: Keyszer Gernot M. , Heer Andreas H. , Kriegsmann JÖRg , Geiler Thomas , Trabandt Andreas , Keysser Martin , Gay Renate E. , Gay Steffen
Published: February 2007

Objective. To compare the expression of cathepsin L, cathepsin D, and collagenase messenger RNA (mRNA) in synovial specimens from patients with rheumatoid arthritis (RA) and osteoarthritis (OA).

Methods. The expression of cathepsins L and D as well as collagenase mRNA in synovial tissues from 8 patients with RA, 6 patients with OA, and 2 patients with noninflamed joints was evaluated using in situ hybridization with digoxigenin‐labeled RNA probes.

Results. Both RA and OA synovial tissue expressed cathepsins L and D as well as collagenase mRNA. The expression of the cathepsins was markedly higher in interstitial regions and, to some extent, in perivascular infiltrates of RA synovial tissue compared with OA specimens.

Conclusion. Cathepsins L and D mRNA are expressed differently in RA and OA synovial tissues, supporting the concept that these enzymes may contribute to the influx of mononuclear cells into RA synovium. Moreover, the data reveal that the expression of collagenase and cathepsins in RA and OA synovial lining is otherwise largely similar, and suggest that the adhesion of synovial cells to cartilage mediates the invasive destructive process in RA.
Amplification of plasmid and chromosome chlamydia dna in synovial fluid of patients with reactive arthritis and undifferentiated seronegative oligoarthropathies
Authors: Bas Sylvette , Griffais Rémy , Kvien Tore K. , Glennås Anne , Melby Kjetil , Vischer Thomas L.
Published: February 2007

Objective. To investigate the hypothesis that whole bacteria might be found in the joints of patients with Chlamydia‐associated reactive arthritis.

Methods. The presence of 2 plasmid‐ and 2 chromosome‐specific sequences of Chlamydia DNA was investigated by amplification with the polymerase chain reaction, in synovial fluid (SF) samples from 71 patients with various arthropathies.

Results. Chlamydia DNA was found in SF samples from 22 patients.

Conclusion. Whole chlamydiae are likely present in the SF of patients with Chlamydia‐associated reactive arthritis.
The antiinflammatory effects of an adenosine kinase inhibitor are mediated by adenosine
Authors: Cronstein Bruce N. , Naime Dwight , Firestein Gary
Published: February 2007

Objective. The acute antiinflammatory effects of methotrexate are mediated, at least in part, by increased extracellular adenosine concentrations at inflamed sites. This observation suggests that other agents that increase extracellular adenosine concentrations might also reduce inflammation. Since adenosine can be rapidly taken up by cells, phosphorylated by adenosine kinase, and maintained intracellularly as adenine nucleotides, we investigated whether a potent inhibitor of adenosine kinase, GP‐1–515, could increase exudate adenosine concentration and thereby diminish inflammation in the murine air pouch model of inflammation.

Methods. We studied the effect of various oral doses of GP‐1–515 on carrageenan‐induced inflammation in air pouches induced on BALB/c mice. Adenosine concentration in pouch exudates was determined by high performance liquid chromatography, and intensity of inflammation was determined by leukocyte counts in the exudate fluid.

Results.There was a greater concentration of adenosine in the pouch exudates of animals treated with GP‐1–515 than of those treated with saline (P < 0.002). GP‐1‐515 inhibited, in a dose‐dependent manner (P < 0.01), leukocyte accumulation in the murine air pouch in response to carrageenan. Inhibition of inflammation by GP‐1‐515 in this model depended upon increased adenosine concentration in the inflamed pouch since injection of adenosine deaminase into the air pouch with the carrageenan completely reversed the antiinflammatory effects of GP‐1‐515 at all doses of GP‐1‐515 tested. Moreover, as previously demonstrated, the antiinflammatory effects of adenosine were mediated via occupancy of adenosine A2 receptors, since the specific adenosine A2 receptor antagonist 3,7‐dimethyl‐1‐propargylxanthine, but not the A1 receptor antagonist 8‐cyclopentyl‐dipropylxanthine, completely reversed the antiinflammatory effects of GP‐1–515. GP‐1–515 also decreased tumor necrosis factor α levels in the air pouch exudates by 51%, most likely as a result of the direct action of adenosine on macrophages.

