Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution and effectiveness of different immunosuppression protocols among recipients of first cadaver donor renal transplants reported to the UNOS Scientific Renal Transplant Registry whose graft survived at least 14 days after transplantation were analyzed. The results showed that between 1988-1993, 50-60% of recipients received triple therapy regimens including cyclosporine, azathioprine and prednisone (CAP). An additional 20% received CAP with antibody induction therapy (OKT3 or ALG). After 1993, there was an increase in the use of other drug combinations which include FK506 and, more recently, Neoral and mycophenylate mofetil. Patient survival was 90% at 3 years regardless of the immunosuppressive protocol. The 3-year graft survival rate was 75% under cyclosporine-based protocols, but was 79% for more recent recipients treated with FK506 (p = 0.015). Antibody induction protocols were not used more frequently for high-risk patients, including those with broadly reactive anti-HLA antibodies, pediatric recipients, transplants with delayed graft function and those with prolonged cold ischemia times. When induction therapies were reported for these higher risk transplants, there was no noticeable improvement in graft survival rates after excluding failures within the first 2 weeks. Any benefit of antibody induction must therefore be manifest with the first 2 weeks after transplantation. Induction protocols significantly reduced the incidence of rejection episodes (prior to hospital discharge) from 31% for those treated with CAP to 12% for those with antibody induction (p < 0.01), however, 24% of those given induction had at least one rejection between discharge and 6 months compared with only 18% of those treated with CAP without induction (p < 0.01). Although graft outcomes might be significantly influenced by the dosing and timing of immunosuppressive drugs, among the different combinations of drugs analyzed, only FK506 resulted in improved graft survival and half life. With the rapid proliferation of newer drugs and immunosuppressive strategies during 1996, it will be interesting to follow the course of these very recent transplants with regard to the effectiveness of changing immunosuppression.
 ...
PMID:Immunosuppressive regimens and their effects on renal allograft outcome. 928 82

Cyclosporin A is a basic immunosuppresive drug after organ transplantation. Morphological and functional features of Cyclosporin A nephrotoxicity caused by Sandimmune (Sandoz) and Consupren (of the Czech origin) were investigated in male Wistar rats. Rats were subjected to a right side nephrectomy followed by 45-minute- ischemia of remaining left kidney. Sandimmune was administered to one group of animals, Consupren to another group, both in the amount of 10 mg/kg/day. The second part of the experiment was performed in animals with right side nephrectomy only (without ischemia of the left side kidney) followed by the same administration of drugs. Changes were checked the 3rd and 21st day after nephrectomy. Ischemic arterial insudation lasted in the 3rd day set of animals with nephrectomy and left kidney ischemia treated by Consupren and was lacking after Sandimmune. Microvascularization of tubular epithelial cells was observed in significant frequency in the 21st day set of animals with unilateral nephrectomy without ischemia after Consupren and not after Sandimmune. The finding correlated with significantly higher blood level of Consupren and higher creatinine concentrations in serum than those of Sandimmune in rats with unilateral nephrectomy only.
 ...
PMID:[Nephrotoxicity of Sandimmune and Consupren in an experiment]. 947 95

After heart transplantation a number of factors such as pre- and postoperative hypoxia of the myocardium, myocardial failure of the early postoperative period, acute rejection episodes, cytomegalovirus infection, and finally the progressive atherosclerosis of the coronary arteries lead to the development of transplanted heart failure. Severe alterations of the myocardial function at this end stage of the process correspond to incurable cardiomyopathy. The target of plasmapheresis in this case is to decrease the extent of the disturbances in the lipoprotein contents and blood rheology for the improvement of the coronary perfusion of the transplanted heart. Nine patients with 3-7 year survival periods after heart transplantations underwent plasmapheresis twice a year using the Haemonetics PCS-plus machine. 2,100-2,700 ml of plasma was removed. Biochemical data, rheology and coagulation, and the concentration of Sandimmune (Sandoz Pharma Ltd., Basel, Switzerland) were controlled, and radionuclide scintigraphy of the myocardium, coronarographia, and transesophageal ultrasound investigations were completed for these patients. The result was the significant improvement of the coronary perfusion of the myocardium. The level of immunosuppression after the plasmapheresis procedures did not change and therefore did not demand any correction. Thus, we think that plasmapheresis can be an effective method of treatment of posttransplantation cardiomyopathy; the improvement of coronary perfusion decreases the extent of chronic ischemia. Further studies are necessary to answer the question as to whether it is possible to prolong the time before retransplantation with the help of plasmapheresis.
 ...
PMID:Plasmapheresis in the treatment of posttransplant cardiomyopathy. 952 79

