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PubMed1999

The impact of (1:1) cyclosporine A conversion to its microemulsion formulation on the kidney function of patients with cardiac allografts.

Due to the large variations in the absorption and bioavailability of conventional cyclosporine A (CyA), 1:1 (mg:mg) conversion to its microemulsion formulation (Neoral) has been advocated in transplant recipients. However, the renal hazards and biochemical effects of such conversions and not known in cardiac transplant recipients. In this study, 68 cardiac transplant recipients who were receiving conventional CyA, for a period of 61.3 +/- 36.0 (mean +/- standard error (SE)) months, were switched to the microemulsion formulation (Neoral). The biochemical and renal function tests were evaluated at 1, 3, 6, 9 and 12 months pre- and post-conversion of CyA. The results obtained post-conversion were compared with those of the baseline (pre-conversion). Serum creatinine and uric acid levels significantly increased post-conversion to the microemulsion formulation. One patient required discontinuation of the microemulsion in an attempt to reverse severe renal failure. In spite of a significant decrease in the microemulsion dose at 6, 9 and 12 months, there was a significant increase in the whole blood CyA trough levels at 9 and 12 months of conversion. There was no significant change in blood pressure, serum total cholesterol or potassium post-conversion. Our results suggest that after 1:1 (mg:mg) conversion of CyA to its microemulsion formulation, there will be a significant rise in serum creatinine, uric acid and whole blood trough CyA levels necessitating significant dose reduction. This effect is probably due to the markedly improved absorption and bioavailability of the latter.

Absorption↗

PubMed1995

Chronic rejection in renal allografts: importance of cardiovascular risk factors.

Using a case-control method, we reviewed retrospectively renal transplants performed at University of Iowa Hospitals & Clinics between April, 1973 and May 29, 1991 to see if cardiovascular risk factors such as obesity, blood pressure, cholesterol, and tobacco use were important risk factors for development of chronic vascular rejection. Of 1161 transplants done during that time, 834 patients had renal allografts which functioned for greater than 365 days. From this subgroup we selected all surviving patients (n = 97) who had a functioning graft for greater than 365 days but whose graft subsequently failed. We also selected all patients (n = 26) who died with a functioning graft. Finally, we selected 52 control patients who were still living with functioning grafts, approximately matched to the study patients for date of transplant. We found no significant difference among the three groups in weight and weight changes, mean blood pressures, mean serum cholesterol values, or tobacco use. Our findings agree with previously published studies indicating a lack of correlation of cardiovascular risk factors with the development of chronic rejection of renal allografts in humans.

Adult↗

PubMed1989

The effects of pancreas transplantation on the glomerular structure of renal allografts in patients with insulin-dependent diabetes.

The microvascular complications of diabetes mellitus may be caused, in part, by poor glycemic control. Diabetic patients who have received renal allografts may have new glomerular lesions that are manifested structurally by increases in mesangial and glomerular volume. Successful pancreas transplantation produces long-term normoglycemia and provides a unique opportunity to evaluate the impact of the normalization of the blood glucose level on the development of the renal lesions typical of diabetes mellitus in transplanted kidneys. We obtained biopsy specimens from the functioning renal allografts of 12 patients with insulin-dependent (Type I) diabetes before successful pancreas transplantation (performed one to seven years after renal transplantation) and repeated the biopsy at least 1.9 years later. In renal biopsy specimens obtained before pancreas transplantation, the mesangial volume was normal or modestly increased and the glomerular basement membrane was moderately thickened. At follow-up, no progression could be detected in any structural measure in the glomerulus. Furthermore, the recipients of pancreas transplants had smaller glomerular volumes than 13 matched diabetic patients who were recipients of renal allografts but who did not undergo pancreas transplantation (mean +/- SD, 1.80 +/- 0.55 vs. 2.47 +/- 0.73 x 10(6) microns 3; P = 0.02) and showed markedly less mesangial expansion (mesangial-volume fraction, 0.19 +/- 0.07 vs. 0.31 +/- 0.10 microns 3 per cubic micrometer; P = 0.004). We conclude that successful pancreas transplantation is associated with significantly less severe diabetic glomerulopathy in kidneys previously transplanted into diabetic patients. These data support the hypothesis that normoglycemia can prevent the progression of diabetic glomerulopathy in humans.