Conclusion. These results indicate that the antiinflammatory actions of GP‐1–515 are mediated by adenosine. The development of agents that promote adenosine release at sites of inflammation is a novel strategy for the treatment of inflammatory diseases such as rheumatoid arthritis.
Biased t cell receptor vβ gene usage during specific stages of the development of autoimmune sialadenitis in the mrl/lpr mouse model of Sjögren's syndrome
Authors: Hayashi Yoshio , Hamano Hironori , Haneji Norio , Ishimaru Naozumi , Yanagi Kumiko
Published: February 2007

Objective. To analyze the repertoire of T cell receptor (TCR) Vβ genes transcribed and expressed within the autoimmune lesions of the salivary gland in the MRL/lpr mouse model of Sjögren's syndrome.

Methods. Monoclonal antibodies (MAb) were used to determine the prevalence of selected V gene elements on T cell infiltrates from salivary glands of MRL/lpr mice. To analyze TCR Vβ gene usage, we used reverse‐transcriptase polymerase chain reaction (RT‐PCR) and single‐strand conformational polymorphism (SSCP) analyses.

Results. A predominance of Vβ 8+ T cells was detected within the inflammatory lesions during development of autoimmune disease (confirmed by flow cytometry). RT‐PCR analysis revealed that in autoimmune sialadenitis, the predominant expression of the Vβ 8 gene segment began in the early stages of disease (2‐month‐old mice) and increased over time. Extensive age‐related diversity of TCR Vβ gene usage was also observed. SSCP analysis demonstrated a distinct and common binding pattern of the Vβ 8 gene PCR product from the cell infiltrates during the course of the disease.

Conclusion. Our data suggest that in the MRL/lpr mouse model of Sjögren's syndrome, there is restricted usage of TCR Vβ elements according to the stage of the disease, and that Vβ 8 are probably used preferentially in the recognition of a single unknown self antigen in the salivary gland.
Even low‐grade synovitis significantly accelerates the clearance of protein from the canine knee: implications for measurement of synovial fluid “markers” of osteoarthritis
Authors: Myers Stephen L. , Brandt Kenneth D. , Eilam Oron
Published: February 2007

Objective. In recent studies, the synovial fluid concentration of molecules derived from the extracellular matrix of articular cartilage has been used to deduce the magnitude of cartilage destruction or repair in osteoarthritic (OA) joints. Because low‐grade synovitis is often present in such joints, we assessed the effect of synovial inflammation on the clearance of a prototypical protein, albumin, from synovial fluid.

Methods. 131‐labeled albumin (RISA) was injected into 1 (control) knee of each of 14 dogs. The concentration of RISA in synovial fluid aspirated 7 hours after the injection and serial measurements of surface radioactivity were used to calculate the volume of distribution (Vd) and clearance of RISA. One week later, synovitis was induced in the contralateral knee by intraarticular injection of various quantities of calcium pyrophosphate dihydrate (CPPD) crystals, after which RISA was injected into that joint and these measurements were repeated.

Results. Intraarticular injection of 500 μg of CPPD crystals produced intense synovitis, with a mean synovial fluid white blood cell (WBC) count of 43,200 cells/mm3, and values for RISA Vd and RISA clearance (36.5 ml and 33.7 μl/minute) were much higher than those for saline‐injected control knees (2.7 ml and 1.5 μl/minute, respectively). Injection of 0.5 μg of CPPD also produced marked synovitis and values for Vd and RISA clearance that were 2–3‐fold greater than those in the contralateral knee. The low‐grade synovitis produced by only 0.05 μg of CPPD, which resulted in synovial fluid WBC counts as low as 1,000–2,000 cells/mm3, was accompanied by increases in the clearance and Vd of RISA to levels ˜40% and ˜80% higher, respectively, than those for the contralateral knee.

