bluuebunny/crossref_metadata_2025 huggingface dataset:
Rheumatoid factor, HLA–DR4, and allelic variants of DRB1 in women with recent‐onset rheumatoid arthritis
Authors: Lee Nelson J. , Dugowson Carin E. , Koepsell Thomas D. , Voigt Lynda F. , Branchaud Ann M. , Barrington Robert A. , Wener Mark H. , Hansen John A.
Published: February 2007

Objective. To examine the relationship of rheumatoid factor (RF) to HLA–DR4 and alleles of DRB1 in women with recent‐onset rheumatoid arthritis (RA).

Methods. Incident cases of RA were identified as part of a prospective, population‐based case–control study. HLA typing was completed for 246 cases meeting criteria for definite or classic RA.

Results. One hundred thirty‐six patients (55%) were positive for DR4, and 130 (53%) were RF positive. DR4 was found to be strongly associated with seropositivity (odds ratio 4.1, P < 0.0001). Patients with a shorter interval from RA onset to RF testing had a higher frequency of seropositivity than those with a longer interval (≤18 months 60%, >18 months 33%). Further analysis of patients who had RF testing within 18 months of RA onset showed that the frequency of seropositivity was significantly greater among DR4‐positive patients who had the shared sequence stretch of DRβ1 associated with RA susceptibility (76% RF positive) than among DR1‐positive patients who had this sequence (45% RF positive) (odds ratio 3.8, P = 0.01). Moreover, the frequency of seropositivity among DR1‐positive patients with the sequence did not differ from that among all patients without the shared sequence (47%) (odds ratio 0.9, P = 0.8).

Conclusion. HLA–DR4 is strongly associated with seropositivity in women with recent‐onset RA. The amino acid sequence of DRβ1 that is associated with susceptibility to RA and is shared between DR4 and DR1 appears not to be the primary determinant of seropositivity in these women.
Differences between men and women undergoing major orthopedic surgery for degenerative arthritis
Authors: Katz Jeffrey N. , Wright Elizabeth A. , Guadagnoli Edward , Liang Matthew H. , Karlson Elizabeth W. , Cleary Paul D.
Published: February 2007

Objective. To determine whether women have worse functional status than men at the time of laminectomy for degenerative spinal stenosis or total joint arthroplasty for degenerative arthritis of the hip and knee.

Methods. Consecutive patients undergoing laminectomy for degenerative lumbar spinal stenosis or unilateral, primary hip or knee arthroplasty for advanced degenerative arthritis were recruited. Functional status was measured with self‐administered questionnaires. We compared preoperative functional status scores of men and women, using linear regression models that adjusted for age, comorbid conditions, work status, education, living arrangement, and body mass index. We also compared the rates of in‐hospital complications and 6‐month followup functional status scores for men and women.

Results. Women had much worse functional status than men prior to laminectomy for spinal stenosis (P < 0.01) and prior to total hip arthroplasty (P < 0.001) and total knee arthroplasty (P < 0.0001). These differences persisted after statistical adjustment for demographic and clinical characteristics. Women had comparable or greater functional improvement following surgery and experienced a similar number of complications compared with men.

Conclusions. The observed gender differences in functional status prior to major orthopedic surgery indicate that women are operated on at a more advanced stage in the course of their disease. These results are not due to gender differences in demographic or clinical characteristics of the patients, and cannot be justified by differences between men and women in the outcome of surgery. The role of patient preferences and differential access to these procedures should be explored in future studies.
Quantitative analysis of crosslinks pyridinoline and pentosidine in articular cartilage of patients with bone and joint disorders
Authors: Takahashi Masaaki , Kushida Kazuhiro , Ohishi Tsuyoshi , Kawana Kouichi , Hoshino Hironobu , Uchiyama Akiyoshi , Inoue Tetsuo
Published: February 2007

Objective. To determine the content of two crosslinks, pyridinoline (a mature crosslink) and pentosidine (a senescent crosslink), in human articular cartilage, and to examine the effect of bone and joint disorders on the content of those crosslinks in articular cartilage.

Methods. After pretreatment with SP‐Sephadex C‐25, high‐performance liquid chromatography was conducted on a hydrolysate of human articular cartilage from 53 patients with one of the following diseases: osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis, femoral head necrosis, and renal osteodystrophy (ROD).

Results. Pyridinoline levels were either unchanged with age or were slightly decreased in elderly patients. Pentosidine levels increased with age in the entire patient population. There was no significant difference in the pyridinoline content among the study groups, but there was a significant difference in pentosidine content (P < 0.001). ROD patients had the highest mean level of pentosidine (407 μmoles/mole of hydroxyproline), and RA patients had a higher mean level than age‐matched OA patients (214 versus 103 μmoles/mole of hydroxyproline).

Conclusion. Bone and joint disorders do not affect the pyridinoline content in articular cartilage, but they do affect the pentosidine content.
Lack of association between fibromyalgia syndrome and abnormalities in muscle energy metabolism
Authors: Simms Robert W. , Roy Serge H. , Hrovat Mirko , Anderson Jennifer J. , Skrinar Gary , Lepoole Steven R. , Zerbini Cristiano A. F. , Luca Carlo De , Jolesz Ferenc
Published: February 2007