Adult↗

PubMed1978

Trimethoprim/sulfamethoxazole and renal function in transplant patients.

Twenty-two patients with functioning renal allografts took part in a double-blind crossover trial during which placebo, sulfamethoxazole, and trimethoprim/sulfamethoxazole were given for periods of 14 days. The patients were divided into 2 groups. The first group consisting of 12 patients had serum creatinine levels less than 0.18 mmol/L and the second group of 10 patients had serum creatinine levels between 0.18 mmol/L and 0.35 mmol/L. Renal function at the end of each period was assessed by clearance of inulin (CIn), p-aminohippurate (CPAH) and endogenous creatinine (CCr). The second group also had a pitressin concentration test as a measure of distal tubule function. There was no change in inulin or creatinine clearance or in maximum concentration after pitressin in any of the patients in any of the phases. In the first group there was an increase in PAH clearance during the sulfonamide and trimethroprim/sulfamethoxazole phases. This change was not seen in the second group of patients with significantly impaired renal function.

Adult↗

PubMed2006

Cardiac surgery in renal transplant recipients: experience from Washington Hospital Center.

BACKGROUND: The number of renal transplant survivors requiring surgical treatment for cardiovascular diseases is increasing. A retrospective study was conducted to determine the outcomes of renal transplant recipients undergoing cardiac surgery. METHODS: Fifty-seven renal transplant recipients whose cardiac surgery was performed between 1987 and 2004, and whose allograft was functioning at the time of cardiac surgery, were identified. We analyzed postoperative mortality and morbidity as well as late mortality. RESULTS: Among 57 patients, 70.2% had hypertension, 54.4% diabetes, and 28.1% poor left ventricular function (ejection fraction < 0.35). Preoperative renal insufficiency (serum creatinine level > or = 3 mg/dL) was noted in 12.3% of the patients. Coronary artery disease was the dominant indication for the surgery. The median interval from renal transplant to cardiac surgery was 60 months. In-hospital mortality was 5.3%. All deaths were cardiac-related. Infectious complications occurred in 17.5% of the patients. Acute allograft failure requiring hemodialysis occurred in 28.6% of the patients with preoperative renal insufficiency, more frequent than those without preoperative renal insufficiency. Multivariable analysis identified preoperative renal insufficiency, mitral valve disease, and left ventricular dysfunction as independent predictors of in-hospital major adverse events (including death, infection, and renal failure). The 3-year survival was 71% after a median follow-up of 34 months. CONCLUSIONS: Infection control and renal protection should be stressed to ensure the safety of cardiac surgery in this patient group, while preoperative renal insufficiency, mitral valve disease, and left ventricular dysfunction are associated with early adverse outcomes. In the renal transplant recipients undergoing an isolated CABG, avoidance of cardiopulmonary bypass and use of arterial grafts might lead to better outcomes.

Cardiac Surgical Procedures↗

PubMed1990

Monitoring of renal allografts by Doppler ultrasound: precision and reference values.

The Doppler ultrasound method was used to obtain blood flow velocity curves from one of the large segmental arteries near the pelvis of transplanted renal allografts. The precision of the method for estimation of the pulsatility index (PI), the ratio between the peak systolic and the least diastolic velocity (A/B ratio) and the ratio of the are under the velocity curve of the first half and the second half of the cardiac cycle (AUC 1/2 ratio) was tested in vivo by examination of six renal allograft patients eight times. Two investigators examined each patient twice in random order upon two successive days. To investigate variation with time the same 10 patients were examined four times with 6-8 week intervals. To establish normal ranges for the PI, the A/B ratio and the AUC 1/2 ratio, a cross-sectional study of 54 patients with stable and well-functioning renal allografts was performed. No systematic variation was found between observers, days or repeated observations. The mean coefficient of variation was 8.3% for the pulsatility index, 5.8% for the A/B ratio and 14.9% for the AUC 1/2 ratio. The longitudinal study showed no systematic variation of the indices with time. For the 54 patients in the cross-sectional study the mean pulsatility index was 0.78, the mean A/B ratio 2.62 and the mean AUC ratio 1.82.

