bluuebunny/crossref_metadata_2025 huggingface dataset:
Distal extremity swelling with pitting edema in polymyalgia rheumatica. Report of nineteen cases
Authors: Salvarani Carlo , Gabriel Sherine , Hunder Gene G.
Published: February 2007

Objective. To determine the frequency and clinical characteristics of diffuse distal extremity swelling with pitting edema occurring in polymyalgia rheumatica (PMR).

Methods. Clinical features and laboratory findings were recorded for all 245 residents of Olmsted County, Minnesota who developed PMR over a 22‐year period (1970–1991). Those who exhibited ≥1 episode of diffuse distal extremity edema with pitting were selected for this study, and were evaluated further.

Results. Thirteen women and 6 men in this incidence cohort of PMR had ≥1 episode of distal extremity swelling with pitting edema. Giant cell arteritis was also identified in 5 patients. In 11 patients, the swelling and edema developed concurrently with proximal PMR symptoms. In 2 patients, the distal swelling was the initial manifestation, and in 6 patients, the distal symptoms developed during relapses or recurrences of PMR. Both upper and lower extremities were affected, usually in a symmetric manner. Other peripheral manifestations were also common. The distal swelling and pitting edema responded promptly to corticosteroids, and slowly or incompletely to nonsteroidal anti‐inflammatory drugs; a similar response was observed in the proximal symptoms. The distal swelling appeared to represent tenosynovitis and synovitis of regional structures.

Conclusion. Distal extremity swelling with pitting edema represents a manifestation of PMR that has not been well described in previous studies. Awareness of this finding will help facilitate the proper diagnosis and institution of appropriate therapy for this disease.
Cross‐cultural adaptation of a brief outcome questionnaire for Spanish‐speaking arthritis patients
Authors: Escalante Agustín , Galarza‐Delgado Dionisio , Beardmore Thomas D. , Baethge Bruce A. , Esquivel‐Valerio Jorge , Marines Ana Laura , Mingrone Michelle
Published: February 2007

Objective. To cross‐culturally adapt a brief self‐assessment questionnaire to measure outcome among English‐ or Spanish‐speaking patients with arthritis.

Methods. A questionnaire containing the following items was translated to Spanish: the 8 activities of daily living (ADL) questions of the Modified Health Assessment Questionnaire; a question about the duration of morning stiffness; and a 10‐point pain scale. Equivalence to the original English, test–retest reliability, and construct, criterion, and discriminant validity were determined on a population of patients from 4 clinical centers.

Results. English–Spanish equivalence and test–retest reliability of the questionnaire were almost perfect (intra‐class correlation coefficients [ri] ≥0.90 for each). Construct validity, measured by comparing questionnaire scores with an occupational therapist's evaluation, was also near‐perfect in both languages (ri = 0.93 for English and 0.89 for Spanish). Both versions of the questionnaire correlated well with the physician‐determined Steinbrocker functional class, as well as with the amount of pain, grip strength, and walking velocity. Patients with systemic lupus erythematosus, rheumatoid arthritis, osteoarthritis, and fibromyalgia differed significantly in their pain: ADL ratios, in both languages.

Conclusion. The items of the Spanish questionnaire that we have adapted are equivalent to the original English versions. This questionnaire is suitable for studying Spanish‐speaking subjects with arthritis in the US and elsewhere.
Healing phenomena of erosive changes in rheumatoid arthritis patients undergoing disease‐modifying antirheumatic drug therapy
Authors: Rau Rolf , Herborn Gertraud
Published: February 2007

Objective. To describe radiographic healing phenomena and reparative changes of joint destruction in rheumatoid arthritis (RA).

Methods. Serial radiographs of 6 patients with erosive RA undergoing long‐term treatment with disease‐modifying antirheumatic drugs (DMARDs) were studied. Radiographs showing healing phenomena were reproduced, and examples of single joints are shown.

Results. The examples show recortication of erosions, filling in of erosions with new bone, and secondary osteoarthrosis with bone sclerosis and osteophyte formation. Commonly used radiographic scoring methods do not have the capacity to account for these reparative changes.

Conclusion. Healing phenomena can be observed in RA patients undergoing long‐term DMARD treatment. These phenomena can be regarded as clinical end points, and their assessment should be incorporated into existing standardized methods for radiologic evaluation and scoring of RA.
Splinter hemorrhages following arterial puncture
Authors: Martens Peter B. , Levine James A. , Hunder Gene G.
Published: February 2007

Splinter hemorrhages can be a feature of the antiphospholipid syndrome. We describe a patient in whom splinter hemorrhages developed following radial artery puncture. The implications of this finding in patients with the antiphospholipid syndrome are discussed.
The mortality of rheumatoid vasculitis compared with rheumatoid arthritis
Authors: Voskuyl Alexandre E. , Zwinderman Aeilko H. , Westedt Marie Louise , Vandenbroucke Jan P. , Breedveld Ferdinand C. , Hazes Johanna M. W.
Published: February 2007

Objective. To determine whether the mortality of patients with rheumatoid vasculitis (RV) is increased in comparison with that of patients with rheumatoid arthritis (RA).

Methods. The mortality of all RV patients identified in 1980–1992 (n = 61) was compared with that of 244 RA controls matched for the year the diagnosis was made in the RV cases. Hazard ratios (HR) of death were calculated with a multivariate survival analysis, adjusting for age, sex, comorbidity, treatment, and parameters of RA severity.

Results. The unadjusted risk of death (HR) in RV patients compared with RA controls was 1.65 (95% confidence interval [95% CI] 1.05–2.58). After adjustment for prognostic factors, the HR was reduced to 1.26 (95% CI 0.79–2.01), mainly due to removal of the effects of age and sex. No excess mortality was seen in RV patients with severe organ involvement when compared with RV patients without severe organ involvement, although the former patients were treated more often with cytostatic and immunosuppressive drugs. Infection was the main cause of death in the RV patients, and cardiovascular disease in the RA controls. Vasculitis was reported as the cause of death in only 1 RV patient.