Objective. To compare parameters of muscle energy metabolism in patients with fibromyalgia syndrome (FMS) and sedentary controls.
Methods. Thirteen female FMS patients and 13 female sedentary controls underwent a standardized clinical assessment (including dolorimeter measurements of the upper trapezius and tibialis anterior muscles) and a standardized aerobic fitness test including measurement of maximum oxygen uptake (VO2max). Phosphorus (31P) magnetic resonance spectroscopy studies of the upper trapezius and tibialis anterior muscles were then performed in FMS patients and controls, at rest and during and following a musclefatiguing exercise protocol.
Results. FMS patients and controls had similar levels of VO2max and of maximum voluntary contraction (MVC) of the upper trapezius and tibialis anterior muscles. After controlling for VO2max and MVC, measurements of phosphocreatine (PCr), inorganic phosphate (Pi), and intracellular pH in these muscles were not significantly different in FMS patients versus sedentary controls either at rest, during exercise, or during recovery. In the patients with FMS, no correlation was found between overall or local pain severity and the principal muscle metabolic parameter, PCr/Pi. Inverse correlations between dolorimeter scores at 2 muscle sites and tibialis anterior PCr/Pi were found both in patients and in controls.
Conclusion. This study demonstrates that under the conditions studied, muscle energy metabolism in FMS is no different than that in sedentary controls. These findings do not support the hypothesis that detectable defects in muscle energy metabolism occur in FMS.
Long‐term effect of omega‐3 fatty acid supplementation in active rheumatoid arthritis
Authors: Geusens Piet , Wouters Carine , Nijs Jos , Jiang Yebin , Dequeker Jan
Published: February 2007

Objective. To study the long‐term effects of supplementation with omega‐3 fatty acids (ω3) in patients with active rheumatoid arthritis.
Methods. Ninety patients were enrolled in a 12‐month, double‐blind, randomized study comparing daily supplementations with either 2.6 gm of ω3, or 1.3 gm of ω3 + 3 gm of olive oil, or 6 gm of olive oil.
Results. Significant improvement in the patient's global evaluation and in the physician's assessment of pain was observed only in those taking 2.6 gm/day of ω3. The proportions of patients who improved and of those who were able to reduce their concomitant antirheumatic medications were significantly greater with 2.6 gm/day of ω3.
Conclusion. Daily supplementation with 2.6 gm of ω3 results in significant clinical benefit and may reduce the need for concomitant antirheumatic medication.
Differential expression of two major cytokines produced by neutrophils, interleukin‐8 and the interleukin‐1 receptor antagonist, in neutrophils isolated from the synovial fluid and peripheral blood of patients with rheumatoid arthritis
Authors: Beaulieu André D. , Mccoll Shaun R.
Published: February 2007

Objective. Neutrophils have been shown to produce interleukin‐8 (IL‐8) and interleukin‐1 receptor antagonist (IL‐1ra) in large amounts compared with other cytokines. Since IL‐8 has a proinflammatory action whereas IL‐1ra is antiinflammatory, our objective was to examine the relative levels of production of these cytokines by synovial fluid (SF) neutrophils isolated from patients with rheumatoid arthritis (RA).
Methods. We measured cytokine production using an enzyme‐linked immunosorbent assay and analyzed messenger RNA accumulation in cells by Northern blot.
Results. SF neutrophils produced significantly more IL‐8 and IL‐1β, but significantly less IL‐1ra, than peripheral blood neutrophils.
Conclusion. These observations provide new information on the production of pro‐ and antiinflammatory molecules by neutrophils in the SF environment, and their possible role in RA.
Evaluation of memory, learning ability, and clinical neurologic function in pathogen‐free mice with systemic lupus erythematosus
Authors: Vogelweid Catherine M. , Wright Dennis C. , Johnson Jane C. , Hewett John E. , Walker Sara E.
Published: February 2007

Objective. To determine if neurologic impairment is related to progressive autoimmune disease in 3 murine models of systemic lupus erythematosus (SLE): MRL/lpr, NZB, and NZB/WF1
Methods. Sensorimotor function, learning, and memory were tested within strains at specific ages, before and after the appearance of SLE. These parameters were also compared between strains for young and older lupus mice and their congenic controls with reduced autoimmune disease (MRL/lpr versus MRL/+; NZB versus NZB/xid).
Results. Abnormal neurologic features were present at a much higher frequency in MRL/lpr mice than in age‐matched MRL/+ control mice, and sensorimotor function deficits were also seen in NZB/WF1 mice. Strains that develop lupus showed deficits on a water‐escape, distal cue discrimination task and on a food‐rewarded, proximal cue discrimination task, but the cognitive impairments were not global.
Conclusion. MRL/lpr, NZB, and NZB/WF1 mice differed in terms of which behaviors were impaired as well as when those impairments appeared.
The role of cytokines in polymyositis
Authors: Kalovidouris Apostolos E. , Horn Claire A. , Plotkin Zoya
Published: February 2007

Objective. To investigate the effect of interferon‐γ (IFNγ) on the adhesive interactions between human peripheral blood T cells and human skeletal muscle cells at various stages of muscle cell differentiation and maturation in vitro.
Methods. Human muscle cell cultures were established from normal muscle biopsy material, using the explant technique. T cells were studied for their capacity to adhere to IFNγ‐treated and untreated myoblasts and myotubes. The role of intercellular adhesion molecule type 1 (ICAM‐1) in cell adhesion to muscle cells was examined in blocking studies, by enzyme‐linked immuno‐sorbent assay (ELISA), and by immunohistochemical staining using monoclonal antibodies (MAb).
Results. Treatment of muscle cells (myoblasts and myotubes) with IFNγ resulted in a significant dose‐dependent increase in the number of adherent T cells. Adhesion of T cells to muscle cells was significantly inhibited by MAb to ICAM‐1 and to lymphocyte function–associated antigen type 1, but not by MAb to HLA–DR. There was no difference in the level of T cell adhesion to IFNγ‐treated allogeneic versus autologous muscle cells. By ELISA and immunohistochemical analysis, ICAM‐1 expression on the surface of cultured human muscle cells was either absent or barely detectable, but was strongly induced by treatment of muscle cells with IFNγ.
Conclusion. Induction of cell adhesion molecules on muscle cells by IFNγ may be an important mechanism for the localization of T cells in the affected muscles of patients with autoimmune myositis.
Treatment of stiff‐man syndrome with intravenous immune globulin
Authors: Karlson Elizabeth W. , Sudarsky Lewis , Ruderman Eric , Pierson Susan , Scott Mary , Helfgott Simon M.
Published: February 2007

