摘要:

In LEW rats treated daily with variable doses of FK506 for 14 days and weekly thereafter, successful intestinal transplantation from fully allogeneic BN donors never was complicated by fatal GVHD. In contrast, with LEW-to-BN transplantation, rejection was difficult to control and GVHD developed after the end of the daily treatment. However, FK506 in high daily doses continued after the initial 14-day course could prevent this GVHD or even reverse it after allowing its onset. Further experiments did not clarify why the BN rat was an “easy” donor and “difficult” recipient. In unaltered animals the lymphocyte population of normal LEW rats had a higher proportion of T cells, fewer B cells, and a lower CD4:CD8 ratio than normal BN rats. However, one-way MLR reactions of the BN and LEW combinations were generally similar in either direction and not affected differently by the addition of FK506 to the medium. The two-way lymphocyte traffic from graft to host lymphoid organs and vice versa also was similar with BN-to-LEW and LEW-to-BN models. The BN rat may be a useful tool to investigate inadequately explained mechanisms of GVHD.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Cyclosporine represents the foundation for current immunosuppressive therapy following solid organ transplantation. CsA use is associated with renal insufficiency and systemic hypertension. We hypothesized that CsA would enhance the vascular actions of endo-thelin (ET). Three groups of anesthesized dogs (n=15) were studied. Group 1 received CsA alone (1 mg/kg), group 2 received ET alone (1 ng/kg/min), and group 3 received combined CsA (1 mg/kg) and ET (1 ng/kg/min). The hemodynamic and renal effects were evaluated after 30 min. Combined treatment resulted in a profound reduction in mean arterial pressure (-62±14 mmHg (P<.05) and cardiac output (-2.2±0.4 1/min (P<.05). The reduction in mean arterial pressure and cardiac output were significantly greater than that observed with CsA or ET alone. Systemic vascular resistance was not significantly changed. Combined CsA and ET resulted in a significant reduction in renal blood flow (195±18to 101±11 ml/mmP<.05) but without evidence of active renal vasoconstriction. The decline in GFR (31.8±5.6 ml/min to being unmeasurable) was of greater magnitude than the change in renal blood flow, suggesting enhanced afferent anteriolar vasoconstriction or an alteration in the ultrafiltration coefficient. These studies demonstrate an important and synergistic cardiode-pressor effect when CsA and ET are combined.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

The present study compares the effect of organ preservation with Euro-Collins solution, cardioplegic histidine-tryptophan-ketoglutarate solution, and University of Wisconsin solution on immediate pancreatic function after cold storage at 4°C for 24 hr. Postischemic organ quality of a porcine pancreas preparation was tested by quantification of physiological and biomedical parameters in a one-line reperfusion system. During reperfusion with a constant arterial pressure the arteriovenous flow rate was significantly higher for HTK (5.7±0.91 ml/min, n=8;P<0.05 vs. EC) and UW (7.4 ± 0.81 ml/min, n=8;P<0.05 vs. EC) than for EC (3.0<0.26 ml/min, n=6). The lowest lactate content in the reperfusate was found after HTK protection (HTK, 64.0±7.2 μmol/50 ml, n=8; versus EC, 114.2 ± 1.7 μmol/50 ml, n=6,P<0.001; versus UW, 148.0 ± 28.6 μwnol/50 ml, n=8,P<0.05). Amylase in the venous effluent was significantly lower (P<0.05) for HTK or UW protection than for EC (HTK, 189×72.6 U/ml; UW, 188 ± 39.4 U/ml; EC, 416 ± 71.7 U/ml). Oxygen consumption during reperfusion was significantly higher for HTK (2.15 ± 0.22 μl/g/ min,P<0.001) and UW (1.80 ± 0.52 μl/g/min,P<0.05) than for EC (0.47 ± 0.13 μl/g/min). We conclude that immediate postischemic organ quality and pancreatic.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

