Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.6 (CAD)
4,420 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclosporine has improved the results of renal transplantation. In 1984, we began using it as part of a sequential immunosuppression protocol (MALG, AZA, P, and delayed administration of CsA) in our pediatric renal transplant recipients. We studied the outcome of the 131 pediatric renal transplants (less than or equal to 18 years of age at transplant) performed at our institution between June 1984 and March 1991. We compared these results with the 144 similar transplants performed since January 1980 that did not involve CsA immunosuppression. In the sequential immunosuppression group, there were 97 primary (74%) (26 [27%] cadaver, 71 [73%] living donor [LD]) and 34 (26%) retransplant (23 [68%] CAD, 11 [32%]) recipients. Age at transplant (mean +/- SD) was 7.4 +/- 5.5. Overall, 1-year actuarial graft survival was 93%; 1-year patient survival was 100%. The mean number of hospital readmissions was 3.0 +/- 3.5; 26 (20%) were readmission-free. The mean number of rejection episodes was .87 +/- 1.3 per patient; 73 (56%) were rejection-free. Importantly, LD (vs. CAD) recipients had fewer rejection episodes (P = 0.06). In the first post-transplant year, the serum creatinine level was significantly lower in primary (vs. retransplant) recipients and in LD (vs. CAD) recipients (P less than 0.05). In the 144 patients not receiving CsA, there were 129 (90%) primary (27 CAD, 102 LD) and 15 (10%) retransplant (7 CAD, 8 LD) recipients. Age at transplant was 6.9 +/- 5.3 years. The 1-year actuarial graft survival rate was 82%; the 1-year patient survival rate was 94%. The mean number of hospital readmissions was 3.3 +/- 2.3; 5 (8%) were readmission-free. The mean number of rejection episodes was 1.2 +/- 1.5; 27 (45%) were rejection-free. There was no difference in the serum creatinine level based on donor source or transplant number. Sequential immunosuppression has significantly improved patient (P = 0.003) and graft survival (P = 0.004) rates. Comparing sequential vs. non-CsA immunosuppression, there was no difference in the number of readmissions (P = 0.47), number of rejection episodes (P = 0.17), or serum creatinine level. The number of rejection-free patients was significantly lower in LD (vs. CAD) recipients (P less than 0.05). There was no evidence of progressive deterioration in renal function in the sequential (vs. non-CsA) recipients.
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PMID:Pediatric renal transplants--results with sequential immunosuppression. 173 84

Prior to 1975 patients with systemic lupus erythematosus were generally not considered candidates for renal transplantation because of concern that immune complex deposition would rapidly destroy the allograft. However, recent evidence suggests that good patient and graft survival rates can be achieved comparable to other renal diseases. Between September 23, 1963 and July 31, 1990, 1070 renal transplants were performed at Washington University Medical Center (WUMC). During this period, 14 patients with SLE (12 female and 2 male) received 16 renal transplants (7 living-related donor [LRD], 1 living-unrelated donor [LURD], and 8 cadaver [CAD]). The mean age at the time of the first transplant was 32.5 +/- 10.3 years. The duration of disease prior to transplant was 88.0 +/- 45.9 months and the duration of hemodialysis prior to transplant was 36.0 +/- 33.7 months. Of these patients, 7/14 (50%) had negative and 3/14 (21%) positive SLE serology pre- and post-transplant, 3/14 (21%) had negative serology pretransplant that became positive posttransplant, and 1/14 (2%) was positive pretransplant and became seronegative posttransplant. Patient survival was 92.8% (13/14), and of the 16 kidneys transplanted 62.5% (10/16) are still functioning with a mean follow-up period of 43.7 +/- 45 months. The current mean serum creatinine was 1.4 +/- 0.26 mg/dl. One noncompliant patient developed recurrent lupus nephritis bringing the total number of cases reported in the literature to seven. The present study demonstrates that patients with SLE can be transplanted with excellent patient and graft survival and function and a low rate of recurrent lupus nephritis. From a review of the literature, there appears to be an association between positive SLE serology pre- and posttransplant and recurrent lupus nephritis.
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PMID:Renal transplantation for systemic lupus erythematosus and recurrent lupus nephritis. A single-center experience and a review of the literature. 194 64