Blood Flow Velocity↗

PubMed2004

Kidney transplant patients with long-term graft survival have altered expression of molecules associated with T-cell activation.

BACKGROUND: Patients with long-term functioning organ allografts may have developed different mechanisms that explain the lack of graft rejection. However, it is not known how these mechanisms interplay or whether one of them predominates in such situations. METHODS: The authors analyzed the expression of T-cell surface molecules involved in alloantigen recognition, signal transduction, co-stimulation, and activation markers on circulating T cells from patients with normal kidney function 10 or more years after transplantation, short-term survival (1-4 years), and chronic rejection and from healthy adults. The percentage and the median fluorescent intensity of each marker were determined by flow cytometry. Proliferative response against specific and third-party donors and mitogenic stimulation were also determined. RESULTS: Peripheral blood lymphocytes from patients with long-term surviving kidneys had decreased expression of T-cell receptor (TCR)-alphabeta (P < 0.01), CD3epsilon (P < 0.05), and CD3 zeta-chains (P < 0.001); diminished percentages of CD4(+)CD28(+) (P < 0.001) cells; and increased expression of CTLA-4(+) (P < 0.01) on CD3(+) cells. CD4(+)CD25(+)CD69(+) cells were also increased in long-term surviving patients. Long-term surviving patients had decreased donor-specific proliferative responses. CONCLUSIONS: The decreased expression of TCR-alphabeta and epsilon- and zeta-chains on circulating T cells of long-term surviving patients suggests that these cells may have defects in alloantigen recognition or signal transduction that may result in decreased numbers of T cells expressing co-stimulatory molecules and activation markers as well as a decreased specific proliferative response. The decrease in the percentage of CD28(+) cells and the increase in CD4(+)CD25(+)CD69(+) cells suggest that regulatory mechanisms of the immune response are still active in such patients.

Adult↗

PubMed2004

[Lung harvesting in Hungary--results of the first two years].

OBJECTIVE: Hungarian patients undergo lung transplantation within bilateral cooperation in Vienna, Austria since 1995. Lung harvesting was introduced in 2002 in Hungary. Before 2002 Hungarian patients get 16 donor lungs from abroad, and 4 patients died while being on the waiting list for transplantation. METHODS: Between 15/1/2002 and 31/12/2003 Hungarotransplant offered 164 potential lung donors to the Korányi National Institute for Pulmonology. Donor selection was performed according to international guidelines. All operations were performed as part of multiorgan harvesting. Immediately before cross clamping the aorta 500 microg epoprostenol (Flolan) was administered intravenously for opening the pulmonary vascular bed. The lung was perfused through the main pulmonary trunk with a single flush of 6 litre 4 degrees C extra cellular type low potassium dextran solution (Perfadex). During the perfusion both thoraces were cooled topical by 0.9% saline ice slush. After back table separation the donor lungs was packed and transported with topical cooling. RESULTS: The offer was refused in 27 cases due to donor history, in 31 cases due to allograft pathology. In 57 cases the harvesting was not performed due to logistic reasons. Forty three donor lungs have been transplanted, 6 harvested lungs underwent only histopathology. From 43 harvested lungs 41 bilateral and 3 single lung transplant procedures were performed. The mean cold ischaemic time (=CIT) was 3 75 +/- 50 minutes (range: 230-560 min). Forty two donor lungs showed excellent primary graft function. One allograft underwent down-sizing lobectomy, where the histology of the specimen showed multiple microembolization, and signs of fibrosis, bronchiolitis and anthracosis. In this case the cold ischaemic time was 385 min. The patient needed an extracorporeal membrane oxygenation (ECMO) support immediately postoperatively, and died on the 4th postoperative day. After induction of lung harvesting in Hungary the average waiting time of Hungarian citizens dropped within one year from 14 +/- 8 weeks (range: 2-36 weeks) to 2.6 +/- 1.3 weeks (range: 1-4 weeks). In 2002 3 Hungarian patients died while being on the waiting list, their waiting time was 1, 1, and 7 days. In 2003 the waiting list mortality for Hungarian patients was 0%. CONCLUSIONS: After the introduction of lung harvesting both the waiting time and the waiting list mortality for Hungarian patients decreased. The potential yearly lung donor pool of Hungary is in the range of 5/1 million people.