Conclusion. Even mild synovitis, as seen in OA, may significantly increase the clearance of a protein from the joint. Synovitis is a significant variable which must be considered in studies of putative chondroprotective drugs if conclusions about the effects of drugs on cartilage metabolism are to be drawn from changes in the synovial fluid concentration of a “marker” protein.
Suppression of antigen‐induced arthritis in lewis rats by oral administration of type ii collagen
Authors: Yoshino Shin , Quattrocchi Emilia , Weiner Howard L.
Published: February 2007

Objective. To assess the effect of orally administered type II collagen (CII) in antigen‐induced arthritis (AIA).

Methods. Arthritis was induced in Lewis rats by immunization with methylated bovine serum albumin (mBSA) in Freund's complete adjuvant, followed by an intraarticular injection of mBSA 2 weeks later. Different doses of CII, mBSA, and an unrelated control protein, keyhole limpet hemocyanin (KLH), were orally administered 5 times over several days prior to the induction of arthritis. Ankle joint swelling and delayed‐type hypersensitivity (DTH) responses were measured.

Results. Joint swelling was significantly reduced at a dose of 3 μg and 30 μg of CII, but not at 300 μg. The most prominent suppression of AIA was observed when rats were fed 10 mg of mBSA, whereas oral KLH had no effect. DTH responses were significantly reduced in the mBSA‐fed rats, but not in rats that were fed CII or KLH.

Conclusion. Oral CII can suppress arthritis in an animal model in which immunity to collagen does not play a role. The effect is dose dependent and occurs at lower doses of CII. These results demonstrate the biologic relevance of bystander suppression associated with oral tolerance, and the potential use of this approach to treat human inflammatory joint disease.
Effects of high‐dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs clinical and immune correlates
Authors: Kremer Joel M. , Lawrence David A. , Petrillo Gayle F. , Litts Laura L. , Mullaly Patrick M. , Rynes Richard I. , Stocker Ralph P. , Parhami Nourollah , Greenstein Neal S. , Fuchs Betsy R. , Mathur Anupum , Robinson Dwight R. , Sperling Richard I. , Bigaouette Jean
Published: February 2007

Objective. To determine the following: 1) whether dietary supplementation with fish oil will allow the discontinuation of nonsteroidal antiinflammatory drugs (NSAIDs) in patients with rheumatoid arthritis (RA); 2) the clinical efficacy of high‐dose dietary ω3 fatty acid fish oil supplementation in RA patients; and 3) the effect of fish oil supplements on the production of multiple cytokines in this population.

Methods. Sixty‐six RA patients entered a double‐blind, placebo‐controlled, prospective study of fish oil supplementation while taking diclofenac (75 mg twice a day). Patients took either 130 mg/kg/day of ω3 fatty acids or 9 capsules/day of corn oil. Placebo diclofenac was substituted at week 18 or 22, and fish oil supplements were continued for 8 weeks (to week 26 or 30). Serum levels of interleukin‐1β (IL‐1β), IL‐2, IL‐6, and IL‐8 and tumor necrosis factor α were measured by enzyme‐linked immunosorbent assay at baseline and during the study.