Objective. To evaluate the efficacy of intravenous immune globulin (IVIG) in the treatment of stiff‐man syndrome (SMS).
Methods. An open, unblinded study of 3 patients with active disease and/or disease refractory to treatment with diazepam and/or corticosteroids.
Results. All 3 bedridden patients improved substantially shortly after infusion with IVIG and regained function.
Conclusion. IVIG may be useful for the treatment of SMS.
Human t lymphocytes express a member of the matrix metalloproteinase gene family
Authors: Conca Walter , Willmroth Frank
Published: February 2007

Objective. T lymphocytes are known to interact with cellular and structural components of the extracellular matrix. We investigated whether T lymphocytes could also contribute to matrix breakdown by expression of a matrix metalloproteinase (MMP) gene.
Methods. Complementary DNA (cDNA) was synthesized from messenger RNA extracted from cultured peripheral blood T lymphocytes after exposure to phorbol myristate acetate and calcium ionophore A23187 and amplified by the polymerase chain reaction with primers derived from two conserved domains in MMP genes.
Results. An amplification product of 402 basepairs was generated and cloned; sequence analysis revealed identity to human stromelysin‐2 cDNA. Using the amplified stromelysin‐2 cDNA as a probe for Northern analyses, we detected a 1.8‐kilobase transcript in stimulated T lymphocytes.
Conclusion. T lymphocytes are a potential source of stromelysin‐2 transcripts and may have a role in the degradation of extracellular matrix constituents.
Bone mineral density of the hand in rheumatoid arthritis
Authors: Peel N. F. A. , Spittlehouse A. J. , Bax D. E. , Eastell R.
Published: February 2007

Objective. To determine the reproducibility, accuracy, and linearity of hand bone mineral content (BMC) measurements, and to evaluate the influence of hand posture; to determine the relationship of hand bone mineral density (BMD) to generalized osteopenia in rheumatoid arthritis (RA); and to determine the relationship between hand BMD and disease severity in early RA.

Methods. Hand BMD was measured by dual‐energy x‐ray absorptiometry (DXA). We studied 70 postmenopausal women with steroid‐treated RA (established RA), ages 49–79, and 20 age‐matched healthy controls to determine the relationship to generalized osteoporosis; we also studied 20 patients ages 23–74 years with early RA to determine the relationship between disease severity and hand BMD.

Results. Reproducibility of hand BMD was to within 1%. In established RA, there was a greater decrease in juxtaarticular BMD (23% at the hand) than in generalized BMD (16% at the femoral neck, 11% at the lumbar spine, and 11% total body) compared with that in age‐matched controls. Hand BMD correlated with skeletal size and BMD at other skeletal sites. In established RA, there was no effect of disease duration, disability, or steroid therapy. In early RA, hand BMD correlated with age and disease activity.

Conclusion. Measurement of hand BMD by DXA is accurate and precise. Hand BMD reflects BMD at other skeletal sites in patients with RA, and is a marker of disease severity in patients with early disease. It may be a sensitive marker of disease progression and response to therapeutic intervention.
Circulating and synovial fluid hyaluronan levels
Authors: Pitsillides Andrew A. , Will Robert K. , Bayliss Michael T. , Edwards JO C. W.
Published: February 2007

Objective. To assess the effect of intraarticular (IA) corticosteroid on hyaluronan (HA) concentrations in synovial fluid (SF) and serum and the clearance of 131I‐labeled albumin from the joints of patients with rheumatoid arthritis (RA), osteoarthritis (OA), and ankylosing spondylitis (AS).

Methods. SF and serum were collected before and 2 weeks and 2 months after IA steroid injection. The HA concentration was assessed using an enzyme‐linked immunosorbent assay and 131I‐albumin clearance from joints was assessed using an external gamma counter.

Results. In RA patients, HA concentrations in the SF were increased following IA steroids, while the serum concentrations were decreased. In OA patients, HA concentrations in SF tended to increase initially (decreasing thereafter), and were associated with increased HA concentrations in serum. There were less marked alterations in the AS patients. Albumin clearance rates were decreased significantly (2 weeks postinjection) only in the RA patients. Estimated HA flux revealed discrepancies between the HA concentration and the rate of flux in RA and AS patients.

Conclusions. These findings suggest that IA steroid injection is associated with a restoration in the relationship between SF and serum HA concentrations toward normal levels.
Expression of granzyme a in salivary gland biopsies from patients with primary sjögren's syndrome
Authors: Alpert Susan , Kang Ho‐Il , Weissman Irving , Fox Robert I.
Published: February 2007

Objective. To determine whether the destruction of salivary gland epithelial cells in Sjögren's syndrome (SS) could be mediated by granzyme A, a serine protease that is contained in the granules of activated lymphocytes.

Methods. We used in situ hybridization and polymerase chain reaction amplification to determine the expression of granzyme A messenger RNA (mRNA) in salivary gland biopsy samples.

