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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Two-step Cox regression analyses showed that, for White recipients of first cadaver transplants, pretransplant transfusions, HLA-DR mismatch, donor race, CIT, size mismatch, PRA, old donor, and recipient age were significant prognostic factors during the first 6 months posttransplant, and after that, older donor, CIT, and size mismatch continued to have effects on graft survival in the longer term. 2. For African-American recipients of first cadaver transplants, pediatric donor, cause of donor death, and increasing second warm ischemia time were major risk factors in the early period, but in the late period, the effect of donor age dominated other factors. 3. Multistep linear logistic regression and two-step Cox regression analyses yielded similar results, with donor-related and histocompatibility factors dominating survival outcome in both the short and long terms.
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PMID:The UNOS Scientific Renal Transplant Registry: multistep regression models on kidney graft survival. 210 61

It has been reported that initial cyclosporine levels over 400 ng/ml posttransplantation result in an increased incidence of delayed graft function (DGF). Several studies have shown early graft function to be a major determinant for long-term graft survival. Continuous intravenous infusion (CIVI) has been employed to induce immunosuppression establishing therapeutic drug levels while minimizing toxicity in renal allograft recipients. This study examines the impact of the achieved serum CsA steady-state concentration (Css) levels upon transplant outcome in 228 patients given CsA by CIVI. In spite of administration of a specific drug dose, interindividual variation in elimination rates yields a broad range of Css levels. Six groups were stratified by CsA Css levels: group A 0-75 ng/ml, group B 76-100 ng/ml, group C 101-150 ng/ml, group D 151-200 ng/ml, group E 201-250 ng/ml, and group F greater than 250 ng/ml. Group A showed a significantly lower age and greater incidence of rejection at 0-10 days. Group F had significantly higher incidences of nephrotoxicity, hepatotoxicity, and delayed graft function. The findings suggest that the antirejection Css threshold for CsA may be at least 75 ng/ml, and the toxicity threshold above 250 ng/ml. Controversy exists about whether CsA influences the incidence of DGF, therefore risk factors for DGF were examined among the groups stratified by CsA Css levels. While cold ischemia time for all 228 patients as a group was highly correlated with DGF (P less than 0.001), neither cold ischemia time nor donor age was significantly different among the groups. There does appear to be a synergistic effect between CsA Css and CIT, since the incidence of DGF was significantly higher when the cold ischemia time was 21-24 hr and CsA Css greater than 200 ng/ml. Long-term graft function did not appear to be affected by early CsA Css levels. The Css of 100-250 ng/ml appears to achieve a satisfactory outcome with a 19.5% incidence of rejection within 10 days, 29.7% DGF, and 5.1% nephrotoxicity. Only 118/228 patients (52%) in this study achieved that range despite a fixed low CIVI of CsA. Thus potential renal allograft recipients may benefit from a pretransplant pharmacokinetic study to predict the proper CIVI dose.
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PMID:The impact of steady-state cyclosporine concentrations on renal allograft outcome. 230 Oct 23

We reviewed 14,005 renal grafts with the temporal opportunity for 10-year survival (transplanted 1975 and earlier) and analyzed 10-year actuarial graft survival and the rate of late (3- through 10-year) graft loss as reflected by half-life. The 10-year graft survival for first transplants in HLA-identical siblings was 67% versus 38% for parental donors and 20% for cadaver donors. Factors with substantial influence on 10-year graft survival include transplant number, transfusions (0, 17%; greater than or equal to 1,33%), HLA-A,B mismatches (0, 29%; 1-2, 20%, 3-4, 17%), cold ischemia time (0-3 hours, 32%; 4-6 hours, 27%; 7-12 hours, 21%; greater than 12 hours, 16%), preservation method if CIT is no more than 24 hours (cold storage, 22%; machine, 17%), recipient race (Caucasian, 23%; black, 11%), original disease, recipient age, recipient sex, donor race, and the quality of early graft function (less than or equal to one month). Factors not significantly influencing 10-year graft survival were panel-reactive antibodies, warm ischemia time, preservation method if CIT was more than 24 hours, and donor sex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Factors important in 10-year kidney transplant survival. 315 94