Results. In the group taking fish oil, there were significant decreases from baseline in the mean (±SEM) number of tender joints (5.3 ± 0.835; P < 0.0001), duration of morning stiffness (−67.7 ± 23.3 minutes; P = 0.008), physician's and patient's evaluation of global arthritis activity (−0.33 ± 0.13; P = 0.017 and −0.38 ± 0.17; P = 0.036, respectively), and physician's evaluation of pain (−0.38 ± 0.12; P = 0.004). In patients taking corn oil, no clinical parameters improved from baseline. The decrease in the number of tender joints remained significant 8 weeks after discontinuing diclofenac in patients taking fish oil (−7.8 ± 2.6; P = 0.011) and the decrease in the number of tender joints at this time was significant compared with that in patients receiving corn oil (P = 0.043). IL‐1β decreased significantly from baseline through weeks 18 and 22 in patients consuming fish oil (−7.7 ± 3.1; P = 0.026).

Conclusion. Patients taking dietary supplements of fish oil exhibit improvements in clinical parameters of disease activity from baseline, including the number of tender joints, and these improvements are associated with significant decreases in levels of IL‐1β from baseline. Some patients who take fish oil are able to discontinue NSAIDs without experiencing a disease flare.
Usefulness of the american college of rheumatology recommendations for liver biopsy in methotrexate‐treated rheumatoid arthritis patients
Authors: Erickson Alan R. , Reddy Vishnu , Vogelgesang Scott A. , West Sterling G.
Published: February 2007

Objective. To test the usefulness and cost savings resulting from application of the new American College of Rheumatology (ACR) guidelines for assessing the risk for the development of clinically significant liver disease in rheumatoid arthritis (RA) patients treated with methotrexate (MTX).

Methods. One‐hundred twelve MTX‐treated RA patients were prospectively followed up for MTX hepatotoxicity and underwent liver biopsies according to modified guidelines of the Psoriatic Task Force (PTF). All biopsies were graded according to the Roenigk classification. The new ACR recommendations were then retrospectively applied to test their usefulness and cost‐effectiveness in this cohort.

Results. Based on the PTF guidelines, 66 patients underwent liver biopsies; a total of 110 liver biopsies were performed. Two patients had biopsy‐related complications. Five patients were found to have Roenigk grade IIIB or IV histologic abnormalities. The total cost for this group was $111,380. Applying the new ACR criteria, only 15 patients would have undergone liver biopsies; there would have been a total of 18 biopsies, with no complications. Four of the 5 patients with Roenigk grade IIIB or IV liver abnormalities would have been identified. One patient with insulin‐dependent diabetes mellitus (IDDM) who was found to have cirrhosis (Roenigk grade IV) on liver biopsy as a result of use of the PTF guidelines would have been missed with use of the ACR guidelines. The total cost for the group receiving biopsies based on the ACR guidelines would have been $16,956. Overall, the new ACR guidelines had 80% sensitivity and 82% specificity and resulted in a cost savings of $1,430 per patient.

Conclusion. The new ACR guidelines on MTX monitoring and biopsy surveillance appear to be clinically useful and result in considerable cost savings. However, 1 IDDM patient with significant liver histologic abnormalities would have been missed. We suggest that IDDM be added to the ACR guidelines as a risk factor for MTX hepatotoxicity.
Access to medical care among persons with musculoskeletal conditions
Authors: Yelin Edward , Bernhard Gerson , Pflugrad Diane
Published: February 2007

Objective. To study access to medical care services, including subspecialty care, among persons with musculoskeletal conditions.

Methods. In early 1993, a random sample of households in San Mateo County, California, was screened for the presence of household members with musculoskeletal conditions, and a member of each household so identified was administered a structured survey about access to medical care and other related subjects.

Results. Eighty‐six percent of all persons with a musculoskeletal condition had ever seen at least one physician for the condition, but only 6.5% had ever seen a rheumatologist. Those without health insurance were only 82% as likely as those with health insurance to have ever seen a physician.

Conclusion. Most persons with a musculoskeletal condition have seen a physician for the condition, but lack of health insurance significantly reduces the proportion who have done so.
Incidence of symptomatic hand, hip, and knee osteoarthritis among patients in a health maintenance organization
Authors: Oliveria Susan A. , Felson David T. , Reed John I. , Cirillo Priscilla A. , Walker Alexander M.
Published: February 2007

Objective. To quantify the incidence of symptomatic hand, hip, and knee osteoarthritis (OA) among members of the Fallon Community Health Plan, a health maintenance organization located in central Massachusetts.