Conclusion. After allowance for general risk factors such as age and sex, there remains only a slight excess mortality in RV patients compared with RA controls.
Long‐term followup of patients with Sjögren's syndrome
Authors: Kruize Aike A. , Hené Ronald J. , van der Heide Agnes , Bodeutsch Cliff , De Wilde Peter C. M. , van Bijsterveld O. Paul , de Jong Jan , Feltkamp T. E. W. , Kater Louis , Bijlsma Johannes W. J.
Published: February 2007

Objective. To assess long‐term outcome in patients with isolated keratoconjunctivitis sicca (KCS), primary Sjögren's syndrome (SS), and secondary SS.

Methods. In 112 patients referred because of dry eyes, an ophthalmologic diagnosis of KCS was made based on results of the Schirmer I test, the tear fluid lysozyme concentration, and rose bengal staining. Subsequent assessments, including sublabial salivary gland biopsy, were performed. Followup assessments were performed 10–12 years after initial diagnosis.

Results. Six patients were excluded because no biopsy specimen was available. Seventy‐three percent of the remaining 106 patients were female, with a mean age of 53.5 years and a mean symptom duration of 3.9 years. Application of the 1987 classification criteria of Daniels and Talal revealed a diagnosis of isolated KCS in 56 patients, primary SS in 31, and secondary SS in 19. At baseline, 2 of 56 patients with isolated KCS and 8 of 31 with primary SS exhibited mild features of organ‐specific autoimmune disease. At followup, 2 of 38 patients with isolated KCS and 4 of 21 with primary SS had developed new features related to autoimmune disease, not necessitating treatment with corticosteroids; none of the patients developed major glandular complications. Three of 30 patients with primary SS died of malignant lymphoma. In 1 of these patients, the possibility could not be excluded that sicca symptoms and infiltrates seen on sublabial salivary gland biopsy had occurred concomitantly with early stages of lymphoma. Malignant lymphoma did not develop in any of the patients with isolated KCS or secondary SS.

Conclusion. Primary Sjögren's syndrome is characterized by a stable and rather mild course of glandular and extraglandular manifestations, in marked contrast to the increased risk for development of malignant lymphoma in these patients. Since patients with isolated KCS do not have an increased risk for development of malignant lymphoma, a presumptive diagnosis of primary SS should be confirmed in patients with sicca syndrome.
Polymyalgia rheumatica in patients with a normal erythrocyte sedimentation rate
Authors: Helfgott Simon M. , Kieval Raphael I.
Published: February 2007

Objective. To ascertain the frequency of polymyalgia rheumatica (PMR) with a normal erythrocyte sedimentation rate (ESR; ≤30 mm/hour) and to determine any defining clinical characteristics.

Methods. A retrospective chart review study of all patients meeting the clinical criteria for PMR seen over a 5‐year period in a hospital and an office‐based rheumatology practice.

Results. We evaluated 117 patients; 26 (22.2%) had a pretreatment ESR of ⩽30 mm/hour (mean ± SD 19.8 ± 7.5 versus 74.4 ± 30.3 mm/hour for elevated ESR group; P < 0.0001). Of the 26 normal ESR patients, 15 (58%) were female compared with 74 of the 91 elevated ESR patients (81%) (P < 0.02, by Fisher's exact test). The mean hemoglobin concentration was significantly lower in the elevated ESR population (mean ± SD 1.23 ± 0.15 gm/liter versus 1.38 ± 0.11 gm/liter; P < 0.0001). The duration of symptoms prior to treatment with prednisone was significantly longer for patients with a normal ESR (149 ± 95 days versus 103 ± 95 days for elevated ESR patients; P <0.04).

Conclusion. In our series, PMR with a normal ESR accounted for approximately one‐fifth of all PMR patients, more commonly in men. The lack of characteristically abnormal laboratory findings may result in a delay in the proper diagnosis and management of this condition.
Methotrexate‐associated lymphoma in patients with rheumatoid arthritis. Report of two cases
Authors: Bachman Teresa R. , Sawitzke Allen D. , Perkins Sherrie L. , Ward John H. , Cannon Grant W.
Published: February 2007

This report describes 2 patients with longstanding seropositive rheumatoid arthritis (RA) treated with oral methotrexate (MTX) who developed large cell lymphoma of B cell phenotype. In situ hybridization studies showed nuclear staining for Epstein‐Barr virus (EBV) within the malignant lymphoid cells. In both cases, the lymphoma was undetectable several weeks after diagnostic biopsy followed by discontinuation of MTX. These observations suggest that, in patients with RA who develop an EBV‐associated lymphoproliferative disorder, a trial of discontinuation of immunosuppressive agents may be warranted before chemotherapy is considered. In addition, there is a need for a heightened awareness of the development of lymphoma in this patient population.
Multiple myeloma–associated systemic vasculopathy due to crystalglobulin or polyarteritis nodosa
Authors: Hasegawa Hisashi , Ozawa Tetsuo , Tada Noriyoshi , Taguchi Youko , Ohno Koichiro , Chou Takaaki , Watanabe Takeshi , Kuroda Takeshi , Nakano Masaaki , Usuda Hiroyuki , Emura Iwao , Arakawa Masaaki
Published: February 2007

