PubMed Health⌕ Search

Biomedical subjects

S J Knechtle

Publications and source records attributed to S J Knechtle.

At least 91 records · Page 5Linked to original sources
PubMed1996

Foot problems in the diabetic transplant recipient.

Diabetic transplant recipients are at a high risk for foot pathology leading to amputation. This retrospective study from 1/85 to 2/95 examines the risk of foot complications in a population (n = 340) of diabetic renal and combined renal/pancreas transplant recipients. All groups suffered high lower extremity amputation and foot fracture rates. Patients with better circulation and protective sensation intact fared better. Smoking had a profoundly negative effect on the amputation rate as did an amputation prior to the transplant. Patients with pretransplant dialysis were at a higher risk for post-transplant amputation. Concomitant pancreas transplant did not in general significantly affect the risk of amputation or fracture. Females had almost twice the fracture rate of males.

Adult↗
PubMed1995

Pretransplant status and patient survival following liver transplantation.

The current liver allocation system has been criticized, since available organs go to those who are the most critically ill. These recipients have the poorest overall survival. Identification of pretransplant risk factors for mortality would allow better allocation of donor livers. This study was a retrospective analysis of pretransplant clinical and laboratory parameters and subsequent postoperative liver transplant mortality to identify high-risk subgroups. Of 347 consecutive consecutive primary liver transplant recipients, 59 (17%) met United Network for Organ Sharing (UNOS) criteria for status 4. Pretransplant factors included liver function, coagulation, albumin and ammonia levels, renal function, the presence of ascites, and etiology of liver disease. Overall 1-year patient survival was significantly worse for the status 4 recipients (89.0% vs. 67.7%; P = 0.01). In a univariate analysis of pretransplant risk factors for all recipients, elevated creatinine (P = 0.008) and ammonia (P = 0.009), and UNOS status 4 (P = 0.01) significantly affected postoperative survival. In multivariate analysis of pretransplant risk factors for all recipients, elevated creatinine (P = 0.003) was the only factor to significantly affect postoperative survival. In UNOS status 4 patients, univariate analysis of pretransplant risk factors and their influence on patient survival demonstrated that prolonged coagulation partial thromboplastin time (P = 0.04) and a higher grade of encephalopathy (P = 0.02) significantly affected postoperative survival. Advanced encephalopathy (P = 0.009) and prolonged partial thromboplastin time (P = 0.01) were the only significant risk factors by multivariate analysis in status 4 patients. In status 4 and non-status 4 patients, we identified risk factors that adversely affected patient survival, but their predictive power was insufficient to deny transplantation. Despite the higher mortality in status 4 recipients, their long-term survival is only slightly worse than that of non-status 4 patients. Until better predictors of survival are ascertained, our data do not support limiting the use of donor livers in UNOS status 4 recipients.

Adult↗
PubMed1995

Successful extrarenal transplantation from non-heart-beating donors.

The current organ shortage has made utilization of organs from less-than-ideal donors more common. Although several transplant centers use kidneys from non-heart-beating donors (NHBDs), there has been reluctance to extend the use of these donors to extrarenal organs. Of the 130 donors referred to our organ procurement organization between January 1993 and May 1994, 16 (12.3%) were NHBDs. Organ retrieval from 10 of these resulted in extrarenal donation, 5 resulted in renal donation only, and 1 resulted in no retrieval as a result of prolonged warm ischemia (> 2 hr). A total of 39 organs were transplanted from these NHBDs. A rapid en bloc retrieval technique was used for extrarenal NHBDs. The mean warm ischemic time was 15.4 min; preservation times were similar for both NHBDs and heart-beating donors. After liver transplantation (n = 5), one episode of primary nonfunction that was technical in origin required retransplantation. Following simultaneous pancreas-kidney transplantation (n = 6), all patients were insulin independent and free of graft pancreatitis; one patient required hemodialysis (16.7%). After isolated renal transplantation (n = 21), 3 patients (14.3%) required hemodialysis. Three of 4 liver recipients are alive after a mean follow-up period of 12.7 months; all simultaneous pancreas-kidney and renal transplant recipients are alive after a mean follow-up period of 8.4 and 8.3 months, respectively. Three liver allografts, 5 pancreas and kidney allografts, and 19 renal allografts are functioning. The lung allograft was lost to rejection 81 days after transplantation; however, the recipient is alive 3 months after retransplantation. Our results demonstrate that in controlled situations, extrarenal organs can be utilized from NHBDs and can be expected to function similarly to organs retrieved from heart-beating donors. We increased the number of transplanted organs by 8.6% using NHBDs for both renal and extrarenal donation. Continued application of these techniques will likely further increase the number of organs retrieved for transplantation.

