摘要:

Background.Simultaneous pancreas-kidney transplantation has become a widely accepted treatment option for selected uremic patients with insulin-dependent diabetes mellitus (IDDM). Patient survival rates at 1 year exceed 90%, and rates of pancreas graft survival, 70%. However, solitary pancreas transplantation for nonuremic patients with IDDM has been controversial because of the less favorable outcome and the need for long-term immunosuppression with its associated morbidity and mortality.Methods.We studied the outcome of 225 solitary pancreas transplants during three immunosuppressive eras: the precyclosporine (CsA) era (n=83), the CsA era (n=118), and the tacrolimus era (n=24). Only patients with labile IDDM(e.g., hypoglycemic unawareness, insulin reactions, ≥2 failed attempts at intensified insulin therapy for metabolic control) underwent solitary pancreas transplantation. Using univariate and multivariate analyses, we looked at patient and graft survival, the risk of surgical complications, and native kidney function during these three eras.Results.Pancreas graft survival improved significantly over time: 34% at 1 year after transplantation in the pre-CsA era, 52% in the CsA era, and 80% in the tacrolimus era (P=0.002). Pancreas graft loss due to rejection decreased from 50% at 1 year in the pre-CsA era, to 34% in the CsA era, to 9% in the tacrolimus era (P=0.008). The rate of technical failures (i.e., the risk of surgical complications) decreased from 30% in the pre-CsA era, to 14% in the CsA era, to 0% in the tacrolimus era(P=0.001). Patient survival rates at 1 year have ranged between 88% and 95% in the three eras (P=NS). Matching for at least one antigen on each HLA locus and avoiding HLA-B mismatches significantly decreased the incidence of rejection. The incidence of native kidney failure due to drug-induced toxicity decreased significantly over time, in part because only recipients with pretransplant creatinine clearance ≥80 ml/min received transplants.Conclusions.Solitary pancreas transplantation has become a viable alternative for nonuremic patients with labile IDDM. The risks of surgical complications and drug-induced nephrotoxicity have significantly decreased over time. Using tacrolimus as the mainstay immunosuppressant, patient and graft survival rates now no longer trail those of simultaneous pancreas-kidney transplantation.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Viral (v) interleukin (IL)-10 is expressed by Epstein-Barr virus(EBV) and has pro- and anti-inflammatory actions similar to human IL-10. EBV is also a known factor in the development of posttransplant lymphoproliferative disorder (PTLPD) in allograft recipients. We observed a patient with widespread PTLPD 9 months after renal transplantation, who subsequently maintained renal function despite minimal immunosuppression, and we investigated a possible link between these factors.Methods.The patient's chart was reviewed for relevant history. EBV DNA in blood and tissues was assessed by polymerase chain reaction. Human and vIL-10 and γ-interferon mRNA were evaluated with reverse transcription-polymerase chain reaction using nested primers.Results.After the diagnosis of PTLPD, the patient was maintained on prednisone (8 mg/day) as the only immunosuppression with preserved renal function for 17 months until death as a result of pulmonary failure. She had continuously high blood levels of EBV DNA, although only mild persistent intrarenal atypical lymphocytic infiltrates. Human IL-10 mRNA was never present; in contrast, intragraft vIL-10 mRNA was identified and associated with resolution of an intervening episode of severe acute transplant rejection.Conclusions.We suggest that the preserved renal function resulted from the anti-inflammatory actions of vIL-10 inhibiting acute rejection in the renal allograft.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Since suitable recipients for hepatic allografts from donors with antibodies to hepatitis B virus (HBV) have not been determined, a review of our 7-year experience with donors positive for hepatitis B surface antibody(anti-HBs), hepatitis B core antibody (anti-HBc), or both was undertaken.Methods.Recipients of hepatic allografts from donors with antibodies to HBV were identified by a retrospective review of procurement records and screened for HBV infection.Results.From January 1, 1990, to January 1, 1997, 2578 liver transplants were performed and 140 (5.4%) recipients received an allograft from a donor with antibodies to HBV. Twenty-five of 48 recipients of a hepatic allograft from a donor positive only for anti-HBs were screened and none developed HBV infection. Twenty-five of 41 naive recipients of a hepatic allograft from an anti-HBc positive donor were screened and 18/25 (72%) developed HBV infection. Four of these 18 naive recipients with HBV infection received an allograft from a donor positive for both anti-HBc and anti-HBs. Seven of 13 anti-HBs-positive recipients of an allograft from an anti-HBc-positive donor were screened and none developed HBV infection. Fifteen of 16 recipients positive only for anti-HBc who received a hepatic allograft from an anti-HBc-positive donor were screened and 2/15 (13%) developed HBV infection.Conclusions.Hepatic allografts from donors positive only for anti-HBs do not transmit HBV infection. Hepatic allografts from anti-HBc-positive donors frequently transmit HBV infection to naive recipients regardless of the donor anti-HBs status, and antiviral prophylaxis may be indicated. Anti-HBs-positive recipients appear resistant to HBV infection after orthotopic liver transplantation with an allograft from an anti-HBc-positive donor. Recipients positive only for anti-HBc infrequently develop HBV infection when transplanted with an allograft from an anti-HBc-positive donor; however, HBV prophylaxis may be justified.