Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CyA is the core immunosuppressant of choice for the majority of transplant patients. The introduction of Neoral, a new microemulsion formulation of CyA. and more recently a range of adjunctive immunosuppressants have further enhanced the efficacy and tolerability of CyA-based immunosuppression. In the first year following transplantation the major causes of morbidity and death are graft failure, acute rejection, and systemic infection. Patients with deteriorated pulmonary circulation before transplantation are at increased risk of early postoperative death. Risk factors for early acute rejection include female donor sex, young donor age, and multiple HLA-DR mismatches. The principal cause of death in the long term is graft vasculopathy which accounted for 40% of all deaths. Risk factors that have been hypothesized to play a role in the pathogenesis of graft vasculopathy include hyperlipidemia, recipient age and gender, donor age, the number of HLA AB and DR mismatches, and CMV infection. Strategies proposed to reduce the risk of graft vasculopathy include aggressive use of lipid-lowering agents, avoidance of low CyA doses, and the use of adjunctive rapamycin or RAD therapy. Rejection surveillance therefore relies on routine serial endomyocardial biopsy. Recent research suggests that a more accurate assessment of the state of the graft can be obtained by considering the results across a number of biopsy samples obtained from different parts of the heart, rather than basing clinical judgment on the worst single result obtained. New molecular markers such as granzyme A mRNA are likely to improve the power of histology to diagnose and predict rejection. Neoral pharmacokinetics give greater bioavailability and less intrapatient variability than Sandimmune. In the keynote OLN 351 study comparing Neoral with Sandimmune in de novo heart transplant recipients, fewer Neoral patients needed antilymphocyte therapy to treat rejection, fewer female patients had rejection episodes in the Neoral group, the tolerability of the two formulations was equivalent, and there was a lower incidence of infections in the Neoral group. The clinical impact of Neoral in comparison with Sandimmune in de novo heart transplant patients has been investigated in a number of additional trials, including long-term studies, which have confirmed that Neoral is associated with: Lower CyA doses than Sandimmune. Equal or greater antirejection efficacy than Sandimmune. Comparable tolerability to Sandimmune. During the administration of intravenous CyA as an induction therapy in the days immediately following transplantation, there is evidence to suggest that a 6-hour infusion given twice daily, which mimics the pharmacokinetic profile of oral dosing, may be clinically more effective than a continuous 24-hour infusion. Milligram-for-milligram dose conversion from Sandimmune to Neoral is feasible. Following conversion, a reduction in the CyA dose may be required in the majority of patients to maintain target levels. In pediatric patients, the rate of elimination of CyA is greater and bioavailability increases with increasing age. Younger patients (less than 8 years of age) may be managed more effectively with a 3-times-daily, rather than a twice-daily dosing schedule. A number of studies have compared the clinical effects of Sandimmune and Neoral in maintenance therapy for cardiac transplant patients. As with de novo patients, these studies have found the new formulation of CyA to be associated with lower rates of acute rejection, lower therapeutic doses, and comparable tolerability. Milligram-to-milligram conversion from the old to the new CyA formulation is generally well tolerated, although in a minority of patients there is a significant increase in CyA levels. These may be associated with a transient increase in side effects which resolve on dose reduction. There is a dose-sparing effect with Neoral. Routine monitoring of both CyA and serum creatinine levels are adv
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PMID:Neoral use in the cardiac transplant recipient. 1081 48

Chronic rejection represents the most common cause of transplanted graft loss in the long term. Rapamycin (sirolimus), and it's derivate RAD, are new and potent, immunosuppressive drugs. They inhibit cell proliferation driven by various growth factors. These drugs were successfully tested in some experimental models of the chronic rejection. Results of the first clinical trials have defined rapamycin pharmacokinetics and proved immunosuppressive efficacy. Rapamycin acts synergistically with cyclosporin A. The side effects are a dose-dependent thrombocytopenia and leukopenia but the most frequent is hyperlipidemia. The question, if rapamycin and RAD inhibit development of chronic rejection in man, will be solved by the prospective clinical trials over years.
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PMID:[Rapamycin: a new immunosuppressive agent capable of inhibiting chronic rejection?]. 1124 80

Renal cell carcinoma (RCC) is one of the most lethal genitourinary malignancies. Recently, there has been a paradigm shift in the management of advanced RCC. New targeted therapies including vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) inhibitors have been developed which have shown promising results in a patient population who otherwise had very few options for treatment. The first mTOR inhibitor, temsirolimus, an intravenous prodrug, has shown improved overall survival in poor prognosis patients. More recently, an oral mTOR inhibitor, everolimus (RAD 001), has been developed which has been shown to delay disease progression in patients with metastatic RCC who have progressed on other targeted therapies. Although a survival advantage in phase III trials is seen with everolimus, associated systemic toxicities, while generally well tolerated, are not insignificant. These include mucositis, hyperglycemia, hyperlipidemia, and pneumonitis. Despite the side effects, emerging evidence points to everolimus as the optimal second-line treatment for patients with advanced renal cell carcinoma.
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PMID:Safety and clinical efficacy of everolimus in the treatment of advanced renal cell carcinoma (RCC). 2170 20