Heart↗
PubMed1995

Relationships between sclerosing cholangitis, inflammatory bowel disease, and cancer in patients undergoing liver transplantation.

BACKGROUND: Liver transplantation has emerged as the definitive treatment for primary sclerosing cholangitis (PSC). Its relationships to inflammatory bowel disease and cholangiocarcinoma were evaluated in this series. METHODS: Fifty-three liver transplantations were performed in 41 patients with PSC at the University of Wisconsin from 1986 through 1994. Fourteen of the patients underwent colectomies for inflammatory bowel disease, eight before transplantation and six after transplantation. Five patients had cholangiocarcinoma on the hepatectomy specimen, and another two had been diagnosed before transplantation. RESULTS: Patient survival for PSC without cholangiocarcinoma was 85% and 62% at 2 and 9 years, respectively. No patient with PSC and cholangiocarcinoma has survived 2 years, although two patients were free of disease 11 and 20 months after transplantation. Despite maintenance immunosuppression seven patients with liver transplants had reactivation of inflammatory bowel disease and colon carcinoma developed in three after liver transplantation. CONCLUSIONS: Liver transplantation should be performed early in the course of PSC to avoid the lethal complications of cholangiocarcinoma. Careful colonoscopic follow-up is necessary in patients undergoing transplantation for PSC because immunosuppressive therapy does not necessarily cause inflammatory bowel disease to be quiescent, nor does it reduce the risk of colon carcinoma developing.

Adenocarcinoma↗
PubMed1995

Living related and unrelated donors for kidney transplantation. A 28-year experience.

OBJECTIVE: The objective of this study was to analyze a single center's 28-year experience with 1000 living donor transplants. SUMMARY BACKGROUND DATA: The number of potential renal transplant recipients far exceeds the number of cadaveric donors. For this reason, living related donors (LRDs) and, more recently, living unrelated donors (LURDs) have been used to decrease the cadaveric donor shortage. METHODS: From November 15, 1966, until August 5, 1994, 1000 living donor transplants were performed; 906 were living related and 94 were living unrelated transplants. Results were divided into precyclosporine (1966-1986, era I) and cyclosporine (1986-1994, era II) eras. Patient and graft survivals were compared between diabetic and nondiabetic recipients, between LRDs and LURDs, and according to human leukocyte antigen (HLA) matching. Donor mortality, morbidity, and postoperative renal function were also analyzed. RESULTS: The 5-, 10-, and 20-year graft survivals were 78.8%, 64.8%, and 43.4%, respectively. Patient and graft survival improved in era II (patient = 87.0% vs. 81.7%, p = 0.03; graft = 72.9% vs. 67.7%, p = 0.04). Nondiabetic patient and graft survivals were better than diabetic patient survivals in both eras. However, diabetic patient survival improved in era II (78.0% vs. 66.9%, p = 0.04). In era II, HLA-identical recipients had better graft survival than haploidentical or mismatched recipients (91.7% vs. 67.3% and 66.1%, p = 0.01). No difference between haploidentical LRDs and LURDs was seen. One donor death occurred in 1970, and 17% of donors developed postoperative complications. CONCLUSION: Living related and unrelated renal donation continues to be an important source of kidneys for patients with end-stage renal disease.

Adult↗
PubMed1995

Simultaneous pancreas-kidney transplantation at the University of Wisconsin.

After a decade of rapid development, SPK transplantation has become routine at our center. There are several developments responsible for the current high level of success: UW preservation solution, improved surgical technique, advances in immunosuppression, and expeditious diagnosis and treatment of complications. The critical modifications in surgical technique have included the avoidance of systemic heparinization, complete mobilization of the iliac vein for a tension-free anastomosis between an unmodified donor portal vein and the recipient iliac vein, oversewing of the revised duodenal staple lines and meticulous hemostasis. The most important recent improvement in immunosuppression is the use of mycophenolate mofetil, which has dramatically reduced rejection. Finally, PDC leaks, the principal and potentially most devastating complication of SPK transplantation, are rapidly diagnosed and treated expeditiously.

Academic Medical Centers↗
PubMed1994

Induction of specific tolerance by intrathymic injection of recipient muscle cells transfected with donor class I major histocompatibility complex.