Systemic vasculopathy is a rare complication of multiple myeloma (MM). We describe a patient diagnosed with MM who developed clinical features of systemic vasculopathy including gangrene, livedo reticularis, hypertension, renal failure, and perforation of the small intestine. Histopathologic examination of the small intestine revealed necrotizing vasculitis in the small arteries, along with crystalline deposits in the small vessels. To our knowledge, previously reported cases of systemic vasculopathy associated with MM include at least 9 cases due to crystalglobulin deposition in vessels and 2 due to polyarteritis nodosa. Deposits of crystalglobulin may have induced systemic necrotizing vasculitis in our patient.
Gastric antral vascular ectasia (watermelon stomach) in patients with systemic sclerosis
Authors: Watson Maria , Hally Robert J. , McCue Peter A. , Varga John , Jiménez Sergio A.
Published: February 2007

This report describes 5 patients with systemic sclerosis (SSc) who developed severe, recurrent upper gastrointestinal (GI) bleeding due to gastric antral vascular ectasia (GAVE). The clinical records, the endoscopic findings, and the histologic appearance of biopsy specimens and surgically resected gastric tissue from the patients were reviewed. All 5 patients developed severe and recurrent episodes of upper GI bleeding leading to severe anemia requiring multiple transfusions. The cutaneous involvement was diffuse in 3 patients and limited in 2. All but 1 had cutaneous telangiectasias. The diagnosis of GAVE was established by endoscopy within 3 years of the diagnosis of SSc in all cases. One patient required heater probe cautery, 2 required laser coagulation, and 2 underwent surgical resection of the gastric antrum for control of the GI bleeding. The possibility of GAVE should be considered in SSc patients who have recurrent upper GI bleeding. It is suggested that the antral vascular lesions in these patients may represent a component of the spectrum of vascular alterations of SSc.
The development and initial validation of the systemic lupus international collaborating clinics/American college of rheumatology damage index for systemic lupus erythematosus
Authors: Gladman Dafna , Ginzler Ellen , Goldsmith Charles , Fortin Paul , Liang Matthew , Sanchez‐Guerrero Jorge , Urowitz Murray , Bacon Paul , Bombardieri Stefano , Hanly John , Jones John , Hay Elaine , Symmons Deborah , Isenberg David , Kalunion Kenneth , Maddison Peter , Nived Ola , Sturfelt Gunnar , Petri Michelle , Richter Martin , Snaith Michael , Zoma Asad
Published: February 2007

Objective. To develop and perform an initial validation of a damage index for systemic lupus erythematosus (SLE).

Methods. A list of items considered to reflect damage in SLE was generated through a nominal group process. A consensus as to which items to be included in an index was reached, together with rules for ascertainment. Each center submitted 2 assessments, 5 years apart, on 2 patients with active and 2 with inactive disease, of whom 1 had increased damage and the other had stable disease. Analysis of variance was used to test the factors physician, time, amount of damage, and activity status.

Results. Nineteen physicians completed the damage index on 42 case scenarios. The analysis revealed that the damage index could identify changes in damage seen in patients with both active and inactive disease. Patients who had active disease at both time points had a higher increase in damage. There was good agreement among the physicians on the assessment of damage in these patients.

Conclusion. This damage index for SLE records damage occurring in patients with SLE regardless of its cause. The index was demonstrated to have content, face, criterion, and discriminant validity.
Disease severity in patients with systemic lupus erythematosus correlates with an increased ratio of interleukin‐10: Interferon‐γ–secreting cells in the peripheral blood
Authors: Hagiwara Eri , Gourley Mark F. , Lee Susie , Klinman Dennis M.
Published: February 2007

Objective. To compare the phenotype and frequency of cells that actively secrete type 1 and type 2 cytokines in systemic lupus erythematosus (SLE) patients (n = 46), versus normal controls (n = 60).

Methods. ELISPOT analysis of freshly isolated peripheral blood mononuclear cells (PBMC).

Results. T cells were the major source of interleukin‐2 (IL‐2), IL‐4, and interferon‐γ (IFNγ), whereas monocytes were the primary source of IL‐6 and IL‐10 in the PB of lupus patients. Significantly fewer PBMC spontaneously secreted IFNγ and IL‐2 (P ⩽ 0.03), while significantly more PBMC produced IL‐6 and IL‐10 (P < 0.001), in lupus patients versus controls. Disease severity in lupus patients correlated with an elevated ratio of IL‐10:IFNγ‐secreting cells (P < 0.001).

Conclusion. SLE is characterized by an imbalance in the ratio of type 1:type 2 cytokine‐secreting PBMC.
Increased bone mass with pamidronate treatment in rheumatoid arthritis. Results of a three‐year randomized, double‐blind trial
Authors: Eggelmeijer Frank , Papapoulos Socrates E. , van Paassen Henk C. , Dijkmans Ben A. C. , Valkema Roelf , Westedt Marie Louise , Landman Jan‐Otto , Pauwels Ernest K. J. , Breedveld Ferdinand C.
Published: February 2007

Objective. Osteoporosis is a frequent complication of rheumatoid arthritis (RA). We therefore investigated the effect of oral pamidronate therapy as a specific bone‐sparing agent in RA.

Methods. The study design was a 3‐year randomized, double‐blind trial of 300 mg oral pamidronate/day compared with placebo in 105 RA patients. Bone mineral density (BMD) measured at 12‐month intervals was the primary efficacy parameter.

Results. In 3 years, lumbar spine and forearm BMD increased significantly in the pamidronate‐treated group (by 8.4 ± 6.9% [mean ± SEM] [P < 0.0001] and 5.2 ± 6.5% [P < 0.005], respectively), compared with nonsignificant changes in the placebo‐treated patients (increase of 0.6 ± 5.2% and decrease of 1.2 ± 5.8%, respectively). Femoral neck BMD increased in the pamidronate‐treated group (by 2.6 ± 8.6%) and decreased significantly in the placebo‐treated group (by 4.0 ± 1.3% [P < 0.005]). The changes in BMD with time at all 3 measurement sites were significantly different between the treatment groups (P < 0.0001). Changes in radiographic signs of joint damage and in disease activity were similar in the 2 groups.

