摘要:

Hepatic artery thrombosis (HAT) is one of the most serious complications after orthotopic liver transplantation, and is associated with a high morbidity and mortality. This study retrospectively reviewed 66 liver transplants in children under the age of 10 years during a year-long period at a single institution. A total of 28 perioperative variables were analyzed to identify responsible factors of HAT. Of the 66 children, 18 (26%) developed HAT within 15 days after the transplant (HAT group); 29 (42%) had an uneventful postoperative course (control group). To avoid the possible influence of other complications 19 patients were excluded. Of the variables compared between the 2 study groups, three surgical factors (diameter of the hepatic artery—greater or less than 3 mm; type of arterial anastomosis—end-to-end versus the use of an iliac graft or aortic conduit; and number of times the anastomosis was redone—one versus more than one), were found to be significantly different (P<.05) between HAT and control groups. Two medical factors also were significantly different: the use of intraoperative transfusion of fresh frozen plasma (FFP) and the administration of postoperative prophylactic anticoagulant treatment. A heparin and dextran-40 protocol appeared to be effective in. preventing HAT (P<.02). Moreover, after multivariate analysis, anticoagulation therapy was demonstrated to

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Orthotopic liver transplantation is frequently associated with hyperfibrinolysis, the origin and clinical relevance of which is largely unknown. In 20 orthotopic liver transplantations, we studied the occurrence and systemic effects of hyperfibrinolysis. Severe fibrinolysis was defined to be present when the euglobulin-clot lysis time and the whole-blood-clot lysis time, as measured by thrombelastography, were shorter than 60 and 90 min, respectively, at some time during the operation. Based on these criteria, 7 patients had minimal fibrinolysis (group I), and 13 patients had severe fibrinolysis (group II). In group II a gradual increase of tissue-type plasminogen activator (t-PA) activity was seen during the anhepatic stage, followed by an “explosive” increase immediately after graft reperfusion (P=0.0004, compared with group I), and a reduction of plasminogen activator inhibitor (PAI) activity. Plasma degradation products of fibrinogen and fibrin increased parallel to t-PA activity, and levels were significantly higher at 45 min after graft reperfusion in group II compared with group I (P<0.04). Thrombin-antithrombin III complexes showed an identical steady increase in both groups, indicating that increased t-PA activity was not related to thrombin formation. A combination of increased endothelial release and reduced hepatic clearance may have caused the increased t-PA activity. The t-PA—associated destruction of fibrinogen and fibrin after graft reperfusion is consistent with the clinical signs of severe oozing often seen in this period. These observations may have important clinical implications for the treatment of bleeding in patients undergoing orthotopic liver transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The aim of this study was to compare the extent of in vitro T cell depletion and recovery of hematopoietic progenitor cells achieved with five methods of T cell depletion. Bone marrow samples from the same source were treated with monoclonal antibody Campath-1 (CP1) and human complement, XomaZyme-H65 (anti-T cell ricin A chain immunotoxin), or soybean agglutinin (SBA) alone or in combination with sheep erythrocytes (EAET) or a cocktail of immunomagnetic beads (B) directly coated with anti-CD2, anti-CD3, or anti-CD8 monoclonal antibodies. Residual T cells were enumerated by limiting dilution analysis, EAETrosetting, and proliferative responses to phytohemagglutinin. The results of this study demonstrated the following reductions in BM T cells as detected by limiting dilution analysis (mean % control): SBA+B (99.9%), SBA+EAET(99.8%), CP1+C' (99.4%), anti—T cell ricin A chain immunotoxin (99.0%), and SBA alone (94.2%). Neither PHA response nor enumeration of residual EAETrosettes provided discriminating differences in the degree of T cell depletion by treatment method when T cell reductions exceeded 99.0% by LDA. These results demonstrate the ability of CP1+C', XomaZyme-H65, and SBA plus sheep eryth-rocyte or magnetic bead depletion to achieve a greater than 99% reduction of BM T cells and the importance of limiting dilution analysis in defining differences in T cell numbers when depletion exceeded 99%.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

We report two cases of pulmonary venocclusive disease (PVOD) in children with acute lymphoblastic leukemia treated by marrow allograft transplantation following conditioning with high-dose 1–3 bis chloroethyl-1 nitrosourea (BCNU), etoposide (VP-16), and cyclo-phosphamide (Cy). Both patients developed symptomatic pulmonary hypertension documented by right heart catheterization. Open-lung biopsy of one patient demonstrated PVOD evident even on frozen sections stained with hematoxylin and eosin. High-dose methylprednis-olone was associated with significant clinical improvement in both patients. Pulmonary symptoms resolved in one patient who subsequently died in leukemic relapse. PVOD resolved in the other patient, only to recur when steroids were discontinued and then again respond to reinstitution of therapy. More aggressive therapy for malignant diseases may increase the incidence of PVOD. Prompt recognition of its subtle clinical and histological manifestations allows early institution of steroid therapy, which may be beneficial.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Transfusion of one unit or more of Rh-positive red blood cells normally causes circulating anti-D antibody to appear 2–6 months later in 80–95% of Rh-persons. We asked whether transplant immunosuppression with cyclosporine and corticosteroids affects Rh immunization. Nineteen Rh-liver, heart, and heart-lung transplant recipients received 3–153 (median: 10) units of Rh+RBCs at surgery and were tested for anti-D >2 months later. Three patients developed anti-D at 11–15 days; one may have had an unusually rapid primary immune response and two were secondary to previous exposure by pregnancy. None of the other 16 patients had anti-D when tested 2.5–51 months later (13 patients, >11.5 months). This low rate of Rhesus immunization in association with cyclosporine immunosuppression allows greater flexibility in meeting the transfusion needs of Rh″ liver and heart transplant patients. Caution is still advised in young females and in patients who may have been previously exposed to Rh+RBCs by transfusion or by pregnancy prior to the availability of perinatal Rh immune globulin twenty years ago. Other humoral immune responses to some vaccines or infectious agents may also be impaired in transplant patients.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Mouse hearts transplanted heterotopically to MHC-disparate recipients can be hyperacutely rejected (HAR) after a single or 3 sequential donor type skin grafts, or a single intradermal injection of lymphoid cells. In the combinations tested, not all hearts are HAR; most of them are rejected in accelerated fashion. Our results with transplanted rat hearts are similar, even in a genetic combination for which HAR of all hearts has been reported. However, in rats, HAR tends to occur more rapidly and to be associated with more-intense vascular changes.Transfer of serum from mice or rats sensitized by 3 sequential skin grafts likewise resulted in occasional hyperacute but never accelerated rejection. Transfer of lymph node cells from mice sensitized with a single skin graft always resulted in accelerated but never in hyperacute rejection; transfer of cells after 3 sequential skin grafts caused neither accelerated nor hyperacute rejection.This work was supported by a Grant-in-Aid of the American Heart Association, Utah Affiliate.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Lewis rats pretreated with UV-B— irradiated donor leukocytes (UV-DL) and peritransplant cyclosporine (CsA… CsA, 20 mg/kg on days 0, +1, and +2) accepted W/F heart allografts permanently. This study of donor-specific immunologic unresponsiveness and its cellular mechanisms shows that the induction phase of unresponsiveness is partially mediated by W3/25+T cells, while its maintenance is dependent on the presence of 0±8+T cells. In vivo adoptive transfer of either splenocytes, T lymphocytes (T cells), or W3/25+T cells from ungrafted, UV-DL-transfused rats into unmodified syngeneic Lewis rats that received test grafts 24 hr later led to significant prolongation of donor-specific graft survival. Adoptive transfer of 0±8+cells did not influence donor-type (W/F) test graft rejection. Adoptive transfer of SpL, T cells and 0±8+cells from UV-DL and CsA-treated recipients of W/F heart allografts at 20 or 180 days after transplantation led to significant donor-specific graft prolongation in naive syngeneic hosts, while adoptive transfer of W3/25+cells, in this group, did not affect test graft survival. However, the adoptive transfer of SpL or of T cell subsets did not influence third-party (ACI) graft survival. In-vitro mixed lymphocyte reaction between thoracic duct lymphocytes obtained at various intervals following grafting from UV-DL and CsA treated Lewis recipients of W/F heart allografts and donor-type SpL resulted in significantly reduced reactivity by 78%, 75%, 69% (P<0.001) and 43% (P<0.02) compared with controls when responder TDL were obtained at 20, 50, 100, and 180 days after transplantation, respectively. In coculture studies, the MLR response to donor SpL was specifically suppressed by 60%, 57%, 46%, and 50% (P<0.01) at 20, 50, 100, and 180 days after transplantation, respectively, compared with controls. These data indicate that the induction of specific unresponsiveness to heart allografts in this model is mediated, in part, initially by the appearance in the host of specific W3/25+ cells either induced or recalled by UV-DL transfusion, and that a stable state of immunologic unresponsiveness is subsequently dependent on the presence of 0±8+suppressor cells.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Previous studies have established that exposure of mice to ultraviolet radiation followed by injection of alloantigen can suppress the induction of delayed hypersensitivity and the rejection of allografts in an antigen-specific manner. In the clinical situation, however, UV irradiation several days prior to transplantation may prove impractical due to the difficulty in predicting when a donor organ will be available. Thus, the purpose of this study was to determine if exposure to UV radiation can suppress the elicitation of the immune response in mice sensitized with alloantigen. The data demonstrate that exposure of mice to UV radiation 1, 3, or 5 days after the injection of alloantigen can significantly suppress the delayed hypersensitivity response to that alloantigen. Present in the spleens of these mice are suppressor T lymphocytes. These suppressor cells are specific for the antigen originally used to sensitize the mice, in that they do not suppress the response to an irrelevant alloantigen. In addition, spleen cells from mice sensitized with alloantigen and exposed to UV radiation 1, 3, or 5 days later are unable to proliferate in response to the alloantigen in a mixed lymphocyte response. These cells do respond to irrelevant third-party cells, demonstrating again the specificity of the suppression. These data demonstrate that exposure of mice in vivo to UV radiation can inhibit the elicitation of the immune response to alloantigen. Since the immunosuppression is specific for the sensitizing antigen, these data suggest that this may provide a novel method of suppressing the immune response to tissue allografts.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

Prodigiosin 25-C (PrG25-C) was discovered as an immunosuppressant in the course of our screening for immunomodulating substances. In this system, PrG25-C inhibited T lymphocytes proliferation and was less suppressive against B lymphocytes. PrG25-C was also a powerful inhibitor of cytotoxic T cell induction by mixed lymphocyte reaction and completely suppressed induction of H-2 specific cytotoxic cells at 12.7 nM. PrG25-C also inhibited in vivo induction of H-2 restricted cytotoxic T lymphocytes at a dose of 0.5 mg/kg but had little myelotoxicity because numbers of blood leukocytes and splenocytes of PrG25-C—treated mice were comparable to those of nonsensitized mice. No inhibitory effects of PrG25-C were observed on the production of anti-SRBC antibody. These results indicate that PrG25-C is a T-lymphocyte-specific immunosuppressant.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID

摘要:

The effect of a pretransplant i.v. infusion of donor-strain spleen cells into recipient mice that were already immune to minor H antigens on the infused cells was studied. The central finding is that a preexisting state of immunity against target minor H antigens on a skin graft is sufficient to overcome the survival-prolonging effect of a pretransplant i.v. infusion of donor-strain spleen cells. Moreover, immunity directed against an irrelevant antigen on the infused cells, rather than against a target antigen on the indicator skin graft, is sufficient to cause the beneficial effect of the infusion to be greatly reduced. A further significant finding is that the ability of a pretransplant infusion of donor-strain spleen cells to prolong the survival of a minor allograft of skin declines as the recipient matures from a 6–9-week-old juvenile to a 12–16-week-old adult.

ISSN:0041-1337    

出版商:OVID    

年代:1989

数据来源: OVID