ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

A new flushout solution for preservation of the pancreas was tested in the dog model of segmental pancreas autotransplantation. The solution osmolality was 320 mOsm/L, K+=120 mM, Na+=30 mM, and it contained the anion, lactobionate, and raffinose as impermeants to the cell. Preservation times studied were 48 and 72 hr. The pancreas was flushed out with about 250 ml of the new solution and stored at 0°C. Dogs were monitored postoperatively for blood glucose and intravenous glucose tolerance (IVGTT). Results were compared with control (no preservation) segmental pancreas autotransplants. Dogs receiving pancreases stored for 48 or 72 hr were normoglycemic on day one and remained normoglycemic for at least 28 days, or until time of sacrifice. Two of four dogs with pancreases stored for 48 hr were sacrificed on day 14 with normal IVGTT for histology. The remaining two dogs had normal pancreatic function for 28 days. Two of eight dogs receiving pancreas grafts after 72-hr cold storage died of causes unrelated to the pancreas graft, which was still functioning at the time of death. Six dogs remained normoglycemic and had a normal IVGTT at least for 28 days. This study demonstrates the feasibility of preserving the pancreas for three days for transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Hepatic transplantation into immorally presensitized patients has occasionally been performed without reported accelerated rejection. To study survival of orthotopic hepatic transplants in sensitized recipients a series of studies in rats were performed. Lewis rats sensitized by three successive skin grafts from fully allogeneic ACI strain donors then underwent orthotopic hepatic transplantation from ACI donors. Nine of ten recipients died within 4 hr with bleeding from the liver surface. By comparison, nine unsensitized recipients survived a mean of 10.7±0.5 days before succumbing with cellular rejection. Death of the sensitized recipients was not due to coagulopathy or technical failure. Histological studies of hyperacuteiy rejected livers demonstrated marked hemorrhage, edema, congestion, and necrosis within the hepatic parenchyma. There was a relative lack of cellular infiltrate compared with livers rejected by unsensitized recipients. Immunofluorescent staining showed IgG bound to perivascular tissues and sinusoids, and complement bound to perivascular tissue. Serum from presensitized, but not control, recipients showed a high titer of donor-specific, complement-dependent cytotoxic activity. It is concluded that hyperacute rejection of hepatic transplants can occur in sensitized rats and is mediated by a humoral mechanism. The immunohistopathology of this process is described.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

The immunosuppressive potency, hepatotoxicity, and nephrotoxicity of Norvaline2-cyclosporine (Nva2-CsA), an analog of cyclosporine (CsA), were tested in a primate cardiac transplant model. After orthotopic cardiac transplantation in cynomolgus monkeys, immunosuppression was maintained with 16 mg/kg/day of either CsA or Nva2-CsA given intramuscularly in two divided daily doses.Immunosuppression was augmented with i.m. methylprednisolone, 1.0 mg/kg/day, which was tapered weekly by. 1 mg/kg/day to a maintenance dose of. 1 mg/kg/day. A group of 6 untransplanted monkeys were treated for a year with this dose of either CsA or Nva2-CsA and steroids. Renal biopsies were performed at one year. Among the transplanted monkeys, mean survival was 77.3 ± 73 days for the CsA group and 16 ± 8 days for the Nva2-CsA group. All 11 animals in the Nva2-CsA group died of cardiac rejection, but only 7 of 10 treated with CsA died of rejection. There was mild hepatic and renal dysfunction in both treatment groups, but no significant difference between groups as judged by blood urea nitrogen, creatinine, total bilirubin, serum glutamic oxaloacetic transaminate, and alkaline phosphatase. Cyclosporine levels were significantly higher in the CsA group. There were important morphological changes in both groups on histological examination of the kidneys, with proximal tubular vacuolation and enlargement of the juxtaglomerular apparatus predominating. It is concluded that Nva2-CsA is a less effective immunosuppressant than CsA when given parenterally in equal doses.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Human fetal pancreas (HFP) represents an ideal tissue source for transplantation into diabetic patients. Transplantation of HFP lacks many of the technical problems associated with whole organ transplantation and HFP is readily available. In order to proceed with clinical HFP transplantation it must be demonstrated that HFP can reverse experimentally induced diabetes, that HFP can respond to glucose challenge in a manner similar to adult tissue, and that the immunogenicity of HFP can be reduced. We transplanted HFP (13–17 weeks gestational age) beneath the kidney capsule of streptozotocin-induced diabetic BALB/c nu/nu mice. Within 6 to 8 weeks following transplantation, 6 out of 7 (88%) animals became normoglycemic. Oral glucose tolerance tests were performed to determine in vivo graft function. Results in cured animals 'were identical to those of normal BALB/c nu/nu mice. In vitro insulin response to glucose challenge demonstrated that grafted HFP was capable of insulin secretion in the presence of high glucose while fresh fetal tissue was not. Human passenger leukocytes, identified immunohistologically at various times after transplantation with monoclonal antibodies to HLA-DR and Leu 10, were greatly reduced by 32 weeks posttransplant. Our data demonstrate that HFP will differentiate and mature in the diabetic nude mouse and that human passenger leukocyte content can be reduced. These findings suggest that HFP is functionally suitable for transplantation into diabetic patients.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Two groups (A and B) of isolated baboon hearts were preserved by continuous hypothermic perfusion storage for 48 hours using perfusates that, according to the manufacturers, differed only in the concentrations of the contaminating trace elements iron, lead, and arsenic. Storage with the perfusate containing the higher concentration of these elements (perfusate B) led to significantly less gain in heart mass, a greater reduction in coronary flow, coronary sinus effluent lactate, and myocardial arteriovenous oxygen difference and a greater increase in coronary sinus effluent lactate dehydrogenase, when compared with perfusate A. Group B hearts totally failed to support the circulation following orthotopic transplantation, whereas group A hearts showed excellent function. Group B hearts had undergone the typical changes of enhanced resting myocardial tension during the storage period (before warm blood reperfusion); we proposed that these changes were brought about by the production of superoxide anions and radicals by the higher relative concentration of iron, or a combination of contaminating trace elements, in perfusate B.To confirm that these perfusates did differ significantly in the concentration of these trace elements, in particular with regard to iron, the superoxide anion activity in both solutions was measured and was found to be significantly higher in perfusate B. The addition of superoxide dismutase to both solutions inhibited superoxide anion activity by more than 80%.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

A retrospective review of 547 renal transplants performed over a six-year period revealed allograft renovascular hypertension secondary to RTAS in 39 (7.1%) patients. Percutaneous transluminal angioplasty (PTA) resulted in immediate cure or improvement in 76% of the patients, increasing to 83% in patients with functioning kidneys at a mean follow-up period of 30 months (1–72 months). The renal artery stenosis (RTAS) was equally distributed between living-related and cadaver kidney recipients and did not appear to be more prevalent in end-to-end or end-to-side anastomoses. The blood pressures fell from pre-PTA levels of 167 ± 22 mmHg systolic to 141 ± 23.7 post-PTA and 102 ± 11 mmHg diastolic pre-PTA to 88 ± 12 mmHg post-PTA (P< 0.01). Of 25 cured or improved patients, 24 are on significantly less hypertensive medication. Two patients died of causes unrelated to the PTA and only one patient lost a kidney because of the procedure. Compared with operation, PTA is a safer and more effective procedure for the initial treatment of RTAS.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Malignancies developed in 141 organ transplant recipients treated with cyclosporine. The cancers showed important differences from those seen following conventional immunosuppressive therapy (CIT). They appeared an average of 20 months after cyclosporine and 60 months after CIT. Non-Hodgkin's lymphomas (NHLs) were the most common tumors, being 41% compared with 12% in CIT patients. They appeared an average of 11 months after transplantation compared with an average of 42 months after CIT. Unlike CIT patients they more often involved lymph nodes, more frequently involved the small intestine, rarely involved the brain, and were more likely to regress after reduction of immunosuppressive therapy. Skin cancers (15% of cancers) were much less common than in CIT patients (40%). Kaposi's sarcomas were more common (8% vs. 3%). In this small series there was a surprising frequency of endocrine-related cancers and renal cell carcinomas. Only 8 patients (6%) were treated with cyclosporine exclusively. The neoplasms probably are not specific to cyclosporine therapy but appear to be a complication of immunosuppression per se.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Two hundred twenty-eight patients from a total of 466 (49%) receiving renal allografts under cyclospo-rine/prednisone (CsA/Pred) immunosuppression experienced at least one episode of posttransplant hepato-toxicity. All patients were documented to have normal serum bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), lactic acid dehydrogenase (LDH), and alkaline phosphatase (AP), as well as negative results of biliary ultrasound and upper gastrointestinal contrast examinations prior to transplantation. Hepatotoxic episodes usually were self-limited (82%), and generally occurred during the very early posttransplant period (76%). Liver function abnormalities included hyperbilirubinemia (48% of patients), elevated SGOT (47%), SGPT (73%), LDH (84%), and AP (59%). The CsA serum trough radioimmunoassay (RIA) was relatively high among hepatotoxic patients with a mean value of 225± 17 ng/ml. Pharmacokinetic parameters, including bioavailability and drug clearance, were significantly altered among this group of patients. The management strategy of CsA dose reduction was effective; however, 11 patients (2.4%) developed biliary calculous disease posttransplant while under CsA/Pred immunosuppression. Seven patients had cholelithiasis, and two patients underwent choledochoduodenostomy because of primary choledocholithiasis. The results contrast with 279 renal transplant recipients from an overlapping nonrandomized group treated with azathioprine (Aza)/Pred in whom cholelithiasis was not identified. Pancreatic abnormalities were relatively common, but clinical pancreatic disease occurred in only six patients. There were two episodes of acute pancreatitis, three patients developed pancreatic abscess, and one patient developed a pancreatic pseudocyst. The apparent proclivity of CsA-treated patients to develop biliary calculous disease, and the occurrence of serious pancreatic complications in a small percentage of patients did not affect the majority of CsA-treated patients. They may, however, represent important problems associated with the use of this immunosuppressive agent.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID

摘要:

Early graft rejection crises in renal transplant patients pretreated with donor-specific transfusions (DST) have been attributed to an antibody-mediated reaction, or an in situ primed lymphocyte test (PLT) reaction in the grafted kidney resulting from priming of recipient T cells. To test these hypotheses, we analyzed the mixed lymphocyte culture (MLC) response to donor stimulator cells in 18 DST + azathioprine (AZA)-treated patients, including 7 with living-nonrelated donors (2 HLA-hap-lotype mismatch) and 11 with living-related donors (1 HLA-haplotype mismatch). Studies of the kinetics of anti-donor MLC responses of PBL obtained from patients before and after DST + AZA treatment revealed shifts in the magnitude and timing of antidonor MLC response. We found an increased peak MLC response to donor and/or third-party in 6/18 patients, 4 of whom had early rejection crises; the other 2 patients had blocking factors in their post-DST plasma that strongly (57− 71%) inhibited their MLC response. Plasma factors were implicated in the mechanism of early graft crisis, in that patients with an enhanced MLC response in the presence of post-DST plasma showed a significantly (P<.02) shorter time to first rejection episodes as compared with patients with plasma blocking factors. Finally, we confirmed the findings of others that a significant proportion (7/18) of DST + AZA-treated patients had a decreased MLC response. Although such patients experienced classic (2nd week or later) rejection episodes, none had a DST-type (<3 day) crisis. Our data supports the concept of T cell priming by DST, and suggests that patients who fail to develop concomitant suppressor cells or humoral blocking factors will develop a rapid onset cellular rejection crisis in the transplanted kidney.

ISSN:0041-1337    

出版商:OVID    

年代:1987

数据来源: OVID