摘要:

Background.Controversy over the relationship of preformed lymphocytotoxic antibodies and liver graft outcome remains. Because graft loss associated with preformed lymphocytotoxic antibodies probably occurs early after transplant, analysis of long-term survival is of questionable value. We therefore prospectively analyzed the effect on short- and long-term graft survival of the presence of lymphocytotoxic alloantibody in 207 primary adult liver allograft recipients.Methods.Pretransplant serum was tested for donor-specific lymphocytotoxic antibodies and panel-reactive antibodies (PRA) using donor splenic lymphocytes and lymphocytes obtained for routine tissue typing.Results.A positive crossmatch was detected in 24 recipients (11.5%): T-cell positive in 11 recipients and B-cell positive in 13 recipients. PRA were detected in 68 of 179 recipients tested (37.4%). High T-cell PRA (>55%) was detected in 17 recipients, and high B-cell PRA was detected in 20 recipients. Low PRA (<15%) against T cells was detected in 19 recipients and against B cells in 24 recipients. Graft failures occurred in 5 of 24 (21%) crossmatch-positive recipients and in 7 of 172 (4%) crossmatch-negative recipients. Graft survival was significantly lower in crossmatch-positive recipients at 1 month after transplant (chisquare=10.3,P=0.00133) but not at 3 months or 1 year. Causes of early graft loss were associated with immunological mechanisms, whereas later losses were due to nonimmunological mechanisms.Conclusions.Early graft loss may be increased in those recipients who are crossmatch positive. However, the logistical problems and consequences associated with allocation probably outweigh the benefits of prospective crossmatching.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.An adequate function test for donor livers is still lacking. The monoethylglycinexylidide (MEGX) test, performed in vivo in the donor to measure the metabolic rate of lidocaine conversion to MEGX, has been proposed as a function test for donor livers to predict postoperative organ function.Methods.In the present study, we investigated whether the MEGX formation rate measured in needle biopsy specimens in vitro correlates with the rate of MEGX formation in vivo. The in vivo MEGX test was performed in the donors and in the recipients on days 1 and 2. The in vivo and in vitro MEGX tests were compared with posttransplant liver function in the recipients in order to investigate their possible relevance as predictors of graft function.Results.The MEGX formation rate in needle biopsy specimens in vitro showed a significant correlation with the MEGX serum concentration found in the donor. A low rate of MEGX formation in the biopsy specimens tended to predict initial poor function of the grafts. In the donor, the MEGX test did not correlate with general liver function after transplantation. Only the MEGX serum concentration in the recipients on day 2 gave an indication of graft function.Conclusions.MEGX formation in liver biopsy specimens in vitro properly reflects metabolic function of the particular liver. Therefore, liver biopsies may be a valuable tool to help predict liver function in vivo. However, the MEGX test alone is not sufficient to provide the gold standard to determine liver function in donor and transplantation livers.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.The optimal prophylactic regimen to prevent cytomegalovirus (CMV) infection and disease in orthotopic liver-transplant patients remains to be established. We tested whether a combination of intravenous ganciclovir (GCV) followed by high dosages of oral acyclovir (ACV) for 4 months provided a higher degree of protection from CMV than oral ACV alone.Methods.One hundred sixty-seven liver-transplant recipients were randomized to receive 120 days of antiviral treatment starting at the time of transplantation consisting of either ACV 800 mg orally four times daily (n=84) or 14 days of GCV 5 mg/kg intravenously every 12 hr followed by oral ACV 800 mg four times daily (n=83). Prospective laboratory and clinical surveillance was performed to determine primary endpoints (onset of CMV infection and CMV disease) and secondary endpoints (rates of fungal and bacterial infection, allograft rejection, and survival after transplantation). One-year event rates are presented as cumulative percentages.Results.During the first year after transplantation, CMV infection developed in 57% of patients treated with ACV and in 37% of patients treated with GCV + ACV (P=0.001). CMV disease developed in 23% of patients treated with ACV and in 11% of patients treated with GCV + ACV (P=0.03). In seronegative recipients of allografts from CMV-seropositive donors (D+/R-), CMV disease developed in 58% of patients treated with ACV and in 25% of patients treated with GCV + ACV (P=0.04). In the D+/R- group, 54% of patients treated with ACV and 17% of patients treated with GCV + ACV developed infection withCandida albicans(P=0.05).Conclusions.Prophylaxis of CMV infection in liver-transplant patients with 14 days of intravenous GCV followed by high-dosage oral ACV is more effective than high-dosage oral ACV alone at reducing CMV infection and disease, even for patients in the D+/R-CMV serological group.