Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Although graft survival for most primary disease processes are similar at one year, significant divergence occurs by 5 years. ALP, IGA, and PC had the highest 5-year graft survival rates (72.8%, 71.2%, and 68.5%, respectively) whereas HTN and NS, the lowest (51.8% and 46.0%, respectively). 2. When primary diseases are grouped by pathogenic, pathophysiologic, and clinical similarities, the group of diseases with systemic manifestations had the lowest 5-year graft survival (55%), and the group including cystic and inherited diseases had the highest 5-year graft survival (69%). Black recipients had a predominance of "systemic" primary diseases (57%). 3. Despite having overall lower graft survival than Whites (p < 0.00001), there was no significant difference between Black and White 3-year graft survival for recipients with PC, ALP, IGA, and SLE. 4. PC recipients enjoyed excellent long-term graft survival (69%). Black recipients with PC had a 5-year graft survival rate of 64.6%. Recipients with PC had decreased posttransplant dialysis need, decreased early rejection rate, and better HLA matching than most other recipients. 5. Recipients with SLE as their primary disease had among the highest fraction of grafts lost to rejection (45.4% of all grafts lost) and the highest pretransplant sensitization rate (59.6%). 6. Recipients with HTN as their primary disease had overall lower 5-year graft survival (58% versus 63% in Whites, 44% versus 47% in Blacks), a lower rate of early allograft function (10% versus 12%, p < 0.00001), and more posttransplant dialysis needs (28.8% of patients requiring dialysis vs 23.5%, p < 0.00001) than recipients without HTN. Blacks with HTN had the lowest long-term graft survival (44.4%) of any other single group. 7. IDDM patients who expressed DR3 and/or DR4 alleles had significantly higher graft survival than patients without these DR groups. Whites expressing DR3 and DR4 and DR3 or DR4 alleles had better overall HLA matching (p < 0.001) and graft survival (75.4% and 70.7% versus 58.5% and 65.1%, p < 0.00001) than Blacks with similar DR expression. 8. SPK recipients had better 5-year graft survival than KAT recipients (66.2% versus 54.6%, p < 0.000001). This effect is most likely due to the selection of "better" lower-risk patients for SPK grafts.
 ...
PMID:Primary disease effects and associations. 754 72

1. Graft survival was similar at one year for the various diseases, but at 3 years, a 16% divergence was noted among diseases. IGAN patients had the highest graft survival rate. 2. Graft survival rates of IGAN, ALP, and PC in Black and White patients were similar, but in all other diseases, a high loss rate was seen after one year among Black patients. 3. Patient survival was almost identical for the various diseases among Whites and Blacks. 4. SLE patients with DR2 or DR3 had higher graft survival rates than SLE patients without these groups (p < 0.05 in Whites). 5. IDDM patients with DR3 or DR4 had higher graft survival rates than IDDM patients without these groups (p < 0.05 in Whites, p = ns in Blacks). 6. Nephrosclerosis patients with DR2 or DR4 had higher graft survival rates than those who did not (p = ns in Whites, p < 0.05 in Blacks). 7. CGN patients with DR1 had higher graft survival rates than CGN patients without DR1 (p < 0.00005 in Whites). 8. IDDM patients with SPK transplants had higher graft survival rates than IDDM patients grafted with a KAT (p < 0.000001). In recent years, almost 30% of IDDM patients had SPK transplants. 9. Patients with SPK grafts compared to KAT were younger, White, were more often DR3/4, and worked full-time. 10. The SPK effect was seen only at the excellent centers. At all other centers, SPK and KAT patients had the same graft survival rates.
 ...
PMID:The long-term effect of primary disease on cadaver-donor renal transplant recipients. 791 83