Results. Granzyme A mRNA expression was detected in salivary glands from SS patients, but not in those from normal controls. Granzyme A mRNA content was significantly correlated (P < 0.001) with the size of lymphocytic infiltrates in the salivary glands and with the clinical activity of the disease.

Conclusion. Cells that express granzyme A mRNA may play a role in the destruction of the target organ (i.e., the salivary gland) in patients with SS. The strong association of granzyme A mRNA expression and larger lymphoid infiltrates in the patients' salivary glands suggests that granzyme A mRNA is expressed at a relatively late stage of the local inflammatory process. Therapies designed to modulate or block granzyme A induction and action should be investigated in SS patients.
Immediate hypersensitivity reaction to cyclophosphamide
Authors: Knysak David J. , Mclean James A. , Solomon William R. , Fox David A. , Joseph Mccune W.
Published: February 2007

We report a case of an acute anaphylactic reaction to intravenous cyclophosphamide in a patient with systemic lupus erythematosus. Skin testing for reactivity to cyclophosphamide and one of its metabolites, 4‐hydroperoxycyclophosphamide, was performed on the patient and on 6 controls. The patient exhibited positive skin test responses; all controls had negative responses. The results suggest an acute hypersensitivity reaction related to sensitivity to cyclophosphamide and to 4‐hydroperoxycyclophosphamide, through a shared antigenic determinant or dual sensitization.
Hypocomplementemic urticarial vasculitis syndrome in identical twins
Authors: Wisnieski Jeffrey J. , Emancipator Steven N. , Korman Neil J. , Lass Jonathan H. , Zaim Tarif M. , Mcfadden E. R.
Published: February 2007

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a syndrome of recurrent urticarial vasculitis, arthralgia/arthritis, and hypocomplementemia. Angioedema, ocular inflammation, glomerulonephritis, and obstructive lung disease are other clinical findings. Although the etiology of HUVS is unknown, its resemblance to systemic lupus erythematosus (SLE) suggests a similar pathogenesis. SLE is known to occur in identical twins. This is the first report of a pair of identical twins with HUVS. Concordance for HUVS in identical twins suggests that the pathogenesis of the disease involves abnormal genetic immunoregulation.
Decreasing incidence and prevalence of rheumatoid arthritis in pima indians over a twenty‐five—year period
Authors: Jacobsson Lennart T. H. , Hanson Robert L. , Knowler William C. , Pillemer Stanley , Pettitt David J. , Mccance David R. , Bennett Peter H.
Published: February 2007

Objective. To evaluate temporal trends in the incidence of rheumatoid arthritis (RA).

Methods. Incident cases of RA were identified among a population‐based cohort of Pima Indians in Arizona over the period 1965–1990.

Results. Among 2,894 subjects, 78 incident cases of RA were identified. The age‐adjusted incidence declined by 55% in men (Ptrend = 0.225), and by 57% in women (Ptrend = 0.017) after controlling for oral contraceptive or estrogen use and for pregnancy experience. During the same period, age‐adjusted prevalence rates of active RA decreased by 29% in men (Ptrend = 0.63) and by 40% in women (Ptrend = 0.02). Fewer than 17% of subjects with known RA were taking slow‐acting antirheumatic drugs (SAARDs) in 1990.

Conclusion. The decrease in incidence and prevalence of RA in this population over such a short period implicates the involvement of an environmental factor(s), other than exogenous estrogens, in the pathogenesis of the disease. However, the possibility that the observed decrease might be explained by an increased use of SAARDs in subjects with RA cannot be excluded.
Serum levels of soluble adhesion molecules intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E‐selectin in patients with wegener's granulomatosis. Relationship to disease activity and relevance during followup
Authors: Stegeman Coen A. , Tervaert Jan Willem Cohen , Huitema Minke G. , Jong Paul E. De , Kallenberg Cees G. M.
Published: February 2007

Objective, To assess the value of measuring serum levels of soluble intercellular adhesion molecule 1 (sICAM‐1), soluble vascular cell adhesion molecule 1 (sVCAM‐1), and soluble E‐selectin for monitoring disease activity in Wegener's granulomatosis (WG).

Methods. A sandwich enzyme‐linked immunosorbent assay was used to measure levels of soluble adhesion molecules at the time of diagnosis in 22 consecutive patients with WG, in 12 WG patients studied serially prior to disease relapse, at the time of upper airways infection in 18 patients with inactive WG, and in 57 controls. Disease activity was assessed by disease activity score and C‐reactive protein levels.

Results. At diagnosis of WG, sICAM‐1 and sVCAM‐1 levels were significantly elevated and correlated with disease activity. At the time of relapse, a significant increase in all 3 soluble adhesion molecules was found compared with levels at 6 months prior to relapse, but only sVCAM‐1 levels were significantly elevated compared with those in controls. Levels of soluble adhesion molecules at the time of relapse did not differ from those measured during an upper airways infection without disease activity.

Conclusion. Elevated serum levels of sICAM‐1 and sVCAM‐1 can be found in active WG and correlate with disease activity. However, their clinical relevance for followup is limited due to lack of sensitivity and specificity for WG disease activity.
Well‐imaged large vessel vasculitis attributed to anticardiolipin antibody
Authors: Roberts W. Neal , Demeo Jonathan H. , Breitbach Sarah A.
Published: February 2007

Objective. We report a case of large vessel vasculitis, compare imaging techniques, and briefly review the literature.

Methods. Anticardiolipin antibody titers, acute‐phase response, and ischemic symptoms in a 50‐year‐old man admitted for treatment of vasculitis‐related ischemia of the fingers were monitored over a 14‐month period. Images from serial magnetic resonance angiography (MRA) were compared with images from conventional arteriography in the evaluation of peripheral arterial circulation.