The Authors report aortic valvular replacement (AVR) and coronary artery bypass graft surgery (CABG) successfully performed in two renal transplant patients. The postoperative blood urea and creatinine levels were comparable to the preoperative values. The first patient underwent isolated AVR. The second patient had an initial AVR combined with CABG followed two years later by a further AVR for prosthetic dysfunction. For many reasons, coronary artery (CAD) and valvular diseases are not uncommon in renal transplant patients. Cardiac surgery is feasible without impairment of the renal function provided some precautions are taken, ie good mean perfusion pressure during cardiopulmonary bypass (CPB), adequate volume replacement, and selected use of mannitol and dopamine.
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PMID:Valvular and coronary surgery in renal transplant patients. 222 52

Cytomegalovirus (CMV) infection was diagnosed in 28% (n = 144) of 516 renal allograft recipients treated with cyclosporine-prednisone (CsA-Pred) immunosuppressive therapy. The majority of infections produced either asymptomatic (n = 37) or mild-to-moderate (n = 75) clinical disease, while 10% were lethal (n = 14). Transplantation from a seropositive donor to a seronegative recipient was associated with an increased incidence of (CMV) infection but did not predispose to more severe clinical disease. Similarly, donor source (cadaver [CAD] vs. living-related donor [LRD]), age greater than or equal to 45 years, and antecedent pulse steroid therapy for the treatment of acute rejection were not correlated with clinically more severe disease. An increase in serum creatinine to greater than or equal to 25% of preinfection nadir values occurred in association with CMV infection in 106 patients, returning to nadir values or below in 74.5% of these individuals. CMV infection did not impact on actual patient survival among recipients of LRD or CAD allografts or on actual 1-year HLA-haploidentical or HLA-identical LRD graft survival. In contrast, actual 1-year cadaveric graft survival was significantly lower among CMV-infected (n = 95) vs. uninfected (n = 198) patients (75.8% vs. 87.8%, P = .01). In association with the finding of reduced actual 1-year CAD graft survival, CMV-infected patients were found to be more predisposed to develop acute rejection episodes. Of the CMV-infected CAD graft recipients, 48.4% developed greater than or equal to 1 acute rejection episode during the first year following transplantation vs. 25.3% of their uninfected counterparts (P less than .001). The impact of CMV infection in CsA-Pred treated renal transplant recipients does not differ substantially from that reported historically in association with prednisone-azathioprine immunosuppressive therapy.
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PMID:The adverse impact of cytomegalovirus infection on clinical outcome in cyclosporine-prednisone treated renal allograft recipients. 283 Jun 86

1. There have been 1,426 renal transplants performed at the University of Minnesota from January 1, 1980 through August 31, 1988. CsA+P was used by 260 adult recipients, CsA+P+AZA(+ALG) by 536. 2. In general, there are no significant differences in actuarial graft or patient survival rates between the 2 CsA protocols. This is true for all adults, for all adult CAD recipients, and for a matched control group of adult CAD recipients. 3. Cox's proportional hazards regression model also indicates that there is no significant difference between the 2 CsA regimens. Donor type, number of transplants, and age at transplant influence graft survival in all adult recipients. The use of LRD is still indicated in the CsA era. Diabetic status, age at transplant, and number of transplants affect patient survival. The model fits the observed data quite well. 4. Actuarial analysis and Cox regression failed to document a beneficial effect of HLA-A, B, and DR matching in patients receiving either CsA protocol. Our data do not support the HLA matching point system currently used by UNOS or the Terasaki proposal to give points based on mismatching. 5. A matched control analysis of adult CAD recipients indicates that CsA+P+AZA+ALG has alleviated the problems of our CsA+P protocol without lowering the graft and patient survival rates. Thus, the sequential therapy group has equivalent graft and patient survival rates but shorter duration of ATN, lower serum creatinine levels at 1 year, and fewer patients who require modifications of protocol. Sequential therapy is our treatment of choice.
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PMID:A comparison of two cyclosporine protocols at the University of Minnesota. 315 98

