Direct and indirect orthotic management of medial compartment osteoarthritis of the knee

Osteoarthritis (OA) is a painful condition and affects approximately 80% of individuals by the age of 55 [1], with knee OA occurring two times more frequently than OA of the hand or hip [2].The condition is more prevalent in the medial compartment and restricts the daily lives of individuals due to pain and a lack of functional independence. Patients with medial compartment osteoarthritis often have a varus alignment, with the mechanical axis and load bearing passing through this compartment with a greater adduction moment leading to greater pain and progression of osteoarthritis [3]. Surgery for the condition is possible although in some cases, particularly younger patients or those not yet requiring surgery, clinical management remains a challenge. Before surgery is considered, however, conservative management is advocated, though no one treatment has been shown to be most effective, and there are few quality biomechanical or clinical studies. Of the conservative approaches the principal orthotic treatments are valgus knee braces and laterally wedged foot inlays. Studies of knee valgus bracing have consistently demonstrated an associated decreased pain and improved function [4], and greater confidence [5]. A laterally wedged foot inlay has a thicker lateral border and applies a valgus moment to the heel. It is theorised that by changing the position of the ankle and subtalar joints during weight-bearing [6] the lateral wedges may apply a valgus moment across the knee as well as the rearfoot, with the assumed reduction on load in the medial knee compartment [7]. However, there has been no study to directly compare these orthotic treatments in the same study. The aim of this research is to investigate the efficacy of valgus knee braces and laterally wedged foot inlays in reducing the varus knee moment

Estimating the Precursor Frequency of Naive Antigen-specific CD8 T Cells

The constraint of fitting a diverse repertoire of antigen specificities in a limited total population of lymphocytes results in the frequency of naive cells specific for any given antigen (defined as the precursor frequency) being below the limit of detection by direct measurement. We have estimated this precursor frequency by titrating a known quantity of antigen-specific cells into naive recipients. Adoptive transfer of naive antigen-specific T cell receptor transgenic cells into syngeneic nontransgenic recipients, followed by stimulation with specific antigen, results in activation and expansion of both donor and endogenous antigen-specific cells in a dose-dependent manner. The precursor frequency is equal to the number of transferred cells when the transgenic and endogenous responses are of equal magnitude. Using this method we have estimated the precursor frequency of naive CD8 T cells specific for the H-2Db–restricted GP33–41 epitope of LCMV to be 1 in 2 × 105. Thus, in an uninfected mouse containing ∼2-4 × 107 naive CD8 T cells we estimate there to be 100–200 epitope-specific cells. After LCMV infection these 100–200 GP33-specific naive CD8 T cells divide >14 times in 1 wk to reach a total of ∼107 cells. Approximately 5% of these activated GP33-specific effector CD8 T cells survive to generate a memory pool consisting of ∼5 × 105 cells. Thus, an acute LCMV infection results in a >1,000-fold increase in precursor frequency of DbGP33-specific CD8 T cells from 2 × 102 naive cells in uninfected mice to 5 × 105 memory cells in immunized mice

Changing patterns of dominance in the CD8(+) T cell response during acute and persistent murine gamma-herpesvirus infection

The murine γ-herpesvirus MHV-68 causes an acute, transient pneumonitis, followed by an infectious mononucleosis (IM)-like illness with splenomegaly, widespread latent infection of B lymphocytes and an expansion of Vβ4 CD8 T cells. CD8 T cells specific for an H-2D-restricted epitope were prominent during the acute respiratory infection, but their prevalence declined rapidly during the mononucleosis. In contrast, CD8 T cells specific for an H-2K-restricted epitope, apparently expressed by virus-infected B lymphocytes, were most numerous during the mononucleosis illness and were maintained at relatively high frequencies thereafter. The prevalence of all peptide-specific CD8 T cells decreased during the expansion of the Vβ4 CD8 population, which did not recognize any peptide epitopes identified and was apparent also in an MHC class I-deficient environment. The CD8 T cell population recognizing productively infected epithelial cells thus differed substantially from that responding during the IM illness