摘要:

Organ transplant rejection is mediated largely by circulating peripheral leukocytes induced to infiltrate the graft by various inflammatory stimuli. Of these, chemotactic cytokines called chemokines, expressed by inflamed graft tissues, as well as by early innate-responding leukocytes that infiltrate the graft, are responsible for the recruitment of alloreactive leukocytes. This report discusses the impact of these leukocyte-directing proteins on transplant outcome and novel therapeutic approaches for antirejection therapy based on targeting of chemokines and/or their receptors.

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.Although reperfusion injury in organ transplantation is presently well established, its exact role in liver transplantation still has to be defined. The aim of this part of the study was to document the reperfusion injury associated with porcine liver transplantation and to evaluate the different components of the reperfusion injury associated with arterial and portal reperfusion.Methods.Large white X Landrace pigs were randomized into two groups: group 1, initial portal reperfusion, and group 2, initial arterial reperfusion. Several indicators of reperfusion injury, endothelial cell function, and hepatocellular damage were assessed. Early histopathological findings in biopsy specimens can predict poor graft outcome, therefore histological findings of the liver biopsies after liver transplantation were also studied.Results.Malondialdehyde concentrations were lower and vitamin A concentrations were higher in the animals subjected to initial portal reperfusion. Serum amino aspartate transferase and serum hyaluronic acid concentrations were higher in the animals subjected to initial portal reperfusion. Histological results showed that hepatocyte vacuolization, neutrophil infiltration, single hepatocyte necrosis, and group cell necrosis of the hepatocytes were all significantly reduced in group 2 compared to group 1.Conclusion.Results of this study indicate that the major part of reperfusion injury is constituted during the portal venous reperfusion and that this injury can be, at least partially, attenuated by initial arterial reperfusion.

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.Preretrieval warm ischemic injury predisposes to both short-term and long-term dysfunction of cadaveric renal allografts. We previously reported that the excretion of the vasoactive peptide, endothelin (ET), is significantly increased during hypothermic perfusion preservation (HPP) of kidneys subjected to preretrieval warm ischemia compared with nonischemic controls. As such, the purpose of this study was to determine if endothelin receptor (ET-R) blockade during HPP would improve glomerular filtration rate (GFR) of kidneys subjected to preretrieval warm ischemia when measured in situ at 2 weeks after transplantation (Tx).Methods.The left kidney was retrieved from 300-g Lewis rats after in situ cold perfusion and transplanted after 2 hr of HPP. A 30-min period of preretrieval warm ischemia was induced. Kidneys were divided into four groups: nonischemic controls (n=9), ischemic (isch) kidneys not receiving ET-R blockade during HPP (n=7), isch kidneys receiving the ETAreceptor antagonist (n=7), and isch kidneys receiving the ETA/Breceptor antagonist (n=8). ET-R blockade was induced by adding the ETA, A-147627, or the ETA/B, A-182086, receptor antagonist (Abbott Laboratories, Abbott Park, IL) directly to the preservation solution (5×10−6M). The kidneys were then isografted into genetically identical Lewis rats and GFR, determined by measurement of urinary iohexol clearance, measured 2 weeks after Tx.Results.Two-week GFRs (mL/min) for each of the study cohorts are as follows: nonischemic controls, 1.18±0.11; ischemic (isch) only, 0.57±0.08 (P≤0.05 vs. nonischemic controls); isch + ETAblockade, 0.95±0.15 (P≤0.05 vs. isch only); isch + ETA/Bblockade, 0.90±0.08 (P≤0.05 vs. isch only).Conclusion.Addition of an ETA, A-147627, or an ETA/B, A-182086, receptor antagonist to preservation solution used during HPP of kidneys subjected to preretrieval warm ischemia resulted in a normalization of GFR measured 2 weeks after Tx. The data provide a basis for further investigation of the impact of ET-R blockade on both the short- and long-term adverse effects of preretrieval warm ischemic injury in cadaveric renal Tx.

