摘要:

Background.Hepatic artery thrombosis (HAT) can be a devastating complication of orthotopic liver transplantation (OLT), but early diagnosis may allow successful revascularization and graft salvage.Methods.We reviewed data on 1,026 liver transplants at our institution. For patients in whom HAT was diagnosed within 30 days after OLT, we recorded indications for ultrasonography and liver function tests at diagnosis, management of HAT, and graft and patient survival.Results.Thirty-two patients (3.1%) developed HAT at 6.8±6.6 days(range, 1-29 days) after OLT. Twelve patients (37.5%) were asymptomatic at diagnosis. In 11 of these 12, HAT was diagnosed on routine duplex at 2.0±1.55 days after OLT; in the 12th patient, HAT was noted during re-exploration for unrelated bleeding on postoperative day 3. Eleven of 12 patients (91.6%) were revascularized; one patient (8.4%) received no treatment with no sequelae. Of the 11 who were revascularized, 9 (81.8%) had graft salvage and 2 (18.2%) received a second transplant, with one death. Twenty patients (62.5%) were symptomatic. In these 20, HAT was diagnosed at 9.85±6.93 days after OLT. Symptoms were: elevated liver function test results (serum glutamic oxaloacetic transaminase: 722±1792 U/ml, serum glutamic pyruvic transaminase: 678±963 U/ml, and bilirubin: 10.2±6.2 mg/dl) in 13 patients (65%); bile leak in 4 patients (20%), and sepsis in 3 (15%). Five of the 20 patients (25%) were revascularized; of these 5, 2 (40%) had graft salvage, 2 (40%) received a second transplant with 1 death, and 1 (20%) died of a liver abscess. Twelve symptomatic patients(60%) had immediate re-OLT; 10/12 are alive, 1 died of sepsis, and 1 died late of unrelated causes. Three symptomatic patients had no treatment; two died of biliary sepsis and one survived. Overall graft salvage was 83.3% in asymptomatic patients and 15% in patients with symptoms(P<0.001). Graft salvage in asymptomatic patients undergoing revascularization was 81.8%, versus 40% in symptomatic patients(P=NS). One-year patient survival was 91.7% in asymptomatic patients and 65% in symptomatic patients (with one late death excluded) (P=NS).Conclusions.Routine postoperative duplex ultrasonography should be performed early after liver transplantation. We believe that emergent revascularization of hepatic artery thrombosis in asymptomatic patients and retransplantation in symptomatic patients lead to improved graft salvage and patient survival with a relatively low incidence of late biliary complications.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Waiting time to liver transplantation (LTx) has dramatically lengthened, but the proportion of candidates who die awaiting transplantation has not increased. We evaluated whether longer waiting time for LTx candidates increases mortality.Methods.A cohort of candidates listed for LTx between 1990 and 1993 by three large transplantation programs was followed for 2 years. The exposure measure was ABO blood type, which is not inherently related to outcome, but is a major determinant of waiting time. The main outcome measure was 2-year mortality, as evaluated by logistic regression analysis that controlled for differences in clinical status at the time of evaluation for LTx.Results.The 308 candidates with type O blood waited longer for LTx (median 109 days) than the 399 candidates with other blood types (median 58 days)(P=0.001). Candidates listed for LTx with type O blood had better clinical status at evaluation, but then had higher pretransplantation mortality (13.3%) than other candidates (7.0%)(P=0.005). Blood group O candidates had higher 2-year mortality (26.6%) than other candidates (22.1%), which on multivariate analysis resulted in a mortality odds ratio at 2 years of 1.52 (95% confidence interval=1.04-2.23). With the difference in median waiting time between blood groups increasing from 44 days in the first year to 108 days in the third year, the 2-year mortality odds ratio also rose from 0.94 to 1.97.Conclusions.When compared with LTx candidates with other blood types, blood type O candidates have longer waiting times and higher pretransplantation mortality, which results in higher 2-year mortality.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Islet xenografts have clinical potential, may avoid hyperacute rejection, and therefore are a good place to examine the cellular xenograft immune response. The aim of this study was to examine the cellular, humoral, and cytokine response in islet xenograft rejection and to determine the difference in the immune response with a different donor species.Methods.Two islet xenograft models (DA rat islets to B6AF1mouse and canine islets to B6AF1mouse) and a mouse syngeneic control model were examined histologically and by a semiquantitative polymerase chain reaction method.Results.There was significant up-regulation of all intragraft cytokines tested (interleukin [IL]-2, IL-4, IL-5, IL-10, and interferon-γ) in both xenograft models compared with the controls. However, the dog islet grafts had higher levels of IL-4 and IL-5 gene expression than the rat islet grafts, which, conversely, had higher levels of interferon-γ gene expression. These differences correlated with the histological and antidonor antibody production differences between the two models. The dog to mouse model had an intense eosinophilic infiltrate and an early up-regulation of anti-donor antibody, whereas there was little eosinophilic infiltrate and a delayed anti-donor antibody up-regulation in the rat to mouse model.Conclusions.The mouse used different mechanisms to reject the rat and canine islets, suggesting that the immune response in islet xenograft rejection may be dependent on the species combination. It may not be possible to characterize the cellular xenograft rejection response in a bipolar manner as has been the case with humoral rejection response. Caution therefore needs to be taken before extrapolating the cellular immune responses seen in animal models to the clinical setting.