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.

ISPD GUIDELINES/RECOMMENDATIONSBeing aware of controversies and lack of evidence in peritoneal dialysis (PD) training, the Nursing Liaison Committee of the International Society for Peritoneal Dialysis (ISPD) has undertaken a review of PD training programs around the world in order to develop a syllabus for PD training. This syllabus has been developed to help PD nurses train patients and caregivers based on a consensus of training program reviews, utilizing current theories and principles of adult education. It is designed as a 5-day program of about 3 hours per day, but both duration and content may be adjusted based on the learner. After completion of our proposed PD training syllabus, the PD nurse will have provided education to a patient and/or caregiver such that the patient/caregiver has the required knowledge, skills and abilities to perform PD at home safely and effectively. The course may also be modified to move some topics to additional training times in the early weeks after the initial sessions. Extra time may be needed to introduce other concepts, such as the renal diet or healthy lifestyle, or to arrange meetings with other healthcare professionals. The syllabus includes a checklist for PD patient assessment and another for PD training. Further research will be needed to evaluate the effect of training using this syllabus, based on patient and nurse satisfaction as well as on infection rates and longevity of PD as a treatment. . Based on the principles of adult learning, these guidelines established a broad description of a course and a set of proposals to aid the teacher/nurse (hereafter called the PD nurse). The committee currently believes that, while the recommendations are still relevant and agree with current teaching practices in PD clinics, there is a need for a more comprehensive course to guide PD nurses.The 2006 Guidelines tried to answer some questions that arise when talking about PD training: Who should be the trainer? Who is the learner? What should be taught? Where should the training occur? What should be the duration of training? How should the patient be taught? However, many of these questions remain unanswered. A search in PubMed using the words "training," "patient education," "peritoneal dialysis," and "peritonitis" found only 17 articles published in the last 5 years, and most of these were about infection prevention. Only 4 were published in the last 12 months. Of these 1 article was a narrative review of the literature of educational interventions in PD which concluded that the topic remained an under-studied aspect of PD (2); another looked at the impact of training hours on infection and suggested a minimum of 15 hours training, to be done before catheter implantation or more than 10 days after (3), and the remaining 2 looked at preventing PD infections (4,5). One further observational study, by Firanek et al., analyzing best practices for nurse-led PD training programs for patients on automated peritoneal dialysis (APD) in the United States, stated that best practices...

A team approach needs to be taken to achieve successful self-management in patients having peritoneal dialysis, as with other chronic disease treatments. Nurses should use multiple strategies based on self-efficacy theory to improve patients' self-efficacy levels and self-management capacities.

Small vessel vasculitis is a life-threatening condition and patients typically present with renal and pulmonary injury. Disease pathogenesis is associated with neutrophil accumulation, activation, and oxidative damage, the latter being driven in large part by myeloperoxidase (MPO), which generates hypochlorous acid among other oxidants. MPO has been associated with vasculitis, disseminated vascular inflammation typically involving pulmonary and renal microvasculature and often resulting in critical consequences. MPO contributes to vascular injury by 1) catabolizing nitric oxide, impairing vasomotor function; 2) causing oxidative damage to lipoproteins and endothelial cells, leading to atherosclerosis; and 3) stimulating formation of neutrophil extracellular traps, resulting in vessel occlusion and thrombosis. Here we report a selective 2-thiouracil mechanism-based MPO inhibitor (PF-1355 [2-(6-(2,5-dimethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamide) and demonstrate that MPO is a critical mediator of vasculitis in mouse disease models. A pharmacokinetic/pharmacodynamic response model of PF-1355 exposure in relation with MPO activity was derived from mouse peritonitis. The contribution of MPO activity to vasculitis was then examined in an immune complex model of pulmonary disease. Oral administration of PF-1355 reduced plasma MPO activity, vascular edema, neutrophil recruitment, and elevated circulating cytokines. In a model of anti-glomerular basement membrane disease, formerly known as Goodpasture disease, albuminuria and chronic renal dysfunction were completely suppressed by PF-1355 treatment. This study shows that MPO activity is critical in driving immune complex vasculitis and provides confidence in testing the hypothesis that MPO inhibition will provide benefit in treating human vasculitic diseases.