ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Backgrounds.Partial portal vein ligation (PPVL) is an established approach in the study of prehepatic portal hypertension in animals. The effect of orthotopic liver transplants (OLT) on hemodynamics in PPVL animals has not been investigated to date. The aim of this study was to develop a model of OLT in PPVL rats and to investigate its hemodynamic consequences.Methods.Three groups of male Lewis rats were investigated (1) control animals (n=7), (2) PPVL (n=9), and (3) PPVL/OLT (n=16). Three weeks after PPVL, 9 animals were taken for hemodynamic measurements. OLT was performed in the remaining 16 PPVL rats (PPVL/OLT), and, 4 weeks later, hemodynamic measurements were made. Blood biochemical analysis was performed at different time points in all 3 groups.Results.The PPVL animals presented with hyperdynamic systemic circulation, extensive collateral vascularization in the hilar region, and portal-systemic shunting (portal systemic shunting; 35.3±5.5%). In the PPVL/OLT group, 15 rats survived for 4 weeks (survival: 93.8%, 15 of 16). Of these PPVL/OLT rats, 3 died during the blood sampling protocol. In 3 PPVL/OLT rats, abnormal liver function and histology were found and deranged systemic and hepatic hemodynamics persisted after OLT. In the remaining 9 PPVL/OLT rats, systemic and hepatic hemodynamics had returned to normal at 4 weeks and portal systemic shunting was markedly reduced (2.5±0.9%). Liver function was in the normal range.Conclusions.(1) The possibility of performing OLT in PPVL rats with a high rate of survival has been confirmed. (2) In the majority of cases, complete reversal of hemodynamic abnormalities in the PPVL animals occurs after OLT (3). PPVL/OLT represents a new and important model in OLT research.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.The surgical procedure of small bowel transplantation normally results in complete disruption of the graft’s lymphatic drainage. The present study was undertaken to determine the impact of lymphatic reconstruction (LR) on the outcome of intestinal grafting, using a microsurgical model that immediately restores lymphatic drainage.Materials.Brown Norway (RT1n) intestinal grafts were orthotopically transplanted into Lewis (RT11) rats either with LR (+LR) or without LR (−LR). Recipients were randomly allocated into the following groups: no treatment or cyclosporine (CsA) at a dose of 2, 5, or 10 mg/kg/day subcutaneously from postoperative day (POD) 0 to 6.Results.There was morphological regeneration of lymphatics in the −LR group between 1–3 weeks as previously reported, whereas normal lymph flow was immediately restored in the +LR group. All untreated and CsA(2 mg)-treated allografts were rapidly rejected in both the +LR and −LR groups. In the groups treated with ∼∼5 mg of CsA, five of six −LR animals died of chronic rejection between 38 and 86 days (mean survival time±SD: 76.7±21 days), while all +LR animals survived unti∼l death on POD 100 (P< 0.05). Histological features of mucosal damage found in −LR grafts were absent in the +LR grafts. All of the animals treated with 10 mg of CsA survived indefinitely. Sequential histology revealed mild rejection in −LR and +LR grafts on POD 45, but +LR animals had significantly higher body weight gains (POD 50: −LR: 117±12% vs. +LR: 136±4%,P< 0.01). LR did not affect donor cell migration and nutritional parameters.Conclusion.LR improves the long-term results of small bowel transplantation resulting in better survival rates, less mucosal damage due to chronic graft rejection, and greater weight gain. We conclude that impairment of lymph flow may contribute to poor outcomes when standard surgical techniques are used for small bowel transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.The preconditioning effect of diadenosine tetraphosphate (AP4A) was reported in ischemia/reperfused hearts, but its effect in heart preservation was unknown. According to the possible role of mitochondrial ATP-sensitive potassium channel (mKATPchannel) in the effect of ischemic preconditioning, the contribution of mKATPchannel to the effect of AP4A was tested.Methods.Isolated rat hearts were arrested and preserved by Eurocollin’s (EC) solution at 4°C for 8 hr. AP4A (80 &mgr;M) or AP4A with the 5-hydroxydecanoic acid (100 &mgr;M), a selective inhibitor of the mKATPchannel, was added into the EC solution. The preischemic and postischemic cardiac functions were evaluated on a buffer-perfused Langendorff apparatus before storage and after 20 min of reperfusion.Results.AP4A administration improved the recovery of poststorage cardiac functions (the rate-pressure production, left ventricular systolic pressure, heart rate, coronary flow rate, and derivative of left ventricular systolic pressure;P<0.05) and reduced the leakage of lactate dehydrate and creatine kinase during reperfusion, compared with EC alone. Those effects of AP4A were completely reversed by 5-hydroxydecanoic acid administration in combination subjects.Conclusion.AP4A administration protects the heart through opening of the mKATPchannel during hypothermic preservation. Thus, addition of AP4A into cardioplegia may be a novel method of ischemic preconditioning in the transplantation context.