Pancreas transplantation at the University of Wisconsin.

Based on the University of Wisconsin experience with 653 cadaver pancreas transplant performed since 1985, we noted that: 1. The overall 5- and 10-year patient survival rates were 87% and 80%, respectively. The 5- and 10-year pancreas graft survival rates were 70% and 60%, respectively, and the 5- and 10-year kidney graft survival rates were 80% and 60%, respectively.

Liver transplantation from controlled non-heart-beating donors.

Background: The use of organs from non-heart-beating donors (NHBDs) has been proposed as one way to increase the donor pool. However, few centers have transplanted livers from NHBDs. We report here the results of 19 liver transplants from controlled NHBDs.

Increased glomerular deposits of von Willebrand factor in chronic, but not acute, rejection of primate renal allografts.

Background: In our previously described primate renal allograft model, T cell ablation leads to long-term graft survival. The role of endothelial cell alteration in chronic rejection was examined in our model.

Methods: Renal transplants were performed in rhesus monkeys using a T cell- depleting immunotoxin, FN18-CRM9.

Knowledge about transplantation tolerance gained in primates.

Research in transplantation tolerance relies on application of successful strategies in a nonhuman-primate organ transplant model for preclinical testing. Three principal approaches are being evaluated: hematopoietic chimerism, lymphocyte depletion and costimulation blockade. Interactive work in these three areas has yielded much new information on mechanisms of tolerance and opened the door to pilot clinical trials.

Long-term results of liver transplantation in older patients 60 years of age and older.

Background: Advances in perioperative care and immunosuppression have enabled clinicians to broaden the indications for organ transplantation. Advanced age is no longer considered a contraindication to transplantation at most centers. Although short-term studies of elderly liver transplant recipients have demonstrated that the incidence of complications and overall patient survival are similar to those of younger adults, transplant center-specific, long-term data are not available.

Potentiation of CD3-induced expression of the linker for activation of T cells (LAT) by the calcineurin inhibitors cyclosporin A and FK506.

The activation of blood cells, including T cells, triggers intracellular signals that control the expression of critical molecules, including cytokines and cytokine receptors. We show that T-cell receptor (TCR) ligation increases the cellular level of the protein linker for activation of T cells (LAT), a molecule critical for T-cell development and function. T-cell activation increased LAT messenger RNA, as determined by reverse transcription-polymerase chain reaction and by Northern blotting.

Simultaneous pancreas-kidney transplantation and living related donor renal transplantation in patients with diabetes: is there a difference in survival?

Objective: To compare the outcome of simultaneous pancreas-kidney transplantation (SPK) and living related donor renal transplantation (LRD) in patients with diabetes.

Summary Background Data: It remains unanswered whether diabetic patients with end-stage renal failure are better served by LRD or SPK.

Methods: Using a longitudinal database, data from all diabetic patients receiving LRD or cadaveric renal transplants or SPKs from January 1986 through January 1996 were analyzed.

Regulation of T cell receptor- and CD28-induced tyrosine phosphorylation of the focal adhesion tyrosine kinases Pyk2 and Fak by protein kinase C. A role for protein tyrosine phosphatases.

The T cell receptor (TCR)-CD3 complex and the costimulatory molecule CD28 are critical for T cell function. Both receptors utilize protein tyrosine kinases (PTKs) for the phosphorylation of various signaling molecules, a process that is critical for the function of both receptors. The PTKs of the focal adhesion family, Pyk2 and Fak, have been implicated in the signaling of TCR and CD28.

T cell activation up-regulates the expression of the focal adhesion kinase Pyk2: opposing roles for the activation of protein kinase C and the increase in intracellular Ca2+.

T cell activation initiates signals that control gene expression of molecules important for T cell function. The focal adhesion kinase Pyk2 has been implicated in T cell signaling. To further analyze the involvement of Pyk2 in T cell processes, we examined the effect of T cell stimulation on the expression of Pyk2.

Current management of esophageal variceal bleeding.

Recent trends in the clinical management of bleeding esophageal varices include a shift away from endoscopic variceal sclerotherapy toward endoscopic variceal ligation. The excellent efficacy of the latter and its lower complication rate favor its increased use. Similarly, the minimally invasive nature of the TIPS procedure and its successful implementation by invasive radiologists have further reduced the need for surgical shunts in general, as well as when endoscopic intervention has failed.

Disseminated aspergillosis involving the brain: distribution and imaging characteristics.

Background And Purpose: Systemic invasive aspergillosis involves the brain through hematogenous dissemination. A retrospective review of 18 patients with aspergillosis involving the brain was performed in order to present imaging findings and thereby broaden the understanding of the distribution and imaging characteristics of brain Aspergillus infection and to facilitate its early diagnosis.

Methods: The neuroimaging studies of 17 biopsy- or autopsy-proved cases and one clinically diagnosed case were examined retrospectively by two neuroradiologists.