Adult↗

PubMedDate not supplied

Transcatheter embolization of biopsy-related vascular injury in the transplant kidney: immediate and long-term outcome.

PURPOSE: To assess the effect of transcatheter embolization for treatment of biopsy-related vascular injury in renal allografts, specifically evaluating technical success, clinical benefit, and long-term effect on renal function. MATERIALS AND METHODS: A retrospective review was performed of all postbiopsy renal allograft vascular injuries referred for embolization during a 113-month period. The likelihood of a prolonged detrimental effect on allograft function was estimated from observed variation in serum creatinine levels before and after the procedure. RESULTS: Embolic therapy with use of metallic coils and superselective technique was performed in 21 renal transplant patients. Technical success was achieved in 95% of cases. There were no serious complications. Eradication of the clinical sign or symptom prompting referral was seen in 15 of 17 (88%) patients. Eleven of 19 (58%) patients analyzed demonstrated no evidence of a long-term detrimental effect on allograft function. A detrimental effect was possibly present in six of 19 (32%) patients, and probable in only two of 19 (10%) patients. CONCLUSIONS: Transcatheter embolization can be an appropriate and effective therapeutic choice for biopsy-related renal allograft vascular injury.

Adolescent↗

PubMed1989

The mechanism of the induction of immunologic unresponsiveness to rat cardiac allografts by recipient pretreatment with donor lymphocyte subsets.

In continuation of our studies using UV-B-irradiated DST and donor leukocyte (DL) recipient pretreatment to induce specific unresponsiveness to organ allografts, we have examined the relative contributions of splenic lymphocyte populations and T lymphocyte subsets in the induction of immunologic unresponsiveness. Our data show that enriched populations of MHC class II-positive B lymphocytes and the W3/25+ T cell subset obtained from splenic leukocytes using immunoadsorbent columns in conjunction with mAbs led to indefinite graft survival (greater than 100 days) in the Lewis-to-ACI rat cardiac allograft model. In contrast, pretreatment with T lymphocytes or the Ox8+ T subset was relatively ineffective in prolonging cardiac allograft survival. In addition, third-party (W/F) W3/25+ T cell recipient pretreatment did not influence the survival of Lewis cardiac allografts in ACI recipients, thus confirming the specificity of pretreatment with the T cell subset in graft prolongation. Furthermore, we have examined the underlying mechanisms of donor-specific unresponsiveness induced by donor spleen cells, B lymphocytes, and W3/25+ T cells using adoptive transfer assays. Serial adoptive transfer studies demonstrated the presence of 0x8+ suppressor T cells in the spleens of unresponsive recipients bearing well-functioning cardiac allografts and of serum "suppressor factors" that have the capacity for specifically prolonging donor-type test graft survival in naive syngeneic rats. Our findings suggest that the induction of specific unresponsiveness in this model is dependent on a sequential collaboration between the appearance of donor-specific serum factor(s) (humoral phase) and donor-specific suppressor T cells (cellular phase). These results may be potentially useful in planning future strategies for the induction of unresponsiveness to clinical organ allografts by immunologic manipulation of the host with MHC class II-positive B cell and CD4+ T cell clones.

Animals↗

PubMed1988

Production in vitro of antibodies directed against alloantigen-specific recognition sites on T cells and on lymphocytotoxic HLA antibodies.

