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The benefits of laparoscopic living-donor nephrectomy (LDN) are well described, while similar data on hand-assisted laparoscopic living-donor nephrectomy (HALDN) are lacking. We compare hand-assisted laparoscopic living-donor nephrectomy with open donor nephrectomy. One hundred consecutive hand-assisted laparoscopic living-donor nephrectomy (10/98-8/01) donor/recipient pairs were compared to 50 open donor nephrectomy pairs (8/97-1/00). Mean donor weights were similar (179.6 +/- 40.8 vs. 167.4 +/- 30.3 lb; p = NS), while donor age was greater among hand-assisted laparoscopic living-donor nephrectomy (38.2 +/- 9.5 vs. 31.2 +/- 7.8 year; p0.01). Right nephrectomies was fewer in hand-assisted laparoscopic living-donor nephrectomy [17/100 (17%) vs. 22/50 (44%); p0.05]. Operative time for hand-assisted laparoscopic living-donor nephrectomy (3.9 +/- 0.7 vs. 2.9 +/- 0.5 h; p0.01) was longer; however, return to diet (6.9 +/- 2.8 vs. 25.6 +/- 6.1 h; p0.01), narcotics requirement (17.9 +/- 6.3 vs. 56.3 +/- 6.4h; p0.01) and length of stay (51.7 +/- 22.2 vs. 129.6 +/- 65.7 h; p0.01) were less than open donor nephrectomy. Costs were similar ($11072 vs. 10840). Graft function and 1-week Cr of 1.4 +/- 0.9 vs. 1.6 +/- 1.1 g/dL (p = NS) were similar. With the introduction of HALDN, our laparoscopic living-donor nephrectomy program has increased by 20%. Thus, similar to traditional laparoscopic donor nephrectomy, hand-assisted laparoscopic living-donor nephrectomy provides advantages over open donor nephrectomy without increasing costs.

We report an experience with 71 simultaneous kidney-pancreas transplant (SKPT) recipients receiving daclizumab induction in combination with tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. The mean follow-up time was 5.9+/-2.5 (SD) months (range 0.5-11 months). The study population included 47 males (65%) and 24 females (35%) with a mean age of 40+/-8 years. The mean pretransplant duration of diabetes and dialysis were 25+/-8 and 1.5+/-0.9 years (34 hemodialysis, 16 peritoneal dialysis), respectively. Mean HLA match was 1.2+/-1.5, with one patient receiving a second transplant. The mean cold ischemic times for the kidney and the pancreas were 15+/-5 and 16+/-4 hr, respectively. Six-month patient, kidney, and pancreas graft survival and rejection rates were 97, 96, 93, and 35%, respectively. There were two deaths, one due to fungal infection and the other due to a cardiac event. There were three kidney graft losses, two immunological, and one death with function. Of the five pancreas graft losses, two were due to infection, one immunological, one thrombosis, and one death with function. The patient population was then stratified according to the number of daclizumab doses: 4-5 doses (n=45) or 1-3 doses (n=26). There were no differences in patient and kidney graft survival rates, 98 vs. 96%, and 92 vs. 92%, respectively. However, there was a trend toward improved pancreas graft survival in the group receiving 4-5 doses (96%) compared with 1-3 doses (85%), P=0.07. Although more patients receiving 1-3 doses had rejection (54%) than patients receiving 4-5 doses (24%), there was no dose response relationship between the total number of doses or the adjusted total mg/kg dose and time to rejection. All patients with functioning grafts have good renal and pancreas allograft function at 6 and 12 months. The overall incidence of major infection was 27% and there were no differences in the incidence of infection between the two groups. No major adverse events were attributed to daclizumab use. In conclusion, excellent short-term outcomes were noted in this retrospective, multicenter survey of initial experience with daclizumab induction in combination with TAC, MMF, and steroids in SKPT recipients. Optimal dosing strategies for SKPT recipients remain to be determined.