Induction of tolerance to allogeneic MHC antigens has been a goal in the field of transplantation because it would reduce or eliminate the need for generalized immunosuppression. Although encouraging results have been obtained in experimental models by exposing recipient thymus to donor cells before transplantation, donor cells are not typically available at that time, and the donor antigens responsible for the effect are poorly defined. In the present study, thymic tolerance was demonstrated without using donor cells. Recipient thymus was injected before transplantation with autologous myoblasts and myotubes that were genetically modified to express allogeneic donor-type MHC class I antigen. Donor-specific unresponsiveness was induced to a completely MHC-disparate liver transplant and to a subsequent donor-type cardiac allograft, but not a third-party allograft. In vitro, recipient CTL demonstrated a 10-fold reduction in killing of donor cells, but not of third-party cells. Our results demonstrate: (1) that recipient muscle cells can be genetically engineered to induce donor-specific unresponsiveness when given intrathymically, and (2) transfected recipient cells expressing only donor MHC class I antigen can induce tolerance to a fully allogeneic donor.

Animals↗
PubMed1994

Immunity to MHC class I antigen after direct DNA transfer into skeletal muscle.

Plasmid cDNA encoding the alpha-chain of either membrane-bound (pcRT.45) or secreted (pcRQ.B3) RT1Aa MHC class I Ag were transferred to Lewis (RT1(1)) rat skeletal muscle by direct injection. Rats were challenged 7 days later with an ACI (RT1a) heterotropic heart transplant, and cardiac allograft survival, RT1Aa-specific antibody levels, and frequency of ACI-specific CTL were monitored. Graft rejection was accelerated by > or = 2 days in an Ag-specific and dose-dependent manner in pcRT.45-injected rats. The pcRQ.B3-injected rats also rejected grafts more rapidly; however, graft rejection was accelerated by only 1 day, and graft infiltrates were less pronounced than in pcRT.45-injected rats. Injection of pcRT.45 resulted in an increase in ACI-specific CTL precursor frequency 3 days post-transplant, whereas there was no significant change in rats pretreated with pcRQ.B3 injection. Compared with rats injected with a control plasmid encoding firefly luciferase, transfer of pcRT.45 resulted in an increase in RT1Aa-specific IgG and IgM antibody 3 days after heart transplantation. Transfer of pcRQ.B3 resulted in a similar mean increase in RT1Aa-specific IgG and IgM antibody after transplantation, but the variability from rat to rat was greater, with some animals exhibiting strong priming, and others showing little or no priming by gene injection. Our results suggest that skeletal muscle can express either membrane-bound or secreted MHC class I Ag after gene transfer, but that the membrane-bound form is more immunogenic than the secreted form in the high responder Lewis rat. Direct DNA transfer to skeletal muscle provides a rapid and specific approach to studying immunity to allogeneic MHC Ag.

Animals↗
PubMed1994

Use of donor serum to prevent passive transfer of hyperacute rejection.

Organ transplantation in presensitized recipients continues to be contraindicated for heart and kidney recipients due to the risk of hyperacute rejection, which has no known treatment at this time. We tested whether donor serum, which contains soluble MHC class I antigen, is able to neutralize the effect of anti-donor antibody in the recipient and prevent hyperacute or accelerated rejection. A rat model of passive immunization was used to test the role of anti-donor antibody in hyperacute rejection. Seven of 10 recipients of hyperimmune serum (HyS), derived from Lewis rats (RT1l) following 3 ACI (RT1a) skin grafts, developed hyperacute or accelerated rejection. Intravenous injection of ACI serum prior to the HyS administration prevented hyperacute rejection in all recipients tested. When third-party (Wistar-Furth, RT1u) serum was given to Lewis rats injected with HyS, hyperacute rejection was not abrogated. When examining the mechanism of this effect, a simple antibody blocking phenomenon was found to be unlikely since flow cytometry analysis showed that ACI serum needed to be present at > or = 256-fold excess compared to HyS to block anti-ACI antibody binding to RT1.Aa+cells by 50%. We tested whether the RT1.Aa class I antigen in ACI serum had other biologic properties that resulted in the prolonged graft survival. However, removal of RT1.Aa antigen from ACI serum prior to use in the passive transfer model did not abrogate the graft prolongation observed previously. These data suggest that components of donor serum other than MHC class I antigen may be useful for preventing the antibody-mediated component of hyperacute rejection.

Animals↗
PubMed1994

100 consecutive liver transplants in infants and children: an 8-year experience.