Methods. Incident OA was defined as the first evidence of OA by radiography (grade ≥2 on the Kellgren‐Lawrence scale of 0–4) plus joint symptoms at the time the radiograph was obtained or up to 1 year before the radiograph was obtained.

Results. The age‐ and sex‐standardized incidence rate for hand OA was 100/100,000 person‐years (95% confidence interval [95% CI] 86, 115), for hip OA 88/100,000 person‐years (95% CI 75, 101), and for knee OA 240/100,000 person‐years (95% CI 218, 262). The incidence of hand, hip, and knee OA increased with age, and women had higher rates than men, especially after age 50. A leveling off or decline occurred for both groups around the age of 80.

Conclusion. In a large study of symptomatic OA we observed incidence rates that increased with age. In women ages 70‐89, the incidence of knee OA approached 1% per year.and women had higher rates than men, especially after age 50. A leveling off or decline occurred for both groups around the age of 80.
Photoexacerbation of cutaneous lupus erythematosus due to ultraviolet a emissions from a photocopier
Authors: Klein Laura R. , Elmets Craig A. , Callen Jeffrey P.
Published: February 2007

This report describes a woman with systemic lupus erythematosus (LE) who worked as a photocopy technician and developed cutaneous LE of the hands, neck, face, and chest. Her skin lesions improved when she discontinued her employment. Testing of several photocopy devices showed emission of small quantities of ultraviolet A (UVA), but no UVB. Phototesting of the patient with UVA and UVB induced skin lesions that were clinically and histopathologically consistent with LE. Thus, the action spectrum of cutaneous LE may be within the UVB range, the UVA range, or both ranges of the solar spectrum, and repeated exposure to short bursts of light may induce clinical disease. This case suggests that occupational sources of UV light should be considered as possible exacerbating factors in LE.
Interleukin‐2 diphtheria fusion protein (dab486il‐2) in refractory rheumatoid arthritis a double‐blind, placebo‐controlled trial with open‐label extension
Authors: Moreland Larry W. , Sewell K. Lea , Trentham David E. , Bucy R. Pat , Sullivan William F. , Schrohenloher Ralph E. , Shmerling Robert H. , Parker Karen C. , Swartz William G. , Woodworth Thasia G. , Koopman William J.
Published: February 2007

Objective. This pilot phase II, double‐blind, placebo‐controlled trial of 1 month duration, with a 2–3‐month open‐label extension, evaluated the safety, tolerability, biologic effects, and efficacy of interleukin‐2 diphtheria fusion protein (DAB486IL‐2) in refractory rheumatoid arthritis (RA).

Methods. Forty‐five RA patients were enrolled in the trial, and were randomized, after a 3–4‐week diseasemodifying antirheumatic drug washout, to receive a daily intravenous dose of either DAB486‐IL‐2 or placebo (saline) for 5 days. A blinded, third‐party observer evaluated arthritis activity. Clinical response was defined as ≥25% improvement in swollen and tender joints and ≥25% improvement in at least 2 of 6 additional parameters. The double‐blind phase was 4 weeks; placebo patients could cross over to receive open‐label treatment for a maximum of 3 monthly DAB486IL‐2 cycles.

Results. In the double‐blind phase, 4 of 22 patients (18%) in the treated group and none in the placebo group (P = 0.05) met the criteria for clinical response. During the open‐label treatment phase, 11 of 36 patients (31%) and 11 of 33 patients (33%) had a clinical response after completing 2 and 3 courses of DAB486IL‐2, respectively. Adverse events included transient fever/chills (45%), nause/vomiting (50%), elevated (≥13x normal) transaminases (55%), and increased joint pain (45%). Twelve patients (8 placebo, 4 DAB486IL‐2) did not complete 3 treatment cycles. No apparent differences were noted in CD4+ CD25+ cells of responders versus nonresponders, or of DAB486IL‐2‐treated versus placebo‐treated patients.

