There is evidence that CGA can improve outcomes in people with hip fracture. There are not enough studies to determine when CGA is most effective in relation to surgical intervention or if CGA is effective in surgical patients presenting with conditions other than hip fracture.
Fibrinogen-like protein 2 (fgl2)/fibroleukin is a member of the fibrinogen-related protein superfamily. In addition to its established role in triggering thrombosis, it is known to be secreted by T cells. The soluble fgl2 (sfgl2) protein generated in a baculovirus expression system bound to both T cells and bone marrow-derived dendritic cells (DC) in a specific manner. sfgl2 exhibited immunomodulatory properties capable of inhibiting T cell proliferation stimulated by alloantigens, anti-CD3/anti-CD28 mAbs, and Con A in a dose-dependent manner; however, it had no inhibitory effects on CTL activity. The time- and dose-dependent inhibitory effect of sfgl2 on alloreactive T cell proliferation could be neutralized by a mAb against mouse fgl2. Polarization toward a Th2 cytokine profile with decreased production of IL-2 and IFN-γ and increased production of IL-4 and IL-10 was observed in sfgl2-treated allogeneic cultures. Exposure of immature DC to sfgl2 abrogated the expression of CD80high and MHC class IIhigh molecules and markedly inhibited NF-κB nuclear translocation, thus inhibiting their maturation. sFgl2-treated DC had an impaired ability to stimulate allogeneic T cell proliferation. Maximal inhibition of proliferation was observed when allogeneic T cells were cultured with sfgl2-treated DC and sfgl2 protein was added in the culture. These data provide the first evidence to demonstrate that sfgl2 exerts immunosuppressive effects on T cell proliferation and DC maturation.
Oxidative stress generated by ischemia/reperfusion is known to prime inflammatory cells for increased responsiveness to subsequent stimuli, such as lipopolysaccharide (LPS). The mechanism(s) underlying this effect remains poorly elucidated. These studies show that alveolar macrophages recovered from rodents subjected to hemorrhagic shock/resuscitation expressed increased surface levels of Toll-like receptor 4 (TLR4), an effect inhibited by adding the antioxidant N-acetylcysteine to the resuscitation fluid. Consistent with a role for oxidative stress in this effect, in vitro H2O2 treatment of RAW 264.7 macrophages similarly caused an increase in surface TLR4. The H2O2-induced increase in surface TLR4 was prevented by depleting intracellular calcium or disrupting the cytoskeleton, suggesting the involvement of receptor exocytosis. Further, fluorescent resonance energy transfer between TLR4 and the raft marker GM1 as well as biochemical analysis of the raft components demonstrated that oxidative stress redistributes TLR4 to lipid rafts in the plasma membrane. Preventing the oxidant-induced movement of TLR4 to lipid rafts using methyl-β-cyclodextrin precluded the increased responsiveness of cells to LPS after H2O2 treatment. Collectively, these studies suggest a novel mechanism whereby oxidative stress might prime the responsiveness of cells of the innate immune system.
Oxidative stress generated by ischemia/reperfusion is known to prime infl ammatory cells for increased responsiveness to subsequent stimuli, such as lipopolysaccharide (LPS). The mechanism(s) underlying this effect remains poorly elucidated. These studies show that alveolar macrophages recovered from rodents subjected to hemorrhagic shock/resuscitation expressed increased surface levels of Toll-like receptor 4 (TLR4), an effect inhibited by adding the antioxidant N-acetylcysteine to the resuscitation fl uid. Consistent with a role for oxidative stress in this effect, in vitro H 2 O 2 treatment of RAW 264.7 macrophages similarly caused an increase in surface TLR4. The H 2 O 2 -induced increase in surface TLR4 was prevented by depleting intracellular calcium or disrupting the cytoskeleton, suggesting the involvement of receptor exocytosis. Further, fl uorescent resonance energy transfer between TLR4 and the raft marker GM1 as well as biochemical analysis of the raft components demonstrated that oxidative stress redistributes TLR4 to lipid rafts in the plasma membrane. Preventing the oxidant-induced movement of TLR4 to lipid rafts using methyl--cyclodextrin precluded the increased responsiveness of cells to LPS after H 2 O 2 treatment. Collectively, these studies suggest a novel mechanism whereby oxidative stress might prime the responsiveness of cells of the innate immune system.
One of the more difficult problems in reconstructive surgery of the head and neck is replacement of bone and soft tissue lost because of injury, osteomyelitis, or malignancy. The radial-forearm osteocutaneous flap is an accepted choice for oromandibular reconstruction. This study was undertaken to review one center's experience with 60 consecutive cases of oromandibular reconstruction with the radial-forearm osteocutaneous flap. Records of the 38 men and 22 women (mean age, 60 years; range, 26 to 86 years) were reviewed for tumor location, defect and bone length, flap failure rate, recipient- and donor-site complications, length of surgery, and hospital stay. Cancer resection was the reason for 97 percent of reconstructions; 33 percent of flaps were used to reconstruct a lateral defect of the mandible, 40 percent a lateral-central defect, and 27 percent a lateral-central-lateral defect. Mean skin flap size was 55 cm2 (range, 15 to 117 cm2) and mean bone length, 9.4 cm (range, 5 to 14 cm). The microvascular success rate was 98.3 percent. Complications included fracture of the donor radius (15 percent), nonunion of the mandible (5 percent), and hematoma (8.3 percent). These results are comparable to results reported in the literature with other radial forearm flaps. The free radial osteocutaneous flap is a safe and reliable choice for mandibular reconstruction. It offers sufficient bone to reconstruct large defects and can provide adequate pedicle length for vessel anastomosis to the contralateral side of the neck. The above attributes make the radial forearm osteocutaneous flap one of the "first line" flap choices for oromandibular reconstruction.
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