To evaluate the efficacy of University of Wisconsin (UW) solution for lung preservation, we performed canine lung allotransplantation with lungs preserved in UW solution. Donor lungs from eight dogs were flushed with UW solution and lungs from four dogs with Euro-Collins solution, and these were preserved for 24 hr in cold storage at 4–6°C. All recipient dogs were given cyclosporin at a dose of 20 mg/kg/day until death. None of the four dogs that received a lung allograft flushed with Euro-Collins solution survived contralateral pulmonary artery and bronchial occlusion. All eight dogs that received a lung allograft flushed with UW solution were alive between 8 and 21 days postoperatively. Six of them survived until pulmonary function tests were performed. The engrafted lungs functioned well until death between days 10 and 21 posttransplantation. The Pa02was 428±26 prior to transplantation, 317±140 at 60 min after transplantation, and 382±76 mmHg at 10 to 21 days after transplantation. In the other two dogs, the grafted lungs functioned poorly, and macroscopically revealed diffuse organizing pneumonia. We conclude that UW solution is useful for up to 24 hr of cold preservation prior to lung allografting. However, we recommend that lungs preserved with UW solution be transplanted within 24 hr, because, despite adequate function, microscopic damage occurs in the grafted lung.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

To determine the tolerance of old livers to prolonged preservation, livers from aged rats (corresponding to humans in the sixth to seventh decades of life) were transplanted after specific periods of cold preservation. Male BN/BiRij rats received orthotopic, arterialized liver grafts from either young (5 month) or old (25 to 28 month) donor rats after liver storage for 12 (n=6), 24 (n=6) or 30 (n=10) hours in University of Wisconsin solution. Outcome was assessed by survival, liver enzymes after transplantation, and histology of the grafts.There were no significant differences in survival rates between recipients of old and young grafts. All rats survived after 12-hr and 24-hr preservation except one recipient of an old graft preserved for 24 hr. After 30-hr preservation recipients of old and young livers had identical survival rates (60%). There was a strong correlation between the highest postoperative AST and ALT and the duration of preservation in all groups (P<0.0001), but only in the 24-hr preservation experiments was the ALT significantly higher in recipients of old grafts than in recipients of young livers (JP=0.025). Age of the donor did not significantly affect the peak AST, but there was a correlation between donor age and the highest postoperative ALT (P=0.007). Although intracellular vacuolization was a prominent histological finding in more than half of the old livers at the end of preservation, it was not associated with an increase in mortality.It is concluded that under the ideal conditions provided in the experiments, old rat livers tolerate long preservation periods with satisfactory graft survival compared with young livers.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Studies were made on the effects in rat lungs of aerobic and anaerobic conditions on the intracellular levels of adenosine triphosphate and its related metabolites, the releases of intracellular enzymes, and the secretion of pulmonary surfactant. After warm ischemia for 120 min, the ATP content of lungs inflated with air was significantly higher (8.0±1.2 μmol/g dry weight) than those of deflated lungs and lungs inflated with nitrogen (0.8±0.7 μmol/g dry weight and 2.0±0.7 μmol/g dry weight, respectively; P<0.001). The amounts of intracellular enzymes, such as lactate dehydrogenase, cyto-solic and mitochondrial aspartate aminotransferase, and protein in the bronchoalveolar lavage fluid (BALF) of air-inflated lungs were significantly less than those in BALFs of deflated and nitrogen-inflated lungs (P<0.001). The BALF-contents of dipalmitoyl phosphatidylcholine (DPPC), the main component of alveolar surfactant of aerobic and anaerobic ischemic lung were, however, similar. During 120-min warm ischemia after lavage, air-inflated lungs secreted significantly more DPPC into the alveolar space than nitrogen-inflated lungs did (P<0.001). We conclude that cell membranes in the lungs are damaged under anaerobic conditions, but that inflation of ischemic lungs with air is effective for protecting them from cell injury and for maintaining the intracellular level of ATP and the ability of the cells to secrete pulmonary surfactant.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

University of Wisconsin cold storage solution differs from Euro-Collins by the presence of adenosine, allo-purinol, and hydroxyethyl starch, which maintains osmotic pressure. It is now experimentally and clinically well established that the use of UW solution is associated with better liver graft recovery parameters after prolonged cold ischemia time. However, it has been also suggested in animal experiments that HES might not be essential for optimal kidney preservation, at least when cold ischemia time remains within 48 hr. Herein, we present a randomized study comparing UW (n=44) and a modified UW (UW-mod) (n=44) solution lacking HES, adenosine, and allopurinol on kidney graft recovery parameters. Forty-one consecutive Euro-Collins flushed kidneys, transplanted immediately before this randomized trial, were used as historical controls. The results indicate that UW-mod was as efficient as UW in preserving the kidney in cold ischemia ranges that did not exceed 48 hr. Both solutions (UW and UW-mod) seemed more effective than Euro-Collins, based on the analysis of several parameters including the number of days until the creatinine was <300 μM.(P<0.05), the level of the serum creatinine at one month (P<0.02), and the Cock-roft index (P<0.04). Since UW-mod is three times less expensive than UW, we suggest that the simplified solution could be routinely used to preserve kidneys for transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Urocanic acid (UCA) was investigated for its activity as an immunosuppressive agent in murine heterotopic allotransplantation. Mice grafted with cornea, pancreas, and skin under the renal capsule were given either intravenous, subcutaneous, or topical cis-UCA in the peritransplant period. Grafts were performed across complete and minor MHC barriers. Peritransplant immunosuppression with cis-UCA prolonged survival of these grafts, but no route of administration was clearly superior to another. Survival of cornea was prolonged more than survival of skin or pancreas in all MHC disparate combinations. cis-UCA was also used to assess its effect on stimulator cells, derived from mice that had received UCA, in mixed lymphocyte responses. cis-UCA adversely affected the ability of stimulator cells to provoke T cell proliferation in an allogeneic MLR. These findings suggest that cis-UCA may be a potentially useful immunosuppressive agent.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