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.Minimally invasive donor nephrectomy has become a favored procedure for the procurement of kidneys from live donors. The optimal minimally invasive surgical approach has not been determined. In the current work, we compared the outcome of kidneys procured using the traditional open approach with two minimally invasive techniques: the standard laparoscopic procedure and a hand-assist procedure.Methods.The function of live-donor kidneys procured by open versus minimally invasive procedures was compared (procedures compared were the traditional open donor nephrectomy [ODN], the standard laparoscopic [LAP] approach, and the hand-assisted [HA] laparoscopic technique). The length of donor operation, donor length of stay in the hospital, surgical complications, and cost of hospitalization for three groups of patients were assessed in a series of 150 live-donor nephrectomies.Results.We found that both minimally invasive procedures yielded kidney allografts with excellent early function and a minimum of complications in the donor. The open procedure was associated with a reduced operative time but increased donor length of stay in the hospital. Resource utilization analysis revealed that both minimally invasive techniques were associated with a slight increase in costs compared with the open procedure, despite a shorter hospital stay.Conclusions.Minimally invasive donor nephrectomy is safe and effective for procuring normally functioning organs for live-donor transplantation. Of the two minimally invasive approaches examined, the hand-assisted technique was found to afford a number of important advantages, including facilitating teaching of residents and students, that it is more readily mastered by transplant surgeons, and that it may provide an additional margin of safety for the donor.

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.A pediatric end-stage liver disease (PELD) score for children with chronic liver disease using easily obtainable, objective, verifiable parameters, would be useful to prioritize children awaiting liver transplantation.Methods.Data from the Studies of Pediatric Liver Transplantation (SPLIT), a consortium of 29 U.S. and Canadian centers, were used to develop the PELD score. Two pretransplantation endpoints were evaluated: (1) death, n=884; and (2) death or moving to the intensive care unit (ICU), n=779. The analyses were restricted to children with chronic liver disease who were listed for a first transplant. Preliminary analyses of 17 possible factors yielded 6 parameters of interest: age <1 year, total bilirubin, international normalized ratio (INR), albumin, growth failure (height or weight Z score <−2), and calculated glomerular filtration rate. In a univariate Cox regression analysis, age, bilirubin, INR, and albumin were significant (P<0.01) predictors of both endpoints; glomerular filtration rate was not significant for either endpoint; and growth failure was significant for death/ICU but not death alone. In the multivariate analyses, age, bilirubin, and INR were significant for the death endpoint; and bilirubin, INR, growth failure, and albumin were significant for the death/ICU endpoint. From these results, three PELD models were evaluated to predict both outcomes at 3 and 6 months: PELD 1 (age, bilirubin, INR); PELD 2 (bilirubin, INR, albumin, growth failure); and PELD 3 (bilirubin, INR, albumin, growth failure, and age). The area under the receiver operating characteristic curve (AUC ROC) was used to compare models. For PELD 3, the most inclusive model, the AUC ROC at 3 months was 0.92 for death and 0.82 for “death–moved to ICU.” A comparison of the AUC ROCs for the other models and for the model of end-stage liver disease ([MELD], the adult end-stage liver disease severity score model), none of which performed better than PELD 3, are presented.Conclusion.A model using five objective parameters can accurately predict death or death–moved to ICU in children awaiting liver transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.This study elucidates the profiles for hepatitis B virus (HBV) reactivation and genetic mutation of the core promoter and precore regions for HBV-carriers receiving hematopoietic stem cell transplantation (HSCT).Methods.Sera from 20 HSCT patients diagnosed with hematological diseases, 13 donors and 36 healthy HBV-carriers, were collected regularly for analysis. The hepatic biochemistry profiles, serological HBV markers, and HBV-DNA titers were checked regularly, and primer-amplification of the HBV core promoter or precore region and sequencing were performed once the mutations were identified.Results.Deteriorated liver function was demonstrated for 13 of 20 post-HSCT patients, compared with none of the 36 controls (P<0.01). The HBV-DNA was detected more frequently for post-HSCT subjects than for controls(P=0.001). Incidence of the HBV precore nucleotide 1896 G-to-A mutation was significantly higher for HSCT patients (P=0.004), and a significant association was demonstrated for carriage of core promoter or precore mutations and the development of hepatitis (P=0.015). Different HBV genotypes were revealed in post-HSCT patients and the respective donors.Conclusions.Intensive chemotherapy and immunosuppression may cause HBV reactivation in HBV carriers receiving HSCT, and more frequent core promoter or precore mutations could be detected in HBV carriers receiving HSCT than healthy HBV carriers, with the chemotherapy/immunosuppression-induced immunocompromise possibly contributing to this effect. Donor HBV genotype did not interfere with that of the recipient after HSCT. Core promoter or precore region mutations were associated with a higher incidence of liver dysfunction than wild-type HBV carriers in the HSCT patients.