Conclusion. The present study provides the first evidence that long‐term treatment with an orally administered bisphosphonate overcomes bone loss and increases bone mass when compared with placebo. This finding may have significance with regard to the treatment of patients with RA.
Gender, paid work, and symptoms of emotional distress in rheumatoid arthritis patients
Authors: Fifield Judith , Reisine Susan , Sheehan T. Joseph , McQuillan Julia
Published: February 2007

Objective. To evaluate the relative contribution of gender‐related work conditions, gender‐related socialization practices, and disease characteristics to the explanation of emotional distress in men and women with rheumatoid arthritis (RA).

Methods. Three hundred sixty‐nine RA patients who were employed outside the home were recruited from a national randomized sample of rheumatology practices. Data on paid work and disease characteristics were obtained by telephone interview. Emotional distress was measured by the Center for Epidemiological Studies Depression (CES‐D) scale. Hierarchical ordinary least‐squares regression was used to assess the relationship of sex, class, work characteristics, and disease characteristics to both the CES‐D summary scale and the CES‐D factor structure.

Results. Differences in emotional distress were explained best by functional ability and pain and secondarily by the characteristics of paid work, with no independent effect for sex. Distress increased with decreasing functional ability, increasing pain, and exposure to such work characteristics as low autonomy, low income, and high demands. No sex differences in any of the CES‐D subscales remained after controlling for disease and work variables.

Conclusion. Among employed RA patients with high levels of functional disability and exposure to stressful work characteristics, men and women are at equal risk of experiencing emotional distress.
Psychiatric diagnoses in patients with fibromyalgia are related to health care–seeking behavior rather than to illness
Authors: Aaron Leslie A. , Bradley Laurence A. , Alarcón Graciela S. , Alexander Ronald W. , Triana‐Alexander Mireya , Martin Michelle Y. , Alberts Kristin R.
Published: February 2007

Objective. To compare the frequency of lifetime psychiatric disorders among 3 groups of subjects: patients with fibromyalgia syndrome (FMS) from a tertiary care setting, community residents with FMS who had not sought medical care for their FMS symptoms (“FMS nonpatients”), and healthy controls.

Methods. We used the Computerized Diagnostic Interview Schedule to assess lifetime psychiatric diagnoses, as well as the Center for Epidemiological Studies Depression scale and the Trait Anxiety Inventory to assess current psychological distress, among 64 patients with FMS, 28 FMS nonpatients, and 23 healthy individuals.

Results. Patients with FMS, relative to FMS nonpatients and healthy controls, were characterized by a significantly greater number of lifetime psychiatric diagnoses (P = 0.002). Nonpatients did not differ from controls in psychiatric diagnoses. Patients also exhibited higher psychological distress levels than nonpatients, and nonpatients showed greater distress than controls. Differences in psychological distress between patients and nonpatients were eliminated after controlling for pain threshold and fatigue ratings.

Conclusion. Psychiatric disorders are not intrinsically related to the FMS syndrome. Instead, multiple lifetime psychiatric diagnoses may contribute to the decision to seek medical care for FMS in tertiary care settings.
Regulation of adhesion molecule expression by human synovial microvascular endothelial cells in vitro
Authors: To Shing S. T. , Newman Peter M. , Hyland Valentine J. , Robinson Bruce G. , Schrieber Leslie
Published: February 2007

Objective. To examine the in vitro expression of E‐selectin, P‐selectin, intercellular adhesion molecule 1 (ICAM‐1), ICAM‐2, vascular cell adhesion molecule 1 (VCAM‐1), and platelet–endothelial cell adhesion molecule 1 (PECAM‐1) by synovial microvascular endothelial cells (SMEC) in comparison with microvascular neonatal foreskin endothelial cells (FSE) and macrovascular human umbilical vein endothelial cells (HUVE).

Methods. Cultured endothelial cells were treated for 4 hours with medium alone or tumor necrosis factor α (TNF α). The expression of endothelial adhesion molecules was evaluated by flow cytometry, cell enzyme‐linked immunosorbent assay, and Northern blot analysis.

Results. SMEC continuously expressed E‐selectin under basal culture conditions, whereas FSE and HUVE did not. TNF α treatment of rheumatoid arthritis (RA) SMEC resulted in sustained peak expression of E‐selectin for up to 24 hours, which subsequently declined but remained elevated even at 72 hours. In contrast, peak E‐selectin expression in FSE and HUVE occurred between 4 hours and 16 hours after TNF α treatment and then declined to near basal levels by 24–48 hours. SMEC expressed significantly higher levels of ICAM‐1 compared with HUVE under basal culture conditions. There was no difference between SMEC, FSE, and HUVE in the expression of P‐selectin, VCAM‐1, ICAM‐2, or PECAM‐1. Northern blot analysis demonstrated that the levels of E‐selectin expression by TNF α‐stimulated endothelial cells correlated with their respective messenger RNA levels.

Conclusion. Regulation of E‐selectin and ICAM‐1 expression in RA synovial endothelium is different from that in neonatal foreskin and human umbilical vein endothelium. The augmented expression of adhesion molecules in RA synovial endothelium may facilitate the recruitment of leukocytes to this site.
The superficial layer of human articular cartilage is more susceptible to interleukin‐1–induced damage than the deeper layers
Authors: Häuselmann H. J. , Flechtenmacher J. , Michal L. , Thonar E. J‐M. A. , Shinmei M. , Kuettner K. E. , Aydelotte M. B.
Published: February 2007

Objective. To compare the responses of chondrocytes from superficial and deep layers of normal human articular cartilage to interleukin‐1 (IL‐1) and IL‐1 receptor antagonist protein (IRAP), and to evaluate the binding sites for IL‐1 on these cells.