1. In transplants performed between 1971 and 1986, first cadaver donor grafts had a half-life ranging from 6.6 to 7.5 years in the period after the first year. Second cadaver donor grafts had a half-life of 5.1 to 6.5 years. Parental donor grafts had a half-life of 9.3 to 11.8 years, whereas HLA identical sibling donor transplants had a half-life of 19.1 to 26.5 years. Siblings with no haplotype in common had an average half-life of 8.7 years. 2. Between 1971 and 1984, white recipients had an average half-life of 7.7 years, which increased to 9.3 years in 1985-1986. Black recipients' half-life decreased from 5.4 years in 1975-1976 to 3.5 years in 1985-1986. The reason for this decrease is not apparent. 3. The half-life of transplants of different recipient ages did not vary significantly. The average half-life during this period of study was 7.4 years for those younger than 21 years of age, 8.2 years for recipients 21 to 50 and 6.7 years for those older than 50. 4. In the early data, there was some evidence that the half-life of kidneys with cold ischemia below 13 hours was superior. However, in the latest period (between 1983 and 1986) the average half-life was 7.6 years for CIT below 13 hours, 7.2 years for those with 13 to 24 hours and 6.4 years for more than 24 hours. 5. For patients receiving kidneys with no HLA-A,B mismatches, the average half-life was 10.1 years. Those with A,B mismatches had a half-life of 6.7 years, and for those with no A,B antigens in common, the average half-life was 6 years. 6. In the period after 1981, the average half-life of patients with no A,B,DR mismatches was 9.1 years compared with 6.5 years for those with A,B,DR mismatches and 5.4 years for those with no A,B,DR antigens in common.
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PMID:Long-term survival. 315 79

The influence of warm and cold ischemic time (WIT and CIT) on renal allograft function and allograft survival rates was analyzed from the Eurotransplant data. From 1977 through 1980 renal allograft recipients were divided into three groups, according to the length of the WIT of their graft: group I, 0-10 min (n = 2,636); group II, 11-20 min (n = 108); group III, 21-35 min (n = 17). Differences in graft function or graft survival have not been observed between these groups. It is concluded that donor kidneys with a WIT up to 20 min are acceptable for transplantation. The transplantation results in group III suggest that 35 min is a safe limit for acceptance, but the small number of transplantations in this group does not justify a firm conclusion. A combined analysis of warm and cold ischemia shows that simple cold storage up to 50 h is safe and acceptable, provided that warm ischemia is kept minimal (less than 10 min). It seems advisable to keep hypothermic preservation within the limit of 30 h, when WIT exceeds 10 min.
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PMID:The influence of warm and cold ischemic time on the outcome of cadaveric renal transplantation. 637 96

The coronary vascular endothelium produces nitric oxide (NO) during the conversion of L-arginine to L-citrulline. Although NO is a potent vasodilator, at lower concentrations, it also has antineutrophil actions that reduce the inflammatorylike components of ischemia-reperfusion injury. The endothelium is damaged in the early minutes after reperfusion, ie, before neutrophils accumulate and before myocardial necrosis fully develops, and this suggests that endothelial injury is a springboard event in the postischemic inflammatory cascade. Studies of coronary artery occlusion and reperfusion suggest that early damage to the coronary endothelium impairs NO production, which, in turn, abrogates the endogenous antineutrophil effects of NO. However, this impaired endogenous NO-related cardioprotection can be restored either by providing specifically at the onset of reperfusion the precursor to NO (L-arginine) or by providing agents that donate NO. In studies, L-arginine or NO donors reduce infarct size in models of coronary occlusion and reperfusion. The mechanism or mechanisms of this cardioprotection involve preservation of endothelial function and inhibition of neutrophil accumulation in ischemic-reperfused tissue. The cardioprotective potential of NO offers a new therapeutic approach to the reduction of ischemia-reperfusion injury after coronary artery occlusion.
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PMID:Attenuation of myocardial ischemia-reperfusion injury with nitric oxide replacement therapy. 767 45

