Objective. Rheumatoid arthritis (RA) is associated with increased rates of cardiovascular disease. Reduced small artery elasticity (SAE) and large artery elasticity (LAE) and increased systemic vascular resistance (SVR) have been found in other high-risk groups. In the present study, we sought to determine whether arterial elasticity was reduced and SVR was increased in RA patients compared with controls matched for coronary artery disease (CAD) status, and to relate the results to vascular disease risk factors, including measures of inflammation.Methods. Arterial elasticity was assessed by pulse wave analysis in RA patients with (n ‫؍‬ 15) and without (n ‫؍‬ 38) CAD, and in controls matched 1:1 for age, sex, and CAD status. Vascular risk factors, including highsensitivity C-reactive protein (hsCRP), soluble vascular cell adhesion molecule 1 (sVCAM-1), and serum amyloid A (SAA) levels, were assessed.Results. SAE and LAE were significantly lower and SVR was significantly higher in RA patients than in controls. RA patients also had higher levels of hsCRP, SAA, and sVCAM-1. SAE and LAE values were inversely correlated with markers of inflammation. Associations of SAE and LAE with RA were independent of conventional risk factors, but were dependent on markers of inflammation.Conclusion. Vascular function is abnormal in RA, with reduced SAE and LAE and increased SVR relative to controls. Arterial elasticity is inversely associated with measures of inflammation. These measures may be clinically useful in the detection and monitoring of vascular disease in RA.

Objectives:Patients with rheumatoid arthritis (RA) have increased cardiovascular mortality. Tumour necrosis factor α (TNFα)-blocking therapy has been shown to reduce RA disease activity measures and joint damage progression. Some observational studies suggest that TNFα blockade reduces mortality and incidence of first cardiovascular events. The mechanisms contributing to these outcomes are unclear. This study assessed the effects of infliximab treatment on vascular stiffness and structure in patients with RA.Methods:A post hoc analysis of longitudinal data from a randomised placebo controlled study evaluated the effect of infliximab on vascular assessments. 26 patients received intravenous infliximab (3 mg/kg) at weeks 0, 2, 6 and every 8 weeks thereafter to week 54. Patients were followed up to 56 weeks of infliximab therapy with assessments of RA disease activity, cardiovascular risk factors, vascular stiffness (pulse wave velocity (PWV)), carotid intima media thickness (CIMT) and carotid artery plaque (CAP). Univariate analyses of changes over time by repeated measures analysis of variance (ANOVA) were followed by multivariate time-series regression analysis (TSRA) if changes were seen.Results:PWV was significantly lower (better) after 56 weeks of treatment with infliximab (ANOVA p<0.01, TSRA p<0.01). However, CIMT (ANOVA p = 0.50) and CAP (χ2 = 4.13, p = 0.88) did not change over the study period. Multiple cardiovascular risk measures did not change with treatment and did not correlate with changes in measures of vascular structure.Conclusions:Arterial stiffness improves with infliximab treatment in RA. This change may help explain the improved cardiovascular disease survival in patients with RA receiving TNFα-blocking therapy.

Aim:  We performed a semiprospective and retrospective review of all admissions to a single institution of systemic lupus erythematosus (SLE) patients, admitted due to active disease. The aim was to describe differences in disease activity as a cause of hospital admissions between patients originating from South‐East Asia/China (SAC) and Caucasians. Method:  There were 210 patients admitted for active disease, with a total of 567 admissions for active SLE over a 16‐year period. Allowing for patients who had left our database, there was a total of 3415 patient years of observation. Results:  Patients from SAC with a flare requiring admission presented earlier in their disease course and with more active disease than did Caucasians (median SLE Disease Activity Index 13 vs. 8, P= 0.002). They had longer inpatient stays (7 vs. 5 days P = 0.03). There was a trend to higher rates of re‐presentation to hospital for flare (59% in SAC patients vs. 41% in Caucasians, P = 0.09) with more subsequent admissions (3 vs. 2 P = 0.06) despite a shorter period of observation. Conclusions:  South‐East Asian/Chinese were more likely to be diagnosed with class III/IV glomerulonephritis and require cyclophosphamide both at presentation and subsequent admissions. More patients from SAC were readmitted to hospital for severe central nervous system disease after their first hospital admission. In this population, lupus patients had more severe flares and more frequently required admission for these than Caucasians.

This study suggests that COX inhibition by indomethacin or rofecoxib do not improve endothelial function in patients with RA.

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The effect of a fat-and liquid-calcium-rich meal on the pharmacokinetics of single and multiple doses of fleroxacin in 20 healthy men and women was investigated in a randomized crossover fashion. Fleroxacin was administered as 400 mg daily for 3 days and as a single 400 mg dose. Concurrent administration of fleroxacin with food resulted in a statistically significant (P c 0.05) decrease in the area under the curve (13.9%Yo for multiple-dose administration, 10% for single-dose administration) and in the peak concentration (25.9% for multiple-dose administration, 27% for single-dose administration) and a lengthening of the time to peak (more than doubled for single-and multiple-dose phases). In addition, by using an equivalence criteria of 80 to 125%, the two one-sided tests procedure indicated that the mean areas under the curves for fleroxacin administered in a fed and a fasted state were statistically bioequivalent (P ' 0.05) for both the single-and multiple-dose regimens. Although a meal high in fat and containing liquid calcium reduces the peak concentration by approximately 25%, a minimal eflect on bioavailability is seen with concomitant food administration. In addition, multiple-dose bioavailability studies appear to give similar information to single-dose studies while representing the clinical setting more closely.Fleroxacin is a new fluoroquinolone anti-infective agent which is structurally related to nalidixic acid but has a broader spectrum of activity and favorable pharmacokinetic properties. This agent is a bactericidal drug whose mechanism of action is through the inhibition of an essential bacterial enzyme, DNA gyrase, which is needed for DNA replication.Fleroxacin has extensive activity against gram-negative bacteria. This high level of antimicrobial activity is combined with excellent penetration in the body fluids and tissues (2, 6). After oral administration of 400 mg, peak concentrations (Cm.) of 3 to 7 ,ug/ml have been reported (6,14). The elimination half-life (t1/2) for fleroxacin ranges from 7.9 to 13 h, the volume of distribution (Vss) ranges from 1.2 to 1.7 liters/kg, and total body clearance (CL) ranges from 5.9 to 10.6 liters/h (6, 14). The drug is approximately 23% protein bound. The oral absorption of fleroxacin is characterized by nearly complete bioavailability. From 45 to 70% of the drug is renally excreted as unchanged fleroxacin.The interaction of fluoroquinolones with food has been studied extensively. Results of pharmacokinetic studies of orally administered ciprofloxacin, lomefloxacin, enoxacin, pefloxacin, and ofloxacin have indicated variation in the pharmacokinetics of some of these agents when administered with food (4,7,9,10,18,20 547-6914. fashion (6,11,17,21). However, no studies have been conducted after administration of multiple-dose regimens. Multiple-dose regimens mimic the manner in which antibiotics are used in the clinical setting more closely than single doses do. In addition, shorter sampling periods are needed, thus decreasing costs associated with spec...

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