Daclizumab (DAC) is a molecularly engineered humanized IgGa monoclonal Ab directed against the alpha chain of the interleukin-2 receptor (IL2R). Inhibiting the amplification of the immune response by blocking IL2R can reduce the frequency of acute rejection without the attendant risk of infection. The purpose of this retrospective study was to compare DAC to antithymocyte (ATGAM) induction in 24 simultaneous pancreas-kidney (SPK) transplants performed between September 1995 and September 1998. The primary endpoints were the incidence within 6 months posttransplant of: 1) biopsy-proven acute rejection; and 2) infection. The two groups (DAC, n = 12; ATGAM, n = 12) were matched on age, race, ESRD, number of HLA mismatches, PRA level, and cold ischemia time. DAC (1 mg/kg) was given on the day of transplant, then every other week (a total of five doses); ATGAM (15 mg/kg) was given on post-transplant day 1, then daily for 7-10 d. Immunosuppressive therapy consisted of cyclosporine (Neoral 8-10 mg/kg/d) or Prograf (0.16-0.2 mg/kg/d), mycophenolate mofetil (Cell- 2-3 g/d) and steroids. Of the 12 DAC patients, 3 patients (25%) had biopsy-proven acute rejection versus 8/12 (67%) of the ATGAM patients. The time to acute rejection was significantly different by group (DAC = 110 d; AT-GAM = 26 d). There was a reduction in the number of patients receiving antilymphocyte drugs for moderate to severe rejection (DAC = 2/12; ATGAM = 4/12), with 2 of the 4 ATGAM patients experiencing more than two episodes of biopsy-proven rejection. There was an increase in infection by group (DAC = 4/12; ATGAM = 7/12): total of three septic infections occurred in the ATGAM group opposed to none in the DAC group. Patient, pancreas, kidney 6-month survival rates were 100% for both groups. We conclude that DAC induction coupled with triple immunosuppressive therapy reduces the incidence of rejection in SPK transplant patients. The time to acute rejection was prolonged in the DAC group compared with the ATGAM group without the attendant risks of rejection.
 ...
PMID:A comparison of daclizumab to ATGAM induction in simultaneous pancreas-kidney transplant recipients on triple maintenance immunosuppression. 1094 80

Tacrolimus and cyclosporine in the microemulsion formulation Neoral have demonstrated improvements in acute rejection rates after renal transplantation compared with conventional cyclosporine formulation, Sandimmune. To evaluate whether these drugs are also associated with improvements in chronic allograft failure (CAF) rates, we retrospectively analyzed 32,040 primary renal allograft recipients reported to the United States Renal Data System (USRDS) between 1994 and 1997. Graft loss secondary to CAF was defined as graft loss beyond 6 months post-transplant, censored for death, acute rejection, thrombosis, infections and noncompliance. A Cox proportional hazard model was used to investigate the relationship between graft loss secondary to CAF and the use of conventional cyclosporine formulation, as opposed to cyclosporine microemulsion and tacrolimus (Prograf). The analysis was corrected for confounding variables, such as acute rejection, sex, race, human leukocyte antigen (HLA) mismatch, % panel reactive antibodies (PRA), delayed graft function (DGF), cold ischemia time, induction therapy, dialysis time, etiology of end-stage renal disease, cytomegalovirus (CMV) risk group, donor source, era effect, and mycophenolate mofetil (MMF) use. Cyclosporine microemulsion use was associated with a significantly lower relative risk (RR = 0.6, Cl = 0.5-0.7) for CAF as opposed to conventional cyclosporine formulation. Likewise tacrolimus as compared with conventional cyclosporine formulation was associated with a significantly lower relative risk (RR = 0.7, CI = 0.6-0.8) for CAF. Conventional cyclosporine formulation treatment was associated with a 87.6% adjusted CAF-free survival rate at 4 years. Both tacrolimus and cyclosporine microemulsion were associated with a significantly better adjusted CAF-free survival at 4years (91.4 and 92.4%, respectively). Both cyclosporine microemulsion and tacrolimus are associated with improved graft survival and a decreased relative risk for CAF when compared with the older conventional cyclosporine formulation. This association is independent of the use of MMF or changes in era.
 ...
PMID:Cyclosporine microemulsion and tacrolimus are associated with decreased chronic allograft failure and improved long-term graft survival as compared with sandimmune. 1209 48