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.There is controversy in the literature as to whether swine coronary endothelium expresses major histocompatibility complex (MHC) class II antigens constitutively.Methods.Because this issue has implications for cell-mediated human anti-swine xenogeneic responses, we stained tissue sections from human, pig, rat, and mouse hearts with the anti-class II monoclonal antibody ISCR3, which has a similar specificity and titer when binding to human, porcine, and rodent class II molecules.Results.Immunoperoxidase staining of human and porcine hearts with ISCR3 resulted in a dense reaction on the coronary endothelium of epicardial arteries, intramuscular arterioles, and capillaries. In contrast, the coronary endothelium of rat and mouse hearts did not stain with ISCR3. When freshly harvested porcine aortic endothelial cells were placed in culture, class II MHC antigen expression was lost within three to four passages.Conclusions.Thus, using a single antibody with cross-species reactivities, we demonstrate that swine coronary endothelium, unlike rodent coronary arteries, expresses similar basal amounts of class II MHC antigens to human coronary vessels. The constitutive expression of class II MHC antigens on swine coronary artery endothelium may contribute to host T cell-mediated xenogeneic responses in clinical pig-to-human cardiac xenotransplantation and thus become a target for therapeutic intervention.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundC57BL/6 (B6) mice generate cytolytic T lymphocytes (CTLs) to a limited number of immunodominant cytotoxic T cell target (CTT) antigens and associated peptides when primed with H2-matched BALB.B spleen cells, despite multiple minor histocompatibility antigen (HA) differences. We previously showed that these CTLs recognize four Kb-bound minor HA peptides derived from CTT antigens. Here, we describe the identification of Db-bound minor HA peptides recognized by B6 anti-BALB.B CTLs.MethodsPeptides were extracted from Dbmolecules immunoprecipitated from lysates of T lymphoblasts from BALB.B mice and mice from the CXB recombinant inbred strains that express H2band segregate minor HA from BALB/c and B6. Peptides were separated by reverse-phase high-performance liquid chromatography and tested for sensitization of targets for lysis by CTLs specific for BALB.B and the CXB strains.ResultsB6 anti-BALB.B CTLs recognized a single Db-bound peptide whose distribution in CXB strains matched that of the previously reported CTT-1 minor HA. An additional Db-bound peptide (CTT-7) was recognized by B6 anti-CXBG CTLs. CTT-1 was expressed by independently derived inbred mouse strains that expressH2b. CTT-1 was recognized by B6 CTLs specific for these inbred strains, except for the LP and 129 strains that stimulated CTL specific for the CTT-8 peptide expressed by these two strains.ConclusionsThese results demonstrate that B6 CTLs primed and boosted with multiple minor HA recognize a maximum of two minor HA peptides regardless of the strain of origin of H2b-matched stimulating lymphoid cells.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Small, resting B cells (rB cells) express major histocompatibility complex (MHC) class II molecules but not the putative costimulatory molecules, B7-1 (CD80) and B7-2 (CD86); they are classified as nonprofessional antigen-presenting cells. rB cells have been shown to be capable of anergizing T cells in vitro and inducing the prolonged survival of skin grafts mismatched for a single minor histocompatibility (miH) antigen, H-Y. The aim of this study was to investigate ability of rB cells to induce unresponsiveness to multiple miH and MHC antigens.Methods.Mice were pretreated with 1 × 107donor rB cells 14 days before transplantation of cardiac grafts mismatched for either a single or multiple miH and/or MHC antigens in vivo.Results.rB cells induced indefinite prolongation of cardiac grafts mismatched for H-Y antigen (C57BL/10 male to female). Moreover, 50% of grafts mismatched for multiple miH antigens (C3H to CBA) were accepted indefinitely in recipients treated with donor rB cells. In marked contrast, when grafts were mismatched for either a single MHC class I antigen, Kb(CBK to CBA), or multiple MHC and miH antigens(C57BL/10 to C3H), pretreatment with rB cells did not prolong graft survival. To investigate why rB cells were ineffective tolerogens for grafts mismatched for MHC antigens, we examined the fate of the cells in vivo. We demonstrate that, after intravenous injection of rB cells, expression of B7-2 was induced within 24 hr.Conclusions.These data suggest that rB cells may be less effective at inducing specific unresponsiveness to MHC antigens because of their rapid activation in vivo.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

BackgroundIt was reported that autoantibodies against cyclophilin are present in sera from systemic lupus erythematosus. We hypothesized that autoantibodies against FKBP12, another immunophilin, may be present in the plasma of liver allograft recipients, which may affect the clinical outcome of liver allografts.MethodsWe investigated the relationship between the presence of anti-FKBP12 autoantibodies and rejection episodes in 47 patients treated with FK506 after living-related partial liver transplantation (LRLT). The patients consisted of two groups: 22 with rejection [R(+) group] and 25 without rejection [R(-) group]. The autoantibodies were measured by an indirect ELISA, and the specificity was confirmed by absorption with antigen and immunoblotting.ResultsThe autoantibodies were detected in 13 of 22 in the R(+) group (IgG: 5; IgM: 6; both: 2) and in 6 of 25 in the R(-) group (IgG: 2; IgM: 3; both: 1) before LRLT (P=0.0193). After LRLT, they were also detected more frequently in the R(+) group (12 of 22; IgG: 1; IgM: 8; both: 3) than in the R(-) group (2 of 25; IgG: 1; IgM: 1)(P=0.001). In the R(+) group, the mortality of the patients who were positive and negative for the autoantibodies was 6 of 12 and 2 of 10, respectively. The autoantibodies were detected in all four patients with chronic or refractory acute rejection. The autoantibodies were not detected in any of the 34 healthy subjects.ConclusionsThese results suggest that the presence of the autoantibodies in patients before transplantation is related to rejection, and the presence after transplantation may be associated with patient outcome.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.We have recently reported that interleukin (IL)-12 prevents acute graft-versus-host disease (GVHD)-induced mortality in a full major histocompatibility complex- plus multiple minor antigen-mismatched A/J→B10 bone marrow transplantation (BMT) model. Because most patients have access to a haploidentical, one haplotype-mismatched donor, we have now investigated the protective effect of IL-12 against GVHD and GVHD-associated immune dysfunction in a haploidentical CBD2F1(H2kxd) → B6D2F1(H2bxd) strain combination.Methods.GVHD was induced by injecting CBD2F1 marrow and spleen cells into lethally irradiated B6D2F1 mice.Results.In untreated control mice, GVHD resulted in 87% mortality by day 8 after BMT, with no survivors beyond day 17. Treatment with a single injection of IL-12 on the day of BMT led to 87% long-term survival, with no significant weight loss, diarrhea or GVHD skin changes. The majority of T cells recovering in these mice showed the CD62L+, CD44low, CD45RBhighnaive phenotype. These T cells showed specific tolerance to both host and donor histocompatibility antigens, but normal anti-third party(H2s) alloresponses in vitro. B-cell proliferative responses to lipopolysaccharide were also normal in IL-12-protected mice. Moreover, normal negative selection of thymocytes bearing T cell receptors with Vβ that recognize endogenous superantigens was observed among CD4+CD8-thymocytes, indicating a lack of GVHD-associated thymic selection abnormalities in IL-12-protected allogeneic BMT recipients.Conclusions.IL-12 provides permanent protection against an otherwise severe, rapidly lethal GVHD, with no clinical manifestations of chronic GVHD, immunosuppression or autoimmune features, in a full major histocompatibility complex haplotype-mismatched murine BMT model.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.In this large, two-center study, 260 cytotoxic T lymphocyte precursor (CTLp) frequency assays, performed to assess patient-donor compatibility, were analyzed in relation to the degree of HLA matching.Methods.While the tissue-typing techniques used at the Royal Postgraduate Medical School (RPMS) and Anthony Nolan Bone Marrow Trust (ANBMT) differ, the results of the analyses on the two sites are analogous, with high CTLp frequencies (> 1:100,000) in 42% and 41% of recipient-donor pairs, respectively.Results.Recipient-donor combinations with class I mismatches and class II identity were associated with high CTLp frequencies (collectively 83% vs. 17% low CTLp). This correlation was not as strong in pairs where class II mismatches were demonstrated (61% high vs. 39% low). Despite using different matching procedures, the RPMS and ANBMT both show that 32% of the“perfectly” matched pairs (i.e., where no mismatch was detected by any of the techniques used here) had high frequencies of recipient-specific CTLp.Conclusions.The failure of conventional methods to identify such a level of histoincompatibilities indicates that the CTLp assay has an important role in the selection of unrelated donors for bone marrow transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Vascular complications remain an important cause of postoperative morbidity in liver transplant patients. Herein, we present an unusual case of nonanastomotic inferior vena cava (IVC) stenosis in a patient with a“piggyback” caval anastomosis.Methods.A 59-year-old woman underwent liver transplantation using a piggyback IVC anastomosis. Her postoperative course was complicated by IVC thrombosis. Catheter-directed thrombolysis, followed by balloon angioplasty and intravascular stent placement, was used to recanalize the IVC and treat a severe retrohepatic IVC stenosis.Results.After 46 hr of catheter-directed urokinase infusion, there was clot lysis and identification of a severe stenosis in the retrohepatic IVC. The lesion was extremely resistant to balloon dilatation alone and a 22-mm-diameter intravascular stent was placed. Simultaneous dilatation of three high-pressure balloons was necessary for maximal stent expansion. The patient remains asymptomatic with no evidence of IVC compromise through 20 months of follow-up.Conclusions.IVC stenosis and thrombosis after liver transplantation may be treated favorably in some patients using catheter-directed thrombolytic therapy followed by balloon dilatation and/or stent placement.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID