Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The introduction of new immunosuppressive agents and protocols has improved outcomes for renal transplant recipients by decreasing the risk of rejection and by increasing the function and lifespan of the allograft. This article reviews the major changes in the combinations of therapies used: calcineurin inhibitors, target of rapamycin inhibitors, mycophenolate mofetil, non-depleting monoclonal versus depleting monoclonal and polyclonal antibodies for induction and increasing emphasis on protocols for reduction or avoidance of steroids and calcineurin inhibitors. The new agents with novel immunological targets such as anti-CD40 ligand, LEA29Y, FTY720, anti-CD20 (rituximab, Rituxan, Mabthera) and anti-CH52 (alemtuzumab, Campath), which are under development but have yet to survive the rigors of clinical trials are also discussed. In the presence of low early rejection rates, immunosuppressive therapy is setting new goals such as better graft function (glomerular filtration rates), reduction in adverse effects such as hypertension, hyperlipidaemia and drug toxicity and, above all, the prevention of late graft deterioration.
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PMID:New developments in immunosuppressive therapy in renal transplantation. 1207 85

Sirolimus was used as a single agent for maintenance immunosuppression in a pilot trial of 29 primary kidney transplant patients using lymphocyte depletion with Campath-1H as an induction strategy. This allowed sirolimus to be analyzed (dose, blood level, and side effect profile) in the absence of steroid and calcineurin inhibitors. A sirolimus dose of 4 mg/day resulted in blood levels in the 8 to 9 ng/mL range. Of the 29 patients, 8 patients (28%) had rejection. The sirolimus levels were not significantly different in patients with or without rejection. The cardiovascular risk profile in terms of lipid profile and hypertension control was favorable. Increase in cholesterol and triglyceride levels at one month (not statistically significant) necessitated treatment in 60% of patients with decline in levels by 6 and 12 months. Management of hypertension was also favorable with the majority of patients (55%) being on one hypertensive medication. Sirolimus monotherapy was well tolerated on the whole. Wound healing, leukopenia, and anemia were not significant problems. In conclusion, monotherapy has been well tolerated with a favorable side effect profile. However, a rejection rate of 28% was noted.
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PMID:Sirolimus monotherapy following Campath-1H induction. 1274 84

The Lung Transplantation program at the University of Pittsburgh began in 1982. From the beginning to December 31, 2009, 1347, lung and heart lung transplantations have been done. (674 double-lung, 310 left single-lung, 227 right single-lung and 130 heart-lung transplantations. University of Pittsburgh maintains a data base, from the time of the inception of the program, of all recipients and donors. There is an increasing trend to do double-lung transplantation, as 5- and 10-year survival is better with double than single lungs. Our experience with heart-lung transplantation is considerable. The 4 most common indications for lung transplantation are: chronic obstructive disease (COPD), idiopathic pulmonary fibrosis (IPF), cystic fibrosis (CF) and pulmonary arterial hypertension. (PAH). Potential recipients are evaluated over 2 weeks. There is also a pathway for accelerated evaluation of sicker patients. Our recipient criteria are expanded and flexible; as many patients, who have been denied lung transplantation, at other major centers have been successfully transplanted by us with good outcomes. The median waiting time on the list in 2009 was 37 days. Our altruistic flexibility in recipient selection, balanced with respect to the altruistic gift of donor families, has been described in considerable detail. To solve the problem of shortage of donor lungs, we have expanded our donor selection criteria beyond the historic ideal donor, without comprising on outcomes. These selection criteria and our donor-lungs management protocol are also described in reasonable detail. We started using lungs from donors after cardiac death (DCD) in January 2007. Recently we reviewed our experience and literature, and devised a protocol; which is given in a robust table. We also participate as faculty in the educational program initiated by the Organ Procurement Organizations (OPO) of Pennsylvania. During procurement we use 500 microg of prostaglandin E-1 into the pulmonary artery just before X clamp, Perfedex infusion after X-clamp, at 70 ml/kg, with 500 microg of prostaglandin and 50 mg of nitroglycerine in the first bag, and retrograde flush of 500 ccs in each pulmonary vein. We have refined our recipient operation, from clam shell incision to bilateral antero-axillary incisions, preserving the sternum and internal mammary arteries, for both double and single-lung transplantation, with good outcomes. This technique and results have been described in generous detail. We use pneumoplegia, similar to cardioplegia, to protect the allograft from ischemic and reperfusion injury (Appendix III). Our technique of bronchial anastomosis and intraoperative management of septic lung disease has remained unchanged. Post-operatively we continue to use the ventilatory management of low FiO2 and high PEEP. Our immunosuppression and infection prophylaxis protocol is the same since 2003, when we started using Alemtuzumab (Campath) for induction, with minimization of the use of steroids. For maintenance, we use Tacrolimus and Mycophenolate Mofetil. Now, we also monitor the functional activity of the T cell by Cylex ImmuKnow. Lowered activity (< 100 ng/ml) suggests an increased risk of infection; and higher activity (> 200 ng/ml) suggests greater risks for rejection. Although we have expanded our recipient and donor pools, our outcomes have continued to improve. The overall survival of double-lung transplantation from 2003-2009 was 82.8% at one year and 56.8% at 5 years. This compares well with the international data which shows an overall survival rate of 80% at one year and 56% at 5 years. Results of lung transplantation will continue to improve, with our increasing understanding of mechanisms and management of ischemic-reperfusion injury, acute rejection and bronchiolitis obliterans syndrome.
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PMID:Lung and heart-lung transplantation at University of Pittsburgh: 1982-2009. 2052 84

Unilateral and bilateral hand transplantations have been performed worldwide with good mid-term functional results. An above-elbow bilateral transplantation was performed in a 29-year-old male patient from a fully HLA-mismatched donor. Alemtuzumab induction and steroid-free maintenance immunosuppression with tacrolimus and mycophenolate was used. Due to acute rejection, steroids were introduced at 6 months. Three acute rejection episodes occurred, one treated with alemtuzumab. New-onset diabetes after transplant, dyslipemia and worsening of previous high blood pressure required treatment. At 26 months post-transplantation, the patient has excellent elbow active movement, active flexion and extension of the thumb and fingers, useful sensation and a gainful job. Based on the functional results of the case reported, bilateral trans-humeral transplantation could be a viable treatment for selected bilateral above-elbow amputees.
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PMID:Bilateral trans-humeral arm transplantation: result at 2 years. 2152 75