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

To avoid the center effect and the possible hidden interactions of multicenter studies, the validity of the Cox Proportional Hazards Model for the analysis of a single-center kidney transplant program was tested, considering 287 renal transplants performed in a 10-year period. The inclusion of type of donor and main immunosuppressive drug as covariates in the model did not violate the proportionality assumption of the Cox model. According to this method, the following covariates were significant in predicting graft survival: cyclosporine, type of donor, good human leukocyte antigen (HLA)-A and HLA-B match (DR data were not considered), highest percentage of reactive antibodies against panel cells, and nephroangiosclerosis as a primary renal disease. Cyclosporine did not significantly improve graft survival in living related donor transplants. Pretransplant blood transfusions, cold ischemia time, and donor ABO blood group were initially significant but dropped out in the step-down procedure. Recipient's age at transplant, cyclosporine, HLA-A and HLA-B match, and nephroangiosclerosis were significant in predicting patient survival. It was concluded that using long-term data of cadaveric and living related renal transplants either on azathioprine or cyclosporine is a valid way to perform multivariate analysis of single-center transplant programs that do not have large samples.
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PMID:An alternative approach for statistical analysis of kidney transplant data: multivariate analysis of single-center experience. 305 83

1. In the past 4 years there has been a definite trend to increase the number of first cadaver transplants using cyclosporine. In 1985, three fourths of the patients were treated with cyclosporine. 2. One-day, one-week, and one-month function data show that there is no increased nonfunction associated with the use of cyclosporine, and in those cases with a nonfunctioning kidney, one-year survival is higher with cyclosporine treatment compared with those patients who are not treated with cyclosporine. 3. Fewer patients treated with cyclosporine are transfused or A,B,DR matched compared with similar groups of noncyclosporine-treated patients. 4. Since the advent of cyclosporine, more kidneys have been used locally and, in addition, ischemia times are lower for cadaver kidneys. In addition, more diabetics are being transplanted with better results. 5. Cyclosporine does not seem to have an effect in living-related transplants that are one- or two-haplotype matched. There may possibly be deleterious effects associated with living-related transplants and the use of cyclosporine. 6. Patient survival since 1972 has increased one to two percentage points each year to the present time. This increase in patient survival is probably associated with those factors that strongly influence graft outcome (i.e., patient care, transfusions, matching, and immunosuppressive therapy).
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PMID:Cyclosporine and trends in kidney transplantation. 315 6

1. Clinical data on 6632 first cadaver transplants performed since January 1983 were analyzed by multivariate (Cox regression) and univariate (life-table) methods. 2. Cox regression analysis showed blood transfusion, recipient's race, HLA mismatch, highest antibody, warm ischemia time, and cyclosporine treatment as significant factors affecting graft survival. 3. A comparison of survival curves predicted by Cox regression analysis and that by the life-table method showed close agreement between the two methods. 4. Cyclosporine was one of the most significant variables affecting graft survival. There was a 13% overall increase in one-year graft survival due to cyclosporine treatment. However, other factors were still significant; they have not become obsolete in the cyclosporine era.
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PMID:Univariate and multivariate analyses of cadaver kidney graft survival data. 315 7

The salient features of one-year regraft transplant survival are as follows: 1. The effect of cyclosporine is less (about 7% increase in one-year graft survival) on regrafted patients than on first grafts. 2. In general we saw a HLA antigen matching effect in cyclosporine- and noncyclosporine-treated retransplant patients. 3. Patients who received living-related HLA two-haplotype matched kidneys did equally as well as a first or regraft recipient. 4. Transfusions seemed to have a minimal effect on regraft survival. 5. It is more important to match in patients who have PRA and the matching benefits translate into 61% and 75% one-year graft survival for zero DR and zero B,DR mismatched regraft patients, respectively. 6. In regrafts, female donor kidneys resulted in 15% lower one-year graft survival than male donor kidneys. 7. Retransplant patients from fair centers showed a significant 13% increase in one-year graft survival with cyclosporine. 8. Cold ischemia time, diabetes, and kidneys used locally or shipped had little effect on the regraft one-year survival. 9. The initial function of the retransplant kidney had a very large effect on the final one-year graft outcome of that kidney and was independent of the use of cyclosporine patients having a functioning kidney at one month had 75% and 72% one-year regraft survival with and without cyclosporine treatment, respectively. Patients having a nonfunctioning kidney at one month had 5% and 8% one-year regraft survival with and without cyclosporine treatment, respectively. 10. Responder and nonresponder classifications as defined by the duration of the first graft resulted in a 10 to 15% difference in regraft survival. 11. The effect of HLA-A,B matching was very strong in responder patients, i.e., there was a 32% difference in one-year regraft survival between zero mismatch and more than two antigens of mismatch. In nonresponder patients, the effect of HLA-A,B matching was only 5%. For HLA-DR locus matching, the difference was 12% for responders and 6% for nonresponders. 12. Cyclosporine use showed about a 10% increase in graft survival in responders and nonresponders. 13. Responder classification was also possible by separating patients who had initial function but no function at one month (responders) from those with function at one month (nonresponders).
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PMID:Regraft kidney transplant survival. 315 19

1. Cyclosporine treatment did not increase nonfunction for one month, delayed function, or first-day nonfunction in comparison with noncyclosporine-treated patients. Despite almost equivalent initial poor function rates, cyclosporine-treated patients had a higher one-year graft survival rate than noncyclosporine-treated patients. Thus, unlike many other factors, cyclosporine did not have its main effect during first-month function. 2. In regrafts there was a higher incidence of one-month and one-day nonfunction. However, these poor-function categories were not significantly increased in cyclosporine-treated patients. 3. Warm ischemia longer than 10 minutes increased the rate of first-day nonfunction and delayed function. 4. Cold ischemia longer than 36 hours increased the rate of first-day nonfunction, delayed function, and one-month nonfunction. Cyclosporine-treated patients with 36 to 48 hours cold ischemia had a one-year graft survival rate of 76% compared with 68% for those with kidneys preserved longer than 48 hours. 5. One-year graft survival rates were similar for machine- and cold-preserved kidneys if cyclosporine was used, although machine preservation led to slightly less early poor function. 6. Cyclosporine had a beneficial effect for first grafts and regrafts preserved by cold storage. However, it had an adverse effect in machine-preserved kidneys for regrafts. 7. In cyclosporine-treated patients, kidneys with delayed function had a higher (3% at one year) survival rate than those with immediate function. This was reversed in noncyclosporine-treated patients where immediate-function kidneys had a 6% higher one-year graft survival rate than those with delayed function. The same relationships held for regrafts. 8. Cyclosporine improved the one-year graft survival of delayed-function grafts by 21% in first grafts and 12% in regrafts. For kidneys which immediately functioned, cyclosporine therapy increased the one-year graft survival rate by 11% for first grafts and 3% for regrafts. Thus, cyclosporine appears to have a greater influence on kidneys with delayed function than on those with immediate function. 9. The incidence of kidneys that did not function for one month was higher (15%) in regraft patients than in first graft patients (8%). The frequency of delayed function was approximately the same for regrafts and first grafts. Thus, the main difference between first and regrafted patients occurs in the higher incidence of kidneys that never functioned among regrafted patients.
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PMID:Preservation. 315 22

Cyclosporine (CSA) is a new immunosuppressant which has selectivity for the immune system and is without systemic side effects at therapeutic doses. In contrast to the cytotoxic class of immunosuppressants, no myelotoxic, teratogenic, mutagenic, or carcinogenic effects were observed. Nevertheless, overdosage may lead to renal dysfunction, which occurs mainly in rats, and often complicates its clinical use. The experimental data also showed that significant nephrotoxicity was only caused under specific conditions at therapeutic doses. These conditions included ischemia, heminephrectomy, concomitant administration of nephrotoxic drugs, and/or genetic predisposition. Thus, concomitant renal damage is a prerequisite in order to obtain overt nephrotoxicity at therapeutic CSA doses. Since these conditions cannot be avoided in patients, nephrotoxicity often occurs at therapeutic doses in man. The rat might be a suitable experimental model of CSA nephropathy displaying similar morphologic and functional changes as observed in man. This model also allows further investigations on the pathogenic mechanisms which are elusive at the present time.
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PMID:Cyclosporine nephrotoxicity. 352 Jul 82

A multivariate analysis dissected the impact of donor procurement variables, immunologic risk factors, and alternate cyclosporine and prednisone induction immunosuppressive regimens on the early and eventual function of 303 consecutive cadaveric renal allografts. Primarily warm, but to a slight extent cold, ischemia time had an adverse impact on allograft function, as did the requirement for vasopressor or diuretic therapy. The occurrence of initial graft non-function adversely affected the probability of three-month graft survival, but did not alter either the longevity of organs, which subsequently recovered function, or patient mortality rate. The major immunologic risk factor was a second or multiple transplant, which was associated with an increased incidence of early graft failure, and impaired renal function in successful transplants. Correlations with HLA-B and DR matching were reflected in the quality of renal function, but not in graft survival rates. Cyclosporine (CsA) administration by continuous intravenous infusion, in order to avert initial elevated mean three-day, serum radioimmunoassay drug levels reduced the incidence of initial graft non-function. High levels were also associated with impaired early and eventual renal function. Rapid posttransplant taper of corticosteroids to 30 mg prednisone by day six was associated with a greater incidence of rejection episodes and early graft failure than a taper that achieved 30 mg prednisone at 60 days. Both the serum creatinine value and the degree of hypertension observed at one month afforded good prognostic indices of eventual graft survival. Therefore, renal allografts in CsA-treated patients were sensitive not only to adverse donor and immunologic risk factors, but also to excessive CsA drug levels in the early postoperative period. These findings suggest an induction immunosuppressive strategy utilizing slightly higher initial doses of steroids for CsA-sparing during the first three days, followed by increased, but judicious, administration of CsA to achieve steroid-sparing by virtue of effective rejection prophylaxis.
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PMID:Multivariate analysis of risk factors impacting on immediate and eventual cadaver allograft survival in cyclosporine-treated recipients. 354 26

To determine whether cyclosporine exacerbated renal ischemic injury and whether or not the timing of cyclosporine administration was important, rats were subjected to 30 or 45 min of ischemia. Cyclosporine was administered either before or after the renal ischemic insult. A single intravenous dose of cyclosporine, 20 mg/kg, before ischemia had no additional deleterious effect on inulin clearance compared with rats subjected to ischemia alone. In contrast, a significant exacerbation of the diminished glomerular filtration rate (GFR) produced by ischemia occurred when a low dose of cyclosporine (5 mg/kg) was given after ischemia. With 30 min of ischemia, GFR was 160 +/- 40 microliter/min/100 g in rats receiving cyclosporine (5 mg/kg) after ischemia compared with 280 +/- 40 microliter/min/100 g in rats subjected to ischemia alone. After 45 min of ischemia, cyclosporine (5 mg/kg) markedly reduced GFR to 20 +/- 10 microliter/min/100 g, a value significantly lower (P less than 0.05) than that observed in rats subjected to 45 min of ischemia alone (290 +/- 100 microliter/min/100 g). Plasma potassium concentrations tended to be higher and urinary potassium and sodium excretion lower in rats subjected to ischemia plus cyclosporine compared with ischemia alone. These findings indicate that even a single low dose of parenteral cyclosporine can exacerbate renal ischemic injury if given immediately after the ischemic insult. This interaction may contribute to the acute renal failure observed with cyclosporine use. In contrast, the kidney appears to be relatively resistant to a single dose of cyclosporine injury when the drug is administered prior to ischemia. These data suggest that the administration of parenteral cyclosporine immediately after transplantation could have deleterious effects and should probably be avoided.
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PMID:Effect of cyclosporine on renal ischemic injury. 359 Feb 99

Cyclosporine-associated arteriopathy was the cause of graft loss in 40 percent of all allografts that failed in a series of 200 consecutive cadaveric renal transplants. Arteriopathy was diagnosed by biopsy and renal uptake of indium 111m labeled platelets in the face of acute renal deterioration. A moderate thrombocytopenia and microangiopathic picture of hemolytic uremia was also present on peripheral blood smear. Immunofluorescence and histologic characteristics of the allograft biopsy specimens failed to show evidence for acute rejection: immunoglobulin M, immunoglobulin A, immunoglobulin G, C1q, C3, and C4 were not present, and there was no evidence of an interstitial or vascular mononuclear cellular infiltrate. Two clinical presentations have been described. In Group I (seven patients), anuria occurred rapidly within the first 2 weeks after transplantation. In Group II (nine patients) renal function gradually diminished 1 to 5 months after starting cyclosporine therapy. Fifteen of the 16 recipients had progressive and irreversible loss of renal function which was pathologically associated with fibrin deposition, intimal proliferation, and thrombotic occlusion of the cortical interlobular and arcuate arteries, with subsequent focal glomerular ischemia and cortical infarction. One recipient with rapid loss of renal function received an intraarterial allograft infusion of streptokinase and subsequent systemic heparinization, which resulted in return of normal allograft function. The syndrome of cyclosporine-associated arteriopathy has been linked to a lack of or reduced amounts of prostacyclin-stimulating factor or prostacyclin.
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PMID:Cyclosporine-associated renal arteriopathy resulting in loss of allograft function. 389 78

Liver regeneration plays a key role in restoring the liver/body ratio after partial liver transplantation. However, hepatic ischemia hinders the proliferative response of the hepatocytes. In this study, different ways of improving the regenerating capacity of ischemic hepatocytes are tested. Following 70% hepatectomy and 15 min of normothermic liver ischemia, the percentage of regenerating hepatocytes and the regenerative gradient are assessed. Cyclosporine A (hepatotrophic agent), superoxide dismutase and folinic acid (antioxidants), administered during the ischemic period, have significantly increased these indices. The later drug has restored the regenerative response to the levels of normoperfused livers.
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PMID:Effect of allopurinol, folinic acid, SOD and cyclosporine A on ischemic liver regeneration. 778 46


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