Challenges to research and innovation to optimize deceased donor organ quality and quantity.

Solid organ transplantation is encumbered by an increasing number of waitlisted patients unrequited by the current organ supply. Preclinical models suggest that advances in deceased donor management and treatment can increase the quantity and quality of organs available for transplantation. However, the science of donor intervention and the execution of high quality, prospective, multi-center, randomized-controlled trials are restricted by a myriad of logistical challenges mired in regulatory and ethical ambiguity. By highlighting the obstacles to conducting research in deceased donors, this report endeavors to stimulate the creation of a multi-disciplinary framework to facilitate the design, implementation and supervision of innovative trials that increase the quantity and/or quality of deceased donor organs.

Tumor necrosis factor-alpha gene expression in human whole blood.

Tumor necrosis factor-alpha (TNF) is recognized as a principal mediator of a variety of pathophysiologic and immunologic events. Lipopolysaccharide (LPS) challenge, either in vitro or in vivo, results in significant TNF production. In this study we present data demonstrating LPS-induced TNF mRNA expression and bioactivity using an in vitro tissue system of whole blood (WB). The kinetics of LPS-induced TNF production by WB was significantly accelerated as compared to isolated cultured peripheral blood monocytes (PBM). At post-LPS challenge, plasma from WB demonstrated a rapid rise in TNF bioactivity, peaking by 4 hr (1,021 units/ml/10(6) cells), plateauing between 4 and 8 hr, and then decreasing over the next 16 hr. In contrast, the highest measured TNF bioactivity from PBM did not occur until the 24-hr time-point (175 units/ml/10(6) cells). Whole blood buffy-coat TNF mRNA was assessed by Northern blot analysis, and demonstrated significant TNF mRNA accumulation at 1 hr and a peak 2 hr post-LPS challenge. By 8 hr TNF mRNA was undetectable. Concomitant administration of LPS with either prostaglandin E2 (10(-6)M) or Dexamethasone (10(-6)M) resulted in significant suppression of LPS-induced TNF production. This data supports WB as a useful in vitro medium for the molecular and cellular analysis of TNF. As specialized connective tissue, WB may provide an important environment to study the pharmacologic manipulation of TNF mRNA and bioactivity.

The interrelationship between portal and arterial blood flow after adult to adult living donor liver transplantation.

BACKGROUND: When adults are transplanted with segmental grafts, disparity between the size of the graft and the native organ is almost universal. These grafts presumably still receive all of the native portal inflow despite a reduced vascular bed and dramatically elevated blood flow may result. The hemodynamic changes after segmental transplantation in adults have not yet been studied and their clinical significance is unknown. METHODS: Portal venous and hepatic arterial blood flow were measured intraoperatively in right lobe liver donors and recipients with electromagnetic flow probes. Postoperative evolution was monitored in recipients with ultrasonography. RESULTS: Portal flow to the right lobe ranged from 601 to 1,102 ml/min before resection and from 1,257 to 2,362 ml/min after transplantation. There was a statistically significant linear correlation between the change in portal flow and graft to recipient body weight ratio. Arterial blood flow ranged from 213 to 460 ml/min before resection and from 60 to 300 ml/min after transplantation. Preoperative portal peak systolic velocity was uniformly around 10 cm/sec. Values on postoperative day 1 were increased to 30 cm/sec in recipients of cadaveric organs, to 50 cm/sec in recipients of organs with graft to recipient body weight ratios of more than 1.2%, and to 115 cm/sec in recipients of organs with ratios less than 0.9%. A decreasing tendency was universally observed. Arterial systolic velocity was inversely related to portal systolic velocity. Neither graft dysfunction nor vascular complications occurred. CONCLUSIONS: The hemodynamic pattern after right lobe transplantation is predictable and intraoperative measurements and ultrasonography are useful for monitoring. The size of the graft influences the magnitude of the hemodynamic changes.

The hepatic artery in liver transplantation.

