How certain autoimmune diseases target specific organs remains obscure. In the 'K/BxN' arthritis model, autoantibodies to a ubiquitous antigen elicit joint-restricted pathology. Here we have used intravital imaging to demonstrate that transfer of arthritogenic antibodies caused macromolecular vasopermeability localized to sites destined to develop arthritis, augmenting its severity. Vasopermeability depended on mast cells, neutrophils and FcgammaRIII but not complement, tumor necrosis factor or interleukin 1. Unexpectedly, radioresistant FcRgamma-expressing cells in an organ distant from the joint were required. Histamine and serotonin were critical, and systemic administration of these vasoactive amines recapitulated the joint localization of immune complex-triggered vasopermeability. We propose that regionally distinct vascular properties 'interface' with immune effector pathways to foster organ-specific autoimmune damage, perhaps explaining why arthritis accompanies many human infectious and autoimmune disorders.
It has been suggested that vascular cell adhesion molecule-1 (VCAM-1) could serve as an early marker for inflammation of the endothelium. The ability to noninvasively image VCAM-1 could thus be a useful tool to diagnose a number of inflammatory diseases at early stages. Here we demonstrate that magnetooptical nanoparticles conjugated to anti-VCAM-1 antibodies can be used to specifically detect VCAM-1 expression on endothelial cells in culture and in vivo. Elevated VCAM-1 expression was detected on cultured murine heart endothelial cells by both fluorescence and magnetic resonance, while only basal expression levels were detected on murine dermal endothelial cells. Intravital microscopy of a murine inflammatory model injected with the VCAM-1 targeted nanoparticles revealed specific labeling of the activated endothelium, with labeling kinetics yielding a maximum vessel wall signal 6 h after injection. In contrast, nontargeted nanoparticles did not exhibit any specific labeling of the endothelium. These studies suggest that the developed nanoparticle would be useful for MR and optical detection of activated endothelium.
Based on the evidence presented in this article, certain interventions are more effective for the treatment of virginal mammary hypertrophy. On diagnosis of virginal mammary hypertrophy, tamoxifen therapy may be considered based on previous literature, barring any medical contraindications. A subcutaneous mastectomy with complete removal of breast tissue is the procedure least likely to lead to recurrence but is more deforming. Reduction mammaplasty gives an improved aesthetic breast, but it is important to counsel the patient on the likelihood of increased recurrence. Tamoxifen therapy following surgery may decrease the recurrence rate.
Although there is little agreement in the literature regarding risk factors for fat necrosis, the authors were able to demonstrate several significant predictors by systematically analyzing 70 articles. Improved knowledge of the risk factors for fat necrosis can help surgeons provide improved preoperative counseling and take measures to minimize the risk of this complication.
A microcomputer based instrument to measure effective thermal conductivity and diffusivity at the surface of a tissue has been developed. Self-heated spherical thermistors, partially embedded in an insulator, are used to simultaneously heat tissue and measure the resulting temperature rise. The temperature increase of the thermistor for a given applied power is a function of the combined thermal properties of the insulator, the thermistor, and the tissue. Once the probe is calibrated, the instrument accurately measures the thermal properties of tissue. Conductivity measurements are accurate to 2 percent and diffusivity measurements are accurate to 4 percent. A simplified bioheat equation is used which assumes the effective tissue thermal conductivity is a linear function of perfusion. Since tissue blood flow strongly affects heat transfer, the surface thermistor probe is quite sensitive to perfusion.
Background
Microsurgical vascularized bone flaps are a versatile technique for reconstructing large bone defects. However, assessment of perfusion is challenging, as clinical examination is difficult intra-operatively and often not possible post-operatively. Therefore, it is important to develop techniques to assess perfusion of vascularized bone flaps, and potentially improve surgical outcomes. Near-infrared (NIR) fluorescence imaging has been previously shown to provide real-time, intra-operative evaluation of vascular perfusion. This pilot study investigates the ability of NIR imaging to assess perfusion of vascularized bone flaps.
Materials and Methods
Vascularized bone flaps were created on female Yorkshire pigs using well-established models for porcine forelimb osteomyocutaneous flap allotransplantation (N = 8) and hindlimb fibula flaps (N = 8). Imaging of the bone flaps was performed during harvest using the FLARE™ intraoperative fluorescence imaging system following systemic injection of indocyanine green (ICG). Perfusion was also assessed using standard of care by clinical observation and Doppler. NIR fluorescence perfusion assessment was confirmed by intermittent clamping of the vascular pedicle.
Results
NIR fluorescence imaging can identify bone perfusion at the cut end of the osteotomy site. When the vascular pedicle is clamped or ligated, NIR imaging demonstrates no fluorescence when injected with ICG. With clamp removal, the osteotomy site emits fluorescence indicating bone perfusion. Results using fluorescence imaging show 100% agreement with clinical observation and Doppler.
Conclusion
Vascularized bone transfers have become an important tool in reconstructive surgery; however, no established techniques adequately assess perfusion. Our pilot study indicates that NIR imaging can provide real-time, intra-operative assessment of bone perfusion.
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