Results. The acute‐phase response and anticardiolipin antibody levels were found to vary in parallel with slow resolution of ischemic symptoms following monthly treatment with pulse methylprednisolone and cyclophosphamide.

Conclusion. Attribution of ischemic symptoms to anticardiolipin antibody is supported by the correlation of anticardiolipin antibody titers, acute‐phase response parameters, and ischemic symptoms. The serial images from MRA demonstrate its usefulness as a noninvasive tool for followup studies of both large and medium‐sized vessels affected by vasculitis.
Severe restrictive lung disease in systemic sclerosis
Authors: Steen Virginia D. , Conte Claudia , Owens Gregory R. , Medsger Thomas A.
Published: February 2007

Objective. We sought to identify risk factors for developing severe restrictive lung disease and to determine the time of onset and rate of progression in patients with systemic sclerosis (SSc).

Methods. Using the University of Pittsburgh Scleroderma Databank, we grouped patients according to their lowest forced vital capacity (FVC) value: <75% predicted, 50—75% predicted, and > 50% predicted. In patients with severe restrictive disease, we examined serial pulmonary function test (PFT) results to determine the rate of loss of lung volume over time.

Results. Of 890 SSc patients, 60% (n = 531) never had an FVC ⩽75% predicted; 27% (n = 243) had moderate restrictive disease, with an FVC value of 50—75% predicted; and only 13% (n = 116) of the patients had severe restrictive disease, with FVC ⩽50% predicted. Black race, male sex, early disease, and primary cardiac involvement due to SSc were the features most frequently associated with severe restrictive lung disease (by multiple logistic regression). Fifty–five patients with severe restrictive lung disease had their first of at least 2 PFTs during the first 5 years after onset of any SSc (not pulmonary) symptoms. In 30 patients, the FVC declined by 32% per year in the first 2 years of illness, in 16 patients the annual loss was 12% in years 2—4 after disease onset, and in 9 patients annual loss was 3% during years 4—6 of disease (P < 0.005 by 1–way analysis of variance).

Conclusion. In SSc patients, black men with early disease who have cardiac involvement are the most likely to have factors associated with the development of severe restrictive lung disease (which is increasingly becoming a major cause of death). Disease subtype (diffuse versus limited cutaneous) and serum antitopoisomerase I antibody do not differentiate between moderate and severe restrictive disease. Careful monitoring of pulmonary function early in the disease, when the greatest loss of lung function occurs, may help identify patients likely to respond to new therapy.
alteration in multijoint dynamics in patients with bilateral knee osteoarthritis
Authors: Pai Yi–Chung , Chang Huan J. , Chang Rowland W. , Sinacore James M. , Lewis Jack L.
Published: February 2007

Objective. To document the alterations of joint motion and torque in patients with bilateral knee osteoarthritis (OA), using a well–defined functional maneuver, the sit–to–stand (STS) task.

Methods. Twelve patients with bilateral knee OA and 12 age–, sex–, and height–matched control subjects performed the STS maneuver from a stool of a standard height at their natural speeds. A motion analysis system and 2 force platforms were employed to determine the dynamic joint motion and the resultant joint torques at the ankle, knee, and hip joints.

Results. The results showed that OA patients exhibited substantially reduced knee extension torques, accompanied by other alterations in initial sitting posture (more extended knee and more plantar–flexed ankle), movement duration (increased), dynamic range of motion at the knee (reduced), and extension torques at the hip (increased).

Conclusion. The alterations in joint dynamics among patients with knee OA may have revealed an adaptive motor behavior characterized by redistributing the load from impaired to less–impaired or nonimpaired joints through multijoint dynamics. Two major potential pitfalls of such a movement strategy have subsequently been postulated.
An open study of dehydroepiandrosterone in systemic lupus erythematosus
Authors: Van Vollenhoven Ronald F. , Engleman Edgar G. , Mcguire James L.
Published: February 2007

Objective. To determine if dehydroepiandrosterone (DHEA) has clinical benefits in patients with systemic lupus erythematosus (SLE).

Methods. Ten female patients with mild to moderate SLE and various disease manifestations were given DHEA (200 mg/day orally) for 3—6 months. The patients were given other medications as clinically indicated, and followed with respect to overall disease activity and specific outcome parameters.

Results. After 3—6 months of DHEA treatment, indices for overall SLE activity including the SLEDAI (SLE Disease Activity Index) score and physician's overall assessment were improved, and corticosteroid requirements were decreased. Of 3 patients with significant proteinuria, 2 showed marked and 1 modest reductions in protein excretion. DHEA was well tolerated, the only frequently noted side effect being mild acneiform dermatitis.

Conclusion. DHEA shows promise as a new therapeutic agent for the treatment of mild to moderate SLE. Further studies of DHEA in the treatment of SLE are warranted.
Corticosteroids and neuropsychological functioning in patients with systemic lupus erythematosus
Authors: Denburg Susan D. , Carbotte Ramona M. , Denburg Judah A.
Published: February 2007

Objective. This study was designed to assess the effects of corticosteroids on select aspects of nervous system functioning, specifically, cognition and mood, as well as disease–related symptoms in individual patients with mild systemic lupus erythematosus (SLE) and mild neuropsychiatric (NP) symptoms.

Methods. Ten women who had not been taking corticosteroids for at least 6 months were selected from a referral–based lupus clinic to participate in an N of 1 double–blind, controlled trial consisting of 3 randomly assigned drug/placebo pairings, with a drug dose of 0.5 mg/kg of prednisone daily.

