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Query: UMLS:C0022116 (ischemia)
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Although the PGs operate mainly in the renal medulla the demonstration of PG biosynthesis in the renal cortex has provided a biochemical basis for a direct relationship between the PGs and the renin-angiotensin system. The formation of PGs is influenced by circulating levels of A I probably by indirect mechanisms. That the release of renin at least under certain experimental conditions is dependent on the PG system is suggested by the following findings: 1. C20:4 increases PRA in the rabbit and rat. 2. Indomethacin decreases PRA in the rabbit. 3. C20:4 stimulates renin release from slices of rabbit kidney cortex. 4. Reduced renal perfusion pressure and ischemia are accompanied by release of both PGs and renin. 5. The release of PG and renin following renal ischemia is blocked by treatment with indomethacin. The actions of the renin-angiotensin system and the renal PGs are, as far as we know them, antagonistic to each other. PGEs are vasodilator, increase renal blood flow, inhibit adrenergic neurotransmission, and cause excretion of electrolytes and water. Conversely, A II is vasoconstrictor, decreases renal blood flow, stimulates adrenergic neurotransmission, and conserves water and electrolytes. Thus, the interaction between the renal PGs and renin seems to be one in which the two hormonal systems stimulate each other's formation or release, but opposes each other's actions. Further studies are necessary to reconcile this apparent contradiction.
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PMID:Interactions between the renal prostaglandins and the renin--angiotensin system. 79 Sep 16

Reaction constants of renin in juxtaglomerular apparatus and plasma renin activity after renal ischemia and hemorrhage. During and after total renal ischemia and acute hemorrhage, renin activity in plasma (PRA) and microdissected juxtaglomerular apparatus (JGA) of rabbits were investigated. In controls, the apparent Michaelis-Mentoen constant (MMC) of semipurified standard renin of rabbits was 1025 plus or minus 223 SD ng/ml. Plasma renin of normal rabbits showed similar values: 1062 plus or minus 138 SD ng/ml. Intrarenal JGA renin, however, showed a great scatter of MMC (920 to 4760 ng/ml) and a significantly higher mean value of 2572 plus or minus 1156 SD ng/ml (pis less than 0.001). After complete renal ischemia by clamping both renal arteries for a 90-min period, the following results wereobtained: 1) Sixty min after the beginning of ischemia, PRA decreased from 20.9 plus or minus 9.8 SD to 7.6 plus or minus 5.2 SD ng/ml-hr (P is less than 0.05) and increased to 103, 68 and 42 ng/ml-hr 10, 30 and 90 min after removal of the clamps, respectively (P is less than 0.05).
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PMID:Reaction constants of renin in juxtaglomerular apparatus and plasma renin activity after renal ischemia and hemorrhage. 113 98

1. From a multivariate log-linear analysis of 35,625 renal transplants between 1988 and 1991, center effects accounted for 28%, 45%, and 27% of all assignable variation in 3-month, 1-year, and 2-year outcomes, respectively. Although center variation dominated 22 other variables, most factors were relatively independent of transplant center (ie, a percent of factor variation due center less than 10%). Recipient race and health status were notable exceptions; both highly influenced by center affiliation. Centers also differed in the age mix of recipients and racial mix of donors in some epochs. Again, we found only extremely weak correlations among a center's 3-month, 1-year, and 2-year graft survival rates. 2. In order of 3-month accountability, the other important factors were PRA, donor age, recipient working status, year of transplant, HLA-A,B mismatching, previous transplant, donor's death, donor relationship, recipient race, body mass, recipient age, cold ischemia time, donor race, donor kidney mode (ie, left/right kidney), original disease, and HLA-DR mismatching. Regarding 1-year outcome, the important factors were recipient race, donor age, donor's death, donor relationship, HLA-A,B mismatching, previous transplant, and recipient sex. Finally at 2 years, the important factors were recipient race, donor age, year of transplant, donor relationship, recipient sex, working status, donor's death, recipient age, CMV status, body mass, and donor sex. 3. Body mass, donor kidney mode, and CMV status were novel factors in our own multifactorial analyses of the UNOS Registry file. An elevated body-mass index (> 30 kg/m2) had a negative impact on short- and long-term graft survival. Recipients receiving left kidneys had nominal improvement in 3-month graft survival, but no impact thereafter. Survival rates over the 4 combinations of donor/recipient CMV statuses, suggest that this covariate was principally long-term and donor related. 4. It is noteworthy that graft failures in the 2 most recent transplant years, 1990 and 1991, have shown both short- and long-term declines, breaking stationary patterns previously reported in this series on clinical transplants. 5. The transitory nature of most transplantation factors was confirmed in this study, implying that future multifactorial studies in renal transplantation must include some mechanism for varying risks.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Multifactorial analysis of renal transplants reported to the United Network for Organ Sharing Registry. 130 7

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

The effects of 1-year antihypertensive treatment with the diuretic fenquizone were evaluated in 16 patients with mild essential hypertension. During treatment with placebo, after 2, 4, 24, and 52 weeks of treatment we measured blood pressure, heart rate, forearm blood flow (FBF) and vascular resistance (FVR) at rest and after 10 minutes ischemia, and forearm venous distensibility. Subjects whose diastolic blood pressure after fenquizone was reduced at least 10% were classified as responders. On this basis, 56% of patients after 1 month and 68% after 1 year responded to fenquizone. Responders, in comparison to nonresponders, were characterized by a greater increase in FBF and a greater decrease in FVR. The reduction in diastolic blood pressure was significantly related to the fall in FVR whereas no correlation was found between blood pressure and venous compliance changes. Nonresponders had a PRA increase similar to that observed in responders but they showed a much greater increase in aldosterone, whose changes were inversely related to modifications of both FVR and blood pressure. Our results demonstrate that chronic therapy with fenquizone causes a reduction of FVR, and that nonresponders have an exaggerated rise in aldosterone. This observation further reinforces the hypothesis that factors influencing the secretion of aldosterone are important determinants of the antihypertensive mechanism of diuretics.
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PMID:Hemodynamic and humoral effects of chronic antihypertensive treatment with fenquizone: importance of aldosterone response. 217 89

1. The one-year graft survival rate of cadaver donor transplants has increased from about 40% in 1965 to almost 80% in 1988. Much of the improvement lies in the reduction of the one-month failure rates, which went down from one quarter in 1965 to 10% in 1988. 2. Kidneys that failed to function in the first month occurred in 5% of first graft patients without cytotoxins and increased to 9% if cytotoxins to more than 50% of the random panel were present. The non-function rate was 9% in regrafted patients without antibodies and double (18%) in those with a PRA of less than 50%. 3. Some indication that the harmful antibodies can be detected by flow cytometry is provided by the fact that low graft survival rates resulted when transplants were done across a positive flow cytometry crossmatch in sensitized patients and in second graft recipients. In non-sensitized patients and in first graft patients, flow cytometry crossmatches against T cells were of no value. 4. The difference between first grafts, second grafts and transplants into sensitized patients disappeared when the grafts that did not function at one month were removed. 5. Cold ischemia time up to 36 hours had no effect on 1-3-year survival rates. Cold ischemia had relatively little effect even on delayed function in first transplants. However, in regrafts and in grafts into patients with preformed cytotoxins, increasing cold ischemia resulted in an increased incidence of delayed function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical kidney transplants, 1988. 265 11

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

Previous clinical evaluation of FK506 in renal transplantation has demonstrated equivalent patient and graft survival when compared with cyclosporine-based regimens. However, lower steroid and anti-hypertensive mediation requirements and lower serum cholesterol levels have been seen in patients receiving FK506. In August, 1991, a prospective, randomized trial was begun, comparing FK506/prednisone with FK506/azathioprine/prednisone. Two-hundred-and-four adults were entered into this trial between August 1, 1991, and October 11, 1992. The mean recipient age was 43.8 +/- 13.7 years, with a range of 17.6-78.0 years. Sixty-one (30%) recipients received a 2nd, 3rd or 4th transplant, while 35 (17%) had a PRA greater than 40% at the time of transplant. Thirty-three (16%) of the transplants were in recipients over 60 years of age, Thirteen percent of the kidneys were from living donors; 13% of the cadaveric kidneys were from pediatric donors less than 3 years of age and were transplanted en bloc. The mean cold ischemia time was 31.4 +/- 8.4 hours, and the mean donor age was 34 +/- 2.10 years, with a range from 4 months to 75 years. With a mean follow-up of 9 +/- 4 months, the 1-year actuarial patient survival is 93%; for the two-drug group it is 95%, and for the three-drug group it is 91% (p = NS). One-year actuarial graft survival is 86%; in the two-drug group it is 90%, while in the three-drug group it is 82% (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A prospective, randomized trial of FK-506 in renal transplantation--a comparison between double- and triple-drug therapy. 753 75

To determine if cardiac allograft outcome is improved among patients with fewer HLA-DR mismatches with their donors, we studied 132 recipients of a primary cardiac allograft who were transplanted between December 1985 and December 1991. These recipients and their donors all had high-confidence-level serological HLA-DR typing, previously shown to correlate highly with DNA DR typing. Patients were divided in two groups based on the HLA-DR mismatch with their donors. Group I consisted of 78 patients with 1 or zero DR mismatch and group II of 54 patients with 2 DR mismatches. Allograft outcome measurements included incidence of moderate rejection, incidence of allograft vasculopathy at 12 months, cardiac function measured as left ventricular ejection fraction (LVEF) and cardiac index (CI), and actuarial graft survival up to 7 years. Groups I and group II were not different with regard to recipient age, donor age, ischemia time, pulmonary vascular resistance, sex, or PRA greater than 0%. Group II had a higher incidence of moderate rejection on the first-week biopsy (47% vs. 25%, P = 0.019), and during the first month (84% vs. 58%, P = 0.006), but no difference was found in frequency of rejection from months 2 to 12. LVEF was not different in the groups at any point. CI was better in group I at 12 months (2.76 vs. 2.5, P = 0.03). No statistically significant difference was found in incidence of allograft vasculopathy (17% vs. 26%, P = 0.204). Actual graft survival at 1 year was better for group I (91% vs. 74%, P = 0.008), and actuarial graft survival at 6 years also favored group I (76% vs. 56%, P = 0.04). Using high-confidence-level serological HLA-DR typing assignments we demonstrated that HLA-DR mismatching correlates highly with cardiac allograft outcome. Implications are that heart transplant survival could be improved if prospective matching were feasible and prioritized or if immunosuppression were tailored to the HLA-DR match.
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PMID:HLA-DR mismatching correlates with early cardiac allograft rejection, incidence, and graft survival when high-confidence-level serological DR typing is used. 811 51

The shortage of cadaveric donors coupled with a rapidly growing number of potential recipients has resulted in an increased use of older donors. In 1992, 10.7% of all cadaveric kidney transplants were from donors above the age of 55 compared with 5.4% in 1988. The present investigation serves as a follow-up of a prior study of the effect of donor age on outcome with a 2-year analysis of more than 30,000 cadaveric kidney transplants performed in the United States between October 1, 1987, and December 31, 1991, that were reported to the United Network for Organ Sharing. There was no difference between the graft survival at 1 and 2 years comparing donors aged 56-65 versus 65 and older, but the older donors (aged 56 and greater) had a 1- and 2-year graft survival that was approximately 10% and 14% less than that for recipients from the ideal age group of donors (16-45 years). There was no practical adverse interaction between donor age and recipient age, gender, diabetic status, peak PRA (panel reactive antibody activity) level of mismatch, cold ischemia time, or recipient race on outcome. The kidneys from older donors had poorer graft survival than the kidneys from younger donors when transplanted into recipients of repeat transplants, though the impact of repeat transplant and donor age on graft survival are independent of one another. These data suggest that kidneys from donors over the age of 55 overall have reduced functional reserve, which has an adverse effect on long-term function. Thus, attempts should be made to better estimate functional reserve among the older age group, but age alone should not be the sole factor for exclusion of a potential donor. The use of older donors appears to present an increased but acceptable risk of graft loss 2 years after transplant.
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PMID:Effect of donor age on outcome of kidney transplantation. A two-year analysis of transplants reported to the United Network for Organ Sharing Registry. 815 34


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