Conclusion. Clinical responses were noted in patients treated with DAB486IL‐2 (18%) compared with placebo (0%) in the double‐blind phase. In the open‐label phase, 33% of patients completing 3 monthly DAB486IL‐2 cycles had improvement in arthritis activity. Further studies of IL‐2 diphtheria fusion proteins are warranted to elucidate factors that may predict clinical response and define mechanism(s) of action.
Longitudinal study of hand bone densitometry in rheumatoid arthritis
Authors: Deodhar Atul A. , Brabyn J. , Jones Peter W. , Davis Martin J. , Woolf Anthony D.
Published: February 2007

Objective. To measure hand bone mineral content (BMC) by dual x‐ray absorptiometry and to seek clinical correlates in patients with rheumatoid arthritis (RA), in a prospective, longitudinal study.

Methods. Eighty‐one patients with non–steroidtreated RA were assessed at baseline and at month 12, for hand BMC and for disease activity and severity. Hand BMC in patients was compared with that in a control group of 95 normal volunteers, and rate of loss was compared with that in 37 controls.

Results. At the initial assessment, male and female patients with RA had lower hand BMC than controls, after correction for age, height, and weight (mean reduction 7.5% in men [P = 0.003] and 7.8% in women [P = 0.01]). After 1 year, there was a further loss of hand BMC in patients (median loss 3.25% in men [P = 0.001] and 1.46% in women [P = 0.05]), but normal controls did not have significant changes in their hand BMC. In patients with disease duration of <2 years at study entry, the parameters of disease activity improved over 1 year, but they lost significant amounts of hand BMC. Hand BMC loss correlated with baseline C‐reactive protein levels. In those with RA of >2 years duration at entry, the Health Assessment Questionnaire scores and Larsen scores had worsened after 1 year, but there was no significant loss of hand BMC.

Conclusion. Patients with RA had low hand BMC compared with normal controls, even within 2 years of disease onset. The rate of loss was highest in patients with early disease and correlated with measures of initial disease activity. This loss continued despite clinical improvement.
Sleep electroencephalography and the clinical response to amitriptyline in patients with fibromyalgia
Authors: Carette Simon , Oakson Gerald , Guimont Chantal , Steriade Mircea
Published: February 2007

Objective. To determine the prevalence and clinical correlations of an anomaly consisting of electroencephalographic (EEG) waves within the alpha frequency band during non–rapid eye movement (NREM) sleep in patients with fibromyalgia, and to evaluate the alpha NREM sleep anomaly as a predictor of response to amitriptyline.

Methods. Twenty‐two patients with fibromyalgia were studied in a 2‐month, double‐blind, crossover trial of amitriptyline (25 mg/day) versus placebo. Nocturnal EEGs were conducted on 2 consecutive nights at baseline and at the end of each 2‐month treatment period.

Results. Six patients (27%) had a clinical response to amitriptyline, while none responded to placebo (P = 0.02). Treatment with amitriptyline or placebo did not result in any changes in the alpha ratings during NREM sleep. Only 8 patients (36%) exhibited the alpha NREM sleep anomaly at baseline. Those patients reported more sleep difficulty, but otherwise were clinically indistinguishable from those without this EEG sleep anomaly. Lower baseline alpha NREM sleep ratings were seen in responders to amitriptyline than in nonresponders, but these differences did not reach statistical significance.