Hepatic artery complications after liver transplantation are uncommon, but represent an important cause of morbidity and mortality. In addition, these complications tax an already limited supply of donor organs because of the frequent need for retransplantation in this group of patients. In this study, we examined the incidence of hepatic arterial anomalies in donors and recipients of orthotopic liver transplants, focusing on the techniques that are available for hepatic arterial reconstruction and on the occurrence of hepatic arterial complications. A total of 77 liver transplants were carried out in 68 patients. Standard recipient anatomy was present in 60 of 68 patients (88%). Anomalous vessels were identified in eight patients (12%), including six cases of replaced right hepatic artery (9%) and two cases of replaced left hepatic artery (3%). Donor liver arterial anatomy was standard in 62 cases (80%). Anomalous arterial supply was identified in 15 of 77 donor livers (20%), including replaced left hepatic artery in nine (12%) and replaced right hepatic artery in six (8%). A variety of methods were used to manage the anomalous vessels. There was one hepatic artery pseudoaneurysm, three cases of hepatic artery thrombosis (4%), and one patient developed a dissection of the native celiac axis. In primary transplants, utilization of the recipient's proper hepatic artery was associated with a significantly higher risk of hepatic artery thrombosis (P less than 0.04) when compared with the common hepatic artery or the branch patch technique. Use of a Carrel patch on the donor artery was associated with a significantly reduced incidence of hepatic artery thrombosis (P less than 0.0003). For retransplantation, it is recommended that a more proximal recipient anastomotic site be chosen. An innovative method is described that provides increased length of the donor arterial supply without the use of an arterial graft.

Hepatocyte transplantation as a bridge to orthotopic liver transplantation in terminal liver failure.

The limited donor organ supply has led to several bridging techniques to sustain patients with acute and subacute liver failure. We report here the prospective, controlled trial of transplanted isolated fresh and cryopreserved human hepatocytes as a bridge to orthotopic liver transplantation. Five hepatocyte transplant recipients with grade IV encephalopathy and multisystem organ failure and four patients of equal illness severity due to liver failure were studied. Medical therapy resulted in a significant (P<0.05), but not normal, fall in blood ammonia, and a significant (P<0.02) resolving biochemical marker of liver injury that did not improve cardiovascular or cerebral stability; this lead to death within 3 days in all control patients. The five hepatocyte-treated patients maintained normal cerebral perfusion and cardiac stability, with withdrawal of medical support for 2 to 10 days before orthotopic liver transplantation. Biochemical evidence of liver injury improved significantly (P=0.004) and blood ammonia levels decreased significantly (P=0.0005) to normal levels in the hepatocyte-treated patients. Three of five patients who successfully bridged to whole liver allograft transplant are alive, home, and normal with more than 20 months of follow-up. No infections or embolic or pulmonary complications resulted from intra-arterial splenic hepatocyte infusion. Specific antiprotease production in a patients with genetically deficient alpha-1-antitrypsin disease, and immunohistochemical and electron microscopic evidence of splenic "hepatization" are presented as evidence of the viability of hepatocyte splenic seeding. In conclusion, splenic transplantation of differentiated adult hepatocytes can control hyper-ammonemia, correct genetic defects in liver function, and bridge life to orthotopic liver transplantation in human liver failure.

Right lobe living donor liver transplantation.

BACKGROUND: The shortage of livers for transplantation has prompted transplant centers to seek alternatives to conventional cadaveric liver transplantation. Left lateral segmentectomy from living donors has proven to be a safe operation for the donor with excellent results in the pediatric population. Left lobectomy, conceived to supply more tissue, still provides insufficient liver mass for an average size adult patient. Right lobectomy could supply a graft of adequate size. METHODS: Donors were considered only after recipients were listed according to United Network for Organ Sharing (UNOS) criteria. Donor evaluation included liver biopsy, magnetic resonance imaging, and celiac and mesenteric angiography. The donor operation consisted of a right lobectomy uniformly performed throughout the series as described herein. RESULTS: Twenty-five right lobe living donor liver transplants were performed between adults, with no significant complications in donors. Recipient and graft survival was 88%, with three recipient deaths secondary to uncontrolled sepsis in patients at high risk for liver transplant; all three had functioning grafts. CONCLUSIONS: Right lobe living donor liver transplantation poses challenges that require a meticulous surgical technique to minimize morbidity in the recipient. Right lobectomies for living donation can be performed safely with minimal risk to both donor and recipient although providing adequate liver mass for an average size adult patient.

