摘要:

During liver transplantation, donor livers are subject to hypoxia and reoxygenation. Recently, because of a shortage of suitable donors, the livers of older donors have been used for transplantation. In this study, we examined the influence of aging and nutritional state on hepatic intracellular pH (pHi) and the susceptibility of the rat liver to hypoxia-reoxygenation injury. Perfused livers from fasted and fed, young (2–3 months) and aged (24–28 months) male Wistar rats were compared during 30 min of nitrogen hypoxia followed by 20 min of reoxygenation. Under control conditions, pHiwas significantly lower and glucose release higher in livers from fed young rats (7.24±0.04, 3.4±1.8 µmol/min/g) than in those from fasted young (7.33±0.04, 0.0±1.3), fasted aged (7.32± 0.03, −0.1±0.5), and fed aged rats (7.29±0.06, 0.9±1.0). In all groups, pHifell by ˜0.15 U during hypoxia. Lactate dehydrogenase (LDH) release from the livers of fed young livers was unaffected by hypoxia-reoxygenation as was that from the livers of fed aged rats, despite features that would be expected to predispose to injury (reduced glucose output and more alkaline pHi). In contrast, livers from fasted young and aged rats had substantially increased LDH release and reduced bile flow during hypoxia. There were no agerelated differences in these parameters, but, during reoxygenation, LDH release was significantly less in the aged livers. These results indicate that the livers of fed rats are resistant to hypoxia-reoxygenation injury and that aging does not increase the susceptibility of the liver to injury in the fasted state.

ISSN:0041-1337    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Small diameter arterial reconstruction is usually achieved by use of the autologous long saphenous vein. As an alternative to this blood conduit, the venous allograft has been used with some success in the past, but is likely to be the target of an immune rejection reaction from the host. This study was designed to characterize humoral immune reactions possibly involved in the outcome of venous allografts. Ten mongrel dogs received a histoincompatible femoral vein allograft and an autograft as interposition grafts to both femoral arteries. They were investigated for donor-specific antibody development using donor splenocytes and cultured vascular endothelial cells (EC). Serum samples were collected at surgery, at 2 weeks, and every month until graft occlusion occurred. All autografts were patent at retrieval except one, and all allografts underwent thrombosis. In all dogs, donor-specific IgG development was observed that appeared specifically at 4 weeks and lasted until graft occlusion was detected. All reactive sera were cytotoxic to donor EC except one, and this reactivity was completely lost after serum absorption on donor splenocytes. This latter absorption resulted in the total loss of flow cytometric reactivity against donor EC in 3 dogs, whereas a low reactivity was still present in 4 dogs. Immunoblotting analysis showed a posttransplant reactivity against various protein bands on donor EC. Absorption of the reactive serum on donor splenocytes resulted in the loss of reactivity to proteins of ˜40,30, and 22 kDa in most experiments. Moreover, as demonstrated by immunofluorescence on cryostat sections of explanted grafts, IgG deposition was seen mainly in the media and the adventitia of the allografts but not in autografts. These results suggest that a donor-specific antibody response directed mainly against MHC antigens might play a role in the thrombosis of histoincompatible venous allografts, thus decreasing the patency rate.

ISSN:0041-1337    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

A retrospective study was performed to identify risk factors affecting the fate of liver allografts transplanted across the ABO barrier. Over a 5-year period, 30 patients received 31 emergency OLTs with ABOincompatible allografts. One-year graft and patient survival rates were 37.1% and 48.4%, respectively. This group was compared with 199 ABO-compatible OLTs performed under similar emergency conditions. Significantly higher incidence of rejection, hepatic artery thrombosis, and biliary stricture were found in ABOincompatible grafts. The graft or patient survival of patients with O blood group or fulminant hepatic failure was not affected by ABO incompatibility. In contrast, the 1-year survival of recipients with non-O blood group was only 13.3% and the 1-year survival of those undergoing retransplantation was only 27.7% after ABO-incompatible OLT. A multivariate analysis using the Cox proportional hazard model identified non-O blood group (relative risk 3.43) and retransplantation (relative risk 2.46) as the most important risk factors for patient survival after ABO-incompatible OLT. We conclude that the use of ABO-incompatible grafts is justified in emergency cases when no other donor is available, but should be proscribed in patients with non-O blood group. The value of ABOincompatible grafts in retransplantation is questionable and requires further investigation.

ISSN:0041-1337    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

We performed 13 pediatric liver transplants from ABO-incompatible living related maternal or paternal donors using a combination of preoperative removal of isohemagglutinin and postoperative immunosuppressive therapy with FK506 and prophylactic OKT3. Tissue near-infrared spectroscopy was applied to evaluate hemodynamics using the hemoglobin of red cells in the sinusoids as an index. The data obtained indicated that the preoperative removal of isohemagglutinin prevented hyperacute humoral rejection with hemorrhagic infiltration in the sinusoids in 10 successful cases. The incidence of acute rejection was not significantly different among ABO-identical, -compatible, and -incompatible groups. The estimated 1-year survival rate of the ABO-incompatible group was 77%.