This study investigated the effects of in vivo inhibition of cerebral nitric oxide synthase by intravenous administration of NG-nitro-L-arginine (NNLA) on the cell membrane Na+,K(+)-ATPase activity in the cerebral cortex of newborn piglets. NNLA was administered intravenously to 22 piglets at doses of 5 mg/kg (n = 3), 25 (n = 3), 50 (n = 4), 75 (n = 4), and 100 mg/kg (n = 2). Control animals (n = 6) received normal saline only. 90 min after infusion the cerebrum was obtained. The cerebral nitric oxide synthase activity, determined by measuring the conversion of [3H]-L-arginine into [3H]-L-citrulline in the brain homogenate, decreased from 9.1 +/- 2.0 pmol/mg protein/min in controls to 1.7 +/- 0.6 pmol/mg protein/min after the administration of 75 and 100 mg/kg NNLA. The Na+,K(+)-ATPase activity was measured in the P2 fraction of cortical tissue homogenate. The Na+,K(+)-ATPase activity was within the normal range (48.3 +/- 4.9 mumol/mg protein/h) up to 75 mg/kg of NNLA. At a dose of NNLA of 100 mg/kg, the Na+,K(+)-ATPase activity decreased to 31.5 +/- 0.7 mumol/mg protein/h (p < 0.05). Four animals developed hypoxemia and lactic acidosis. The results demonstrate that inhibition of the cerebral nitric oxide synthase activity in vivo in newborn piglets by intravenous administration of NNLA did not affect the cortical cell membrane Na+,K(+)-ATPase activity up to a dose of 75 mg/kg. Doses of 100 mg/kg decreased the Na+,K(+)-ATPase activity, probably by inducing cerebral hypoxia-ischemia.
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PMID:Brain cell membrane Na+,K(+)-ATPase activity after inhibition of cerebral nitric oxide synthase by intravenous NG-nitro-L-arginine in newborn piglets. 872 86

Several hours after an hypoxic-ischemic injury to the developing brain, hyperemia, then seizures, edema, and infarction can develop. The roles of nitric oxide (NO) synthesis and excitotoxin accumulation during these later phases of injury are not known. The time course of extracellular levels of amino acids within the parasagittal parietal cortex were measured with microdialysis during and for 3 d after 30 min of cerebral ischemia in nine chronically instrumented near-term fetal sheep (119-133 d). Cortical electroencephalographic (EEG) activity and extracellular space (ECS) were quantified simultaneously with real-time spectral analysis and cortical impedance measurements, respectively. Amino acid concentrations were measured using HPLC. During ischemia, citrulline (by-product of NO synthesis), glutamate, glycine, and gamma-aminobutyric acid (GABA) concentrations rose to 147 +/- 18%, 180 +/- 20%, 290 +/- 50% and 4800 +/- 1300% of baseline respectively (p < 0.05). The excitotoxic index ([glutamate] x [glycine]/[GABA]) decreased to 15 +/- 8%. Upon reperfusion, the cytotoxic edema and amino acid accumulation largely resolved within 1 h, and the EEG was depressed. Citrulline began to rise again by 4 h (p < 0.05), reaching a maximum (273 +/- 21%) at 32 +/- 2 h. Seizure activity developed at 7 +/- 2 h, and impedance plus the excitotoxic index then rose progressively and peaked at 32 +/- 2 h (480 +/- 170%). At 72 h, there was severe neuronal loss and laminar necrosis within the parasagittal cortex. These data suggest that, several hours after a severe hypoxicischemic injury, NO synthesis increased, then seizures arose, and edema developed concomitantly with the accumulation of excitotoxins.
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PMID:Accumulation of cytotoxins during the development of seizures and edema after hypoxic-ischemic injury in late gestation fetal sheep. 872 30

Overall one-, 5-, and projected 10-year graft survival rates were 81%, 58% and 39%, respectively for 51,442 cadaveric kidney transplants performed at 251 U.S. transplant centers from October 1987-December 1994. The comparable results for recipients of living donor kidneys were significantly higher, 91%, 75%, and 60% (p<0.001). One-year first cadaver graft survival rates improved from 77% for transplants performed in 1987-1988 to 84% for transplants performed in 1991-1992 (p<0.001). Recipients of second cadaveric transplants in 1987-1988 had a 69% one-year graft survival rate compared with 81% for those transplanted after 1990 (p<0.001). Graft survival rates have been stable since 1991. The percentage of broadly sensitized first transplant recipients decreased from 13% before 1991 to 7% after, and the one-year graft survival rates increased by 4-6% for both sensitized and nonsensitized recipients between the 2 periods (p<0.001). Among retransplanted patients, the percent of broadly sensitized recipients fell from 40-33% over the same periods (p<0.01). One-year graft survival rates increased by 7-8% for sensitized and nonsensitized patients (p<0.001). One-year graft survival rates improved from 74-83% for Blacks (p<0.001) and from 78-85% for non-Blacks (p<0.001) transplanted for the first time when comparing transplants performed in 1987-88 with those performed in 1993-94. The cause of donor death had a significant effect on graft survival. The 5-year graft survival rate was 61% for 28,923 recipients of trauma donor kidneys compared with 54% for 16,956 transplants from CVA donors (p<0.001). Kidneys from CVA donors increased from 28% of all cadaveric kidneys in 1988 to 38% in 1994. The donor's age was a more important determinant of long-term survival, however, and correlated strongly with the cause of donor death. Only 16% of CVA donors were reportedly age 30 or less, compared with 75% of trauma donors. First cadaver graft survival decreased by approximately 2% for each 12 hours of cold ischemia time. Although there was a significant increase in the incidence of delayed graft function from 19% when the CIT was less than 12 hours to 35% when the CIT was more than 36 hours, there was no significant long-term effect of cold ischemia time. The recent change in UNOS policy to share zero-HLA mismatched kidneys resulted in a 2-fold increase (from 8%-16%) in the number of HLA-matched transplants performed during the first 6 months following the change. The percentage of Blacks who have received matched kidneys following this change has increased from less than 2% to more than 5%, a 3-fold increase. The 163 Blacks who received an HLA-matched kidney prior to 1995 had a 65% 4-year graft survival rate compared with 53% for mismatched Blacks (p<0.001). The incidence of early rejections was also reduced by 25% among matched recipients and the graft half-life was 8 years compared with 5 years for mismatched Blacks. About 25% of HLA-matched kidneys were transplanted to ABO compatible but not identical recipients. Although the effect of the policy allowing compatible transplants did not result in a large number of type O kidneys transplanted to non-O recipients when only 8% of kidneys were shared, the recent change in allocation policy may be detrimental to type O waiting patients.
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PMID:The UNOS scientific renal transplant registry. United Network for Organ Sharing. 879 51

Nitric oxide synthase, the mammalian enzyme catalyzing the oxidation of L-arginine to L-citrulline and nitric oxide, is present in three isoforms that have distinct physiological roles. Overstimulation or overexpression of individual nitric oxide synthase isoforms plays a role in a wide range of disorders including septic shock, arthritis, diabetes, ischemia-reperfusion injury, pain and various neurodegenerative diseases. Animal studies and early clinical trials suggest that nitric oxide synthase inhibitors could be therapeutic in many of these disorders, but preservation of physiologically important nitric oxide synthase functions might require use of isoform-selective inhibitors. Within the past few years both amino acid and nonamino acid nitric oxide synthase inhibitors with pharmacologically useful isoform selectivity have been reported. Selectivity has been achieved on the basis of initial binding affinity and, for mechanism-based inactivators, on the basis of isoform-dependent catalytic activation; particularly interesting are N5-(1-imino-3-butenyl)-L-ornithine, ARL 17477, 1400W and S-(2-aminoethyl)isothiourea.
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PMID:Design of isoform-selective inhibitors of nitric oxide synthase. 973 22


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