We have examined the mechanism of immunological unresponsiveness in a recipient (P.S.) with a long-term functioning renal allograft. P.S., whose HLA type is A1, A30; B14, B18; DR1, w8; DRw52; DQw1 and in whose serum we had earlier demonstrated the presence of antiidiotypic antibodies, received a kidney from a cadaver donor of HLA type A1, A10, B8 in March, 1970. Peripheral blood B lymphocytes from the patient were transformed with Epstein-Barr virus (EBV), and by the cluster-picking technique a B cell line was propagated with continuous production of antibodies. Antiidiotypic antibodies with two distinct biological functions were demonstrable; one specifically inhibiting the lymphocytotoxic activity of anti-HLA-B8, B5, and DR3 reference typing sera, and the other specifically inhibiting proliferative responses in MLC of the recipient's lymphocytes and of third party cells sharing B14, DR1, DQw1 with the patient against stimulator cells carrying B8, DR3 antigens. Immunodepletion experiments demonstrated that the inhibitory activity was associated with the IgM fraction. Absorption experiments suggested that different antibodies may be responsible for the inhibition of lymphocytotoxic activity of anti-HLA sera and of the proliferative responses in MLC. Antiidiotypic antibodies have been postulated to be important in maintaining allograft tolerance in vivo, thereby enhancing renal allograft survival. The availability of such antibodies in large quantities, produced in vitro, could provide antisera for the immunochemical characterization of specific idiotypic receptors on immunoglobulins and T lymphocytes.

Antibody Specificity↗

PubMed1985

T suppressor lymphocytes reverse ongoing acute allograft rejection.

(LEW X BN)F1 cardiac allografts are rejected within 8 days in untreated LEW recipients. At the critical time point of 5 days after transplantation, the obviously rejecting grafts are enlarged and maximally infiltrated by host cells as shown by 111In-labeled lymphocyte tracer studies. However, when such hearts were retransplanted back to naive (LEW X BN)F1 secondary hosts, they survive indefinitely, showing that even late rejection is reversible in the absence of sustained host immunological drive. Attempts were then made to abrogate this advanced immune responsiveness using Cyclosporine (CsA). CsA therapy (15 mg/kg/day for 7 days) starting from day 5 produced indefinite graft survival, similar as if initiated at the time of operation. Addition of exogenous IL-2, which drives the proliferation of Tc, could not reverse this effect. Serial changes in phenotype of lymphocyte subpopulations infiltrating both acutely rejecting and indefinitely functioning cardiac allografts in unmodified and CsA treated hosts, respectively, were then studied. Ratio of Th:Tc/s cells in acutely rejecting grafts was 1.6 by day 3; it inverted abruptly to 0.7 by day 5-6, suggesting predominance of Tc/s during the later stages of allograft rejection. Similarly, treatment with CsA produced a transient depression of Th, with recovery of original Th:Tc/s ratio during the next 2-3 weeks. Adoptive transfer experiments were then performed to investigate the functional significance of these findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Limb salvage surgery in end stage renal disease: is it worthwhile?

The role of limb salvage surgery in patients with end stage renal disease (ESRD) is controversial. In view of this debate, we reviewed our experience with 54 primary and 15 secondary revascularizations for limb salvage in patients with ESRD over the past decade. Thirty-seven patients required dialysis and 10 had functioning renal transplants. Severe limb threatening ischemia was the indication for all revascularizations. The 2-year cumulative secondary graft patency rate was 56.2% with an associated limb salvage rate of 71.4%. There was no significant difference in graft patency or limb salvage rates between patients requiring dialysis and those with functioning renal allografts (p = 0.5). The 30-day operative mortality for the 99 surgical procedures (69 arterial bypasses and 30 additional operations) was 13% and the 2-year patient survival was 45.6%. Six of the 15 amputations were performed despite a patent graft on limbs which had extensive infection and gangrene. We conclude that limb salvage surgery should only be undertaken with recognition of these risks in patients with ESRD or functioning renal transplants. Surgery should be performed before gangrene and infection become extensive. Patients with unrelenting infection or mid-forefoot gangrene should be considered for primary amputation.