ISSN:0041-1337    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The outcome after OLT was studied in 53 patients with chronic hepatitis B virus (HBV)* infection, 15 of whom had, in addition, evidence of hepatitis delta virus (HDV) superinfection. Nine of 53 patients received short-term immunoprophylaxis with anti-hepatitis B surface (HBs) hyperimmunoglobulin up to 1 week after OLT and 44 of 53 patients received long-term unlimited immunoprophylaxis. Eight of 9 (89%) patients with short-term immunoprophylaxis showed reactivation of replication with HBV DNA in serum > 10 pg/ml independently of the preoperative HBV DNA level and HBsAg reappeared in all cases. Four (44%) patients in this group lost their graft because of fulminant hepatitis or cirrhosis and required retransplantation, and 2 patients (22%) died after reinfection in the second graft. Nineteen of 44 (43%) patients with long-term immunoprophylaxis developed HBV values > 10 pg/ml after transplant and 12 of 44 (27%) became HBsAg+again. Most of them had quantifiable HBV DNA levels before OLT. Retransplantation was required in 5 of 44 (11%) patients and 4 of them died after HBV recurrence. The frequency of HBV reactivation and the development of viral hepatitis after OLT were associated with the preoperative presence of HBV, as determined by the molecular hybridization assay. With nested polymerase chain reaction, all 53 patients were HBV-DNA+in the serum before and after OLT. with just one exception, none of the patients with HDV superinfection died, in spite of increased HDV replication after OLT. The data indicate that long-term immunoprophylaxis with anti-HBs hyperimmunoglobulin after OLT improves the prognosis in HBV-infected patients. The preoperative detection of HBV DNA in serum by molecular hybridization assay is correlated with graft infection and represents a prognostic parameter. The presence of HDV may have a protective effect after OLT.

ISSN:0041-1337    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Many transplant centers are reluctant to accept alcoholic patients for OLT because of their supposed potential for alcoholic recidivism and poor compliance with the required immunosuppressive regimen, both of which result in graft failure. Only inconclusive data related to these arguments are available. From May 1982 to January 1993, 58 patients received OLT at our institution for end-stage cirrhosis, where alcohol was the only toxic component. The indication for OLT in these patients was considered with particular attention to recidivism and compliance. Overall survival in this group was 71% and 63% at 1 and 5 years, respectively, with an average survival time of 78 months. Actuarial survival of patients transplanted since January 1989 (n=37) was 86% and 83% at 1 and 2 years (average survival 42 months). Nonfatal clinical endpoints were analyzed in those patients surviving at least 3 months (n=44). Return to alcohol abuse has been documented in 14 persons at routine short-term outpatient checkups. The estimated risk for alcoholic recidivism amounts to 31%, with a median follow-up of 33 months. Compliance with immunosuppressive regimen was expressed as a dependent value of acute rejection episodes (0.3 per patient, median follow-up 33 months), chronic rejection (occurred in none of the patients), and measurements of CsA HPLC blood trough level (92.2% within the target range). The preversus postoperative improvement of employment, marital, and social status after OLT showed a statistically significant difference.Unwillingness to offer OLT to individuals with alcoholic liver disease because of failure to demonstrate 100% long-term abstinence appears difficult to defend in the face of good results in survival, compliance, and social rehabilitation.

ISSN:0041-1337    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Despite overall improved graft survival, renal graft thrombosis (RGT) remains an important cause of graft loss. Of 6153 consecutive renal transplants (RTx), 134 index cases of graft loss from RGT were reported to the Australian and New Zealand Dialysis and Transplant Registry between 1980 and 1992. Two groups were selected for comparison: (1) institutional controls (n=127), the previous RTx at the same institution as each index case; and (2) graft controls (n=107), the contralateral cadaveric donor kidney of each index case. RGT cases that coincidentally occurred in control groups were deleted from those groups (6 of institutional controls, 2 of graft controls). RGT within the first 30 days after RTx occurred in 1.9% of all RTx and was constant from 1980 to 1992. In contrast, RGT caused an increasing proportion of early (within 30 days of RTx) graft losses (P=0.01). The cumulative occurrence of RGT in those who thrombose was 62.6%, 83.7%, 90.2%, and 93.5% at 2, 7, 14, and 30 days after RTx, respectively. By comparison, with the control groups, no association with RGT was demonstrated for recipient age or sex, primary renal disease, type of dialysis, treatment with CsA, degree of HLA mismatch, panel reactive antibody levels, perfusion solution and perfusion technique, or immunosuppressive therapy. There was a significantly increased incidence of RGT with both extremes of donor age, female donors, and prolonged total ischemic time.