We describe the normal radiologic appearance of pancreatic allografts transplanted using portal venous drainage with enteric drainage of exocrine secretions. We also describe the radiologic appearance of postsurgical complications.Of 56 patients who received pancreatic transplants using the portal-enteric technique, 24 patients subsequently required radiologic examination for suspected complications involving the pancreatic allograft. Twenty-three patients underwent CT scanning; a total of 58 CT scans were obtained. Nine abdominal sonograms were obtained in five patients, and one patient underwent angiography. The radiologic appearance of each transplant and the complications were analyzed retrospectively and correlated with the clinical course.The most common indications for CT scanning were fever, elevated levels of serum amylase, and evaluation or follow-up of fluid collections. CT showed the normal and abnormal anatomy of the allograft. Abnormal findings seen in the 58 CT scans included fat stranding (30 scans), ascites (21 scans), peripancreatic fluid or pseudocyst (13 scans), and heterogeneity of the allograft (five scans). One patient had pancreatic infarction with pneumatosis and pneumoperitoneum. The allograft was obscured by bowel gas on three sonograms. Four sonograms showed no abnormalities (one Doppler sonogram showed the arterial supply and venous drainage), and one sonogram showed a pseudocyst. In the one patient who underwent angiography, imaging showed no arterial blood flow to the transplant.Pancreatic transplantation with portal venous drainage and enteric drainage of exocrine secretions and the complications of such transplantation were revealed with CT, sonography, and angiography. Knowledge of normal anatomic configuration will allow proper interpretation of normal and abnormal findings.

Ag-specific T cell activation requires a CD28-mediated costimulatory interaction. This observation has suggested novel approaches to suppress donor-specific immunity, including the use of soluble CD28 antagonists, such as CTLA4Ig, which suppresses transplant rejection in small animal models. In this study, CTLA4Ig therapy was examined in a non-human primate model of allogeneic pancreatic islet transplantation. Two of five CTLA4Ig-treated monkeys showed prolonged graft survival, which correlated with donor-specific hyporesponsiveness in vitro. Humoral responses to the transplanted tissue were suppressed in all treated animals. These results suggest that CTLA4Ig is effective in suppressing both humoral and cellular immune responses in a non-human primate model of allogeneic transplantation.

The aim of this study was to determine the outcome of venous conduits used in living donor liver transplantation (LDLT). We analyzed the portal vein complications in 66 LDLT recipients and 48 cadaveric reduced-size liver transplant (RLT) recipients performed from November 1989 through January 1995. Three different venous conduits were utilized in the LDLT recipients: Group 1, reconstructed vein from the living donor, n=18; Group 2, cadaveric cryopreserved iliac vein, n=37; and Group 3, cadaveric cryopreserved femoral vein, n=11. Overall, 47 percent of the patients were less than one year of age; the age distribution was not significantly different among the groups. The incidence of early thrombosis was significantly greater in LDLT Group 1, (33%) than any of the other groups (LDLT Group 2, 8%; LDLT Group 3, 9%; and RLT, 4%:P

The incidence, risk factors, and outcome of posttransplant lymphoproliferative disease (PTLD) were examined for 298 children undergoing liver transplantation. The overall incidence of PTLD was 8.4% (25 of 298). Intensity of immunosuppression was found to be a major risk factor for the development of PTLD. Cyclosporine and tacrolimus when used as primary immunosuppression were associated with the development of PTLD in 4.3% and 6.6% of cases (P=NS). OKT3 and tacrolimus, when used as rescue therapy for steroid-resistant rejection, were associated with a comparable increase in the risk of developing PTLD (10.9% and 11.1%, P=NS). Patients requiring both OKT3 and tacrolimus to treat refractory rejection were at significantly increased risk for PTLD (28.1% vs. 4.3% or 6.6%, P