Results. Analysis of variance on the group data yielded significant positive drug effects for cognition (P = 0.02), mood (P = 0.003), and SLE symptom ratings (P = 0.0002). Drug efficacy was also evaluated by an objective decision rule, which yielded evidence of overall drug benefit in 5 of the 8 patients who completed the trial, and a deleterious drug effect in 1 patient. Posttrial clinical results indicated that for the 8 women who completed the trial, “acceptable” decisions, leading to remission of SLE symptoms or appropriate withholding of steroids, were made on the basis of this rule.

Conclusion. Improvement in cognition, mood, and/or SLE symptom ratings can be observed following brief exposure to relatively low doses of corticosteroids in individual women with mild SLE; these persist over repeated drug exposure. The current application of N of 1 methodology represents the first systematic study of steroid efficacy in central nervous system (CNS)—related problems in SLE. The results can now be applied to the design of randomized, controlled trials of the effects of corticosteroids on CNS function in SLE.
The large granular lymphocyte syndrome with rheumatoid arthritis. immunogenetic evidence for a broader definition of felty's syndrome
Authors: Bowman S. J. , Sivakumaran M. , Snowdendegs N. , Bhavnani M. , Hall M. A. , Panayi G. S. , Lanchbury J. S.
Published: February 2007

Objective. To assess whether the HLA—DR4 association found in rheumatoid arthritis (RA) is also seen in the large granular lymphocyte (LGL) syndrome.

Methods. HLA—DR genotyping was performed using restriction fragment length polymorphism and polymerase chain reaction analysis.

Results. LGL syndrome patients with RA showed the same HLA–DR4 association seen in RA/Felty's syndrome (FS), while LGL syndrome patients without arthritis did not.

Conclusion. It is proposed that FS and the LGL syndrome represent different variants of a broader syndrome comprising RA, neutropenia, LGL expansions, HLA—DR4 positivity, and splenomegaly.
Formation of nodular structures resembling mature articular cartilage in long–term primary cultures of human fetal epiphyseal chondrocytes on a hydrogel substrate
Authors: Reginato Anthony M. , Iozzo Renato V. , Jimenez Sergio A.
Published: February 2007

Objective. To establish long–term cultures of human fetal epiphyseal chondrocytes under conditions that allow the preservation of a cartilage–specific phenotype.

Methods. Chondrocytes isolated from 20—24–week human fetal epiphyseal cartilage were cultured for up to 180 days on plastic dishes previously coated with the hydrogel, poly–(2–hydroxyethyl methacrylate). Morphologic, ultrastructural, and biochemical characteristics of the cultures were examined at various intervals, and the expression of genes encoding types I, II, and IX collagen and aggrecan core protein was determined by Northern hybridizations of total cellular RNA with human–specific complementary DNAs.

Results. Human fetal epiphyseal chondrocytes cultured for 180 days under conditions that prevented their attachment to the underlying substratum formed nodular structures with morphologic and structural characteristics resembling mature articular cartilage. The cells in the center of the nodules remained spherical and were surrounded by an abundant cartilaginous extracellular matrix, as evidenced by histochemical and ultrastructural examinations. The cells in the periphery of the nodules acquired a discoid morphology and were surrounded by a sparse extracellular matrix. Biosyn–thetic studies demonstrated the maintenance of a cartilagespecific phenotype throughout the 180 days of culture, with the production of aggrecan and types II, IX, and XI collagens but not type I collagen. Northern hybridizations showed high levels of messenger RNAs (mRNAs) for aggrecan core protein, type II procollagen, and type IX collagen, but type I procollagen mRNA was not detectable even at 180 days of culture.

Conclusion. The human chondrocyte culture system described here allows the maintenance of a chondrocyte–specific phenotype for prolonged periods (up to 180 days). The long–term chondrocyte cultures formed nodular structures that resemble mature articular cartilage morphologically, ultrastructurally, biosynthetically, and in the pattern of cartilage–specific gene expression.
Type vi collagen—specific messenger rna is expressed constitutively by cultured human synovial fibroblasts and is suppressed by interleukin–1
Authors: Bathon Joan M. , Hwang John J. , Shin Lynn H. , Precht Patricia A. , Towns Marilyn C. , Horton Walter E.
Published: February 2007

Objective. Type VI collagen is a prominent constituent of the synovial extracellular matrix. The cellular source of this matrix protein and the identity of local factors in synovium that may regulate its expression have not been delineated, however. We examined the capacity of human fibroblast–like synovial cells to synthesize type VI collagen as well as the effect of interleukin–1 (IL–1) on this expression.

Methods. RNA was extracted from cultured human synovial cells derived from patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Northern blots were analyzed using sequence–specific probes, and steady–state messenger RNA (mRNA) levels of the 3 α(VI) procollagen chains were measured. The effect of IL–1 treatment on these levels was determined.

Results. Abundant expression of 3 characteristic mRNA transcripts, corresponding to the α1 (4.2–kb), α2 (3.5–kb), and α3 (8.5–kb) chains of type VI procollagen, was observed in untreated cells derived from RA and OA patients. IL–1 treatment consistently suppressed steady–state mRNA levels for all 3 α(VI) procollagen chains in a time– and dose–dependent manner. Tumor necrosis factor α induced a response similar to that of IL–1, while IL–2 was ineffective in this regard. Indomethacin partially restored α(VI) mRNA expression in IL–1–treated cells.

Conclusion. These studies provide novel data demonstrating abundant steady–state levels of mRNA transcripts coding for all 3 type VI procollagen polypeptides in human synovial fibroblast–like cells, as well as coordinated down–regulation of these transcripts by IL–1. Local production of IL–1 may thus constitute an important means in vivo of regulating the production of type VI collagen.
Increased collagen synthesis in skin fibroblasts from patients with primary hypertrophic osteoarthropathy. evidence for trans–activational regulation of collagen transcription
Authors: Padula Steven J. , Broketa Goran , Sampieri Alicia , Arakawa Masami , Matucci –Cerinic Marco , Downie Elaine , Korn Joseph H.
Published: February 2007

Objective. To investigate collagen synthesis in skin fibroblasts from patients with primary hypertrophic osteoarthropathy (HOA), a disorder characterized clinically by skin thickening.

Methods. Collagenase–digestible protein, messenger RNA (mRNA) levels, and transcriptional activity of the α1(I) procollagen gene were assessed in skin–derived fibroblast lines.

Results. Compared with fibroblasts from uninvolved skin, fibroblasts from involved skin had elevated levels of collagen synthesis and α1(I) procollagen mRNA, and increased transcriptional activity of the α1(I) procollagen promoter.

Conclusion. Abnormalities of collagen synthesis in fibroblasts from patients with primary HOA can be accounted for, at least in part, by a trans–activated upregulation of collagen transcription.
Esophageal involvement in wegener's granulomatosis
Authors: Spiera Robert F. , Filippa Daniel A. , Bains Manjit S. , Paget Stephen A.
Published: February 2007

Wegener's granulomatosis (WG) is characterized by granulomatous vasculitis, renal disease, and upper and lower respiratory tract disease. Although most organ systems can be involved, gastrointestinal (GI) manifestations are notably uncommon. We describe a patient with WG whose presentation was unique for the prominence of odynophagia. Esophagoscopy revealed erosive esophagitis, which on biopsy was shown to be due to direct involvement by the underlying vasculitis. This is first antemortem documentation of esophageal disease secondary to WG. The GI manifestations of WG are reviewed.
Clonally expanded lymphocytes in the minor salivary glands of sjögren's syndrome patients without lymphoproliferative disease
Authors: Pablos Jose L. , Carreira Patricia E. , Morillas Luis , Montalvo Gregoria , Ballestin Claudio , Gomez‐Reino Juan J.
Published: February 2007

Objective. To determine whether clonally expanded B cells are present in the early infiltrates of minor labial salivary glands (LSG) of Sjögren's syndrome (SS) patients.

Methods. Available paraffin‐embedded LSG biopsies from 14 patients with primary SS were studied. DNA from LSG tissue was amplified by a polymerase chain reaction directed toward rearranged immunoglobulin gene DNA.

Results. All LSG specimens showed oligoclonal or monoclonal B cell expansion. In one patient with plasma cell neoplasm, tumor and LSG specimens obtained at the same operation displayed different immunoglobulin gene rearrangements.

Conclusion. Clonal expansion is characteristic of primary SS, and it is uniformly found in the early LSG infiltrates of patients who do not experience further progression to pseudolymphoma or lymphoma (mean followup 4.1 years after biopsy). This feature, together with the clonal discordance between the LSG and the B cell neoplasm found in one patient, suggests that additional steps are critical for the progression to malignancy.
Analysis of the specificity of anti‐pm‐scl autoantibodies
Authors: Ge Qun , Wu Yajuan , Trieu Edward P. , Targoff Ira N.
Published: February 2007

Objective. To compare the specificity of anti‐PM‐Scl autoantibodies in serum samples from 43 patients with myositis, scleroderma, or both.

Methods. Anti‐PM‐Scl immunoprecipitates from HeLa cell extract were used as antigen for immunoblot analyses to determine the antigenic components. A series of complementary DNA fragments was expressed in Escherichia coli for immunoblot examination of the reaction with the 100‐kd protein.

Results. The immunoblot against immunoprecipitates was sensitive and specific for detecting reactions with components of the PM‐Scl antigen: 42 of 43 sera (97.7%) reacted with the 100‐kd, 27 of 43 (62.8%) with the 70‐kd, and 5 of 43 (11.6%) with the 37‐kd protein (not previously recognized as antigenic). Forty‐one sera reacted with N‐terminal protein S1 (amino acids 11–437), 39 with central protein S2 (amino acids 439–749), and 24 with C‐terminal protein S3 (amino acids 750–882). Of 42 sera tested, 28 (66.7%) reacted most strongly with S1, and 6 (14.3%) reacted most strongly with S2. Absorption studies implied additional, conformational epitopes not present on the bacterially expressed antigen.

Conclusion. There was an overall similarity in reactivity to the PM‐Scl antigen, but there were differences in the reactivity to the 70‐kd and 37‐kd proteins, as well as in the relative strength of the reactivity to the S2 protein.
A cross‐sectional and longitudinal comparison of the rome criteria for active rheumatoid arthritis (equivalent to the american college of rheumatology 1958 criteria) and the american college of rheumatology 1987 criteria for rheumatoid arthritis
Authors: Jacobsson Lennart T. H. , Knowler William C. , Pillemer Stanley , Hanson Robert L. , Pettitt David J. , Mccance David R. , Bennett Mb Peter H. ,
Published: February 2007

Objective. To compare the diagnostic properties of the Rome 1961 criteria for active rheumatoid arthritis (RA) and the American College of Rheumatology (ACR; formerly, the American Rheumatism Association) 1987 criteria for RA with regard to their ability to classify, diagnose, and predict outcome in RA.

Methods. Analysis of cross‐sectional and longitudinal data from repeated health examinations and review of clinical records of 3,509 Pima Indians followed up from January 1966 to December 1990.

