Endotoxemia Is Associated with Altered Innate and Adaptive Immune Responses in Untreated HIV-1 Infected Individuals

BACKGROUND: Microbial translocation may contribute to the immunopathogenesis in HIV infection. We investigated if microbial translocation and inflammation were associated with innate and adaptive immune responses in adults with HIV. METHODOLOGY/PRINCIPAL FINDINGS: This was an observational cohort study. Sera from HIV-infected and HIV-uninfected individuals were analyzed for microbial translocation (soluble CD14, lipopolysaccharides [LPS], endotoxin core antibody, and anti-α-galactosyl antibodies) and inflammatory markers (high sensitivity C-reactive protein, IL-6, IL-1 receptor antagonist, soluble tumor necrosis factor receptor II, and IL-10) with enzyme-linked immunosorbent assays. Peripheral blood mononuclear cells (PBMC) from HIV-infected persons and healthy controls (primed with single-stranded HIV-1-derived RNA) were stimulated with LPS, and cytokine production was measured. Finally, HIV-infected patients were immunized with Prevnar 7vPnC±CpG 7909 followed by Pneumo Novum PPV-23. Effects of microbial translocation and inflammation on immunization were analyzed in a predictive regression model. We included 96 HIV-infected individuals, 76 on highly active antiretroviral therapy (HAART), 20 HAART-naive, and 50 healthy controls. Microbial translocation and inflammatory markers were higher among HIV-infected persons than controls. Cytokine levels following LPS stimulation were increased in PBMCs from HAART-naive compared to HAART-treated HIV-infected persons. Further, RNA-priming of PBMCs from controls acted synergistically with LPS to augment cytokine responses. Finally, high serum LPS levels predicted poor vaccine responses among HAART-naive, but not among HAART-treated HIV-infected individuals. CONCLUSIONS/SIGNIFICANCE: LPS acts synergistically with HIV RNA to stimulate innate immune responses in vitro and increasing serum LPS levels seem to predict poor antibody responses after vaccination among HAART-naive HIV-infected persons. Thus, our results suggest that microbial translocation may be associated with innate and adaptive immune dysfunction in untreated HIV infection

Inversion injury biomechanics in functional ankle instability : a cadaver study of simulated gait.

Contains fulltext : mmubn000001_151930872.pdf (publisher's version ) (Open Access)Promotores : E. de Boer en C. Hilbers133 p

Reconstruction of the anterior cruciate- and anterolateral ligament deficient knee with a modified iliotibial graft reduces instability more than with an intra-articular hamstring graft

PURPOSE: To compare knee kinematics before and after anterior cruciate ligament ACL reconstruction (ACL-R) using hamstring graft (HG) and a double-stranded iliotibial tract graft attached to Gerdy's tubercle (providing an extra-articular anterolateral tenodesis) (named the modified iliotibial tract graft = MIT). METHOD: Eighteen cadaveric knees were tested in a 6 degree of freedom kinematics rig. An optical tracking system recorded kinematics of the knee from 0 to 80 degrees of flexion applying no load, internal/external rotation (IR/ER), valgus/varus rotation (VGR/VRR), simulated pivot shift (SPS), anterior translation (AT) and posterior translation loads. The knee was tested before and after resection of the ACL and the anterolateral ligament (ALL), respectively; then after HG-ACL-R and MIT-ACL-R. Grafts were fixed at 20° of flexion. Results were compared to the intact knee. RESULTS: ACL resection resulted in a significant increase in AT (p < 0.05) over the entire range of motion, peaking at 20° of flexion, mean difference 6.6 ± 2.25 mm (p = 0.0007). ACL-R with HG-ACL and MIT-ACL restored AT. Resection of the ALL increased IR in the fully extended knee, mean difference 2.4 ± 2.1° (p = 0.024). When compared to the intact knee and the knee after HG-ACL-R, MIT-ACL-R knee reduced IR/SPS significantly (p < 0.05) in deep flexion angles (60°-80°), peaking at 80° of flexion. The MIT-ACL-R caused significantly less VRR at 80° flexion (p = 0.02). CONCLUSION: MIT-ACL-R restored AT equally to the HG-ACL-R. The MIT-ACL-R reduced IR and SPS in deep flexion, resulting in overconstraint. MIT-ACL-R can be used as an alternative to standard reconstruction methods