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Bile acids are synthesized and secreted by the liver. During liver failure and hepatic dysfunction, a marked reduction of bile acid synthesis has been shown. The purpose of this study was to determine whether the biliary bile acid pattern was affected by preservation injury and rejection and whether it was a reliable marker for graft function in pediatric liver recipients after liver transplantation.Methods.We prospectively measured the biliary bile acid pattern in 126 serial bile samples obtained from 15 consecutive pediatric liver recipients by reversed phase high pressure liquid chromatography and correlated our results with clinical findings: preservation injury, no rejection, rejection, or infection.Results.There was a significant change of the bile acid pattern during the first 3 days after transplant. Total biliary bile acids, cholic acid (CA), and CA/chenodeoxycholic acid (CDCA) ratio increased in 12 of 15 patients with mild preservation injury. These changes of the bile acid pattern were markedly delayed in patients with severe preservation injury. During 16 rejection episodes, total biliary bile acid, CA, and CA/CDCA ratio decreased significantly, but returned to normal after successful treatment of rejection. Bacterial infection, observed in nine children, and cyclosporine toxicity, observed in three children, seemed to have no affect on the biliary bile acids.Conclusions.Liver cell damage as a result of preservation injury or rejection leads to a reduction of biliary CA, resulting in a decrease of total biliary bile acids and the CA/CDCA ratio in pediatric liver recipients. This might be caused by a diminished secretion of bile acids and by a decreased synthesis of bile acids.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Chronic anemia is common in adults after successful cardiac transplantation. However, the prevalence of anemia in children after cardiac transplantation is uncertain. The purpose of this study was to investigate the prevalence and causes of chronic anemia in well children after cardiac transplantation and in particular to define the role, if any, of iron deficiency, which is important and relatively common in normal children.Methods.Twenty children (ages 7 months to 16 years) who were well 4 months to 6 years after cardiac transplantation were studied. Fourteen children (70%) were anemic and enrolled in a prospective trial of iron supplementation.Results.In the majority of children, serum iron and erythropoietin levels were low, although serum ferritin and zinc protoporphyrin levels tended to be normal or high. Only one child demonstrated a definite response to iron supplementation, although the hemoglobin level remained low.Conclusions.Anemia is highly prevalent in this population, and, despite the presence of low serum iron and transferrin saturation, anemia is not usually due to iron deficiency. Although the diagnosis of iron deficiency in this group is difficult and must not be missed, inappropriate therapy should be avoided. In the majority of children, there appears to be an anemia of chronic disease which may be secondary to chronic inflammation or an effect of cyclosporine on erythropoietin production.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Prior to organ harvesting, an attempt was made to modulate the donor's immune responses against prospective xenogeneic recipients by infusion of “recipient-type” bone marrow.Methods.For this purpose, baboons conditioned with total lymphoid irradiation were given 6×108unmodified human bone marrow cells/kg body weight with no subsequent treatment.Results.Animals survived until they were euthanized at 18 months. Using primers specific for human chorionic gonadotrophin gene, the presence of human DNA was confirmed by polymerase chain reaction in the blood of one animal for up to 18 months after cell transplantation; in the other animal, xenogeneic chimerism became undetectable in the blood at 6 months after bone marrow infusion. However, tissue samples obtained from both animals at the time they were euthanized had evidence of donor (human) DNA. Additionally, the presence of donor DNA in individually harvested colonies of erythroid and myeloid lineages suggested that infused human bone marrow cells had engrafted across the xenogeneic barrier in both baboons.Conclusions.Bone marrow transplantation from human to baboon leads to establishment of chimerism and modulation of donor-specific immune reactivity, which suggests that this strategy could be reproducibly employed to create“surrogate” tolerogenesis in prospective donors for subsequent organ transplantation across xenogeneic barriers.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.The method for mouse vascularized heart transplantation have been described using suture and cuff techniques. Technical problems have limited its widespread use. Here, we describe our method of modified cervical heterotopic transplantation with the cuff technique.Methods.By using a smaller Teflon cuff (external diameter 0.6 mm, internal diameter 0.4 mm) and superfine-tip forceps, it became possible to directly pull the edge of the carotid artery and evert the proximal end of the artery over the cuff. Similarly, the external jugular vein could be easily everted over a 22-gauge cuff with this direct pulling method.Results.By these modifications, the operation time was reduced. It usually takes 20 min for the donor harvest, 15 min for preparation of the cervical vessels, and 15 min for anastomosis. All procedures from the donor harvest through skin closure of the recipient mice can be completed within 1 hr, and ischemic time is within 25-40 min.Conclusions.This method can be used to investigate cyclophosphamide-induced tolerance and mechanisms of reperfusion injury.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.The influence of infection-associated cellular activation on chronic rejection of kidney grafts was assessed in an established rat model by administration of lipopolysaccharide (LPS), an endotoxin and a potent stimulator of various cell populations including mononuclear cells and renal epithelial cells.Methods.Lewis recipients of F344 kidneys were treated with low-dose cyclosporine (1.5 mg/kg/day × 10 days). Animals with well-functioning grafts received a single dose of LPS (2 mg in 1 ml of NaCl, intraperitoneally) at 4 or 8 weeks after engraftment. Untreated control rats, which later experienced chronic rejection, were given 1 ml of NaCl.Results.Administration of LPS during the early quiescent phase of chronic rejection accelerated the chronic process, functionally (proteinuria), morphologically, immunohistologically, and by reverse-transcriptase polymerase chain reaction as compared with untreated controls. Infiltration of macrophages and their associated factors was especially affected.Conclusions.As the later events of chronic rejection seem to be mediated primarily by macrophages and their products, administration of LPS accelerated the tempo and activity of these cells in the development of chronic rejection. These findings may explain the clinical observation that infection may be an important risk factor for chronic allograft rejection.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.Intestinal transplants using cadaver donors have become an alternative to total parenteral nutrition (TPN) for the treatment of irreversible intestinal failure. Intestinal transplants using living-related donors have rarely been attempted, and the surgical technique has not been standardized.Methods.We performed a living-related intestinal transplant for a paraplegic, 16-year-old boy with life-threatening TPN complications, including lack of vascular access, recurrent line infections, and intermittent liver dysfunction.Results.A four antigen-matched donor (father) underwent resection of 200 cm of the ileum on a vascular pedicle comprising the ileocolic artery and vein. This resection left the donor with 300 cm of proximal small bowel, 20 cm of the most distal terminal ileum, the ileocecal valve, and all of the large intestine. The donor's ileocolic artery and vein were anastomosed to the recipient's infrarenal aorta and cava; bowel continuity was restored with an end-to-end anastomosis between the recipient's jejunum and the donor's ileum. Both donor and recipient had uneventful postoperative courses. Recipient maintenance immunosuppression has been with tacrolimus, mycophenolate mofetil, and prednisone. One year after transplant, urine methylmalonic acid indicates good vitamin B12absorption in both the donor and recipient. The recipient has been completely off TPN since discharge (posttransplant day 21), has gained 20 kg, and has had no evidence of rejection, infection, or graft-versus-host disease.Conclusions.Intestinal transplants from living-related donors can be lifesaving for selected patients with chronic intestinal failure and can be done with minimal risk to the donor.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Background.We report the first documented case of pulmonary toxicity to mycophenolate mofetil in this article.Methods.A 51-year-old woman experienced systemic reactions beginning 10 days after cadaveric renal transplantation.Results.Recurrent respiratory failure and documented progressive pulmonary fibrosis ensued. Cultures were negative and other agents were discontinued. It was not until the mycophenolate was stopped did the patient improve.Conclusions.Mycophenolate mofetil can cause acute respiratory failure simulating opportunistic infection or pulmonary edema. If not recognized, this may lead to the rapid development of severe pulmonary fibrosis, some of which may not be reversible.

ISSN:0041-1337    

出版商:OVID    

年代:1997

数据来源: OVID