The impact of a positive crossmatch upon outcome after liver transplantation.

Recent reports have shown that liver allografts transplanted against a positive lymphocytotoxic crossmatch (CDC+) are susceptible to an increased frequency of rejection, and decreases in patient and graft survival. The implication of a positive flow cytometric crossmatch (FCXM+) in liver transplantation remains controversial. The purpose of this study was to determine what impact a pretransplant IgG crossmatch due to CDC+ or FCXM+ had upon the clinical outcome following liver transplantation. Preoperative crossmatch status was determined prospectively in 110 consecutive liver transplants performed between July 1991 and January 1995. Allografts were divided into three groups: negative crossmatch (NXM), positive flow cytometric crossmatch FCXM+, and positive lymphocytotoxic crossmatch CDC+. Crossmatch status did not impact patient or graft survival. Actuarial patient survival was similar between groups at 12 months (88% vs. 95% vs. 92%, NXM vs. FCXM+ vs. CDC+) and 24 months (81% vs. 93% vs. 92%, NXM vs. FCXM+ vs. CDC+) (P=0.1938). Actuarial allograft survival was similar between groups at 12 months (76% vs. 93% vs. 85%, NXM vs. FCXM+ vs. CDC+) and 24 months (76% vs. 89% vs. 85%, NXM vs. FCXM+ vs. CDC+) (P=0.0738). CDC+ allografts had a significant increase in early rejection episodes compared with NXM (46% vs. 7%, CDC+ vs. NXM) (P=0.003) or FCXM+ allografts (46% vs. 10%, CDC+ vs. FCXM+) (P=0.006). CDC+ allografts experienced significantly more rejection episodes per year than NXM (53% vs. 20%, CDC+ vs. NXM) (P=0.015) or FCXM+ allografts (53% vs. 23%, CDC+ vs. FCXM+) (P=0.02). CDC+ allografts had a significant increase in numbers of additional nonconventional therapeutic interventions compared to NXM allografts (0.9+/-0.5 vs. 0.2+/-0.1, CDC+ vs. NXM) (P=0.039). The presence of cytotoxic antibodies pretransplantation is associated with increased incidences of early rejection, and rejection episodes per year. With careful monitoring and aggressive therapeutic interventions the presence of cytotoxic antibodies are not deleterious to patient or liver allograft survival.

A prospective randomized trial of mycophenolate mofetil with neoral or tacrolimus after orthotopic liver transplantation.

BACKGROUND: The success of liver transplantation in this decade has become the stimulus to extend the donor and recipient pool. Reducing early posttransplant morbidity to maintain our success, as we expand our frontiers, has led us to focus on balanced testing of multidrug immunosuppression regimens. METHODS: A prospective trial in orthotopic liver transplantation using Mycophenolate Mofetil and an identical steroid taper with randomization of patients to Neoral (N) or Tacrolimus (FK) is the basis of this report. This was an intent-to-treat study designed to compare the 6-month primary endpoints of rejection and infection and to compare the 6-month secondary endpoints of liver function, renal function, bone marrow function, hypertension, and serum cholesterol levels. RESULTS: Ninety-seven patients completed the 6-month follow-up period (N=49, FK=48). The actual 6-month patient and graft survival rates were 98% and 94%, respectively. There was no difference in the number of patients with rejection episodes (N=11, FK=8) (P=0.61). There were 24 infections (3 cytomegalovirus) in the FK group and 30 infections (9 cytomegalovirus) in the N group. The cholesterol levels at 6 months were not significantly different (P=0.07) between the groups. The other secondary 6-month endpoints were not significantly different, except total bilirubin, which was lower in the FK arm (P=0.02). CONCLUSIONS: The use of Mycophenolate Mofetil with N or FK and an identical steroid taper after orthotopic liver transplantation is associated with excellent graft and patient survival, and at 6 months, only 191% of the patients experienced rejection, with a 48% overall infection rate.

Liver regeneration and function in donor and recipient after right lobe adult to adult living donor liver transplantation.