Data were obtained in an operational air traffic control (ATC) setting from seven (7) FAA Air Route Traffic Control Centers (ARTCCs) for 65 air space sectors within those centers. Measures used for study analysis were obtained during 90 minute data collection sessions and included: (a) ATC system inputs in the form of time of day, facility location, air traffic volume and air traffic configurational complexity, (b) the presence of a single radar controller or a two-person controller team, (c) work activity parameters obtained as frequencies of occurrence for tasks involving communications, computer interactions, flight strip activities and handoffs, and (d) controller performance outcomes based on observed performance pressures exhibited by the controller. A hypothesized path (causal) model incorporating the above variables was constructed and tested for its explanatory value. Computations of direct effects within the model showed generally significant linkages between work activities and traffic volume, level of traffic complexity, and controller configuration (e.g. higher levels of traffic volume and complexity, and the presence of a controller team were associated with higher levels of task activity). Most consistently significant, however, in its causal linkages to work activity was air traffic complexity. This was the dominant predictor, by far, of rated controller performance pressure when all other variables - including traffic volume - were accounted for by the analysis method. The time of day and facility location variables were erratic in their effect and difficult to interpret. On the basis of the study results, it was recommended that further research focus on development of the application of air traffic complexity as a measurement construct of potentially unique importance; one which seems to have been little understood and generally neglected in the research literature.

A randomized, multicenter, prospective study was conducted at 18 pancreas transplant centers in the United States to determine the role of induction therapy in simultaneous pancreas-kidney (SPK) transplantation. One hundred and 74 recipients were enrolled: 87 recipients each in the induction and noninduction treatment arms. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil, and corticosteroids. There were no statistically significant differences between treatment groups for patient, kidney, and pancreas graft survival at 1-year. The 1-year cumulative incidence of any treated biopsy-confirmed or presumptive rejection episodes (kidney or pancreas) in the induction and noninduction treatment arms was 24.6% and 31.2% (p = 0.28), respectively. The 1-year cumulative incidence of biopsy-confirmed, treated, acute kidney allograft rejection in the induction and noninduction treatment arms was 13.1% and 23.0% (p = 0.08), respectively. Biopsy-confirmed kidney allograft rejection occurred later post-transplant and appeared to be less severe among recipients that received induction therapy. The highest rate of Cytomegalovirus (CMV) viremia/syndrome was observed in the subgroup of recipients who received T-cell depleting antibody induction and received organs from CMV serologically positive donors. Decisions regarding the routine use of induction therapy in SPK transplantation must take into consideration its differential effects on risk of rejection and infection.

Background. Hepatic resection is an accepted therapeutic modality for isolated colorectal metastases (CRM) and primary hepatobiliary cancers (PC). Controversy continues regarding the safety, efficacy, and appropriateness of resection for noncolorectal metastases (NCM). Methods. A retrospective review of 167 resections in 160 patients was performed to evaluate the impact of demographics and perioperative data on survival and recurrence. Statistical analyses were performed by Student t test, analysis of variance, and Kaplan-Meier survival estimates. Results. Resections were performed for CRM, 110 of 167 (66%), NCM, 31 of 167 (19%), and PC, 26 of 167 (15%). The interval from primary to metastases was significantly longer in the NCM group than the CRM group (34.7 ± 45.1 vs 18.7 ± 23.7 months; P

Preexisting renal dysfunction has been reported to significantly increase the morbidity and mortality associated with orthotopic liver transplantation (OLT). OLT alone has been recommended for adults and children with end-stage liver disease and reversible causes of renal failure (i.e., hepatorenal syndrome), whereas combined liver and kidney transplantation (LKT) has been shown to be an effective treatment for adults with combined end-stage liver and kidney disease. The purpose of this study was to examine the role of LKT in children.Between October of 1984 and 1997, 385 children less than 18 years of age underwent OLT at the University of Chicago. During this same time period 12 patients underwent LKT. Data were gathered by retrospective review of the patients medical records and by interviews conducted with the patients' families.Actuarial patient survival was comparable for children who underwent OLT alone and LKT (69% versus 67% at 5 years). All allograft losses in the LKT group were the result of patient death and occurred within the first 90 postoperative days. Factors associated with decreased patient survival included severity of illness as reflected by United Network of Organ Sharing status and LKT after failed OLT or cadaveric renal transplant.In children with concomitant endstage liver and kidney disease, LKT can be considered an effective therapeutic option in selected patients. Long-term patient survival in patients undergoing LKT is comparable to that of patients with normal renal function undergoing OLT alone.

Clinical liver transplantation was originally described and performed on children. 1 However, because of the low prevalence of disease that progresses to end-stage liver disease, a shortage of organs appropriate for pediatric transplantation, and the lack of surgical expertise, the accumulated experience in pediatric liver transplantation is significantly less than in adult liver transplantation. Living-donor liver transplantation was first reported by Raia et al in 1989 2 and by Strong et al in 1990. 3 To expand the donor pool and thus allow timely transplantation of children with end-stage liver disease, the University of Chicago instituted the first prospective systematic application of living-donor liver transplantation in 1989. 4 Since then, we have performed more than 100 such transplants. The experience at the University of Chicago accounts for almost 50% of the living-donor liver transplants performed in the United States during this period. After the successful reports from Australia and Chicago in 1992, the use of living-donor liver transplantation has gained widespread acceptance for the treatment of children with liver disease, especially in Japan, where it has supplied most of the grafts for liver transplantation. 5–14 The advent of this procedure was accompanied by several new technical challenges in an already technically demanding field. As with most innovative advances, subsequent modifications have been made in an attempt to resolve unforeseen complications. 15 At the University of Chicago, we have defined various phases of the living-donor liver transplant program by the technical modifications of the recipient operation. These modifications affect the performance of living-donor transplants and the growing number of split-liver transplants being performed. We analyzed the first 104 living-donor liver transplants performed at the University of Chicago from November 1989 to January 1998, with particular focus on the technical conduct of the operation, to identify factors important to a favorable outcome.

Insulin-dependent diabetes mellitus (IDDM) is the second most prevalent chronic illness of children. Investigation of the treatment of IDDM is hindered by the lack of a reproducible and easily maintained non-human primate model of this disorder.We induced IDDM in 11 juvenile cynomolgus monkeys after a single (150 mg/kg) intravenous injection of streptozotocin (STZ). All diabetic monkeys were treated with insulin twice daily, based on a sliding scale. Subcutaneous vascular access ports were surgically placed in each monkey to facilitate serial blood sampling and drug administration. Allogeneic pancreatic islet cells from unrelated donors were subsequently transplanted into the mesenteric circulation of all STZ-treated monkeys.Mild, transient nausea and vomiting occurred in all animals after STZ injection; however, no additional signs of toxicity occurred. Within 36 hr, all monkeys required twice daily administration of exogenous insulin to maintain a non-ketotic state. Serum C-peptide levels decreased from1.2 ng/ml before STZ, to between 0.0 and 0.9 ng/ml after STZ, confirming islet cell destruction. Animals were maintained in an insulin-dependent state for up to 147 days without any observable clinical complications. Subcutaneous vascular access port patency was maintained up to 136 days with a single incidence of local infection. Islet cell transplantation resulted in normoglycemia within 24 hr. Serum C-peptide levels increased (range: 2-8 ng/ml) for 6 - 8 days in immune competent animals, and for 39-98 days after transplant in immunosuppressed monkeys.IDDM can be consistently induced and safely treated in juvenile cynomolgus monkeys. Chronic vascular access can be maintained with minimal supervision and complications. This model is appropriate for studies investigating potential treatments for IDDM including islet cell transplantation.

Background. The limited supply of organ donors has led some groups to reconsider the role of retransplantation. Historically, except for children with malignancies, extrahepatic sources of sepsis, or severe irreversible neurologic injuries, our institution has offered all children with failing liver grafts the option of retransplantation regardless of their current severity of illness. The purpose of this study was to examine the outcome of hepatic retransplantation in children in an attempt to identify factors predictive of outcome and to assess the results of our approach to retransplantation. Methods. Between-October 1984 and December 1995, 314 children less than 15 years of age underwent a total of 441 liver transplants. Data were obtained retrospectively by review of hospital records. Results. With a mean follow-up period of 5.3±2.7 years, the overall patient survival rates at 1 and 5 years were 77.1% and 67.1%, respectively. Primary allograft survival rates were 65.6% and 56.5%, respectively. Of the 137 patients who developed failure of their primary allograft, 92 underwent retransplantation (29.3% of all primary transplants). Both patient and allograft survival rates were significantly decreased after retransplantation (P

Ag-specific T cell activation requires a CD28-mediated costimulatory interaction. This observation has suggested novel approaches to suppress donor-specific immunity, including the use of soluble CD28 antagonists, such as CTLA4Ig, which suppresses transplant rejection in small animal models. In this study, CTLA4Ig therapy was examined in a non-human primate model of allogeneic pancreatic islet transplantation. Two of five CTLA4Ig-treated monkeys showed prolonged graft survival, which correlated with donor-specific hyporesponsiveness in vitro. Humoral responses to the transplanted tissue were suppressed in all treated animals. These results suggest that CTLA4Ig is effective in suppressing both humoral and cellular immune responses in a non-human primate model of allogeneic transplantation.

Although FK 506 has been shown to effectively reverse refractory renal allograft rejection, its ability to reverse accelerated renal allograft rejection as a primary agent has not been specifically addressed. Herein evidence of the ability of FK 506 to reverse accelerated renal allograft rejection is presented. A 16-yr-old highly sensitized (PRA 75%) male underwent a second cadaveric renal transplant procedure. Despite induction immunosuppression with ATGAM, cyclosporine, azathioprine, and corticosteroids, a marked elevation in serum creatinine (1.6--2.1 ng/dl) and reduction in urine output (4000 ml/d--1000 ml/d) were observed on the sixth post-transplant day. Renal allograft biopsy performed at that time revealed typical features of accelerated rejection including neutrophil margination in glomerular and interstitial capillaries, and C3, IgG, and fibrin deposition in glomerular and interstitial capillaries (by immunofluorescence). FK 506 therapy was promptly instituted and ATGAM therapy discontinued. Serum creatinine peaked within 3 d of FK 506 therapy (2.5 mg/dl) and subsequently progressively dropped to 1.2 mg/dl. Repeat biopsy on FK 506 treatment day 12 revealed marked histologic improvement. Renal function remains excellent (1.3 mg/dl) 18 months after initiation of FK 506 therapy, and recurrent rejection has not been observed. This experience provides evidence that FK 506 therapy may effectively reverse accelerated renal allograft rejection, and that it provides a means for treating antibody-mediated mechanisms of allograft rejection.

Despite numerous options for pediatric transplantation, closure of the abdominal wall after liver transplantation is occasionally difficult, resulting in increased abdominal pressure and possible vascular compromise. Since 1990, we have utilized a 2-mm thick sheet of polytetrafluoroethylene (PTFE) to overcome this situation in 21 transplants for 17 patients. The median age was 0.9 months. Ten of the 21 transplants utilized full-size grafts. The donor to recipient weight ratio was 1.7+/-1.2. Cadaveric left lateral segments were used in 8 of 21 transplants (weight ratio, 7.4+/-5.9), living donor left lateral segments were used in 3 of 21 transplants (weight ratio, 13.2+/-6.7). We were able to remove 14 of 21 patches with one additional operation, whereas 4/21 patches required two operations and 3/21 required three operations. Reoperations identified two cases of hepatic artery thrombosis not previously identified by duplex ultrasonography. There were no technical problems or adverse effects associated with the use of the PTFE patch. After patch removal, the fascia was closed with a nonabsorbable suture and the skin was allowed to close by secondary intention. There were no wound infections, portal vein thrombosis, or fluid and electrolyte abnormalities. PTFE is a safe, temporary alternative to primary wound closure in liver transplantation when the size of the graft or intestinal and graft edema does not allow conventional closure of the abdomen. Infectious, fluid/electrolyte, or ventilatory complications were not noted. The necessity of a second-look operation is useful in assessing the graft and vascular patency. The majority of patches can be removed within the first postoperative week.

The aim of this study was to determine the outcome of venous conduits used in living donor liver transplantation (LDLT). We analyzed the portal vein complications in 66 LDLT recipients and 48 cadaveric reduced-size liver transplant (RLT) recipients performed from November 1989 through January 1995. Three different venous conduits were utilized in the LDLT recipients: Group 1, reconstructed vein from the living donor, n=18; Group 2, cadaveric cryopreserved iliac vein, n=37; and Group 3, cadaveric cryopreserved femoral vein, n=11. Overall, 47 percent of the patients were less than one year of age; the age distribution was not significantly different among the groups. The incidence of early thrombosis was significantly greater in LDLT Group 1, (33%) than any of the other groups (LDLT Group 2, 8%; LDLT Group 3, 9%; and RLT, 4%:P0.0005 vs. reduced graft and0.03 vs. other LDLT groups). The incidence of late portal vein stenosis or thrombosis was significantly higher in the LDLT Group 2, (51%) than any of the other groups (LDLT 1, 16%; LDLT Group 3, 9%; RLT 4%;P0.005 vs. cadaveric and0.02 vs. LDLT Group 1 and LDLT Group 3). Five year arterial graft and patient survival for patients who have experienced portal vein thrombosis or stenosis is 61% and 67%, respectively, versus 67% and 71% for those patients who have not experienced portal vein pathology, P=ns. Based on this experience, we recommend avoiding the use of cryopreserved iliac vein for portal vein reconstruction in liver transplantation. Every effort should be taken to eliminate the need for venous conduits in liver transplantation. If venous conduits must be utilized, cryopreserved femoral veins seem to provide superior patency rates. Careful clinical and ultrasonopraphic monitoring of patients at high risk for late venous thrombosis permits therapy with excellent graft and patient survival.

FK 506 has proven to be an effective immunosuppressive agent in liver transplantation, but its role in renal transplantation remains to be defined. Since the initial availability of FK 506 for treatment of refractory renal allograft rejection, we have applied an aggressive approach consisting of institution of rescue therapy at an early point in the rejection process combined with assiduous monitoring of FK 506 blood levels and the histologic response to therapy. A total of 17 adult patients were treated for refractory renal allograft rejection with this approach. Median follow-up was 9 months post-initiation of FK 506 therapy. Median time to first rejection was 26 d post-transplant, and median time to FK 506 rescue therapy was 113 d post-transplant. Sixteen of 17 patients received either ATGAM or OKT3 induction therapy. Prior to FK 506 rescue therapy, patients received the following antirejection therapy: corticosteroids 40 + 21 mg/kg (prednisone or Solumedrol), OKT3 (median 14 d), ATGAM (3 patients, 14 d each). FK 506 rescue therapy was successful in reversing the rejection process in all 17 patients. Fifteen patients (88%) demonstrated rapid reversal of rejection (i.e. reversal within 14 d), whereas three patients demonstrated delayed reversal. Nine month actuarial patient and graft survivals were 92% and 84%. When censored for documented noncompliance, nine month actuarial graft survival was 92%. Good long-term renal function was observed (pre-FK 506 baseline creatinine 2.1 +/- 0.5 mg/dl, current serum creatinine 2.1 +/- 0.6 mg/dl. Six recurrent rejection episodes occurred in 5 patients (29%) with a median time to recurrent rejection of 59 d post-initiation of FK 506 rescue therapy. Each recurrent rejection episode was successfully treated by corticosteroids and/or increased FK 506 dose. CMV disease and lymphoma were not observed. Histologic evidence of FK 506 nephrotoxicity (hyaline necrosis in preglomerular arterioles) was observed in 6 patients 30% (median time to diagnosis 49 d). FK 506 blood levels (whole blood TDX) between 10 and 20 ng/ml provided effective reversal in most patients. Current FK 506 dose and blood levels are 0.18 +/- 0.09 mg/kg/d and 7 +/- 2 ng/dl). FK 506 rescue therapy also allowed aggressive reductions in prednisone dose: (mean current prednisone dose 0.08 +/- 0.05 mg/kg/d). In conclusion, an aggressive approach toward FK 506 rescue: 1) provides prompt, effective reversal of refractory renal allograft rejection, 2) good long-term renal allograft function, 3) balanced immunosuppression with respect to recurrent rejection, opportunistic infection and PTLD, 4) acceptable toxicity, and 5) aggressive reduction in corticosteroid dosing. Based on these findings, FK 506 rescue therapy is now the treatment of choice in our program for renal allograft rejection episodes that occur following antilymphocyte antibody therapy.