From July 4, 1999, when a liver transplantation program was started in Cuba, to October 2003, 66 procedures had been performed in 60 patients. The most frequent reason was cirrhosis caused by hepatitis C virus (29%), and alcoholic cirrhosis (22%). Two patients received simultaneous liver-kidney transplants. Half of the patients were men. Patient ages ranged from 12 to 62 years; the average surgical time was 6 hours; and cold ischemia time was 4 to 14 hours. The average blood consumption was 2033 mL; 2900 mL of plasma and 8 units of platelets were used in 7 cases. Immunosuppression was mainly cyclosporine (Neoral), mycophenolate mofetil or azathioprine, and prednisone. Acute cellular rejections were treated in almost all cases with 3 doses of methylprednisolone. The most frequent complications were biliary (24%), hepatic arterial thrombosis (12%), post-surgical bleeding (10%), acute cellular rejection (24%), and ductopenic rejection (2%). The overall 1-year survival rate was 73.7%.
 ...
PMID:Liver transplantation at the Cuban Center for Medical and Surgical Research. 1586 56

We carried out a prospective study of the safety and efficacy of daclizumab combined with triple immunosuppression in adult recipients of at least one HLA-mismatched cadaveric renal allograft. All studied patients received the same immunosuppression: a daclizumab infusion of 1 mg/kg immediately before transplantation, and at 2, 4, 6, and 8 weeks following the transplantation. Infusion of cyclosporine (CsA) (0.08 mg/kg/h) was started at the time of the operation and continued by CsA microemulsion (CsA-Neoral), 3 mg/kg twice daily on day 2, methylprednisolone, 0.4 mg/kg intravenously at operation, and mycophenolate mofetil started on day 1. The dose of CsA-Neoral was adjusted to maintain target blood trough levels. Oral methylprednisolone was tapered by 4 mg per week to achieve a maintenance dose of 0.08 mg/kg/day. Fifty-five patients, with a mean age of 48 +/- 11 years, were studied. Six of them received a second renal allograft. The mean donor age was 38 +/- 14 years. Mean cold ischemia time was 19.5 +/- 6.5 h, mean value of HLA-antigen mismatches was 2.7 +/- 0.9, mean latest PRA value was 3 +/- 7%. Fifteen patients experienced delayed graft function. During a follow-up period of 3 months three acute rejection episodes occurred. One patient died because of systemic aspergillosis. After 3 months mean serum creatinine was 104 +/- 38 micromol/L. Five renal allografts failed, one of them due to rejection. Patient and graft survival was 98.2% and 90.9%, respectively. Daclizumab with this triple therapy represents safe and efficient immunosuppression strategy, demonstrated with low incidence of early acute rejection episodes and an acceptable adverse event profile in cadaveric renal allograft recipients.
 ...
PMID:Prevention of early acute rejection with daclizumab and triple immunosuppression in cadaveric renal allograft recipients. 1596 3

We studied prospectively the efficacy and safety of basiliximab combined with triple immunosuppression in adult recipients of > or = 1 HLA-mismatched deceased donor renal grafts. All studied patients received equal immunosuppressive drugs: 20 mg infusion of basiliximab on day 0 and on day 4, cyclosporine microemulsion (Neoral), mycophenolate mofetil, and methylprednisolone. An analysis of 1-year data assessed the incidence of acute rejection episodes, safety of this therapy, renal graft function, and patient and graft survivals. One hundred seventy-two patients were studied. The HLA-antigen mismatches were 2.9 +/- 0.9 (mean +/- SD), and the cold ischemia time was 22.0 +/- 7.5 hours. Fifty-three (31.5%) patients experienced delayed graft function. At 12 months, 5 (3.0%) patients experienced acute rejection. Six renal grafts were lost, but not from rejection. Two patients died. Sixty-six infections required treatment in the hospital. One carcinoma of cervix (in situ) and two basal cell carcinomas of skin were detected. Hypersensitivity reactions and cytokine-release syndrome were not observed. At 12 months, serum creatinine was significantly higher (119 +/- 46 micromol/L; P < .001) in patients with delayed graft function than in patients with immediate graft function (99 +/- 26 micromol/L). Patient and graft survivals were 98.8% and 97.1%, respectively. Basiliximab combined with this triple therapy was an efficient and safe immunosuppression strategy, demonstrated with very low incidence of acute rejections, an acceptable adverse event profile, excellent graft function, and high short-term survival rates in adult recipients of deceased donor renal transplant.
 ...
PMID:Effective immunoprophylaxis with basiliximab plus triple therapy in renal transplantation: five-year single-center experience. 1711 47