BACKGROUND: Regeneration of the liver to a predetermined size after resection or transplantation is a well described phenomenon, but the time course over which these events occur has not been well defined. It is not clear how initial liver mass, reperfusion, immunosuppression, or steatosis influence this process. METHODS: Liver regeneration was assessed prospectively by volumetric magnetic resonance imaging (MRI) in living right lobe liver donors and the recipients of these grafts. Imaging was performed at regular intervals through 60 days after resection/transplantation, and liver mass was determined. Liver function tests and synthetic function were monitored throughout the study period in donors and recipients of these grafts as well as recipients of cadaveric grafts. RESULTS: MRI consistently overestimated liver mass by a mean of 45 g (+/-65) (range 10-123). Donor liver mass increased by 101%, 110%, 115%, and 144% at 7, 14, 30, and 60 days after resection, respectively. Recipient liver mass increased by 87,101, 119, and 99% at 7, 14, 30, and 60 days after transplantation, respectively. Steatosis did not influence the degree of regeneration or graft function, nor was there a functional difference between grafts of >1% graft to recipient body weight ratio or <1%. CONCLUSIONS: MRI accurately determines right lobe mass. Most liver regeneration occurs in the 1st week after resection or transplantation, and the time course does not differ significantly in donors or recipients. The mass of the graft or remnant segment affects the duration of the regeneration process, with a smaller initial liver mass prolonging the course. Steatosis of <30% had no bearing on liver function or regeneration and, therefore, should not be an absolute criterion for exclusion of donors. A calculated graft to recipient body weight ratio of 0.8% is adequate for right lobe living donor liver transplantation.

Emergency adult to adult living donor liver transplantation for fulminant hepatic failure.

BACKGROUND: The high mortality rate associated with fulminant hepatic failure combined with the limited availability of cadaveric organs requires consideration of alternatives to conventional cadaveric transplantation. Use of the donor right lobe in adult-to-adult living donor transplantation holds promise in a variety of circumstances, including high-acuity situations. METHODS: A 28-year-old male with fulminant hepatic failure secondary to hepatitis B was referred to our institution. He rapidly progressed to grade IV encephalopathy, and laboratory values were indicative of a poor prognosis without transplantation. He was listed for transplantation as UNOS status I. Three siblings were simultaneously evaluated for living liver donation. Following established protocols, we completed donor evaluation in less than 24 hr, and donor right lobectomy and living donor transplantation were performed within 36 hr of the recipient's admission to our center. RESULTS: The donor surgery was uncomplicated, and the patient was discharged on postoperative day 4. The recipient experienced full recovery and was discharged home on postoperative day 14. Of note, the first offer for a cadaveric liver came more than 60 hr after living donor transplantation. CONCLUSIONS: Thorough donor workup can be completed in less than 24 hr without inappropriate abbreviation of the evaluation. Simultaneous workup of willing individuals prevents unnecessary delay. Living donor transplantation should be considered for patients with fulminant hepatic failure who are appropriate transplant candidates.

Emergency portacaval shunt for control of hemorrhage from a parenchymal fracture after adult-to-adult living donor liver transplantation.

As more adults undergo transplantation with partial liver grafts, the unique features of these segments and their clinical significance will become apparent. A patient presented with life-threatening hemorrhage from an iatrogenic laceration to a right lobe graft 11 days after transplantation. The creation of a portacaval shunt effectively controlled the bleeding, allowing more elective replacement of the organ with another right lobe graft. The regeneration process combined with increased portal blood flow and relative outflow limitation may have set the stage for this complication. Any disruption of the liver parenchyma during transplantation should be securely repaired and followed cautiously. Portacaval shunting is an option for controlling hemorrhage from the liver in transplant recipients. The timely availability of a second organ was likely the ultimate determinant of survival for this patient.

Selection and outcome of living donors for adult to adult right lobe transplantation.