ISSN:0041-1337    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

During posttransplant acute renal failure (ARF), the diagnosis of allograft rejection constitutes a major problem. We evaluated the value of Doppler ultrasonography in identifying grafts at risk of rejection during ARF. In 184 recipients of a renal allograft, Doppler examinations were performed on the first and fifth postoperative day. Doppler spectra were quantitatively analyzed with a user-written computer program. Doppler findings were not used in clinical decision making. ARF was defined as a diuresis < 400 ml/24 hr and/or the necessity for dialysis. Doppler spectra obtained on the first day after transplantation showed a resistance index (RI) of 0.59±0.09 in recipients with immediately functioning cadaveric grafts (n=123), while living related donor grafts (n=20) showed a lower RI (0.55±0.07;P<0.05). Grafts with ARF (n=41) showed a considerably higher RI (0.67±0.13;P<0.05). When grafts with a duration of ARF ≤ 4 days (n=17) were compared with ARF > 4 days (n=24), RI was not significantly different (0.63±0.07 vs. 0.68±0.15; NS). However, the acceleration time of the systolic deflection of the spectrum waveform (Tmax) was shorter in grafts with ARF > 4 days (86±47 msec vs. 128±39 msec;P<0.05). On the fifth day after transplantation, Doppler spectra in grafts with ARF > 4 days (n=24) snowed a Tmax < 90 msec in 9 patients, 8 of whom experienced rejection during ARF (positive predictive value, 8/9=89%). In the 15 patients with Tmax ≥ 90 msec, only 2 rejections occurred (negative predictive value, 13/ 15=87%). For the RI (< 0.85), positive predictive value was 4/5=80% and negative predictive value (RI≤0.85) was 13/19=68%.In conclusion, a short acceleration time of the Doppler waveform on the first day after transplantation is associated with a longer duration of ARF. Quantitative analysis of Doppler spectra can be helpful in the identification of patients at risk for rejection and in the timing of allograft biopsy during ARF. Persistently short Tmax values on the fifth day after transplantation perform better in identifying grafts at risk of rejection than high RI values.

ISSN:0041-1337    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Initial treatment of heterotopic cardiac transplant recipients with anti-CD4 mAb promotes long-term (> 60 days) allograft survival. We have used modified limiting dilution analysis to quantitate donor alloantigen- reactive helper T lymphocytes (HTL) and CTL in mice bearing long-term cardiac allografts. Despite repopulation of lymphoid tissues with CD4+T cells, donor alloantigen-reactive IL-2 producing and IL-4-producing HTL were rare or not detectable in lymphoid tissues or in the graft. While donor-reactive precursor CTL were present in lymphoid tissues, modified limiting dilution analysis revealed that stimulated (“antigen-conditioned”) CTL were not detectable, and few CTL were present in the graft. In addition, antibodies reactive with donor alloantigens were not detectable in the sera of mice bearing long-term cardiac allografts. To determine whether additional in vivo stimulation with donor alloantigens would elicit an immune response, sponge allografts were implanted into mice bearing long-term cardiac allografts. Previous reports from this laboratory have demonstrated that T cell infiltration of sponge allografts is dependent upon antigen-driven cytokine production. While third-party sponge allografts were readily infiltrated by third-party-reactive HTL and CTL, sponge allografts of the same strain as the cardiac allograft were not infiltrated by T cells. However, donor strain sponge allografts induced an IgM (but not IgG) alloantibody response. These data indicate that IgM alloantibody could be induced in the absence of a cellular response to the sponge allograft. Kinetic studies revealed that a transient IgM (but not IgG) response was induced by the initial cardiac transplantation in the absence of CD4+cells. These IgM alloantibodies disappeared by day 21 despite the persistence of the allograft. These observations indicate that transient depletion of CD4+T cells induces allograft-specific T cell tolerance, but does not eliminate the ability to mount an allograft-specific IgM response. To our knowledge, this is the first report of a transient humoral response to alloantigens that occurs in the absence of CD4+T cells, and can be reinduced in “tolerant” animals that fail to mount a cellular immune response. Potential mechanisms involved in the development and maintenance of anti-CD4 mAb-induced tolerance are discussed.

ISSN:0041-1337    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Human embryonic myoblasts isolated from 13- to 19-week embryos were treated for 24 to 144 hr with 0.1–500 U/ml IFN-γ and the constitutive and IFN-γ-inducible MHC expression was examined by flow cytometry. Low levels of constitutive MHC I were expressed that increased with both developmental age and incubation time. In contrast, no constitutive MHC II was detected on human embryonic myoblasts at any age or incubation time. Both classes of MHC can be induced by IFN-γ. Maximal MHC I induction increased in parallel with age, i.e., maximal induction occurred on 19-week myoblasts, while MHC II induction peaked at 17 weeks. IFN-γ-induced expression of MHC I and II also increased with incubation time. Induced expression of MHC I antigen reached plateau levels at 72 hr of IFN-γ incubation, whereas MHC II increased to a plateau level at 120 hr. The immunological importance of these findings for myoblast transfer therapy is discussed.

ISSN:0041-1337    

出版商:OVID    

年代:1994

数据来源: OVID