ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Concentric and eccentric left ventricular hypertrophy are common progressive disorders in dialysis patients and are associated with cardiac failure and death. Although partial regression of these abnormalities is known to occur during the first posttransplant year, their long-term evolution is unknown.Methods.A total of 143 of 433 dialysis patients participating in a long-term prospective cohort study received renal transplants. Laboratory parameters were assessed monthly. Echocardiography was performed annually. Left ventricular mass index (LVMI) and cavity volume index were calculated according to standard formulae. Multiple linear regression was used to model change in LVMI as a function of baseline clinical and laboratory variables.Results.LVMI fell from 161 g/m2at 1 year to 146 g/m2(P=0.009) g/m2after 2 years. No further regression was seen in years 3 and 4. Left ventricular volume index showed similar trends, with a decline from year 1 to year 2 (P=0.05) followed by stabilization in years 3 and 4. Older age, long duration of hypertension, need for more than one antihypertensive, high pulse pressure in normal-size hearts, and low pulse pressure in dilated hearts were significantly associated with failure of regression of LVMI between the first and second years (MLR,P<0.000001, r2=0.57).Conclusions.Regression of left ventricular hypertrophy continues beyond the first year after renal transplantation, reaching a nadir at 2 years and persisting into the third and fourth posttransplant years. Failure to regress was associated with older age, hypertension, high pulse pressure in normal-size hearts and low pulse pressure in dilated hearts.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.This study was designed to assess the protective effects of the mitochondrial adenosine triphosphate-sensitive potassium channel (KATP) opener diazoxide as an additive to heart preservation solution.Methods.Forty isolated isovolumic buffer-perfused rat hearts were divided into four groups. Groups I and III hearts were arrested with and cold-stored in Celsior solution for 4 hr and 10 hr, respectively. In Groups II and IV, hearts underwent a protocol similar to that used in Group I and III, respectively, except that Celsior was supplemented with 100 &mgr;mol/L of diazoxide.Results.The protective effects of diazoxide were primarily manifest as a better preservation of diastolic function and a reduction of myocardial edema. The improvement of postischemic systolic function was observed only after prolonged exposure to diazoxide in Group IV, compared with Group III. The endothelium-dependent and endothelium-independent coronary flow postischemic responses were not affected by the supplementation of Celsior with diazoxide.Conclusions.Pharmacologic activation of mitochondrial KATPchannels seems to be an effective means of improving preservation of cold-stored hearts, which is consistent with the presumed role of these channels as end effectors of the cardioprotective preconditioning pathway.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.The transplantation of pig organs into humans requires a detailed knowledge of similarities and differences between the two species in the molecular physiology of host defense mechanisms. We therefore set out to identify porcine intercellular adhesion molecule (ICAM)-1 and to characterize its expression by endothelial cells.Methods.Porcine ICAM-1 cDNA was isolated from an endothelial cell cDNA library. An anti-pig ICAM-1 monoclonal antibody was generated and used to investigate the regulation by cytokines of ICAM-1 expression by porcine aortic endothelial cells (PAEC), using flow cytometry.Results.We found that porcine ICAM-1 was similar in primary structure to human ICAM-1, with five Ig-like domains. COS-7 cells transfected with porcine ICAM-1 supported &bgr;2but not &agr;4integrin-dependent adhesion of human T lymphoblasts. There was a low-level surface expression of ICAM-1 on unstimulated PAEC and increased expression after stimulation with tumor necrosis factor (TNF)-&agr;. However expression of ICAM-1 seemed to be significantly lower than that of vascular cell adhesion molecule-1, both on unstimulated and TNF-&agr;-activated PAEC. Recombinant porcine interferon-&ggr; weakly stimulated ICAM-1 expression when incubated alone with PAEC but had an inhibitory effect on the increase in ICAM-1 due to TNF-&agr;, both at 8 and 24 hr.Conclusions.Our observations confirm the existence of ICAM-1 in the pig and provide novel insights into how porcine and human endothelial cells differ in terms of adhesion molecule expression and cytokine responsiveness. Such differences are potentially important in interpreting models of inflammation in the pig and also in understanding the process of rejection of porcine xenografts.