Dose-response relationships for anti-CD3 monoclonal antibody (mAb) therapy remain undefined, particularly with respect to higher dose ranges. The clinical efficacy and safety of an OKT3 dosing regimen that incorporates higher doses (escalating dose regimens) was examined in a pilot trial. Patients undergoing acute rejection were treated with a 7-d course of OKT3 in which the daily OKT3 dose was escalated during treatment course (daily doses 5, 5, 5, 5, 10, 15, 25 mg). The total amount of OKT3 given was equal to a standard 14-d course (70 mg). A total of 10 primary cadaveric renal transplant recipients were treated, and data analyzed from a median follow up of 5 months (range 3-13 months). Pre-OKT3 immunosuppressive therapy consisted of ATGAM induction therapy (n = 8), and corticosteroid rejection therapy (n = 6, 18.6 +/- 11.4 mg/kg). Median time of first rejection was 32 d (12-48 d) and median time to OKT3 was 33 d (range 15-42 d). Pre-OKT3 histology (by Banff criteria) included: mild ACR (n = 6), moderate ACR (n = 2), AVR (n = 1), ACR and acute transplant glomerulopathy (n = 1). Rejection reversal rate with escalating dose OKT3 was 100%, and each patient experienced a rapid reversal of rejection (i.e. reversal within 14 d initiation of OKT3 therapy). Six recurrent rejection episodes were diagnosed in 5 patients with a median time to recurrent rejection of 30 d following cessation of OKT3 therapy. All recurrent rejection episodes were successfully treated (FK 506 n = 4, corticosteroids n = 1, and OKT3 n = 1). CMV disease was limited to a single episode of CMV viremia in one patient. PTLD was observed in one patient who had coexisting vascular rejection at the time of PTLD diagnosis. Short- and long-term graft function is excellent (pre-rejection baseline creatinine 1.8 +/- 0.4 mg/dl, current creatinine 1.75 +/- 0.4 mg/dl). Monitoring of OKT3 serum levels revealed that patients maintained therapeutic serum levels for an average of 4 d following the last OKT3 dose. Circulating CD3+ and CD5+ cells were maintained below baseline levels for at least 10 d following the last OKT3 dose. Anti-OKT3 antibody formation occurred in 22% of patients, however, anti-idiotypic responses were of low titer. Adverse reactions experienced during dose escalation were minimal compared to first dose reactions, and consisted primarily of mild headaches and arthralgias in a minority of patients. OKT3 EDR, by obviating monitoring and administration costs, are cost effective [OKT3 EDR $8088, OKT3 SDR (10 d) $9684, OKT3 SDR (14 d) $13,224]. In conclusion, escalating dose regimens of OKT3: 1) provide rejection reversal rates similar to standard dose regimens, 2) provide high OKT3 serum levels and reliable CD3+ cell depletion, 3) induce minimal adverse reactions during dose escalation, and 4) may decrease costs by obviating the need for monitoring peripheral blood T cells and by decreasing administration costs and outpatient visits.

Over the past 5 years, we have employed several strategies to increase the donor pool for both the pediatric and adult populations. The innovative expansion of the donor pool with the use living-related donors for children and cadaveric, high-risk donors for adults has increased our ability to serve our recipients and transplant them at an earlier stage in the disease process, thereby improving survival. As Hepatitis C is now the leading indication for liver transplantation in the adult population, the investigation of the natural history of Hepatitis C prior to and after transplantation provides a major challenge and is currently a focus of both laboratory and clinical efforts. For those recipients of Hepatitis C-positive-donor livers, determining the role of recipient and donor genotypes in the progression of recurrent hepatitis should help define the proper utilization of these organs. For patients on CsA-based immunosuppression regimens who experience steroid-resistant rejection, tacrolimus has proved to be extremely effective in reversing the rejection episodes and maintaining normal graft function. The long-term results of this therapy appear to be superior to OKT3 therapy. The recipients of living-related liver transplantation continue to have a survival advantage in comparison to recipients of cadaveric grafts. The donor operation can be routinely performed with minimal risk. Because of the superior results achieved and minimal donor risks, we feel that providing the option of living-donor transplantation is ethically justified, and medically necessary. Despite the encouraging results from living-donor transplantation, unexpected complications including portal vein complications and hepatic artery thrombosis have forced technical modifications of the original technique which may have implications to pediatric liver transplantation in general. As the volume of pediatric liver transplants and the number of immmunosuppressive regimens have increased over the years, posttransplant lymphoproliferative disease has been identified as a problem which requires more inspection. We have determined that the severity of rejection and the subsequent treatment, and primary Epstein-Barr virus are the primary risk factors for developing of PTLD. Identification of the risk factors and early detection may provide some hope for treatment of the disease while allowing long-term graft function. Results of our preliminary data show that, following transplantation, 3/4 of the children or parents report minimal impairment with regard to developmental or physical milestones. Patients and their families, however, continue to report significant levels of stress in their lives and occasional pain. Further research on outcome needs to be performed on our pediatric recipients to ensure the long-term benefit of our efforts.