BACKGROUND: The shortage of cadaveric livers has sparked an interest in adult-to-adult living donor transplantation. Right lobe donor hepatectomy is frequently required to obtain a graft of adequate size for adult recipients. Careful donor selection is necessary to minimize complications and assure a functional graft. METHODS: A four-step evaluation protocol was used for donor selection and satisfactory results of all tests in each step were required before proceeding to the next. Donors were selected based on a battery of laboratory studies chosen to exclude unrecognized infection, liver disease, metabolic disorders, and conditions representing undue surgical risk. Imaging studies included ultrasonography, angiography, magnetic resonance imaging, and intraoperative cholangiography and ultrasonography. The information obtained from liver biopsy was used to correct the estimated graft mass for the degree of steatosis. RESULTS: From March 1998 to August 1999, 126 candidates were evaluated for living donation. A total of 35 underwent donor right lobectomy with no significant complications. Forty percent of all donors that came to surgery were genetically unrelated to the recipient. A total of 69% of those evaluated were excluded. ABO incompatibility was the primary reason for exclusion after the first step (71%) and the presence of steatosis yielding an inadequate estimated graft mass after the second step (20%). CONCLUSIONS: Donor selection limits the application of living donor liver transplantation in the adult population. Unrelated individuals increase the size of the donor pool. Right lobe hepatectomy can be performed safely in healthy adult liver donors. Preoperative liver biopsy is an essential part of the evaluation protocol, particularly when the estimated graft mass is marginal.

Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation.

BACKGROUND: Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation. METHODS: A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.5 mg/kg/ day) or Atgam (15 mg/kg/day). The primary end point was rejection reversal (return of serum creatinine level to or below the day 0 baseline value). RESULTS: A total of 163 patients were enrolled at 25 transplant centers in the United States. No differences in demographics or transplant characteristics were noted. Intent-to-treat analysis demonstrated that Thymoglobulin had a higher rejection reversal rate than Atgam (88% versus 76%, P=0.027, primary end point). Day 30 graft survival rates (Thymoglobulin 94% and Atgam 90%, P=0.17), day 30 serum creatinine levels as a percentage of baseline (Thymoglobulin 72% and Atgam 80%; P=0.43), and improvement in posttreatment biopsy results (Thymoglobulin 65% and Atgam 50%; P=0.15) were not statistically different. T-cell depletion was maintained more effectively with Thymoglobulin than Atgam both at the end of therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 90 days after therapy, occurred less frequently with Thymoglobulin (17%) versus Atgam (36%) (P=0.011). A similar incidence of adverse events, post-therapy infections, and 1-year patient and graft survival rates were observed with both treatments. CONCLUSIONS: Thymoglobulin was found to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.

The effect of CO(2) enrichment on leaf photosynthetic rates and instantaneous water use efficiency of Andropogon gerardii in the tallgrass prairie.

Open-top chambers were used to study the effects of CO(2) enrichment on leaf-level photosynthetic rates of the C(4) grass Andropogon gerardii in the native tallgrass prairie ecosystem near Manhattan, Kansas. Measurements were made during a year with abundant rainfall (1993) and a year with below-normal rainfall (1994). Treatments included: No chamber, ambient CO(2) (A); chamber with ambient CO(2) (CA); and chamber with twice-ambient CO(2) (CE). Measurements of photosynthesis were made at 2-hour intervals, or at midday, on cloudless days throughout the growing season using an open-flow gas-exchange system. No significant differences in midday rates of photosynthesis or in daily carbon accumulation as a result of CO(2) enrichment were found in the year with abundant precipitation. In the dry year, midday rates of photosynthesis were significantly higher in the CE treatment than in the CA or A treatments throughout the season. Estimates of daily carbon accumulation also indicated that CO(2) enrichment allowed plants to maximize carbon acquisition on a diurnal basis. The increased carbon accumulation was accounted for by greater rates of photosynthesis in the CE plots during midday. During the wet year, CO(2) enrichment decreased stomatal conductance, which allowed plants to decrease transpiration while still photosynthesizing at rates similar to plants in ambient conditions. During the dry year, CO(2) enrichment allowed plants to maintain photosynthetic rates even though stomatal conductance and transpiration had been reduced in all treatments due to stress. Estimates of instantaneous water-use efficiency were reduced under CO(2) enrichment for both years.

Preoperative risk factor assessment in liver transplantation.