A randomized, prospective multicenter trial was conducted to compare the safety and efficacy of OKT3 as an induction therapy with that of conventional immunosuppressive therapy administered to cadaveric renal allograft recipients. Two hundred fifteen patients were treated either with OKT3 plus azathioprine and steroids for 14 days with the delayed addition of cyclosporine on day 11, or with conventional immunosuppression (steroids, azathioprine, and cyclosporine). OKT3 patients had significantly fewer rejection episodes (51% vs. 66%,P=0.032), a longer time to initial rejection (46 days vs. 8 days,P=0.001), and fewer rejection episodes per patient (0.82 vs. 1.14,P=0.014) than conventionally treated patients. Kaplan-Meier estimates of two-year graft and patient survival rates were 84% and 95%, respectively, for the OKT3-treated group, and 75% and 94%, respectively, for the conventionally treated group. Following a subsequent first rejection episode, OKT3 reversed 93% of the rejections in patients receiving OKT3 induction therapy and 94% in patients receiving conventional therapy.Adverse experiences reported during OKT3 induction therapy were similar to those seen when the drug was used for rejection. Following initial exposure, 40.3% of the patients tested were positive for anti-OKT3 antibody, only 6.7% of which were of high titer (1:1000). In the presence of low titer (1:100 or less) antibody, OKT3 was successful in reversing rejection in five of six retreated patients tested. In conclusion, treatment with OKT3 (in combination with azathioprine, steroids, and the delayed addition of cyclosporine) is an effective approach for renal allograft maintenance.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID

摘要:

Kidney transplantation is a successful treatment for end-stage renal disease. We studied demographic and psychosocial variables that relate to compliance behaviors following renal transplant.One hundred and five renal allograft recipients, with a minimum of 18 months follow-up, were studied. A biographical questionnaire, the Center for Epidemiologic Studies Depression Scale, the Multidimensional Health Locus of Control Scale, and the Social Support Appraisals Questionnaire were used as measuring instruments. Specifically for this study, we designed a Health Belief Model Questionnaire, a Patient and Provider Relationship Questionnaire, a Compliance Self-Report Questionnaire, and a Self-Efficacy Questionnaire. Compliance was determined by cyclosporine whole blood levels >30 ng/ml, maintenance of ideal body weight (<20% gain), and percentage of missed clinic visits (<20%). Data was analyzed using discriminant analysis, Pearson's correlation, and chi-square.Four groups were identified, i.e., overall compliant (n=25), noncompliant with diet (n=29), noncompliant with medication (n=27), and overall noncompliant (n=29). No patient missed >20% of clinic visits. Discriminant function analysis distinguished patients who were compliant from those who were not. Males were more likely to be noncompliant with medication, whereas females were more likely to be noncompliant with diet. Noncompliance was also associated with increased numbers of prescribed medications, depression, black race, locus of control attributed to powerful others, unemployment, as well as the perceived amount of social and family support. Patients with failed grafts (n=14) were more depressed (P<0.05), perceived less benefit from the treatment regimen (P<0.01), and had less confidence in their care providers (P<0.05) than those recipients of successful grafts (n=91).In conclusion, this study identifies a number of psychosocial and demographic variables that impact on patient compliance behaviors after renal transplant. Interventional strategies to obviate noncompliance will need to consider these heterogeneous variables in order to maximize long-term renal allograft survival.

ISSN:0041-1337    

出版商:OVID    

年代:1993

数据来源: OVID