Local anesthetic systemic toxicity in the pediatric patient.

Lidocaine and prilocaine are local anesthetics, a class of medications which are frequently used in clinical medicine to minimize pain in a variety of procedures. They are commonly found in over-the-counter products such as topical anesthetic creams advertised to relieve localized muscle and joint pain. While safe and well-tolerated when used appropriately, an overdose of these anesthetics increases the risk for local anesthetic systemic toxicity (LAST), which in severe cases can present with seizures, cardiac dysrhythmias, and ultimately cardiovascular collapse.

A Mixed-chimerism Protocol Utilizing Thymoglobulin and Belatacept Did Not Induce Lung Allograft Tolerance, Despite Previous Success in Renal Allotransplantation.

Background: In kidney transplantation, long-term allograft acceptance in cynomolgus macaques was achieved using a mixed-chimerism protocol based on the clinically available reagents, rabbit anti-thymocyte globulin (ATG), and belatacept. Here, we have tested the same protocol in cynomolgus macaques transplanted with fully allogeneic lung grafts.

Methods: Five cynomolgus macaques underwent left orthotopic lung transplantation.

Allorecognition by T Lymphocytes and Allograft Rejection.

Recognition of donor antigens by recipient T cells in secondary lymphoid organs initiates the adaptive inflammatory immune response leading to the rejection of allogeneic transplants. Allospecific T cells become activated through interaction of their T cell receptors with intact allogeneic major histocompatibility complex (MHC) molecules on donor cells (direct pathway) and/or donor peptides presented by self-MHC molecules on recipient antigen-presenting cells (APCs) (indirect pathway). In addition, recent studies show that alloreactive T cells can also be stimulated through recognition of allogeneic MHC molecules displayed on recipient APCs (MHC cross-dressing) after their transfer cell-cell contact or through extracellular vesicles (semi-direct pathway).

Donor exosomes rather than passenger leukocytes initiate alloreactive T cell responses after transplantation.

Transplantation of allogeneic organs and tissues represents a lifesaving procedure for a variety of patients affected with end-stage diseases. Although current immunosuppressive therapy prevents early acute rejection, it is associated with nephrotoxicity and increased risks for infection and neoplasia. This stresses the need for selective immune-based therapies relying on manipulation of lymphocyte recognition of donor antigens.