Conclusion. The alpha NREM sleep anomaly is present in only a small proportion of patients with fibromyalgia. It does not correlate with disease severity nor is it affected by treatment with amitriptyline. A larger sample size will be needed to adequately assess the value of this sleep anomaly in predicting the response to amitriptyline.
A longitudinal study of functional disability in a national cohort of patients with polymyositis/dermatomyositis
Authors: Clarke Ann E. , Bloch Daniel A. , Medsger Thomas A. , Oddis Chester V.
Published: February 2007

Objective. To analyze changes in functional status and the factors contributing to disability in a national inception cohort of 257 patients with polymyositis/dermatomyositis (PM/DM).

Methods. Data were gathered from patients' self‐reports on questionnaires: one concerning disease‐ and treatment‐related complications, and the other concerning disability, as reflected by a disability index (DI) derived from the Health Assessment Questionnaire (HAQ).

Results. Based on certain characteristics that differentiated disability patterns, 3 groups of patients were identified. Group 1 patients (n = 153) were ≥60 years old and never had avascular necrosis (AVN) or a vertebral compression fracture (CF), Group 2 patients were >60 and never had AVN or a vertebral CF, and Group 3 patients reported AVN or a vertebral CF irrespective of age. As measured by the HAQ DI, disability increased very gradually over time in Group 1 patients and more rapidly in Group 2 and Group 3 patients. The increase in disability in patients experiencing AVN was greater than that in patients with similar pre‐AVN disease characteristics who did not develop AVN (P = 0.003).

Conclusion. In this prospective study of disease course and iatrogenic factors related to functional disability in PM/DM, the HAQ DI increased with disease duration. Corticosteroid‐related morbidity, as reflected by the development of AVN or CF, significantly contributed to patient‐reported functional disability.
Nonsteroidal antiinflammatory drug‐induced gastroduodenal injury in children
Authors: Dowd James E. , Cimaz Rolando , Fink Chester W.
Published: February 2007

Objective. To determine the incidence of abdominal pain and gastroduodenal injury in children with arthritis taking nonsteroidal antiinflammatory drugs (NSAIDs).

Methods. A retrospective review of the records of all children (570 patients) receiving followup care in an academic rheumatology clinic between 1991 and 1993 was performed.

Results. There were 344 patients who used NSAIDs during the study period. Abdominal pain was recorded in 27.9% of patients taking NSAIDs and 14.6% of patients not taking NSAIDs. Abdominal pain in 47 patients (49%) taking NSAIDs and 14 patients (42%) not taking NSAIDs was evaluated radiographically and/or endoscopically. Among those patients evaluated, gastric or duodenal injury was found in 16 (34.0%) who were taking NSAIDs and 1 (7.1%) who were not. This represented a relative risk for gastroduodenal injury of 4.8 for patients taking NSAIDs (P = 0.09). The incidence of injury did not change when analyses were controlled for prednisone or slow‐acting antirheumatic drug use. None of the children were hospitalized or died as a result of gastroduodenal injury during the 3‐year period.

Conclusion. We conclude that NSAID use in children with arthritis frequently leads to gastroduodenal injury, with an estimated incidence and relative risk that are comparable to the rates found in adults with arthritis taking NSAIDs, but that hospitalization or death as a result of this injury is uncommon.
Number of children as a risk factor for low back pain in men and women
Authors: Silman Alan J. , Ferry Susan , Papageorgiou Ann C. , Jayson MALCOLM I. V. , Croft Peter R.
Published: February 2007

Objective. To estimate the influence of the number of liveborn children on the risk of low back pain.

Methods. The study design was a cross‐sectional population‐based survey. The 4,501 respondents to a postal survey were asked to provide data on the occurrence of low back pain and on any children they had. Data on some potential confounding variables were also obtained.

Results. There was an increased risk of low back pain in those who were married compared with those who were unmarried, among both men (odds ratio 1.7) and women (odds ratio 1.6). Among married individuals, there was a linear trend of increasing risk with increasing numbers of children.

Conclusion. The risk of low back pain is related more to childrearing than to childbearing, although this effect might be partially mediated by unknown confounders associated with increasing family size.