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Current organ shortage has led to a reconsideration of non-heart-beating cadaveric donation.Methods.We assessed the effectivity of dual, i.e., arterial and portal-venous versus exclusive, arterial gravity perfusion for procurement of rat livers after 30 min and 60 min of cardiac arrest, analyzing the rate and homogeneity of microvascular perfusion by in situ fluorescence microscopy.Results.After 30 min of cardiac arrest, a nearly 100% recovery of acinar perfusion with a sinusoidal density not significantly different from that of normal, nonischemic livers was achieved by dual gravity perfusion. Prolongation of cardiac arrest to 60 min caused an almost 50% deficit of acinar and sinusoidal perfusion (P<0.05) with a concomitant 2–3-fold increase of heterogeneity of hepatic microperfusion. Regardless of the warm ischemic time period, dually perfused livers exhibited significantly (P<0.05) higher rates of both acinar and sinusoidal perfusion with increased homogeneity of microcirculation when compared with exclusive arterial perfusion.Conclusion.These data underline the need and benefit of dual perfusion as well as the limitation of warm ischemic tolerance to 30 min for safe liver procurement of non-heart-beating donors.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Donor leukocytes may exert positive immunoregulatory effects on allograft acceptance. Most recent studies have focused on pretreatment protocols. In this study, the effect of postoperative infusion of donor leukocytes on graft survival and the phenotypic and functional requirements for infused cells were investigated in fully major histocompatibility complex (MHC)-mismatched rat heart transplant models.Methods.LEW (RT1l) heart grafts were implanted heterotopically into abdomens of LEW.1W (RT1u), and different types of cells were infused postoperatively. Immunohistochemistry was used to evaluate histopathological changes of grafts.Results.In the absence of any immunosuppressive agents, a single dose of viable donor spleen cells (SC), but not bone marrow cells, was able to prolong heart allograft survival to about 21 days, while they were rejected promptly at day 7 in controls. Infusion of T cell-depleted donor SC, irradiated donor SC or third-party (BN) SC showed no effect on graft survival. Compared with resting cells, neither in vitro nor in vivo prestimulation of infused donor SC improved graft survival. Clinical signs of graft-versus-host reaction were not observed in all above groups. Histology showed remarkable reduction in the severity of graft infiltrate and interleukin-2 receptor-positive cells in grafts of cell-treated animals. Postoperative infusion of SC of F1 generation between different strain combinations showed two requirements for infused cells to be effective: (1) expression of donor-type MHC antigens and (2) strong alloreactivity against the host MHC antigens.Conclusion.Postoperative infusion of viable donor SC can lead to allospecific down-regulation of alloreactivity by a graft-versus-host-associated effect.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.Previous studies suggest a link between cytomegalovirus (CMV) infection and chronic rejection. Since these studies, more sophisticated diagnostic methods with high sensitivity and specificity for CMV have been developed and effective therapy/prophylaxis for CMV is now available. We sought CMV prospectively by polymerase chain reaction of serum and urine and by conventional methods in a group of 33 patients undergoing 57 transplants during 1993 or 1994, selected from a larger series. There were 13 grafts lost to chronic rejection. The remaining 44 grafts that did not develop chronic rejection served as controls and comprised 15 successful primary grafts, 15 second transplants, 8 third transplants, and 6 primary grafts that were lost for reasons other than chronic rejection.Results.The combination donor CMV antibody negative with recipient antibody positive and the duration of CMV infection >30 days were associated with an increased relative risk of chronic rejection. In contrast, the presence of CMV infection alone, symptomatic CMV infection, the detection of CMV by PCR of serum or urine, and the peak/cumulative viral load were not predictive. CMV infection occurred earlier in those undergoing a second transplant for chronic rejection than for those undergoing a second transplant for other reasons. In addition, a human leukocyte antigen B mismatch was associated with prolonged CMV infection.Conclusion.These data are consistent with the hypothesis that prolonged subclinical cytomegalovirus infection is associated with an increased risk of chronic rejection.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.The shortage of available kidneys for renal transplantation could be addressed, to some extent, by expanding the criteria for acceptance of marginal donors.The study of these criteria is limited by the selection of grafts actually retrieved and transplanted, therefore reduced to a study of risk factors. We have evaluated the potential of procurement renal biopies as an instrument for acceptance or refusal of donor kidneys for transplantation.Methods.This was a prospective study of a consecutive series of 200 donors. Biopsies were performed by wedge technique at the donor operation and were evaluated for proportion of glomerulosclerosis, vascular and tubular changes, and interstitial fibrosis. The study included 387 renal grafts with a representative biopsy, transplanted, and followed-up for survival and functional evaluation; 24 hr creatinine clearance at 1 and 3 weeks, and 3, 6, 12, 18, and 24 months.Results.Factors associated with initial graft function included cold ischemia time, number of DR mismatches, tubular changes, although donor age showed the strongest correlation with short- and long-term level of graft function. DR mismatches and retransplantation appeared to be the only significant risk factors for graft loss. The proportion of glomerulosclerosis (mean 8%, range 0–48%) correlated with graft function in the simple regression analysis. However, when age was taken into account glomerulosclerosis did not correlate significantly with graft function. Furthermore, glomerulosclerosis as high as 25% or more had an acceptable 3-year graft survival rate of 74.7%.Conclusion.Procurement biopsy provides only limited information for the decision whether or not to accept a kidney donor.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

DNA of the epidermodysplasia-verruciformis associated subgroup of HPV (EV-HPV) is frequently detected in biopsies of premalignant lesions and nonmelanoma skin cancers of renal transplant recipients.The prevalence of EV-HPVs, however, has never been systematically studied in benign keratotic skin lesions of patients with or without a history of skin cancer. This study included 42 renal transplant recipients with and 36 without a history of skin cancer. A total of 176 skin biopsies were tested for the presence of EV-HPV DNA, using a nested polymerase chain reaction (PCR).Method.EV-HPV typing was done by comparison of the sequence of the amplified PCR products with the sequence of all known EV-HPVs. The natural history of the development of keratotic skin lesions was studied. The number of keratotic skin lesions rapidly increased after transplantation. This increase was most pronounced in patients who developed skin cancer. The prevalence of EV-HPV DNA in benign keratotic skin lesions was equally high in patients with and without a history of skin cancer, i.e., 55 and 53% in the two groups, respectively. A large variety of EV-HPV types was found, but of these none were predominantly present in either patient groups. A higher prevalence of EV-HPV DNA was found in benign skin lesions from sun-exposed sites, but only in patients with a history of skin cancer. The association between the number of keratotic skin lesions and the development of skin cancer strongly supports the hypothesis that EV-HPVs play a role in cutaneous oncogenesis. The equally high prevalence of EV-HPV infection in patients with and without a history of skin cancer, however, may indicate that besides EV-HPV infection, other factors, such as sun exposure may also be important.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID

摘要:

Background.The introduction of potent new immunosuppressive agents may allow simultaneous kidney-pancreas transplantation to be performed without antilymphocyte induction.Methods.We analyzed 30 simultaneous kidney-pancreas transplantations receiving tacrolimus, mycophenolate mofetil, and steroids without without antilymphocyte induction. Eighteen patients underwent pancreas transplantation with portal-enteric (P-E) drainage and the remaining 12 had systemic bladder (S-B) drainage. Target 12 hr trough tacrolimus levels for the first 3 months after simultaneous kidney-pancreas transplantation were 15–20 ng/ml. The oral mycophenolate mofetil dose was 2–3 g/day begun immediately posttransplant in two to four divided doses. Steroids were tapered according to protocol.Results.All patients experienced immediate function of both kidney and pancreas grafts. One-year actuarial patient, kidney, and pancreas graft survival rates are 93, 93, and 90%, respectively. Nine patients (30%) had a total of 13 rejection episodes (12 biopsy proven) including 4 within 2 weeks, 6 between 2 weeks and 3 months, and 3 beyond 3 months after simultaneous kidney-pancreas transplantation. Three rejection episodes were treated with steroids alone and 10 were treated with antilymphocyte therapy (5 OKT3 and 5 ATGAM). A total of seven patients (23%) received antilymphocyte therapy. Three patients (10%) had more than one rejection episode. Two pancreas grafts (7%) and one kidney graft (3%) were lost from rejection. Four patients (13%) developed cytomegalovirus infection, but none had tissue-invasive cytomegalovirus. At present, 22 surviving patients (81%) remain on triple immunosuppression with tacrolimus, mycophenolate mofetil, and prednisone with excellent dual graft function.Conclusion.Tacrolimus, mycophenolate mofetil, and prednisone immunosuppression without without antilymphocyte induction is safe and effective after simultaneous kidney-pancreas transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:2000

数据来源: OVID