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Chronic nephrotoxicity is an important adverse effect of cyclosporine A (CsA) therapy. Tubulo-interstitial lesions and arteriolopathy are common histologic findings. Glomerular lesions are also described, but they are of variable severity. The aim of our study is to determine whether CsA has a direct effect on mesangial cells and whether the cellular response depends on the genetic background.Methods.We studied mesangial cells isolated from mice susceptible (ROP/Le-+Es1b/+Es1a, ROP) and resistant to glomerulosclerosis (B6SJLF1, C57). We previously showed that sclerosis-prone and sclerosis-resistant phenotypes are maintained in vitro. We examined whether CsA exposure directly affected extracellular matrix turnover in mesangial cells and whether the response is determined by the genetic background. Extracellular matrix synthesis and degradation were studied by proline incorporation, ELISA, reverse transcription-polymerase chain reaction, zymography, and reverse zymography. We chose a CsA dose that induced neither cytotoxicity nor apoptosis (1 &mgr;g/ml).Results.At the dose of 1 &mgr;g/ml total collagen accumulation was increased in ROP but not in C57 cells. Matrix metalloproteinase (MMP)-2 activity and mRNA levels were selectively decreased in ROP cells. CsA exposure did not affect tissue inhibitors of MMP (TIMP)-1 and -2 activity or TGF-&bgr;1mRNA expression and protein synthesis in either cell line.Conclusion.CsA increases total collagen accumulation in mesangial cells from sclerosis-prone mice by decreasing MMP-2 activity, but does not affect cells from sclerosis-resistant mice. Thus, CsA directly affects mesangial cells, but only those with a permissive genetic background for glomerulosclerosis.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.The correlation between an elevated Epstein-Barr virus(EBV) viral load in the peripheral blood and the subsequent development of EBV-associated posttransplant lymphoproliferative disease (PTLD) is the basis for strategies using serial measurements of the EBV viral load to guide preemptive therapy (PT). Neither the frequency, duration of monitoring, nor the predictive negative value of viral load monitoring for asymptomatic patients with persistent low or nondetectable viral loads against the development of PTLD has been established.Methods.Since April 1994, children undergoing intestinal transplantation (ITx) underwent serial monitoring of the EBV viral load in their peripheral blood using a quantitative competitive EBV polymerase chain reaction assay (PCR). Samples were obtained every 2 weeks for the first 3 months and then every 1–3 months depending on the patients clinical condition. EBV viral loads ≥40 (for patients who were EBV seronegative pre-ITx) and≥200 (for those who were seropositive) genome copies/105peripheral blood lymphocytes were felt to identify patients at increased risk for PTLD and generally prompted PT.Results.A total of 30 ITx recipients were compliant with our monitoring protocol; 23/30 are alive 6–59 months post-ITx. A total of 12/30 never had a viral load >40 and did not receive PT. In contrast, 18/30 had ≥1 high viral load (≥200); the first high viral load was measured a median of 59 days post-ITx (range 1–440). A late rise (>6 months post-ITx) was seen in only 2/18 children. A total of 0/12 patients with persistently low viral loads received PT and none developed PTLD. In contrast, 5/18 with ≥1 one high viral load (including 2/14 who received and 3/4 who did not receive PT) developed PTLD. All five children with PTLD were EBV seropositive pre-ITx and experienced their first high EBV PCR within the first 3 months after ITx.Conclusions.The predictive negative value of persistently low or nondetectable EBV viral loads was 100% in this study. Patients with nondetectable or low viral loads for the first 6 months after ITx did not develop PTLD regardless of their pretransplant EBV serological status. The frequency of viral load monitoring can be safely decreased for patients whose viral loads remain low for the first 6 months ITx.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID