Search

Objective: Adenosine exerts antiinflammatory effects via activation of the A3 adenosine receptor (A3AR), a Gi protein-associated cell-surface receptor, overexpressed in synovial tissue and peripheral blood mononuclear cells (PBMC) in patients with active rheumatoid arthritis (RA). CF101 is a highly specific orally bioavailable A3AR agonist., Methods: This was a multicenter study, blinded to dose, designed to assess the clinical activity and safety of CF101 in active RA. Seventy-four patients were randomized to receive 0.1, 1.0, or 4.0 mg CF101 bid for 12 weeks. The primary efficacy endpoint was American College of Rheumatology 20% response (ACR20) at Week 12. A3AR expression levels were analyzed in PBMC from 18 patients., Results: . Maximal responses were observed with 1.0 mg bid, lower at 0.1 and 4.0 mg bid. At 12 weeks, 55.6%, 33.3%, and 11.5% of the patients receiving 1.0 mg CF101 achieved ACR20%, 50%, and 70% responses, respectively. CF101 was generally well tolerated, with mild headache (4.1%), nausea (2.7%), and rash (2.7%) being the most common treatment-related adverse events. Statistically significant correlations between A3AR overexpression at baseline and ACR50 and ACR70 responses were observed., Conclusion: CF101 administered bid for 12 weeks resulted in improvement in signs and symptoms of RA that did not achieve statistical significance, and was safe and well tolerated. The expression level of A3AR was directly correlated with patient responses to CF101, suggesting its utilization as a biomarker for the pharmacodynamic and therapeutic effects of this novel agent. These findings require confirmation in a double-blind randomized placebo-controlled trial, currently under way.

Objective: To investigate whether whiplash injury may be a trigger for the onset of fibromyalgia (FM)., Methods: One hundred fifty-three patients presenting to the emergency room with the diagnosis of whiplash injury were examined. The control group included 53 patients hospitalized with fractures of the limbs, spine, and ribs due to road accident. The study and control groups were interviewed shortly after presenting and then followed prospectively. Patients complaining of musculoskeletal symptoms during followup were examined and a count of 18 tender points was conducted. FM was diagnosed if the patient fulfilled currently accepted 1990 American College of Rheumatology criteria., Results: The mean followup period for the study and control groups was 14.5 months (range 12-18) and 9 months (range 6-14), respectively. There were no differences between the groups with regard to age, sex, marital, education, or employment status. During the followup period only one patient in the study group and no patients in the control group developed signs and symptoms of FM. Three patients in the study group (2%) and 15 patients in the control group (16%) filed insurance claims; none was associated with FM., Conclusion: Whiplash injury and road accident trauma were not associated with an increased rate of FM after more than 14.5 months of followup.

Objective: To compare the prevalence of antibodies against alpha-fodrin in Sjögren's syndrome (SS) classified according to San Diego and European Community Study Group (ESG) criteria., Methods: The prevalence and mean concentrations of IgA and IgG autoantibodies against alpha-fodrin were determined and compared in patients with SS classified either according to San Diego criteria or to criteria of the ESG by ELISA., Results: IgA antibodies against alpha-fodrin were detected in 88% and IgG antibodies against alpha-fodrin in 64% and either of these antibodies in 93% of 85 patients classified according to San Diego criteria. Antibodies against Ro were present in 38% of these sera. IgA antibodies against alpha-fodrin were detected in 61%, IgG antibodies against alpha-fodrin in 51%, and any of these antibodies in 73% of 51 patients classified according to the ESG criteria. The mean concentrations of both IgA and IgG antibodies against alpha-fodrin that seem to correlate with disease activity were higher in patients classified according to the San Diego criteria., Conclusion: Antibodies against alpha-fodrin are detectable in almost all sera obtained from patients with SS classified according to the San Diego criteria and are significantly more prevalent than antibodies against Ro. The lower prevalence of the autoantibodies in patients classified according to the ESG criteria reflects the lower specificity of these criteria for SS.

Objective: To compare the clinical and laboratory characteristics of patients with primary Sjögren's syndrome (SS) with an elderly onset to those with a younger onset., Methods: The study group comprised 85 consecutive patients (79 women and 6 men) attending the Sjögren's clinic. Primary SS was diagnosed according to the San Diego criteria. Elderly onset disease (EOD) was determined as the appearance of symptoms suggestive of SS after age 65. Clinical and laboratory variables for EOD were compared to those of a younger onset disease (YOD). Salivary and serum samples of all patients were examined for concentrations of interleukin 6 (IL-6) and hyaluronic acid (HA)., Results: Seventeen patients with SS (20%) matched the definition of EOD and their median disease onset was 71 years (range 65-80). No significant differences were noted in the clinical disease manifestations between the 2 groups of patients. Rheumatoid factor and anti-Ro(SSA) antibodies were more common in the YOD group (p = 0.012 and p = 0.023, respectively). Significant elevations of salivary IL-6 and HA levels were detected in the YOD group compared to the EOD group with SS (17.3 +/- 3.6 vs 8.8 +/- 2.1 pg/ml and 230.2 +/- 41.1 vs 128.8 +/- 33.3 ng/ml, respectively) (p < 0.0001)., Conclusion: EOD SS has somewhat milder clinical symptoms with fewer immunological manifestations than YOD. The elevations of salivary IL-6 and HA in the younger group of SS patients support in part the differences in the inflammatory process between the 2 groups.

Objective: To determine whether anti-Ro antibodies are associated with gold induced side effects., Methods: A retrospective chart review of 208 patients with rheumatoid arthritis (RA) and examination of sera for the presence of anti-Ro antibodies by enzyme linked immunosorbent assay., Results: Anti-Ro antibodies were detected in 44 (21%) of our patients with RA and their presence correlated with positive rheumatoid factor, antinuclear antibody, and secondary Sjögren's syndrome. Thirty-three out of 48 patients with gold induced side effects (69%) were anti-Ro positive in contrast to 11 patients (7.5%) with positive antibodies with no side effects (p < 0.001). Mucocutaneous reactions had the only significant correlation (p < 0.01) with the presence of anti-Ro antibodies., Conclusion: Patients with RA with anti-Ro antibodies are prone to develop mucocutaneous side effects to gold salts.

Forty-nine members of 4 families with multiple cases of rheumatoid arthritis (RA) were investigated. Nine patients with RA, one patient with primary Sjögren's syndrome (SS) and one patient with systemic lupus erythematosus (SLE) were detected among them. Anti-Ro (SSA) antibodies were found in 11 members (22%) of the investigated group; 6 suffered from RA, SLE or primary SS, and 5 were healthy first degree relatives. Anti-La (SSB) antibodies were detected in only one family member with primary SS. Secondary SS was evident in 5 patients with RA, 3 of whom had anti-Ro antibodies; HLA-DR4 was present in 7 of 9 patients with RA (78%) but in only 7 of 26 asymptomatic relatives (27%) (p less than 0.05). All patients with RA and their relatives who had anti-Ro antibodies were found to have HLA-DR4. Our results demonstrate that anti-Ro antibodies are present in relatives of patients with RA and are strongly associated with HLA-DR4.

Forty-one patients with rheumatoid arthritis were treated for 2 weeks at a Tiberias spa hotel. Randomized into 2 groups, Group 1 received a combination of mineral baths and mud packs, and Group 2 had tap water baths only. Both groups had a significant but temporary improvement in Ritchie index. Group 1 showed a significant improvement in grip strength. No improvement was noticed in morning stiffness, 15 meter walk time and laboratory variables of disease activity in either group. Twelve patients with osteoarthritis (OA) received 2 weeks of treatment with mineral baths and mud packs. Statistically significant improvement for a period of 6 months was noticed in night pain, pain on passive motion, tenderness on palpation and in the index of severity of OA of the knee.

Sequential daily measurements of erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) were performed for one week after an I.V. injection of 7.5-13 mg methotrexate (MTX) in 18 patients with rheumatoid arthritis. Early decreases of ESR and CRP were observed. Serum CRP was more sensitive than ESR, displaying more pronounced falls from baseline to both the minimal and to the 7th day levels. Patients receiving their first dose of MTX (n = 9) exhibited a more prominent reduction of CRP levels in comparison to veteran MTX users (n = 9). The prompt response of acute phase reactants to MTX may correspond to the relatively rapid clinical effect of the drug in RA. It may also support an antiinflammatory mechanism of action of low dose MTX.

Two patients with classical rheumatoid arthritis and a mild nondeforming relapsing polychondritis are presented. DR4 antigen and depressed C4 levels were found and possible autoimmune mechanisms are discussed. The need for specific questioning to detect this rare association is proposed.

Bronchoalveolar lavage (BAL) was performed to assess the nature of pulmonary involvement in 12 asymptomatic nonsmoking patients with rheumatoid arthritis (RA). All 12 patients had normal lung function tests, including diffuse capacity for carbon monoxide and normal blood gases. Four patients (33%) had mild basilar interstitial changes on chest radiographs. In these 4 patients an elevated lymphocytic count in BAL fluid (30.7 +/- 8.3%) was found, as compared to the 8 patients with normal chest roentgenograms (7.2 +/- 1.9%; p less than 0.001). We suggest that BAL may be used as a sensitive tool for early diagnosis of pulmonary involvement in patients with RA.