Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It is thought that many common variant gene loci of weak effect act additively to predispose to common autoimmune diseases, while the contribution of rare variants remains unclear. Here we describe that rare coding variants in lupus-risk genes are present in most SLE patients and healthy controls. We demonstrate the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK1, which are present alone, or in combination, in a substantial proportion of lupus patients. The rare variants found in patients, but not those found exclusively in controls, impair suppression of IRF5 and type-I IFN in human B cell lines and increase pathogenic lymphocytes in lupus-prone mice. Thus, rare gene variants are common in SLE and likely contribute to genetic risk.

Study Design: Single-group, pre-, and postintervention repeated measures design. Objective: To determine the impact of custom semirigid foot orthotics on pain and disability for individuals with plantar fasciitis. Background: Few studies have examined the efficacy of foot orthotics for plantar fasciitis, and no single study has yet examined the effects of semirigid foot orthotics on an established quality-of-life instrument. Methods and Measures: Eight men and 7 women (mean ages 44.7 ± 9.0 years) who reported having plantar fasciitis symptoms for an average of 21.3 ± 23.7 months participated in the study. Subjects were timed for a 100-m walk at a self-selected speed, then they rated the pain they experienced during the walk using a 10-cm visual analog scale. Subjects also completed the pain and disability subsections of the Foot Function Index questionnaire. All measures were acquired before the fabrication of custom semirigid foot orthotics and 12 to 17 days following onset of foot orthotic use. Results: Postorthotic 100-m walk times were not significantly different (t = 0.39, P = 0.70) than preorthotic values. Postorthotic pain ratings (mean = 0.7 ± 0.7) for the 100-m walk were significantly less than (Wilcoxon t = 1, P Ͻ 0.005) preorthotic pain ratings (mean = 3.0 ± 1.7). Postorthotic Foot Function Index pain subsection ratings (Wilcoxon t = 0, P Ͻ 0.005) were significantly less than preorthotic ratings, demonstrating a 66% reduction in pain ratings. Postorthotic Foot Function Index disability subsection ratings (Wilcoxon t = 0, P Ͻ 0.005) were significantly less than preorthotic ratings, demonstrating a 75% reduction in disability ratings. Conclusion: Custom semirigid foot orthotics may significantly reduce pain experienced during walking and may reduce more global measures of pain and disability for patients with chronic plantar fasciitis.

The pharmacokinetics and bioavailability of phenobarbital were examined in six healthy adult subjects after a 2.6 mg/kg intravenous and a 2.9 mg/kg oral dose. Serum concentrations of phenobarbital were followed by means of a high pressure liquid chromatographic assay for 21 days after drug administration. After the intravenous dose, the mean distribution half-life was 0.18 hour and the mean elimination half-life was 5.8 days. Mean total body clearance and mean renal clearance were 3.0 ml/hr/kg and 0.8 ml/hr/kg, respectively. The apparent volume of distribution was 0.60 liter/kg. After administration of phenobarbital tablets, the maximum phenobarbital serum concentration was 5.5 mg/liter at 2.3 hours after the dose. Adjusted absolute availability of phenobarbital from the tablets studied was 94.9 per cent (range 81-111.9 per cent). The elimination half-life averaged 5.1 days for the oral dose. There was no evidence of autoinduction of phenobarbital elimination over the study period.