Biochemical analyses from endomyocardial biopsies indicate that cardiac energy metabolism is altered in patients with end-stage cardiac failure. Myocardial energy production is predominantly based on fatty acid oxidation. Carnitine, a naturally occurring compound, plays an essential role in fatty acid oxidation by carrying long-chain fatty acids into the mitochondrial matrix where they undergo beta-oxidation. In experimental animals, myocardial carnitine deficiency may cause cardiomyopathies which are reversible with carnitine substitution. Rare human diseases, as systemic carnitine deficiency, are associated with impaired cardiac function. We therefore investigated carnitine metabolism in patients with cardiac failure. Plasma and myocardial carnitine levels were measured in 55 patients undergoing cardiac transplantation because of end-stage cardiac failure based on dilated cardiomyopathy (DC, n = 30) or coronary artery disease (CAD, n = 22). Elevated plasma carnitine levels (controls: 49 +/- 12 microM; DC: 82 +/- 38 microM; p less than 0.001, CAD: 86.9 +/- 21.6 microM; p less than 0.05) were found in both patient groups (Fig. 1). Plasma carnitine did not correlate with creatinine (Fig. 2). Compared to controls, myocardial carnitine levels were significantly reduced: DC: 5.9 +/- 1.45 nmol/mg NCP; CAD: 5.84 +/- 1.84 nmol/mg NCP; controls: 15.6 +/- 5.4 nmol/mg NCP (Fig. 3). No correlation between myocardial and plasma levels was found (Fig. 5).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Carnitine metabolism--changes in the end stage of dilated cardiomyopathy and ischemic heart muscle disease]. 332 28

Previous studies suggest stable renal transplant recipients can have either prednisone (P) or cyclosporine withdrawn; however, 30% of these patients undergo rejection requiring reinstitution of P or CsA. Some patients return to baseline creatinine levels, while others either stabilize at a higher creatinine level or lose their graft. It would be ideal to establish immunologically based criteria for selecting patients who can be successfully withdrawn or tapered from immunosuppression. We have investigated the development of donor antigen-specific hyporeactivity by using donor cells and/or homozygous typing cells defining the HLA-Dw specificities of the donor cells as stimulator cells in the mixed lymphocyte culture (MLC) and comparing the pre- and posttransplant responses of peripheral blood mononuclear cells from 199 kidney transplant recipients. Of these, 27% of the haploidentical living-related donor and 25% of the cadaver recipients developed in vitro donor antigen-specific hyporeactivity. The LRD recipients who did so have lower mean creatinine levels at 6, 12, and 24 months posttransplant (1.3, 1.3, and 1.2, respectively) than those who remained responsive to the donor antigens (1.6, 1.7, and 1.8) (P < 0.05). However, no differences in the mean creatinine levels were observed between CAD recipients who developed donor antigen-specific hyporeactivity and those who remained responsive. Rejection episodes were common in all groups in the first 3 months posttransplant; however, recipients who developed donor antigen-specific hyporeactivity tended to experience fewer rejection episodes after 3 months posttransplant. The percentage of recipients who remained rejection-free after 3 months post-transplant was 95% for CAD recipients who developed donor antigen-specific hyporeactivity vs. 83% for those who remained responsive. Only 1 hyporesponsive recipient (0/15 LRD; 1/20 CAD) developed chronic rejection vs. 12 (5/41, LRD; 7/60, CAD) recipients who remained responsive. For those with graft function at 3 months (when hyporesponsiveness was first determined), the actuarial 36-month graft survival was higher in the hyporesponsive (92%, LRD; 94%, CAD) than in responsive groups (LRD, 76%; CAD, 91%). No differences in the degree of HLA-DR mismatching (MM) were observed for the LRD hyporesponsive (1.20 DR MM) vs. reactive (0.98 DR MM) groups or for the CAD hyporesponsive (1.35 DR MM) vs. reactive (1.30 DR MM) groups. Donor antigen-specific hyporeactivity could not be determined (UND) for 30 of the LRD recipients and 33 of the CAD recipients due to lack of mismatching for DR antigens (0.03 DR MM and 0.25 DR MM, respectively).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Evidence that improved late renal transplant outcome correlates with the development of in vitro donor antigen-specific hyporeactivity. 768 34

