When FcγRs I, IIA, and IIIA bind to their ligands, the receptor complex becomes activated and triggers the phosphorylation of the immunoreceptor-activating motifs (ITAMs). This leads to various genes becoming activated, which causes a cytoskeletal rearrangement that mediates phagocytosis in cells of the monocyte/macrophage lineage. Because Syk plays an important role in FcγR-mediated signal transduction and inflammatory propagation, it is considered a good target for the inhibition of various autoimmune conditions, including rheumatoid arthritis and lymphoma. Clinical trials
Fostamatinib has been in clinical trials for rheumatoid arthritis, autoimmune thrombocytopenia, autoimmune hemolytic anemia, IgA nephropathy, and lymphoma. The drug is currently being used in a Phase 1 trail to test the safety of the combination of the study drugs fostamatinib and paclitaxel for patients with ovarian cancer.The investigation of fostamatinib began with studies involving the treatment of mouse models with cytopenia. Mice were used to measure the effectiveness of R788, a small molecule prodrug of the biologically active R406, a Syk inhibitor. In animal models, treatment with R406/R788 was shown to be safe and effective in reducing inflammation and joint damage in immune-mediated rheumatoid arthritis. The models responded favorably to treatment so the study progressed to Phase 2 trials involving humans. Human studies have shown that R788 has good oral bioavailability, biologic activity, is well tolerated, and does not exhibit collagen or ADP-induced platelet aggregation. In NCT00706342, 16 adults with chronic ITP were entered into an open-label, single-arm cohort dose-escalation trials beginning with 75 mg and rising to 175 mg twice a day.
Post-vagotomy diarrhea is a form of diarrhea which occurs in 10% of people after a truncal vagotomy, which can range from severe to debilitating in approximately 2% to 4% of patients. However, the occurrence of post-vagotomy diarrhea is significantly reduced after proximal selective vagotomy, specifically when celiac and hepatic branches of the vagus are retained. Diagnosis
Treatment
Surgical treatment for refractory post-vagotomy diarrhea is rarely needed and at least one year from the occurrence of symptoms should be allotted to ensure all non-surgical treatments have been appropriately explored. Under severe cases, where surgical intervention does become necessary, a 10 cm reverse jejunal interposition is usually the procedure of choice. == References ==