Results. The ACR 1987 criteria identified ˜50% of the cases identified by the Rome 1961 criteria, in both cross‐sectional and longitudinal analyses. The ACR 1987 criteria were better predictors of subsequent development of a clinically supported diagnosis and treatment with slow‐acting antirheumatic drugs (both P < 0.001), but were less sensitive than the Rome 1961 criteria for detecting cases for which there already was a clinically supported diagnosis (P < 0.001).

Conclusion. In a population‐based analysis, the ACR 1987 criteria are less sensitive for detecting clinical disease, but predict a clinically more severe prognosis, compared with the Rome 1961 criteria. The sensitivity of both sets of criteria to identify clinical disease is improved if multiple examinations or inactive disease are taken into account.
Radiologic evidence of disease modification in rheumatoid arthritis patients treated with cyclosporine. results of a 48‐week multicenter study comparing low‐dose cyclosporine with placebo
Authors: Md ØYstein FØRre
Published: February 2007

Objective. To evaluate the therapeutic efficacy of 46 weeks of treatment with cyclosporine (5 mg/kg/day) in patients with rheumatoid arthritis (RA).

Methods. A 48‐week randomized, double‐blind, placebo‐controlled, multicenter study of cyclosporine was conducted in 122 patients with active RA. Patients were evaluated by objective and subjective clinical and radiologic measurements at baseline and at the end of the study.

Results. Statistically significant improvement and clinically important changes were seen for the number of tender joints, number of swollen joints, pain score, duration of morning stiffness, and Lee's functional index in the cyclosporine‐treated group at the end of the study. Radiographic examination showed that cyclosporine was capable of retarding joint destruction. In the cyclosporine‐treated group, serum creatinine levels increased by 17.5 μmoles/liter (23%) at week 24 and by 21.8 μmoles/liter (26%) at week 48. There was no significant difference in mean serum creatinine levels in patients treated with cyclosporine alone and those treated with cyclosporine plus nonsteroidal antiinflammatory drugs. Five patients had to be treated with antihypertensive drugs, and 2 patients were withdrawn from the study because of increased serum creatinine.

Conclusion. The study shows that cyclosporine seems to have disease‐modifying effects in RA.
Unique clinical and psychological correlates of fibromyalgia tender points and joint tenderness in rheumatoid arthritis
Authors: Urrows Susan , Affleck Glenn , Tennen Howard , Higgins Pamela
Published: February 2007

Objective. We investigated the relationship of fibromyalgia (FM) tender points to other manifestations of rheumatoid arthritis (RA).

Methods. Sixty‐seven RA patients completed questionnaires at study entry and described symptoms, emotionally significant events, and mood every evening for 75 days. Joint and tender point examinations were conducted every 2 weeks.

Results. Controlling for joint tenderness, the tender point count correlated with the degree of daily stress. Depression was not significantly related when daily stress was controlled for.

Conclusion. We conclude that FM tender point counts correlate uniquely with RA patients' reports of daily stress.
Characteristics of hprt‐mutant t cell lines in a lupus patient treated with cyclophosphamide
Authors: Wood Geryl M. , Dawisha Sahar , Gourley Mark
Published: February 2007

This report describes T cell lines derived from a patient with subacute cutaneous lupus after treatment with intravenous pulse cyclophosphamide. We selected for mitotically active, hypoxanthine‐guanine phosphoribosyltransferase—deficient (HPRT—) T cells, by culture in a selective medium containing 6‐thioguanine. When HPRT— cell lines were derived 6 days after pulse cyclophosphamide (CYC) treatment, they were predominantly CD8+ and T cell receptor (TCR) γ/δ+, producing interferon‐γ (IFNγ). Cell lines derived 21 days after CYC treatment were CD4+, TCRα/β+ and produced both IFNγ and interleukin‐4. These results support a possible role for γ/δ+ T cells in subacute cutaneous lupus and suggest a mechanism for the therapeutic effect of CYC.
Stress fractures of the distal fibula presenting as monarticular flares in patients with rheumatoid arthritis
Authors: Wei Nathan
Published: February 2007

Monarticular flares occurring in patients with rheumatoid arthritis (RA) usually signify either a worsening of the underlying condition or a superimposed septic process. This report describes 2 patients with RA who had stress fractures of the fibular head, masquerading as monarticular flares of ankle arthritis.
Effects of local heat and cold treatment on surface and articular temperature of arthritic knees
Authors: Oosterveld Fredrikus G. J , Rasker Johannes J.
Published: February 2007

Objective. To evaluate and compare the effects of locally applied heat and cold treatments on skin and intraarticular temperature in patients with arthritis.

Methods. Thirty‐nine patients with arthritis of the knee were divided at random into 4 treatment groups (ice chips, nitrogen cold air, ligno‐paraffin, and placebo short wave). A temperature probe was inserted into the knee joint cavity and another placed on the overlying skin, and changes in temperature over 3 hours were recorded for each treatment group.

Results. The mean temperature of the surface of the skin dropped from 32.2°C to 16.0°C after application of ice chips and from 32.6°C to 9.8°C after application of nitrogen cold air; the mean intraarticular temperature decreased from 35.5°C to 29.1°C and from 35.8°C to 32.5°C, respectively, after these treatments. Treatment with ligno‐paraffin increased the surface temperature by 7.5°C and the temperature in the joint cavity by 1.7°C. No significant changes were observed with placebo short wave diathermy.

Conclusion. The traditional model, that intraarticular temperature is decreased by superficial heat and increased by superficial cold, must be discarded. In arthritis patients, intraarticular temperature is increased by superficial heat and decreased by superficial cold. This has clear consequences for treatment policy.