Orthotopic liver transplantation has become the treatment of choice for most children and infants with end-stage liver disease. The purpose of this retrospective study was to examine the results of 100 consecutive liver transplants performed in infants and children at a single institution. During an 8-year study period (July 1984 to December 1992), 100 pediatric liver transplants were performed in 76 patients. Thirty-four patients (44.7%) were infants (mean age, 7.0 months; mean weight, 6.1 kg), and 42 (55.3%) were children (mean age, 8.2 years; mean weight, 30.6 kg). There were 36 reduced-size liver transplants (RLT) and 64 whole-size transplants (WLT). Eight infants (23.5%) and 10 children (20.7%) required retransplantation. After transplantation, 71% of the patients had one or more rejection episodes, 66% had one or more infections, 17.1% had biliary complications, and 39.4% required one or more reoperations. There were 17 deaths. The actuarial 8-year survival rate for the patients with biliary atresia was 82.3%; for all infants in this series, it was 77.6%. No difference in patient survival was noted when RLT was compared with WLT. The overall 8-year actuarial patient survival rate for infants and children was 77.3%.

Adolescent↗
PubMed1994

Monitoring of kidney and simultaneous pancreas-kidney transplantation rejection by release of donor-specific, soluble HLA class I.

Using an HLA-A2-specific ELISA we monitored daily pretransplantation and posttransplantation sera from five kidney and eight simultaneous pancreas-kidney HLA-A2-negative recipients of HLA-A2-positive transplants during hospitalization. We found that, unlike liver transplants, neither kidney nor simultaneous pancreas-kidney transplants continuously secreted donor HLA proteins. However, three of four rejection episodes in kidney recipients and seven of seven rejection episodes in simultaneous pancreas-kidney recipients were accompanied by elevated serum levels of donor sHLA-A2 (> 5 ng/ml). In only one kidney patient was there a release of donor antigen without evidence of rejection, but in the simultaneous pancreas-kidney group most patients had at least one time point of detectable sHLA-A2 without strong evidence of kidney rejection. While total sHLA levels were also elevated during rejection, the rise in donor-specific sHLA was more dramatic when compared to pretransplantation background levels. We hypothesized that the release of donor sHLA class I proteins by transplanted organs might be a systemic indication of rejection in both pancreas and kidney allografts. The detection of donor sHLA in recipient sera could be an important noninvasive monitor of rejection, especially in the pancreas, which is currently difficult to monitor as a single-organ transplant.

Adult↗
PubMed1994

Clinical experience with human anodal trypsinogen (HAT) for detection of pancreatic allograft rejection.

To date one of the major dilemmas in clinical pancreas transplantation is the lack of a reliable indicator for pancreas rejection. In a consecutive series of 52 patients undergoing simultaneous pancreas and kidney (SPK) transplantation with bladder drainage technique between October 1991 and December 1992 a new test using serial levels of serum human anodal trypsinogen (HAT) was evaluated for its efficacy to detect pancreas rejection. Postoperative baseline levels of HAT were compared to peak HAT values at time of rejection. HAT profiles at time of rejection were calculated and compared to profiles of urinary amylase, serum amylase, fasting blood sugar and serum creatinine. In this series one year patient survival was 97%, graft survival of the pancreas 86% and of the kidney 90%. In 71% of the patients at least one rejection episode occurred. At time of kidney-biopsy proven rejection with a concurrent serum creatinine rise a significant HAT level rise to more than 1000 ng/ml was observed from baseline levels of 200 ng/ml (P < 0.001) indicating kidney and pancreas rejection (73%). Urinary amylase levels decreased in the majority of rejection episodes at the same time from baseline levels to less than 20,000 U/l. In 25% of the rejection episodes a significant serum creatinine rise was observed without a HAT rise or urinary amylase decrease indicating kidney-only rejection, while in 2% a urinary amylase decrease and simultaneous HAT also was observed with a negative kidney biopsy indicating pancreas-only rejection. We feel that increase in HAT levels significantly correlates with pancreas rejection. After SPK, determination of HAT is an additional helpful non-invasive test. In pancreas transplantation alone HAT can be a useful indicator to detect rejection and facilitate timing of a pancreas biopsy and initiation of antirejection treatment.

Adult↗
PubMed1994

Living-unrelated renal donor transplantation: the UNOS experience, 1987-1991. United Network for Organ Sharing.

1. LURD transplants were associated with excellent one-year graft survival of 92%. This survival was superior to that for cadaver transplants performed during the same period. 2. High-risk groups for LURDs are children (age < 18 years) and repeat transplant recipients. Both groups were associated with significantly decreased graft survival. 3. The effects of HLA matching and donor-specific transfusions are not significant. 4. Because of the critical shortage of donor organs and the increasing waiting time for renal transplantation, the use of LURDs can be recommended as a means to expand the number of available organs.

Adolescent↗