One of the major problems in clinical immunity is that neoplastic and virally infected cells are insufficiently immunogenic to trigger an immune response. During the past several years, our laboratory has explored the use of T-cell-specific reagents including monoclonal antibodies (MAbs) and staphylococcal enterotoxins to amplify immune responses. This report summarizes our efforts to augment immunity with these agents.

Background. Preexisting renal dysfunction has been reported to significantly increase the morbidity and mortality associated with orthotopic liver transplantation (OLT). OLT alone has been recommended for adults and children with end-stage liver disease and reversible causes of renal failure (i.e., hepatorenal syndrome), whereas combined liver and kidney transplantation (LKT) has been shown to be an effective treatment for adults with combined end-stage liver and kidney disease. The purpose of this study was to examine the role of LKT in children. Methods. Between October of 1984 and 1997, 385 children less than 18 years of age underwent OLT at the University of Chicago. During this same time period 12 patients underwent LKT. Data were gathered by retrospective review of the patients medical records and by interviews conducted with the patients' families. Results. Actuarial patient survival was comparable for children who underwent OLT alone and LKT (69% versus 67% at 5 years). All allograft losses in the LKT group were the result of patient death and occurred within the first 90 postoperative days. Factors associated with decreased patient survival included severity of illness as reflected by United Network of Organ Sharing status and LKT after failed OLT or cadaveric renal transplant. Conclusions. In children with concomitant end-stage liver and kidney disease, LKT can be considered an effective therapeutic option in selected patients. Long-term patient survival in patients undergoing LKT is comparable to that of patients with normal renal function undergoing OLT alone.

An investigation of the importance of water contact, cooling, and apnea to the development of the diving reflex in humans was performed in two experimental series. The first series involved exposure of different parts of the face to direct water contact, while the second consisted of face immersion in water baths of varying temperatures. Data were obtained on heart rate (ECG's) and peripheral vasoconstriction (by indirect blood pressure using sphygmomanometry). Results were interpreted to indicate that the diving reflex is actuated by both facial cooling and apnea, but not by any direct effect of water contact other than cooling.

Untersuchungen an Laboratoriums-FledermausenMyotis lucifugus wahrend aller Phasen der Winterschlaflethargie zeigen, dass Unbeweglichkeit der Tiere entscheidend auf den Verlust an Knochenmineralien wirkt. Die Vermehrung an Osteoklasten sowie die Hyperkalzemie und die Hypophosphatemie bei winterschlafenden Fledermausen weisen ebenfalls in Richtung der Resorptionsvorgange im Knochen.

Plasma und Knochensubstanz von Mikrochiropteren wurden auf Natriumgehalt untersucht. Der Knochen-Natriumgehalt nimmt im Verlauf der Winterschlaflethargie ab und kehrt zu hoheren Werten bei Sommerfledermausen zuruck. Die Knochen-Natriummenge ist bei aktiven Fledermausen, die in ihren Bewegungen wahrend des Sommers und Winters behindert wurden, niedriger als bei freigelassenen Fledermausen. Dies zeigt, dass die Bewegung keinen starken Einfluss auf den Mineralgehalt der Knochen hat. Der Plasma-Natriumgehalt der Fledermause ist hoher als in den meisten andern Saugetieren und scheint zudem zu Beginn des Winterschlafs besonders hoch zu sein.