Because of its requirement for signaling by multiple cytokines, Janus kinase 3 (JAK3) is an excellent target for clinical immunosuppression. We report the development of a specific, orally active inhibitor of JAK3, CP-690,550, that significantly prolonged survival in a murine model of heart transplantation and in cynomolgus monkeys receiving kidney transplants. CP-690,550 treatment was not associated with hypertension, hyperlipidemia, or lymphoproliferative disease. On the basis of these preclinical results, we believe JAK3 blockade by CP-690,550 has potential for therapeutically desirable immunosuppression in human organ transplantation and in other clinical settings.
Although the operative mortality rate decreased over time for patients with aortic dissection, the risk for those with acute aortic dissection during the last 10 years (1983 to 1992) is probably more realistic than that observed in the preceding 5-year interval (1978 to 1982). The operative mortality rates for patients with chronic aortic dissection have remained relatively static. Earlier diagnosis of acute aortic dissection before development of cardiac tamponade and renal impairment is critical to improve the operative salvage rate. Long-term outcome still is not optimal, which emphasizes the need for better serial postoperative aortic imaging surveillance and medical follow-up and blood pressure control.
The incidence of post-transfusion hepatitis C has decreased markedly since the implementation of donor screening for surrogate markers and antibodies to HCV. The current risk of post-transfusion hepatitis is about 3 per 10,000 units transfused.
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