Methods. Cartilage and chondrocytes from superficial and deeper layers of human femoral condyles were cultured with and without IL‐1 in the presence and absence of IRAP. The effect of these agents on 35S‐proteoglycan synthesis and catabolism and production of stromelysin and tissue inhibitor of metalloproteinases 1 (TIMP‐1) were measured by biochemical and immunologic assays. Receptor binding was evaluated using 125I‐labeled IL‐1.

Results. IL‐1 induced more severe inhibition of proteoglycan synthesis and a lower ratio of secreted TIMP‐1:stromelysin in chondrocytes from superficial cartilage than those from deeper cartilage. IRAP blocked responses to IL‐1 more effectively in chondrocytes from deep cartilage than those from superficial cartilage. Chondrocytes from the articular surface showed approximately twice the number of high‐affinity binding sites for IL‐1 as did cells from deep cartilage.

Conclusion. Chondrocytes from the surface of articular cartilage show a greater vulnerability to the harmful effects of IL‐1 and are less responsive to the potential therapeutic effects of IRAP than cells in the deeper layers of the tissue.
Disease‐modifying activity of SK&F 106615 in rat adjuvant‐induced arthritis. Multiparameter analysis of disease including magnetic resonance imaging and bone mineral density measurements
Authors: Bradbeer Jeremy N. , Kapadia Rasesh D. , Sarkar Susanta K. , Zhao Hugh , Stroup George B. , Swift Barbara A. , Rieman David J. , Badger Alison M.
Published: February 2007

Objective. To evaluate the effect of SK&F 106615 on joint integrity in rats with adjuvant‐induced arthritis (AIA).

Methods. AIA was induced in Lewis rats on day 0, and the animals were treated either prophylactically (days 0–16 or days 0–23) or therapeutically (days 10–23) with SK&F 106615. Efficacy was determined by measurements of paw inflammation, bone mineral density (BMD) using dual x‐ray absorptiometry, and magnetic resonance imaging (MRI). Joint integrity was also determined histologically, and serum interleukin‐6 (IL‐6) levels were measured as a marker of the antiinflammatory effects of the compound.

Results. Prophylactic treatment (days 0–16) of AIA rats with SK&F 106615 significantly inhibited paw volume at doses of 5–45 mg/kg/day given orally on 5 days each week. Extensive evaluation of joint integrity in rats treated with SK&F 106615 20 mg/kg/day orally for 23 days showed inhibition of paw volume, normalization of BMD, and significant improvement in disease by MRI and histologic assessment compared with the AIA controls. Elevated levels of serum IL‐6 in AIA rats were reduced dramatically by SK&F 106615. Therapeutic treatment (days 10–23) resulted in similar protective effects measured by paw inflammation, BMD, and MRI. In the therapeutic protocol, serum IL‐6 appeared to be a more sensitive marker of antiinflammatory activity than paw edema.

Conclusion. Symptoms of AIA in rats are significantly reduced by prophylactic and therapeutic treatment with SK&F 106615. Of particular note, this compound appears to exert a protective effect on joint integrity and to have disease‐modifying properties.
Some autoantibodies to Ro/SS‐A and La/SS‐B are antiidiotypes to anti–double‐stranded DNA
Authors: Zhang Wei , Reichlin Morris
Published: February 2007

Objective. To determine the relationship of anti–Ro/SS‐A and anti–La/SS‐B antibodies to anti–double‐stranded DNA (anti‐dsDNA) in sera from patients with systemic lupus erythematosus.

Methods. Sera with anti–Ro/SS‐A alone (n = 5) or those with anti–Ro/SS‐A and anti–La/SS‐B (n = 7) were absorbed with purified Ro/SS‐A and La/SS‐B, respectively. The absorbed sera were then tested for reactivity with MOLT‐4 extract by Western blot and dsDNA by enzyme‐linked immunosorbent assay (ELISA). With selected sera, anti‐dsDNA was isolated on DNA cellulose columns and anti–Ro/SS‐A and anti–La/SS‐B were isolated on antigen‐affinity columns. Reactivity between anti‐dsDNA and autologous anti–Ro/SS‐A or anti–La/SS‐B, as well as inhibition by cognate antigens, was studied.

Results. After absorption, all sera showed reactivity with small nuclear RNP A and D bands in Western blots, and some showed reactivity with dsDNA by ELISA. Anti‐dsDNA populations (n = 4) were purified on dsDNA cellulose columns. Anti–Ro/SS‐A (n = 1) and anti–La/SS‐B (n = 3) were affinity purified from the same sera as the anti‐dsDNA. In all cases, anti‐dsDNA bound autologous anti–Ro/SS‐A and anti–La/SS‐B much more strongly than it bound normal pooled IgG. Moreover, dsDNA, but not RNA, blocked these interactions. In addition, Ro/SS‐A blocked anti–Ro/SS‐A and La/SS‐B blocked anti–La/SS‐B in these same interactions.

Conclusion. In sera with anti–Ro/SS‐A and anti–La/SS‐B, there are subpopulations of these antibodies that bind and mask anti‐dsDNA. We hypothesize that these anti–Ro/SS‐A and anti–La/SS‐B antibodies are antiidiotypes to idiotypes on anti‐dsDNA and that they both mask and down‐regulate these anti‐dsDNA antibodies.
Enhancement of sparc (osteonectin) synthesis in arthritic cartilage: Increased levels in synovial fluids from patients with rheumatoid arthritis and regulation by growth factors and cytokines in chondrocyte cultures
Authors: Nakamura Shigeo , Kamihagi Kyoko , Satakeda Hisashi , Katayama Masahiko , Pan Haiou , Okamoto Hiroshi , Noshiro Mitsuhide , Takahashi Koichiro , Yoshihara Yasuo , Shimmei Masayuki , Okada Yasunori , Kato Yukio
Published: February 2007

Objective. To investigate the roles of SPARC (secreted protein, acidic and rich in cysteine) (osteonectin) in arthritis, using cartilage and synovium specimens and synovial fluids (SF) from patients with rheumatoid arthritis (RA) or osteoarthritis (OA), and to examine the effects of cytokines, growth factors, and hormones on SPARC synthesis by chondrocytes in culture.

Methods. SPARC in cartilage and synovium was immunostained with monoclonal antibodies. SPARC synthesis by cultured chondrocytes was measured by Northern blot analysis, immunoblotting, and sandwich enzyme‐linked immunosorbent assay.

Results. SPARC was identified in numerous chondrocytes in the superficial and middle zones and in regenerating chondrocytes of RA and OA joints, whereas such staining was absent in these zones of normal cartilage, except for weak signals from a few chondrocytes in the deep zone. In addition, SPARC synthesis was enhanced in synovial cells of RA and OA joints. The average SPARC level in SF was 10‐fold higher in the RA than in the OA population. In rabbit articular chondrocyte cultures, administration of transforming growth factor β1 (TGFβ1) and bone morphogenetic protein 2 increased SPARC levels at 24–48 hours, whereas interleukin‐1β (IL‐1β), IL‐1α, tumor necrosis factor α, lipopolysaccharide, phorbol myristate acetate, basic fibroblast growth factor, and dexamethasone decreased SPARC levels at 24–72 hours. TGFβ increased SPARC messenger RNA (mRNA) levels at 24 hours, whereas IL‐1β caused a marked decrease in SPARC mRNA levels at 24 hours. Furthermore, IL‐1 decreased the glycosylation of SPARC.

Conclusion. These findings suggest that various growth factors and cytokines, including TGFβ1 and IL‐1β, regulate the production of SPARC by chondrocytes at pre‐ and posttranslational levels, and that SPARC synthesis is markedly enhanced in arthritic joints.
Fibronectin synthesis in superficial and deep layers of normal articular cartilage
Authors: Hayashi Takeshi , Abe Etsuko , Jasin Hugo E.
Published: February 2007

Objective. To study the distribution and synthesis of fibronectin (FN) in superficial and deep layers of normal articular cartilage.

Methods. Superficial and deep bovine and human articular cartilage slices were used to extract and quantitate FN by radioimmunoassay. Chondrocytes were also isolated by collagenase digestion for FN extraction and culture. Superficial and deep cartilage explants were cultured with and without stimulation by cytokines. Quantitation of newly synthesized FN was carried out by incubation with 35S‐methionine. FN was purified on gelatin‐agarose columns and further characterized by polyacrylamide gel electrophoresis. FN messenger RNA (mRNA) was quantitated by Northern blot analysis.

Results. Freshly isolated bovine chondrocytes from deep cartilage contained 2.3 ± 0.2 times more FN than was found in superficial cells (P < 0.025). Deep cartilage explants contained 1.2 times more FN than was found in superficial tissue. Explants obtained from deep cartilage synthesized 2.4 times more FN per cell than did superficial tissues (P < 0.01). FN synthesis as a fraction of total protein synthesis was significantly greater in deep explants (P < 0.01) compared with superficial tissues. Isolated deep chondrocytes in culture synthesized 1.89 ± 0.33‐fold more FN than did superficial cells (P < 0.05). Cytokine‐stimulated superficial cartilage explants failed to respond in terms of FN synthesis. FN mRNA quantitation showed no significant differences between superficial and deep populations.

Conclusion. Since FN plays a major role in cell adhesion to damaged cartilage surfaces, our results suggest that modulation of FN synthesis near the articular surface of cartilage may be one of the factors that impede pannus invasion following an inflammatory insult to the joint.
Cell‐type specificity of anti‐CD45 autoantibodies in systemic lupus erythematosus
Authors: Czyzyk Jan , Fernsten Philip , Shaw Melody , Winfield John B.
Published: February 2007

Objective. To determine the specificity of anti‐CD45 autoantibodies in systemic lupus erythematosus (SLE) for native CD45 and for CD45 expressed by T cells and B cells, and at different stages of cellular activation.

Methods. CD45 purified from different types of lymphocytes was examined by immunoblotting with sera from patients with SLE. Indirect immunofluorescence experiments were performed with purified anti‐CD45 autoantibodies.

Results. IgM anti‐CD45 autoantibodies in SLE recognize native CD45 expressed on the surface membrane of viable lymphocytes and CD45 purified from activated peripheral T cells and certain T cell lines, but not CD45 purified from B cells or resting peripheral T cells. The presence or absence of reactivity is independent of the individual isoforms expressed.

Conclusion. Recognition of CD45 by IgM antilymphocyte autoantibodies in SLE varies with the lineage and state of activation of the lymphocyte target. This pattern of reactivity is consistent with autoantibody specificities involving CD45 glycoforms, rather than CD45 isoforms.
Defective antigen‐presenting cell function in patients with systemic lupus erythematosus: Role of the B7‐1 (CD80) costimulatory molecule
Authors: Tsokos George C. , Kovacs Birgit , Sfikakis Peter P. , Theocharis Stamatis , Vogelgesang Scott , Via Charles S.
Published: February 2007

Objective. Patients with systemic lupus erythematosus (SLE) who exhibit defective in vitro responses to recall antigens and normal responses to alloantigens have been shown to have an abnormality in antigenpresenting cell (APC) function. This study was undertaken to further characterize this defect in APC function in lupus patients.

Methods. Mononuclear cells (MNC) from the peripheral blood of patients with SLE and from normal individuals were cultured in the presence of either recall antigen tetanus toxoid (TT), anti‐CD3 (OKT3) monoclonal antibody, or alloantigens, and proliferative or interleukin‐2 responses were assessed. Cell surface expression of B7‐1 was assessed by flow cytometry.

Results. MNC from all normal individuals and from 7 patients with SLE responded to both TT and alloantigen and were designated +/+. Twelve SLE patients did not respond to TT but did respond to alloantigen stimulation and were designated ‐/+. In both normal subjects and SLE patients, the ability to respond to OKT3 correlated strongly with the ability to respond to recall antigen. A defect in APC costimulatory function was suggested by data demonstrating that interferon‐γ‐induced expression of B7‐1 was significantly reduced in SLE patients compared with controls. Neither controls nor SLE patients expressed detectable amounts of surface B7‐1 molecule on resting APC. Defective recall and anti‐CD3‐stimulated responses could be enhanced in SLE patients in the presence of B7/BB1‐transfected P815 murine mastocytoma cells underscoring an SLE‐associated defect in costimulatory activity. However, nontransfected P815 cells were also able to enhance responses to OKT3 in ‐/+ patients; blocking experiments showed that this was mediated through an IgG Fc receptor‐dependent mechanism.

Conclusion. These data indicate that SLE‐associated defects in APC function in vitro can be accounted for by abnormalities in APC surface membrane molecules such as B7, IgG Fc receptors, and possibly others.
A pilot trial of oral type II collagen in the treatment of juvenile rheumatoid arthritis
Authors: Barnett Martha L. , Combitchi Daniel , Trentham David E.
Published: February 2007

Objective. To evaluate the efficacy of oral chicken type II collagen (CCII) in the treatment of juvenile rheumatoid arthritis (JRA).

Methods. Ten patients with active JRA were treated with CCII for 12 weeks. Efficacy parameters, which included swollen and tender joint count and score, grip strength, 50‐foot walking time, duration of morning stiffness, and patient and physician global scores of disease severity, were assessed monthly.

Results. All patients completed the full course of therapy. Eight patients had reductions in both swollen and tender joint counts after 3 months of CCII. The mean changes from baseline in swollen and tender joint counts for the 8 responders at the end of the study were –61% and –54%, respectively. Mean values for other efficacy parameters also showed improvement from baseline. There were no adverse events that were considered to be treatment related.

Conclusion. Oral CCII may be a safe and effective therapy for JRA, and its use in this disease warrants further investigation.
Elevated nitric oxide production in rheumatoid arthritis: Detection using the fasting urinary nitrate:creatinine ratio
Authors: Grabowski Peter S. , England Amanda J. , Dykhuizen Roelf , Copland Mhairi , Benjamin Nigel , Reid David M. , Ralston Stuart H.
Published: February 2007

Objective. To develop a simple method for assessing endogenous nitric oxide (NO) production applicable to routine clinical practice in rheumatology.

Methods. NO production was assessed in patients with rheumatoid arthritis (RA) as serum nitrate levels and as the urinary nitrate:creatinine ratio in morning samples of urine following an overnight fast. The influence of dietary intake of nitrate on these measurements was investigated in healthy volunteers. The clinical value of the urinary nitrate:creatinine ratio was validated in patients with infectious gastroenteritis, in whom its production is known to be increased.

Results. Urinary nitrate:creatinine ratios were significantly elevated in patients with RA (average 3‐fold elevation over controls; P < 0.005) or infectious gastroenteritis (average 10‐fold elevation, P < 0.001). Serum nitrate was significantly elevated only in patients with infectious gastroenteritis (P < 0.001). Dietary intake of nitrate had no significant influence on the fasting morning urinary nitrate:creatinine ratio in the healthy volunteers, showing that this parameter is a useful indicator of endogenous NO production.

Conclusion. We have developed a simple procedure for evaluating endogenous NO production that is readily applicable to routine clinical practice. Assessment of NO production will help in our understanding of its role in inflammatory conditions such as RA.
Hair dye use and the risk of developing systemic lupus erythematosus: A cohort study
Authors: Sanchez‐Guerrero Jorge , Karlson Elizabeth W. , Colditz Graham A. , Hunter David J. , Speizer Frank E. , Liang Matthew H.
Published: February 2007

Objective. To investigate the role of hair dye use in the etiology of systemic lupus erythematosus (SLE).

Methods. Participants included 106,391 women enrolled in the Nurses' Health Study, a prospective cohort study. The subjects were ages 30–55 years in 1976, and were free from SLE and any other connective tissue disease at the time of enrollment. In 1976, 1978, 1980, and 1982, subjects were classified as never‐users or ever‐users of permanent hair dye, based on self‐report. Incidence rates of SLE meeting American College of Rheumatology classification criteria were ascertained and confirmed by chart review.

Results. Compared with never‐users of permanent hair dye, the age‐adjusted relative risks (RR) for the development of SLE among ever‐users (n = 85 cases) was 0.96 (95% confidence interval [95% CI] 0.63–1.47). Duration of hair dye use was not related to risk of SLE. Women with 15 or more years of use had no increased risk (RR = 0.92, 95% CI 0.46–1.83). There was no relationship between frequency of use or time since first use and risk of SLE. The results were similar when less stringent criteria for SLE were used.

Conclusion. We found no evidence that permanent hair dye use, age at first use, frequency of use, or duration of use is associated with the development of SLE.
Homozygous hereditary C1q deficiency and systemic lupus erythematosus: A new family and the molecular basis of C1q deficiency in three families
Authors: Slingsby Jason H. , Norsworthy Peter , Pearce Glen , Vaishnaw Akshay K. , Issler Helen , Morley Bernard J. , Walport Mark J.
Published: February 2007

Objective. To describe a new kindred with C1q deficiency and to identify the molecular lesions responsible for complete functional C1q deficiency in this and 2 other previously described kindreds.

Methods. The A‐, B‐, and C‐chain genes of C1q were amplified by polymerase chain reaction, cloned, and sequenced. The DNA sequence was checked for mutations.

Results. Patient 1 had a homozygous G‐to‐A change at codon 6 of the C chain, causing an amino acid change from Gly to Arg. Patient 2 had a homozygous deletion of a C nucleotide at codon 43 of the C‐chain, causing a frame shift, leading to a premature stop codon at codon 108. Patient 3 had a homozygous C‐to‐T mutation at amino acid position 41 of the C chain, resulting in a premature stop codon.

Conclusion. In the homozygous state, the mutations are sufficient to cause complete deficiency of C1q. The mutation in patient 1 has been previously reported in a patient of different ethnic origin. A survey of a series of 158 DNA samples from patients with systemic lupus erythematosus showed no other examples of this mutant allele.
Antiribosomal P antibodies in pediatric patients with systemic lupus erythematosus and psychosis
Authors: Press Joseph , Palayew Karen , Laxer Ronald M. , Elkon Keith , Eddy Allison , Rakoff David , Silverman Earl D.
Published: February 2007

Objective. To study antibodies directed against ribosomal P proteins, a sensitive and specific marker of depression and psychosis in systemic lupus erythematosus (SLE), in pediatric patients with SLE.

Methods. One hundred six serum samples were obtained from 79 patients with SLE. Sixty age‐ and sex‐matched control sera were obtained, and 12 samples were obtained from children with primary psychosis. Antibodies to recombinant ribosomal P (rRP) protein were detected using a standard enzyme‐linked immunosorbent assay.

Results. All 12 children with non–SLE‐associated psychosis had normal levels of anti‐rRP antibodies. Elevated levels of anti‐rRP were found in 11 of 64 pediatric SLE patients without a history of psychosis (17%). In the group of 13 SLE patients with psychosis, 5 (38%) had increased anti‐rRP antibody levels during the time of acute psychosis, and which significantly decreased during remission. In addition, most of the SLE patients without a history of psychosis had a good correlation between anti‐rRP antibody levels and disease activity. The patients with psychosis had significantly less renal involvement than the patients without a history of psychosis. This apparent protection from renal disease was not related to the presence or absence of either antiribosomal P or anti‐DNA antibodies.

Conclusion. Elevated serum levels of antibodies to ribosomal P protein can distinguish SLE‐associated psychosis from primary psychosis of childhood. In SLE, elevated antiribosomal P antibody levels were not specific for psychosis. Serial assays were useful for monitoring the disease activity.
Thallium perfusion defects predict subsequent cardiac dysfunction in patients with systemic sclerosis
Authors: Steen Virginia D. , Follansbee William P. , Conte Claudia G. , Medsger Thomas A.
Published: February 2007

Objective. To determine the significance of thallium perfusion defects in patients with systemic sclerosis (SSc).

Methods. This is a followup study of a series of 48 SSc patients who underwent thallium perfusion scans in the early 1980s. Their cardiac history and survival information over the last 10 years were obtained as part of the Pittsburgh Databank's yearly evaluation. We determined the frequency of subsequent development of arrhythmias requiring treatment or of congestive heart failure through patient and physician information.

Results. Patients with larger thallium perfusion defects had a significantly increased risk of developing subsequent cardiac events or death. The size of the initial thallium defect was the best predictor of later adverse events compared with other disease‐related features, in a logistic regression analysis.

Conclusion. We conclude that patients with SSc who have significant thallium perfusion defects are at a significantly increased risk of developing subsequent cardiac disease or death.
IgA multiple myeloma presenting as Henoch‐Schönlein purpura/polyarteritis nodosa overlap syndrome
Authors: Birchmore Daniel , Sweeney Christine , Choudhury Devasmita , Konwinski Martin F. , Carnevale Kevin , D'Agati Vivette
Published: February 2007

We report the unusual case of a man with a 5‐year history of relapsing Henoch‐Schönlein purpura (HSP) and macroscopic polyarteritis nodosa (PAN) as early manifestations of IgAκ multiple myeloma. The glomeruli contained monoclonal IgAκ deposits, without other immunoglobulins or λ light chains. Glomerular deposits lacked the usual electron density but could be demonstrated by immunoelectron microscopy. Multisystem large vessel vasculitis (antineutrophil cytoplasmic antibody negative) produced aneurysms of renal and hepatic arteries, whereas small vessel vasculitis affected the skin and glomeruli, producing a symptom complex of HSP with dermal and glomerular deposits of IgA. We conclude that HSP/overlap syndrome may be the initial manifestation of IgA myeloma and should be considered within the spectrum of monoclonal IgA deposition disease.
Detection of Borrelia burgdorferi by DNA amplification in synovial tissue samples from patients with lyme arthritis
Authors: Jaulhac Benoǐt , Chary‐Valckenaere Isabelle , Sibilia Jean , Javier Rose‐Marie , Piémont Yves , Kuntz Jean‐Louis , Monteil Henri , Pourel Jacques
Published: February 2007

Objective. To compare the detection rates of chromosomal flagellin gene from Borrelia burgdorfen in synovial tissue (ST) and synovial fluid (SF) using polymerase chain reaction (PCR) techniques.

Methods. B burgdorferi DNA was sought in SF and ST from 12 consecutive patients with Lyme arthritis and from 29 patients with noninfectious diseases (controls).

Results. No DNA amplification was observed in samples obtained from the 29 control patients, whereas B burgdorferi DNA was detected in all ST and/or SF samples from the 12 patients with Lyme arthritis. Results from 1 ST sample were not interpretable because of PCR inhibitors. Among the 11 remaining patients, 10 had positive ST samples, whereas only 4 had positive SF samples (P < 0.05).

Conclusion. These data suggest that detection of chromosomal B burgdorferi DNA may be more efficient in ST than SF.