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Familial amyloidosis (FAP) is characterized by the progression of neurologic and cardiac impairment ultimately leading to death within 7 to 15 years after the onset of the disease. Liver transplantation represents the only definitive therapy for this disease and has been performed since 1990.Methods.To determine the effect of liver transplantation on disease progression, electrocardiography and Doppler echocardiography were performed and blindly analyzed on 11 patients with FAP who were followed 0.8 to 8.6 years before liver transplantation and 0.8 to 4.1 years after liver transplantation.Results.After liver transplantation, five patients showed progression of left ventricular wall thickening with increased left ventricular mass, and three of these five showed a reduction in electrocardiographic voltage despite abolition of the mutant protein from the serum. Of the five patients showing progressive wall thickening, four had the transthyretin variant Glu 42 Gly and one patient had the Ala 36 Pro variant; none of the remaining six patients, all of whom possessed the Val 30 Met variant, showed echocardiographic changes. Although 9 of the 11 patients have shown symptomatic improvement in neurologic symptoms, 1 patient has developed heart failure and a second patient has suffered a sudden cardiac death.Conclusions.After liver transplantation, patients with FAP should have regular clinical evaluations including electrocardiographic and echocardiographic examinations to look for continued deterioration in heart structure or function.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Expansion of the current program of national sharing of cadaveric kidney allografts is of uncertain benefit, and the logistical barriers to expanding organ sharing are large. This study estimated the improvement in allograft survival from expanding organ sharing in the United States.Methods.A decision analysis based on allograft survival data from cadaveric allograft recipients throughout the United States compared the mean allograft survival resulting from four allograft-sharing strategies: no national sharing, national sharing of allografts matched at 6 histocompatibility alleles, national sharing of allografts matched at 4 or more alleles, and national sharing of allografts matched at 2 or more alleles.Results.Sharing allografts matched at 4 or more alleles was optimal (mean allograft survival=6.35 years). This survival was little better than the mean survival of the other three strategies (no national sharing, 6.21 years; national sharing of allografts matched at 6 alleles, 6.31 years; and sharing of allografts matched at 2 or more alleles, 6.33 years). The increment in the proportion of allografts surviving 4 years or more under the optimal strategy compared with no national sharing was <2%. A similar decision model comparing kidney transplant outcomes before and after the introduction of cyclosporine showed that this drug has had a much greater impact on mean allograft survival than would be expected to occur with national allograft sharing: 6.07 years with cyclosporine versus 3.79 years without cyclosporine.Conclusions.Expanding national allograft sharing would achieve little improvement in mean allograft survival. The limited benefit and logistical barriers to expansion of allograft sharing should be considered before following recommendations to expand the current U.S. allograft-sharing program.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.The purpose of this study was to compare retroperitoneal laparoscopic nephrectomy in transplant recipients and in other patients scheduled for nephrectomy.Methods.From February 1994 to July 1996, 15 transplant recipients and 17 other patients underwent a total of 36 retroperitoneal laparoscopic nephrectomies for various indications. Operative time, morbidity, and hospital stay were compared between the two groups.Results.The average operating time for the 36 procedures was 95±38 min (range, 35-180 min). It was shorter in transplant recipients (81±32 min) than in other patients (100±39 min,P<0.05). There was one postoperative complication in the transplant recipient group. The average length of the postoperative hospitalization was 3.7±1.4 days (range, 2-8 days).Conclusions.The retroperitoneal laparoscopic approach for nephrectomy is as safe and effective in renal transplant recipients as in other patients. Postoperative stay and delay to resumption of oral immunotherapy are short. This approach has become our first-line approach for native nephrectomy in transplant recipients.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Transplant immunosuppression using cyclosporine (CsA) leads to renal dysfunction as well as gingival overgrowth. The underlying alteration in both these lesions is characterized by an excessive accumulation of extracellular matrix components (fibrosis). To investigate the relationship between CsA-induced nephrotoxicity and gingival overgrowth, the renal function as well as the occurrence of gingival overgrowth was evaluated in pediatric renal transplant recipients: 38 boys and 30 girls, ranging in age from 2 to 20 years, who had been on a CsA-based immunosuppressive regimen for at least 12 months.Methods.Gingival overgrowth was determined on the basis of measurements of sulcus depth and was diagnosed as positive when the probing depth was ≥4 mm without exhibiting a loss of periodontal attachment. Renal function tests were performed using inulin and para-aminohippuric acid clearances for evaluating glomerular filtration rate, effective renal plasma flow (ERPF), and filtration fraction (FF).Results.Nineteen percent of the children exhibited gingival overgrowth. The occurrence of gingival overgrowth was positively related (P<0.05) to the mean oral daily dose of CsA, the mean CsA trough blood level, and concomitant administration of nifedipine. The children who were on antihypertensive treatment exhibited lower ERPF and significantly higher FF than the normotensive children. The mean FF value was significantly higher (P<0.05) in the children with gingival overgrowth than in those without gingival overgrowth, whereas glomerular filtration rate and ERPF did not differ between the two groups.Conclusions.The study suggests that there is a positive correlation between the degree of gingival enlargement and changes in renal function expressed as filtration fraction.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Peripheral blood lymphocyte (PBL) analysis by flow cytometry has been inconsistently reported as an adjunctive method for diagnosing acute kidney transplant rejection. However, there is good evidence that lymphocytes infiltrating renal grafts differ from those found at the peripheral level. We hypothesized that the study of aspiration biopsy samples in conjunction with PBL by flow cytometry would enable us to diagnose acute rejection crisis reliably.Methods.Lymphocytes from PBL and aspiration biopsies of kidney transplant patients were analyzed. Fifty-one stable patients, rejection-free for the first 6 months, were studied on day 7 and day 30 after transplantation and were compared with 32 patients with 40 acute rejection episodes.Results.Significant differences were observed for several lymphocyte subpopulations on aspiration biopsy samples comparing stable patients with rejection patients. In contrast, PBL analysis was not helpful in differentiating the two groups of patients. By combining the expression of several activation markers inside the graft with CD3DR and CD3CD25 aspiration biopsy to peripheral blood ratios, we obtained very good values for sensitivity and specificity-83.9% and 90.5%, respectively. The positive predictive value for rejection among dysfunctional grafts reached 85.8%.Conclusions.Flow cytometry study of aspiration biopsy samples of kidney transplant patients is a reliable and powerful method to diagnose acute rejection episodes, although it is needed to consider several lymphocyte phenotypes; cytofluorometric analysis of PBL is important because it provides graft-infiltrating cell to peripheral blood lymphocyte ratios. This safe and rapid test may significantly improve the management of kidney transplant patients.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Both acute rejection episodes and delayed graft function (DGF) have been shown to be associated with decreased 1-year renal allograft survival. In our center, the incidence and the intensity of acute rejection episodes have been reduced by cyclosporine-based triple-drug therapy. We have also shown that DGF alone is not a risk factor for long-term graft survival.Methods.We have now investigated whether an acute rejection episode together with DGF significantly effects long-term graft outcome. This study involved 862 first cadaveric renal allografts and 182 regrafts.Results.The incidence of DGF was 33% after first transplants and 44% after retransplants. The overall incidence of acute rejection episodes was 23% in first grafts and 28% in regrafts. After first grafts, there were no statistically significant differences in graft survival rates and half-lives between the early graft function (EGF) and DGF groups with or without acute rejection. In regrafts, graft survival was significantly higher in the EGF group without acute rejection than in the DGF group with acute rejection. However, if all other causes except chronic rejection were censored, the half-life in the EGF group without acute rejection was 17.3 years in first grafts, and in the DGF group with acute rejection, that number was 11.5 years in first grafts; for regrafts, the half-life was 12.3 years and 6.1 years, respectively.Conclusions.Acute rejection together with DGF could contribute to initial damage to the graft, and this might lead to later chronic allograft failure. In our study, this effect was evident only in the case of retransplants.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

In a prospective longitudinal study, detection of cytomegalovirus (CMV) DNA in plasma (plasma polymerase chain reaction [PCR]) was compared with PCR of CMV DNA in peripheral blood leukocytes (PBL PCR), the CMV pp65 antigenemia assay, and viral cultures from blood, urine, and throat of 29 patients, 14 of whom received pp65 antigenemia-guided early ganciclovir treatment and 15 of whom received ganciclovir at engraftment. Among 328 blood samples tested by all methods, PBL PCR was the most sensitive test, followed by the pp65 antigenemia assay, plasma PCR, and viremia. In the 14 patients who received pp65 antigenemia-guided early treatment, the incidence of PBL PCR, pp65 antigenemia, plasma PCR, and viremia before day 100 was 79%, 79%, 71%, and 27%, respectively, with a median day of onset of day 32, 42, 45, and 51, respectively. Nine patients (64%) became positive by PBL PCR, pp65 antigenemia, and plasma PCR. Of 15 patients who were treated with ganciclovir at engraftment, 12 (80%) became positive by PBL PCR, plasma PCR, and/or pp65 antigenemia while receiving ganciclovir; 3 (20%) had breakthrough infection with all three methods, including 2 with high-grade antigenemia (more than three positive cells in duplicate staining); none of these patients subsequently developed positive CMV cultures or disease. In 49 specimens, PBL PCR and/or pp65 antigenemia assay could not be performed because of insufficient neutrophil counts. In conclusion, the sensitivity of plasma PCR is significantly lower than that of PBL PCR but similar to that of the pp65 antigenemia assay. Plasma PCR may be particularly useful in clinical situations in which a less sensitive and possibly more specific assay is warranted or in which leukocyte counts are inadequate to perform cell-based assays.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID