摘要:

To investigate the causes of gastrointestinal bleeding (GIB) and its impact on patient and graft survival after orthotopic liver transplantation (OLTx), the first 1000 consecutive OLTx using tacrolimus were studied. Our patient population consisted of 834 adults. The bleeding episodes of patients with GIB (n=74) were analyzed, and patients without GIB (n=760) were used as controls. The mean age, gender, and United Network for Organ Sharing status were similar in both groups. Endoscopy was done in 73 patients with GIB and yielded a diagnosis in 60 patients (82.2%): 39 with a single, and 21 with multiple GIB episodes. In the remaining 13 patients (17.8%), the bleeding source was not identified. Of 92 GIB episodes with endoscopic diagnoses, ulcers (n=25) were the most common cause of bleeding, followed by enteritis (n=24), portal hypertensive lesions (n=15), Roux-en-Y bleeds, and other miscellaneous events (n=28). The majority (73%) of the GIB episodes occurred during the first postoperative trimester. The patient and graft survival rates were statistically lower in the GIB group compared with the control group. The adjusted relative risk of mortality and graft failure was increased by bleeding.In summary, the cumulative incidence of GIB was 8.9%. Endoscopy identified the source of GIB in most cases. Ulcers were the most common cause of GIB after OLTx. The onset of GIB after OLTx was an indicator of decreased patient and graft survival.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Cytomegalovirus (CMV) titer in blood seems to be the principal determinant of clinical symptoms in immunosuppressed patients. We have developed an assay for quantitation of CMV DNA in serum. The assay requires the coamplification by polymerase chain reaction (PCR) of extracted serum DNA with 1000 molecules of mutated internal standard DNA, and then an ELISA detection system.We examined 133 paired buffy coats and sera from 15 patients with symptomatic infection. Sera were examined by quantitative PCR, and buffy coats were examined by qualitative PCR (with a detection threshold of approximately 40 copies per 150,000 cells). Serum viral titers peaked during the seventh week after transplant (median day 40, range 26-58) at about the time of symptom onset. Mean viral titer measured during the seventh week was 1.2×105copies per milliliter of serum (standard error 6.5×104). Buffy-coat PCR results were generally concordant with results of serum PCR (overall concordance 103/133=77.4%). Serum CMV titer fell, as symptoms resolved with reduction of immunosuppression and specific antiviral therapy. High titers and poor response to antiviral therapy were observed in the context of excessive immunosuppression and bacterial sepsis.Measurement of serum CMV titer may be useful for the management of immunosuppressed transplant recipients, and provides a tool for the better understanding of factors that enhance or inhibit viral replication.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Cyclosporine (CsA) and tacrolimus (FK506) have recently been reported to inhibit canalicular transport of bile acids in vitro and thereby possibly induce cholestasis. A relative reduction of chenodeoxycholic acid (CDCA) has been observed after liver transplantation when CsA is used as immunosuppressant. We tested the hypothesis that CsA induces cholestasis and reduces CDCA secretion as compared with treatment with monoclonal antibodies (OKT3), and that CsA differs from FK506 with regard to its effects on biliary lipid secretion.Bile flow, biliary lipid secretion rates, and biliary bile acid composition were determined during the first 10 days after transplantation in 29 liver transplant recipients. Two prospective randomized studies were performed that compared CsA and OKT3 and compared CsA- and FK506-based regimens. In study 1, bile acid output averaged 0.75±0.15 μmol/min in the CsA I group and 0.54±0.11 μmol/min in the OKT3 group on postoperative day 1. Bile flow and bile acid output then increased, and there was no significant difference between the two groups. The relative proportion of CDCA decreased to the same extent in both groups. In study 2, mean bile acid outputs on postoperative day 1 were 0.57±0.26 μmol/min and 0.55±0.15 μmol/min in the CsA 2 and FK506 groups, respectively. The following increase in bile acid secretion was significantly larger in the FK506 group. After transplantation, the relative proportion of CDCA decreased with time in both groups, but the reduction was more rapid in the FK506 group.In conclusion, CsA did not inhibit bile secretion during short-term treatment after liver transplantation. Compared with patients given CsA-based treatment, patients with FK506-based treatment recovered bile secretion more rapidly.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Posttransplantation malignancy in the allograft is a rare complication of orthotopic liver transplantation. In the described case, an abnormal T-tube cholangiogram, performed 6 months after orthotopic liver transplantation between a male donor and a female recipient, prompted needle liver biopsy. A moderately differentiated adenocarcinoma was found. Fluorescence in situ hybridization for the Y chromosome indicated male origin of malignancy. Donor-related disease was confirmed by comparative DNA analysis of genomic sequences from the donor liver, associated tumor, and recipient peripheral blood. Results of these investigations qualified the recipient for a second liver transplant.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

The significance of a positive cross-match in liver transplantation remains controversial, as documented by a number of recent conflicting reports. In this study, we evaluated 195 consecutive orthotopic liver transplant recipients in whom the cross-match was either negative or positive for T or B cells. Special emphasis was placed on the outcome of patients with high levels of preformed IgG antibodies directed against donor T cells. IgG anti-donor antibodies were confirmed by flow cytometry in all cases. Of 10 patients with strong T-cell antibodies, there was one early death due to nonimmunological causes. Transplantation was successful in 9/10 patients followed for 3 months to 3 years. Graft survival, incidence of acute rejection, and number of liver biopsies in patients with a positive cross-match (strong T, weak T, or B cell) were not significantly different from those of patients with a negative cross-match. In the strong T cell antibody group, one patient had early graft dysfunction, with extensive hepatic necrosis and histological signs of antibody-induced damage. Two other patients also showed some evidence of possible antibody-mediated events, such as neutrophil infiltration and hepatocyte swelling. These lesions were reversible, and the patients had uneventful recoveries. Thus, in our experience, preformed antibodies did not preclude good graft survival.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Non-heart-beating (NHB) donors are a valuable source of kidneys for transplantation. The organs, however, sustain substantial warm ischemic damage that may jeopardize the transplantability and result in nonfunction of the grafts. Quantification of warm ischemic time (WIT) and prediction of transplant outcome are essential for the use of NHB donor organs.During machine preservation (MP) the viability of NHB donor kidneys was evaluated through calculating intrarenal vascular resistance and determining lactate dehydrogenase and α-glutathione S-transferase (αGST) in the perfusate. Thirty-seven functioning (F) and nine nonfunctioning kidneys (NF) were compared.WIT was longer in NF; serum creatinine, donor age, and preservation time were not different. WIT correlated well with αGST after 4 and 8 hr of MP (r=0.353,P=0.009, and r=0.346,P=0.011, respectively). When compared with F, intrarenal vascular resistance was increased in NF after 4 and 8 hr of perfusion (P<0.05); at all time points, αGST levels were elevated in NF (P<0.05). Lactate dehydrogenase activity was not different between the groups, but could identify immediate functioning grafts within the F group.In conclusion, αGST levels correlated strongly with WIT and were also able to distinguish NF from F grafts. αGST can adequately predict the functional outcome of NHB donor grafts before transplantation; levels of αGST can be used to define reliable safety margins for viability. Therefore, MP is useful in evaluating the viability of NHB donor kidneys, and the parameters discussed will help to select nonviable grafts from this valuable pool of kidneys for transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

We have previously demonstrated that administration of the nitric oxide (NO) synthesis inhibitor aminoguanidine (AG) to mice undergoing nonlethal graft-versus-host disease (GVHD) results in less destruction of host tissue and enhanced proliferative responses of splenic lymphocytes. Subsequently, we have determined whether the amelioration of GVHD pathology associated with inhibition of NO synthesis affects survival in a lethal GVHD model. Utilizing a C57BL/6 to C57BL/6×DBA2JF1 model, administration of parental lymph node lymphocytes instead of splenocytes results in 80-90% lethality by week 4 after GVHD induction. Administration of AG resulted in significantly decreased lethality coincident with decreased serum NO2-+NO3-levels. AG therapy had no effect on donor anti-host cytolytic T cell activity, which indicates that destruction of host tissue via this pathway was unaffected by the therapy. Histological evaluation of spleen, small intestine, bone, and mesenteric lymph node did not reveal any difference in the histological correlates of disease in the treated mice. AG increased various hematopoietic indices, including red blood cell count, white blood cell count, and hemoglobin, which indicates that the disruption of hematopoiesis during acute GVHD is mediated in part by NO. In addition, the number of GVHD mice with endogenous bacterial infections in the spleen and liver was significantly decreased in mice receiving AG therapy. These data indicate that NO plays a detrimental role during GVHD that appears to result in decreased hematopoietic indices and concomitant susceptibility to bacterial infection.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Chronic renal allograft rejection is characterized by gradual progression suggesting persistent low-grade injury. Apoptotic cell death may be initiated by low-grade injury secondary to external factors, making apoptosis a potential pathway of chronic rejection. In the present investigation, protocol kidney biopsies of 20 pediatric renal allograft recipients (12 with chronic rejection and 8 with normal histology), 9 pediatric liver allograft recipients, and 7 children with minimal change nephrotic syndrome were evaluated. The presence of apoptotic cell death was studied by determining apoptosis-induced oligonucleosomal DNA fragmentation in the biopsy specimens using 3′ end labeling with terminal transferase, gel fractionation, and Southern blotting. The specific cell types with increased DNA fragmentation were determined by in situ 3′ end labeling performed on sections of the biopsies. Significant DNA fragmentation was found only in the specimens from patients with chronic rejection. In situ investigation revealed increased apoptosis of both proximal and distal tubular epithelial cells, but not in the glomeruli or interstitium. The mean number of apoptotic tubular epithelial cells per 400× magnified field was higher in the renal allografts than in kidneys of liver transplant recipients or patients with minimal change nephrotic syndrome (2.3 vs. 0.8,P<0.05, in both cases). Our data provide biochemical evidence of increased apoptotic cell death of renal tubular epithelial cells in patients undergoing chronic renal allograft rejection.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Anti-CD3 monoclonal antibody (mAb) OKT3 is immunosuppressive, but causes severe adverse effects during the first administration (“first-dose reaction”). These adverse effects are presumably caused by cytokine release that results from T-cell activation. In vitro, T-cell activation by anti-CD3 mAb requires interaction with monocyte Fc receptors. The Fc receptor for murine IgG1, FcγRIIa, is polymorphic. In some individuals, murine IgG1 anti-CD3 mAb causes T-cell proliferation and cytokine release in vitro (high responders [HR]), whereas in individuals with the low-responder (LR) phenotype it does not. We have now investigated the role of this FcγRIIa polymorphism in the release of cytokines in vivo and the occurrence of adverse effects after the administration of WT31, a murine IgG1 anti-CD3/T cell receptor mAb. WT31 caused an increase of plasma tumor necrosis factor-α in all four HR patients and none of the five LR patients. In all HR patients except one, plasma γ-interferon and interleukin 6 also increased, and a first-dose response was observed, whereas no cytokine release or adverse effects occurred in any of the LR patients. WT31 caused lymphopenia in all HR and none of the LR patients. FACS analysis demonstrated that in HR patients, after the initial disappearance of CD3+cells from peripheral blood, modulation of CD3 occurred, whereas in LR patients a high degree of coating of the lymphocytes was observed. Surprisingly, WT31 also induced a marked granulocytopenia, as well as a decrease of thrombocytes, in three of the four HR patients (and in none of the LR patients). These data provide direct clinical evidence that Fc receptor interaction determines the release of cytokines and the occurrence of adverse effects after administration of anti-CD3/T cell receptor mAb. Furthermore, these data suggest that tumor necrosis factor-α by itself is not sufficient to induce the first-dose reaction.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Combined treatment with anti-leukocyte function-associated antigen-1 (LFA-1) and anti-intercellular adhesion molecule-1 (ICAM-1) monoclonal antibodies leads to allograft tolerance in murine cardiac transplantation. In the present study, we analyzed the mechanisms for this tolerance induction. In the tolerant mice, proliferative response of splenic T cells against donor-type cardiac myocytes and of CD8+T cells against donor-type alloantigens was impaired as compared with responses in naive or rejected mice, but was completely restored with exogenous interleukin 2. This suggests that class I-restricted CD8+T cells of tolerant mice were rendered anergic against donor-type alloantigens in the periphery. In contrast, proliferative response of CD4+T cells against donor-type alloantigens in vitro was comparable between tolerant and naive mice. When heart and skin grafts from the same donor (BALB/c [H2d]) were simultaneously transplanted to C3H mice (H2k), both were rejected within 29 days, even though the mice were similarly treated with anti-LFA-1 and anti-ICAM-1 monoclonal antibodies. In contrast, when heart graft from BALB/c and skin graft from third-party donor (C57BL/6 [H2b]) were simultaneously transplanted to C3H mice under the same condition, the heart graft was accepted indefinitely and the skin graft was rejected. These findings suggest that the peripheral tolerance against cardiac allografts could be induced by selective inactivation of alloreactive CD8+T cells resulting from the lack of cognate help by CD4+T cells.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID