Effect of age at disease onset in the clinical profile of spondyloarthritis: a study of 1424 Brazilian patients.

OBJECTIVES: To analyse demographic and clinical variables in patients with disease onset before and after 40, 45 and 50 years in a large series of Brazilian SpA patients. METHODS: A common protocol of investigation was prospectively applied to 1424 SpA patients in 29 centres distributed through the main geographical regions in Brazil. The mean age at disease onset was 28.56 ± 12.34 years, with 259 patients (18.2%) referring disease onset after 40 years, 151 (10.6%) after 45 years and 81 (5.8%) after 50 years. Clinical and demographic variables and disease indices (BASDAI, BASFI, BASRI, MASES, ASQoL) were investigated. Ankylosing spondylitis was the most frequent disease (66.3%), followed by psoriatic arthritis (18%), undifferentiated SpA (6.7%), reactive arthritis (5.5%), and enteropathic arthritis (3.5%). RESULTS: Comparing the groups according to age of disease onset, those patients with later onset presented statistical association with female gender, peripheral arthritis, dactylitis, nail involvement and psoriasis, as well as negative statistical association with inflammatory low back pain, alternating buttock pain, radiographic sacroiliitis, hip involvement, positive familial history, HLA-B27 and uveitis. BASDAI, BASFI and quality of life, as well as physicians and patient's global assessment, were similar in all the groups. Radiographic indices showed worse results in the younger age groups. CONCLUSIONS: There are two different clinical patterns in SpA defined by age at disease onset: one with predominance of axial symptoms in the group with disease onset ≤ 40 years and another favouring the peripheral manifestations in those with later disease onset.

A simple simulated public speaking test for evaluating anxiolytic drugs.

1. We evaluated the feasibility of using a simulated public speaking (SPS) test to assess the activity of anxiolytic drugs. SPS was achieved by requesting subjects to present a speech to an audiocassette recorder. Thirty volunteers were randomly assigned to one of three groups treated with 10 mg diazepam, 10 mg buspirone or placebo, under double-blind conditions. One h after drug administration, subjective states were measured by the Visual Analogue Mood Scale (VAMS), the State-Trait Anxiety Inventory (STAI) and by a Bodily Symptoms Scale (BSS). Heart rate and blood pressure were also recorded. 2. SPS induced both physiological and subjective changes characteristic of anxiety. Moreover, diazepam attenuated experimentally induced increases in excitement (as measured by VAMS) and agitation (as measured by BSS). Therefore, SPS using an audiocassette recorder is sensitive to a prototypical anxiolytic and may thus be a useful test for evaluating putative anxiolytics. 3. No effect was observed with the new anxiolytic drug buspirone. However, the present negative result may be explained by clinical data indicating that patients may experience a longer lag period before the onset of the anxiolytic effect of buspirone.

The chemokine receptor CCR5 genetic polymorphism and expression in rheumatoid arthritis patients.

OBJECTIVES: To identify the genetic polymorphism of the chemokine receptor CCR5 (the Delta32 allelic variant) in patients with rheumatoid arthritis (RA) and compare the findings with healthy controls. To compare the CCR5 phenotypic expression in T cells and monocytes isolated from the peripheral blood and synovial fluid in a subgroup of RA patients. METHODS: CCR5 genes of 92 RA patients and 160 healthy controls were genotyped using specific primers flanking the region of deletion. The ethnic distribution was similar between the groups. Flow cytometric analysis was used for immunophenotyping the T cells and monocytes isolated from the peripheral blood and synovial fluid of eight RA patients. The isolated cells were triple stained with CD4 or CD8, CD25 and CCR5 monoclonal antibodies. RESULTS: There was no difference in the CCR5Delta32 genotypic frequency between the RA patients and the control group (0.055 and 0.063, respectively, p = 0.989). No homozygote for the CCR5Delta32 allele was seen in either group. Five heterozygotes were identified in the RA patient group, whose disease was shown to be aggressive. A significant enrichment of activated CCR5+ monocytes was seen in the synovial fluid of the RA patients subjected to arthrocentesis, who were all homozygotes for the CCR5 wild-type genotype. CONCLUSION: A protective role for the CCR5 allelic variant in RA development was not observed. Disease severity in the heterozygotes suggests that other proinflammatory mechanisms might overcome this mutation in vivo. The activated CCR5+ monocyte enrichment in the rheumatoid synovial fluid might indicate that this cell population has an important role in the pathogenesis of the disease.

Enrichment of differentiated CD45RBdim,CD27- memory T cells in the peripheral blood, synovial fluid, and synovial tissue of patients with rheumatoid arthritis.

OBJECTIVE: To delineate in greater detail the phenotype of T cells that reside in the synovial tissue (ST) and synovial fluid (SF) of patients with rheumatoid arthritis (RA), in order to determine their precise differentiation status, and to determine whether the accumulation of these specific T cell subsets in these synovial compartments could be related to their capacity for transendothelial migration. METHODS: Lymphocytes from normal subjects or from the peripheral blood (PB), ST, and/or SF of RA patients were phenotypically analyzed by flow cytometry. Normal PB CD4+ T cells were also characterized using an in vitro assay of transendothelial migration. RESULTS: ST and SF were found to be enriched with memory (CD45RA-,CD45RO+,CD11abright,CD44bright and activated (CD69+) T cells. Moreover, ST and SF cells from RA patients were enriched in differentiated CD4+,CD45RBdim,CD27- T cells, a subset of mature memory T cells that develops after prolonged antigenic stimulation. In addition, PB of some RA patients contained an increased number of CD4+,CD45RBdim,CD27- T cells. The CD4+,CD11abright,CD44bright memory T cells, which included the CD45RBdim,CD27- more mature memory cells, exhibited an enhanced capacity for transendothelial migration that is likely to contribute to their enrichment in the rheumatoid synovium. CONCLUSION: RA patients manifest an increased number of mature memory T cells in the SF and ST, and some also have an increased number of these cells in PB that is likely to reflect chronic antigenic stimulation. The enrichment of these cells in the SF and ST reflects, in part, an enhanced capacity to migrate from the vascular space into inflamed tissue.

A simple simulated public speaking test for evaluating anxiolytic drugs

We evaluated the feasibility of using a simulated public (SPS) test to assess the activity of anxiolytic drugs. SPS was achieved by requesting subjects to present a speech to an audiocassette recorder. Thirty volunteers were randomly assigned to one of three groups treated with 10 mg diazepam, 10 mg buspirone or placebo, under double-blind conditions. One h after drug adminsitration, subjective states were measured by the Visual Analogue Mood Scale (VAMS), the State-Trait Anxiety Inventory (STAI) and by a Bodily Symptoms Scale (BSS). Heart rate and blood pressure were also recorded. SPS induced both physiological and subjective changes characteristic of anxiety. Moreover, diazepam attenuated experimentally induced increases in excitement (as measured by VAMS) and agitation (as measured by BSS). Therefore, SPS using an audiocassette recorder is sensitive to a prototypical anxiolytic and may thus be a useful test for evaluating putative anxiolytics. No effect was observed with the new anxiolytic drug buspirone. However, the present negative result may be explained by clinical data indicating that patients may experience a longer lag period before the onset of the anxiolytic effect of buspirone