Renal allograft glomerular filtration rate (GFR) was measured at 4-month intervals for up to 1 year in 43 CsA-treated patients using x-ray fluorescence determination of plasma iohexol clearance. Study patients were divided into cohorts based on time (years) after transplantation at study entry (0-1; 1-2; 2-3; and > 3 years) and entry GFR levels (20-29; 30-39; 40-49; and > or = 50 ml/min/1.73 m2). GFR at study entry was 42 +/- 2 and was comparable in CAD (n = 31) versus LRD (n = 12) allografts (42 +/- 2 and 44 +/- 4 ml/min/1.73 m2, respectively). Range of entry GFR levels was similar in each of the "time at entry" cohorts defined above. Serum creatinine concentrations of 1.5-2.5 mg% were associated with GFR levels of 20-60 ml/min/1.73 m2. Serial GFR levels obtained at 4-month intervals for 1 year (n = 34 patients) were not consistent with a pattern of progressively declining GFR occurring as a function of either time after transplantation or absolute GFR level at study entry (intraindividual coefficient of variation 10.3 +/- 1.0%). Patients in the lower quartile of "entry GFR" levels (< 34 ml/min/1.73 m2) were more likely than their counterparts to have had a history of acute rejection. Results are consistent with retrospective population studies of aggregate serum creatinine levels, indicating that long-term CsA use is not uniformly associated with accelerated loss of renal allograft function consequent to a progressive, toxic nephropathy. The data also suggest that neither absolute GFR level nor time after transplantation represent indications for routine dose reduction or conversion to AZA.
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PMID:Stability of renal allograft glomerular filtration rate associated with long-term use of cyclosporine A. 849 74

Studies in animals and humans have demonstrated that an increased heart rate is a predictor for the development of coronary atherosclerosis and overall cardiovascular mortality. In contrast, we have previously reported that the need for pacemaker implantation because of bradycardia in heart transplant recipients is associated with an increased prevalence of transplant coronary artery disease (TxCAD). Hence, the relevance of changes in heart rate to the development of TxCAD remains unclear. Intra-coronary ultrasound examinations (ICUS) were therefore analyzed in 130 heart transplant recipients (age 50 +/- 11 yr) studied at annual evaluations (3.7 +/- 3.0 yr after transplantation). Quantitative ultrasound measurements were obtained by calculating mean coronary artery intimal thickness (MIT) obtained by examination of the left anterior descending artery. The presence of TxCAD was defined as MIT > 0.3 mm. Resting heart rates (HR) were recorded with the patients in the supine position during routine echocardiography. Based on HR recordings, two groups were defined: group 1, HR below; or group 2, HR above the median. TxCAD was detected in 40% of the ICUS studies overall. The prevalence of TxCAD was higher in group 1 (49%) compared with group 2 (33%), p < 0.05. There was no significant difference in donor ischemic time or donor gender, recipient age, gender, body weight, CMV status, creatinine, total cholesterol, use of lipid lowering drugs or diltiazem. Donor age and use of beta-blockers were higher in group 1 compared with group 2 (29 +/- 10 vs. 25 +/- 9 yr, and 15% vs. 5%, for donor age and beta-blocker use, respectively). By multivariate regression analysis only donor age and years after transplantation were independently correlated with TxCAD. After excluding patients taking beta-blockers and diltiazem, the prevalence of CAD was still higher in group 1 (50%) vs. group 2 (34%). In conclusion, transplant coronary artery disease is more prevalent in patients with lower, rather than higher, heart rates. The reason for this is unclear, but may reflect impaired blood flow to the sinoatrial node.
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PMID:Importance of decreased heart rate in predicting transplant coronary artery disease. 940 98

Of the 10 chronic haemodialysis patients whose serum TnT levels exceeded the threshold value of 0.1 microg.L(-1) at entry into the study, four were dead at 1 year and three others had a diagnosis of CAD. Of the 20 chronic haemodialysis patients with normal serum TnT levels at entry, one died and none had CAD. All five deaths were cardiac related, either arising from acute myocardial infarction or by sudden death. When serum TnT levels were compared with accepted predictors of death in chronic haemodialysis patients, such as serum creatinine, serum albumin and haematocrit, in the present study serum TnT proved to be more accurate and had excellent sensitivity and specificity. Serum TnT was also superior to serum TnI, which proved to be no more discriminating than the non-specific muscle marker, aldolase.
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PMID:Troponin T, a predictor of death in chronic haemodialysis patients. 985 37


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