Adult↗

PubMed2002

Successful treatment of posttransplant lymphoproliferative disorder in a renal transplant patient by autologous peripheral blood stem cell transplantation.

Posttransplant lymphoproliferative disorder (PTLD), a well recognized complication of organ transplantation, comprises a wide spectrum of heterogeneous lymphoid proliferations ranging from self-limiting mononucleosis through aggressive monoclonal non-Hodgkin's lymphoma (NHL). There has been marginal success in treating PTLD using a number of treatment modalities, including combination chemotherapy. There have been few reports of the use of high dose chemotherapy with stem cell rescue as a treatment for PTLD. We report a renal allograft recipient who developed PTLD of the diffuse large cleaved B cell, NHL type. Reduction of immunosuppression was initially effective, however the patient relapsed, and was treated successfully with CHOP chemotherapy. Two years later he again relapsed and was treated with high dose melphalan followed by autologous peripheral blood stem cell transplantation (PSCT). The patient has remained in complete remission for 4 years with no major organ toxicities and a functioning renal allograft on minimal immunosuppression. This case illustrates a potential role for high dose chemotherapy with stem cell transplantation for the treatment of PTLD.

Adult↗

PubMed1983

Partial splenic ablation in preparation for renal transplantation in children.

Patients with end-stage renal disease who develop hypersplenism, patients with mild neutropenia, and those patients whose WBC fails to increase in response to cortisol administration will develop significant neutropenia following transplantation with routine doses of azathioprine. This "intolerance" of azathioprine mandates a reduction in the dose of azathioprine often resulting in allograft rejection. Splenectomy will prevent azathioprine-induced neutropenia, but the hazards of splenectomy in these immunosuppressed patients have led to attempts to salvage at least part of the spleen. Partial splenic ablation by embolization has been utilized in adults prior to transplantation to prevent azathioprine-induced neutropenia while preserving the spleen's protective mechanisms against infection. Eight children in our series of transplant candidates required a reduction of splenic function to prevent azathioprine induced neutropenia. One child had a functioning renal allograft but had recurrent neutropenia limiting the azathioprine dose. Partial splenic embolization was attempted in four children and was initially successful in two. Both patients later developed recurrent neutropenia and needed partial splenectomy. The two patients in whom partial splenic embolization was unsuccessful and five further patients in whom embolization was not attempted also underwent partial splenectomy. Approximately 75% to 80% of the spleen was resected. Six children have since undergone renal transplantation and one child had a transplant with chronic rejection at the time of partial splenectomy. Routine doses of azathioprine have been used in these children with no episodes of neutropenia or sepsis observed. We recommend partial splenectomy in those children requiring renal transplantation who are at risk for development of azathioprine induced neutropenia.

Azathioprine↗

PubMed1996

Bile secretory function of the arterialized versus nonarterialized rat liver allograft.

Arterialized and nonarterialized rat models of orthotopic liver transplantation are widely used for studying various aspects of graft function. Although bile duct damage has been implicated in graft nonarterialization, any impact on graft secretory function is unknown. This study sought to investigate whether nonarterialized orthotopic liver transplantation (NOLT) is a valid model for studying bile formation after the animal has fully recovered from the perioperative period. Twenty-four-hour bile collections were performed on eight arterialized and eight nonarterialized rats 4 weeks after transplantation to avoid the confounding effects of preservation-reperfusion injury and perioperative stress. Eight unoperated rats were used as control. There was no difference in mortality or biliary complications between the two transplant groups. The nonarterialized rats exhibited a higher serum aminotransferase level, but serum bilirubin was normal. NOLT resulted in more portal lymphocytic infiltration and bile ductular proliferation. Despite these histologic changes, bile duct epithelial cells remained intact, and spontaneous graft rearterialization was evident in the NOLT group. Bile salt secretion, pool size, and synthesis in both transplant groups did not differ from unoperated rats. NOLT did not adversely affect either bile acid-dependent or bile acid-independent flow. Biliary cholesterol secretion was markedly reduced in both transplant groups, resulting in a more favorable cholesterol saturation index. In conclusion, hepatic allograft secretory function is well maintained at 4 weeks even in the absence of hepatic arterial reanastomosis. Compensatory mechanisms possibly prevent irreversible hepatobiliary damage in NOLT. The NOLT model is quite reasonable to study bile formation after transplantation.