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.African American kidney transplant recipients generally exhibit poor long-term graft survival compared with other ethnic groups. The combination of sirolimus, tacrolimus, and corticosteroids has proven to be effective in reducing rejection episodes in high-risk organ and islet cell transplant recipients but has not yet been tested in a large number of African American patients.Methods.The outcomes of 56 African American adult, primary kidney transplant recipients treated with corticosteroids, sirolimus, and tacrolimus targeted to relatively low trough blood levels were compared with those of a concurrent group of 65 white patients treated with steroids, mycophenolate mofetil, and tacrolimus targeted to relatively high blood levels. Induction antibody therapy was not routinely used in either group.Results.The incidence of acute rejection in the first 3 posttransplantation months was 7.1% in African Americans and 16.9% in whites (P=NS). Actuarial 2-year patient, graft, and rejection-free graft survival rates were equivalent in the two groups. Posttransplantation diabetes mellitus occurred in 36% of the African American patients, despite similar doses of corticosteroids and lower trough levels of tacrolimus, compared with 15% of white patients (P=0.024).Conclusions.The combination of corticosteroids, sirolimus, and relatively low doses of tacrolimus results in acute rejection, graft survival, and patient survival rates equivalent to those achieved in white patients receiving steroids, mycophenolate mofetil, and relatively high doses of tacrolimus, even without the routine use of induction antibody therapy. Posttransplantation diabetes mellitus remains a problem for African Americans receiving this combination of immunosuppressants, despite relatively low tacrolimus blood levels.

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.Posttransplant lymphoproliferative disease (PTLD) is a common Epstein-Barr virus (EBV)-associated complication of transplantation which, despite treatment, is often fatal. This study was undertaken to monitor persistent EBV infection in transplant recipients, to compare EBV load and gene expression in healthy individuals and EBV-associated diseases, and to highlight differences in PTLD that could be used to define those at risk of the disease.Methods.A cohort of 96 cardiothoracic transplant recipients was monitored posttransplant for up to 1110 days (median 268 days). Levels of EBV DNA and viral mRNA transcripts in peripheral blood mononuclear cells (PBMs) were measured at regular intervals and compared with those found in healthy individuals, infectious mononucleosis (IM) patients, and 12 PTLD patients bled at the time of diagnosis. Overall posttransplant levels were significantly higher than pretransplant and healthy subjects, and correlate with dose of immunosuppression. EBV DNA levels in both IM and PTLD were significantly higher than in healthy recipients, with the highest levels in PTLD patients. Individual measurements in 12 healthy transplant recipients reached levels seen in PTLD, and thus single estimations are not of predictive significance for PTLD development.Results.Analysis of viral gene expression in peripheral blood mononuclear cells showed a restricted (LMP 2 only) pattern in healthy subjects, and an unrestricted (latency 3) pattern with lytic replication in 14% of IM blood and 45% of cases of PTLD. A total of 55% of healthy transplant recipients had additional transcripts in one or more blood samples, and this finding correlated with high viral load. Analysis of the 12 samples from healthy recipients with viral loads equivalent to those seen in PTLD showed additional transcripts in all cases and latency 3 with lytic replication in 33%. Thus, an isolated finding of high viral load and/or unrestricted latent and lytic gene expression is not indicative of PTLD.

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID

摘要:

Background.The mechanism that underlies delayed graft function (DGF) is still poorly defined. Previous studies using tubular function tests have shown that postischemic injury to the renal transplants results in profound impairment of paraimmunohippurate (PAH) extraction through the tubules.Methods.Using99mTechnetium-mercaptoacetyltriglycine (99mTc-MAG3) renography and tubular function slope (TFS), a study of the tubular uptake of99mTc-MAG3 was undertaken in a prospective study of renal transplant recipients with immediate graft function (IGF) and those with DGF.Results.A total of 37 consecutive recipients of a cadaveric graft and 5 kidneys from living donors was evaluated within 48 hours after transplantation and in week 2, months 3 and 6, and 3 years after transplantation. In addition to the protocol scans, recipients with DGF were examined every other day until function was resumed. Repeated measurement two-way analysis of variance and a change point analysis were performed to determine the difference in the follow-up of TFS values between the two groups. Fourteen patients were classified as having DGF and 28 immediate graft function. In the DGF group, the initial TFS value was significantly lower than in the immediate graft function group (0.54 [±0.01] and 1.75 [±0.16], respectively;P=0.002), a difference that persisted for up to 3 years. Change point analysis revealed that the postischemic tubular excretion improved with time in both groups in the first 3 to 4 weeks, but both groups remained different up to 3 years after transplantation. Multivariate analysis revealed that only the cold ischemic time was an independent risk factor for a low TFS value. After the initial recovery from postischemic injury, the TFS may be used as a marker for functional renal mass.Conclusion.We propose that the tubular defect in DGF, as defined by99mTc-MAG3 renography, is irreversible and may be a marker of initial graft function.

ISSN:0041-1337    

出版商:OVID    

年代:2002

数据来源: OVID