Surgical portosystemic shunts for treatment of portal hypertensive bleeding: outcome and effect on liver function.

Background: Since the advent of liver transplantation and transjugular intrahepatic portosystemic shunts (TIPS), the role of surgical portosystemic shunts in the treatment of portal hypertension has changed. However, we have continued to use portosystemic shunts in patients with noncirrhotic portal hypertension and in patients with Child's A cirrhosis.

Methods: We performed 48 surgical portosystemic shunt procedures between 1988 and 1998.

Peripheral vascular disease and renal transplant artery stenosis: a reappraisal of transplant renovascular disease.

Background: Renal transplant artery stenosis (RTAS) continues to be a problematic, but potentially correctable, cause of post-transplant hypertension and graft dysfunction. Older transplant recipients, prone to peripheral vascular disease (PVD), may have pseudoRTAS with PVD involving their iliac system.

Methods: We retrospectively analyzed 819 patients who underwent kidney transplantation between 1993 and 1997 to determine the contribution of pseudoRTAS to renal transplant renovascular disease.

The impact of hypoalbuminemia in kidney-pancreas transplant recipients.

Background: Hypoalbuminemia is associated with poorer outcomes in renal transplantation. Diabetes can compound hypoalbuminemia's detrimental effects. Kidney-pancreas transplantation alters the diabetic milieu; yet, some patients continue to be hypoalbuminemic.

CD28 ligation induces rapid tyrosine phosphorylation of the linker molecule LAT in the absence of Syk and ZAP-70 tyrosine phosphorylation.

CD28 is a T cell surface molecule that is important for T cell activation. CD28-triggered T cell stimulation involves protein tyrosine phosphorylation, a process that is critical for CD28 function. Recently, a linker molecule has been identified as LAT (Linker for Activation of T cells).

Treatment with humanized monoclonal antibody against CD154 prevents acute renal allograft rejection in nonhuman primates.

CD154 is the ligand for the receptor CD40. This ligand-receptor pair mediates endothelial and antigen-presenting cell activation, and facilitates the interaction of these cells with T cells and platelets. We demonstrate here that administration of a CD154-specific monoclonal antibody (hu5C8) allows for renal allotransplantation in outbred, MHC-mismatched rhesus monkeys without acute rejection.

Iliac artery pseudoaneurysm following renal transplantation presenting as lumbosacral plexopathy.

A renal transplant patient developed chronic and progressive back and lower extremity pain followed by foot weakness. The correct diagnosis of lumbosacral plexopathy was made after electromyography and nerve conduction studies and the etiology of radiculopathy due to nerve root compression was excluded. This prompted further investigations that led to the discovery of a large internal iliac artery pseudoaneurysm.

CD28 ligation induces tyrosine phosphorylation of Pyk2 but not Fak in Jurkat T cells.

Protein tyrosine kinases are critical for the function of CD28 in T cells. We examined whether the tyrosine kinases Pyk2 and Fak (members of the focal adhesion kinase family) are involved in CD28 signaling. We found that ligating CD28 in Jurkat T cells rapidly increases the tyrosine phosphorylation of Pyk2 but not of Fak.

A study comparing mycophenolate mofetil to azathioprine in simultaneous pancreas-kidney transplantation.

Background: Mycophenolate mofetil (MMF; Cell-Cept) is a potent and selective inhibitor of B and T lymphocyte proliferation that has proven effective in reducing the incidence of acute rejection in cadaveric kidney transplant recipients in several randomized, blinded clinical studies. Because the frequency and characteristics of rejection episodes may be different and more severe after combined pancreas-kidney transplantation, we hypothesized that MMF would have a significant impact on pancreas-kidney rejection and graft outcome. Therefore, we compared the efficacy of MMF versus azathioprine (AZA) in cyclosporine-treated simultaneous pancreas-kidney transplantations.

Posttransplant infection in enteric versus bladder-drained simultaneous pancreas-kidney transplant recipients.

Background: Although bladder drainage of the pancreas remains the most common site for drainage of exocrine secretions, enteric drainage is becoming more common in the United States. The most common cause of morbidity after pancreas transplantation is infection, particularly recurrent urinary tract infection.

Methods: We examined the incidence of infectious complications for enteric-drained (ED) versus bladder-drained (BD) simultaneous pancreas-kidney transplants (PTx) to determine the incidence of post-transplant infection.

Modulation of alloimmunity to major histocompatibility complex class I by cotransfer of cytokine genes in vivo.

Major histocompatibility complex (MHC) class I antigen is a potent stimulus for alloimmune responses and is the principal immunologic target mediating acute cellular rejection of allografts. Using a method of direct in vivo gene transfer of cDNA encoding donor type MHC class I, we showed in a rat model that recipient muscle could express the transferred MHC class I cDNA, resulting in alloimmunization of the recipient. This was most graphically demonstrated by accelerated rejection of cardiac allografts expressing the same MHC class I as encoded by the immunizing cDNA.