Alanine Transaminase↗

PubMed2000

Fas ligand gene transfer prolongs rat renal allograft survival and down-regulates anti-apoptotic Bag-1 in parallel with enhanced Th2-type cytokine expression.

BACKGROUND: Fas ligand (FasL) induces apoptosis of cells bearing Fas receptor, and may play a role in the acquisition of immune privilege. We have previously shown that adenovirus (Ad)-mediated FasL gene transfer significantly prolongs survival in a strongly major histocompatibility complex-incompatible rat kidney allograft model. This study analyzes putative mechanisms of FasL-mediated effects, with particular emphasis on Th1 and Th2 immune activation and Bag-1 expression, a Bcl-2-binding anti-apoptotic protein. METHODS: Kidney transplants were performed in Wistar-Furth to Lewis rat combination. Donor kidneys were perfused in situ with Ad-FasL or Ad-beta-Gal, and then transplanted. Kidney allografts were harvested at days 2, 7, and 56 and were evaluated by hematoxylin and eosin and immunohistochemical staining. The expression of FasL, Bag-1, and Th1/Th2 cytokine genes was assessed by Northern blots, Western blots, and competitive template reverse-transcriptase polymerase chain reaction, respectively. RESULTS: Intragraft expression of FasL was enhanced, whereas that of anti-apoptotic Bag-1 gene was diminished throughout, in Ad-FasL-transduced well-functioning renal allografts, compared with Ad-beta-Gal-treated rejecting controls. In parallel, the expression of mRNA coding for IL-2 and IFN-gamma remained depressed, whereas that of IL-4 and IL-10 reciprocally and progressively increased in the Ad-FasL animal group. CONCLUSIONS: Prolonged survival in Ad-FasL-transduced rat renal allograft model correlates with down-regulation of Bag-1, a novel anti-apoptotic gene, and preferential Th2-type cytokine elaboration profile at the graft site. Because Th1-like cells are sensitive to FasL-mediated cytotoxic effects, T-cell apoptosis may preferentially spare Th2-like cells, with resultant prolonged graft survival.

Animals↗

PubMed1991

Small intestinal transplantation in nonhuman primates.

Small intestinal transplantation represents a potentially therapeutic procedure for individuals with short gut syndrome. The purpose of this study was to develop a model for small intestinal transplantation in primates that is: technically feasible without microsurgery; consistent in the prevention of allograft rejection; functional in terms of nutrient absorption; and compatible with harvest for multiple organ procurement. First, autotransplantations on four rhesus monkeys were performed in order to study a variety of harvesting techniques and vascular anastomoses. Then, a study was performed with 14 heterotopic allotransplants in 4 baboons and 10 rhesus primates. The successful donor model consisted of division of the pancreas, harvesting the small bowel with a superior mesenteric artery and portal vein pedicle. The allograft vascular pedicle was anastomosed to the recipient's common iliac vessels in end-to-side fashion. The graft was transplanted as an out-of-continuity loop, both ends being exteriorized as stomas providing access for absorption studies and biopsy. Three immunosuppressive regimens were tested: (1) cyclosporine A (CyA) 20 mg/kg/d, solumedrol (SML) 2 mg/kg/d, and graft irradiation (150 rad) (n = 4); (2) CyA 20 mg/kg/d and SML 2 mg/kg/d (n = 3); and (3) CyA 40 mg/kg/d, SML 2 mg/kg/d, and azathioprine 5 mg/kg/d (n = 3). There were 4 deaths due to technical error in the first 24 hours. Weekly graft biopsy, serum CyA levels, complete blood count, and automated 24-channel serum analysis were performed. Grafts surviving greater than 14 days underwent absorption study via luminal perfusion with sucrose, maltose, dextrose, Pregestimil, xylose, and cyclosporine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