Many patients receiving primary cadaver renal transplants have complications in their early post-transplant courses which can affect and possibly confound long-term outcome analyses. Forty-four percent of primary cadaver recipients in the present study were excluded because of early events: delayed graft function (DGF) and early rejection episodes (ERE). Even with these exclusions, similar conclusions to the previous study (1) were noted: that is, the patients with systemic diseases (NS, HTN and IDDM) had the lowest 5-year graft survivals (57-62%) compared to those with diseases that were primarily renal (ALP, IGA and PC) which had better 5-year graft survival results (76-81%). Long-term half-life calculations also demonstrated improved graft survival prognoses in patients with primarily renal diseases (15-18 years in ALP, IGA and PC vs 6-8 years in IDDM, HTN and NS). Again, with the exclusions of patients with early events, Black recipients with HTN did not fare as well as non-Blacks (5-year graft survival of only 52% vs 69%). Many long-term graft losses were due to deaths, oftentimes from cardiovascular diseases. This was especially prominent in disease states with the greatest potential for arteriosclerosis (IDDM, HTN and NS). When patients with early events were excluded, the percent of graft losses attributable to patient death ranged from 21-58%, but were the highest with HTN, PC (age related) and IDDM: 41%, 45% and 58%. A similar analysis in IDDM patients receiving either a LD, SPK or KAT-type transplant revealed that although there was a 10% reduction in 5-year graft survival for KAT patients, most of these graft losses were owing to patient death. Outcomes in SPK and LD in IDDM patients were similar, suggesting selection bias and center effects with the latter two types of transplants going to healthier IDDM patients. It is too soon to conclude whether FK506 has a particularly beneficial role in one primary disease or another as compared to CsA. Combined kidney transplantation with a liver or heart transplant appears to be a reasonable risk. When graft losses due to patient deaths are accounted for, kidney graft survival was approximately that of kidney alone transplantation, suggesting again that graft loss due to patient death must be accounted for when analyzing transplant graft survival.
 ...
PMID:Primary disease effects and associations in patients without early posttransplant events. 879 82

Clinical and experimental evidence suggest that increased rates of fatty acid oxidation in the myocardium result in impaired contractile function in both normal and diabetic hearts. Glucose utilization is decreased in type 1 diabetes, and fatty acid oxidation dominates for energy production at the expense of an increase in oxygen requirement. The objective of this study was to examine the effect of chronic treatment with trimetazidine (TMZ) on cardiac mechanical function and fatty acid oxidation in streptozocin (STZ)-diabetic rats. Spontaneously beating hearts from male Sprague-Dawley rats were subjected to a 60-minute aerobic perfusion period with a recirculating Krebs-Henseleit solution containing 11 mmol/L glucose, 100 muU/mL insulin, and 0.8 mmol/L palmitate prebound to 3% bovine serum albumin (BSA). Mechanical function of the hearts, as cardiac output x heart rate (in (mL/min).(beats/min).10-2), was deteriorated in diabetic (73 +/- 4) and TMZ-treated diabetic (61 +/- 7) groups compared with control (119 +/- 3) and TMZ-treated controls (131 +/- 6). TMZ treatment increased coronary flow in TMZ-treated control (23 +/- 1 mL/min) hearts compared with untreated controls (18 +/- 1 mL/min). The mRNA expression of 3-ketoacyl-CoA thiolase (3-KAT) was increased in diabetic hearts. The inhibitory effect of TMZ on fatty acid oxidation was not detected at 0.8 mmol/L palmitate in the perfusate. Addition of 1 mumol/L TMZ 30 min into the perfusion did not affect fatty acid oxidation rates, cardiac work, or coronary flow. Our results suggest that higher expression of 3-KAT in diabetic rats might require increased concentrations of TMZ for the inhibitory effect on fatty acid oxidation. A detailed kinetic analysis of 3-KAT using different concentrations of fatty acid will determine the fatty acid inhibitory concentration of TMZ in diabetic state where plasma fatty acid levels are increased.
 ...
PMID:The effects of chronic trimetazidine treatment on mechanical function and fatty acid oxidation in diabetic rat hearts. 1763 88