BACKGROUND: Despite the increasing success of liver transplantation, there is lack of objective data defining appropriate candidate suitability. This study was undertaken to determine preoperative risk factors that independently or in combination affected outcome after orthotopic liver transplantation. METHODS: We reviewed data on 229 consecutive adult liver transplant recipients. Thirty-one preoperative risk factors recorded at the time of listing and immediately before transplantation were analyzed. Outcome variables included hospital mortality rates, bacterial or fungal sepsis, and the need for renal support. RESULTS: The overall hospital mortality rate was 15.7%. Patients who were in the intensive care unit immediately before transplantation had the highest hospital mortality rate (32.6%; p = 0.006), incidence of bacterial sepsis (51%; p = 0.001), fungal infection rate (27.6%; p = 0.001), and need for renal support (38.7%; p = 0.001). Preoperative renal dysfunction was significantly associated with sepsis and was reflected in higher hospital mortality rates (29.5%; p = 0.011). Child-Pugh class C was associated with higher mortality rates (23.9%; p = 0.017), an increased incidence of bacterial (37.2%; p = 0.020) and fungal infection (20.3%; p = 0.049), and a 30.4% requirement for postoperative renal support (p = 0.004). CONCLUSIONS: These results emphasize the need for earlier referral and transplantation in patients with advanced liver disease. Further studies are needed to refine identified risk profiles and devise strategies to decrease morbidity and mortality rates.

Aortic revascularization of orthotopic liver allografts: indications and long-term follow-up.

BACKGROUND: Occasionally because of certain conditions that would imperil arterial supply to a hepatic graft, it is necessary to base the arterial supply on the aorta. METHODS: Twenty orthotopic liver transplants (OLTs) in 19 patients were performed with arterial revascularization based on the aorta (Ao-OLT). In two patients the donor celiac axis was anastomosed directly to the aorta and in 18 to a conduit anastomosed to either the supraceliac (n = 10) or infrarenal (n = 8) aorta. RESULTS: One thrombosis occurred 2 months after the placement of a supraceliac conduit in an adult patients, accounting for a cumulative 1-year hepatic artery patency rate of 91.7% +/- 8.0% for 16 grafts placed in 15 adults and 100% for four grafts placed in four children. In comparison, hepatic artery-based transplantation was associated with a 1-year patency rate of 92.6% +/- 1.9% for 245 adults and 94.7% +/- 5.1% for 19 children (difference not significant compared with Ao-OLT). By logistic regression analysis, the only factor independently associated with hepatic artery thrombosis was retransplantation (1-year hepatic artery patency rate 85.7% +/- 5.9% [n = 38] for retransplants vs 93.9% +/- 1.7% for primary transplantation [n = 246]; p < 0.05). For retransplantation, Ao-OLT revascularizations were superior to those based on the hepatic artery (1-year patency rate 100% [n = 11] vs 79.9% +/- 8.1% [n = 27]; p < 0.05). CONCLUSIONS: Indications for Ao-OLT include poor hepatic arterial inflow, small or anomalous recipient hepatic arteries, friable or attenuated native hepatic arteries as may be present during retransplantation, and recipient age less than 1 year, especially those less than 15 kg or in whom the recipient artery is less than 3 mm in diameter. In these more precarious situations, Ao-OLT achieves patency rates similar to those of primary, uncomplicated OLT, is superior for retransplantation, and has technical advantages in the small pediatric liver recipient.

Resource utilization and outcome of liver transplantation for alcoholic cirrhosis. A case-control study.

Liver transplantation for alcoholic cirrhosis remains controversial at some transplantation centers. We compared resource utilization and outcome in alcoholic and nonalcoholic cirrhotic patients undergoing liver transplantation. Data were collected from 56 patients who underwent transplantation for alcohol-related cirrhosis from August 1985 to February 1991 and compared with data from a control group matched for age, sex, Child-Pugh class, and date of transplantation. No significant differences were noted in the resource utilization variables examined or in outcome (as assessed by indicators of early graft function, frequency of sepsis, incidence of rejection, renal function, and retransplantation rate). One-year survival was not significantly different (75% for the alcoholic cirrhotic group vs 76% for the nonalcoholic cirrhotic group). We conclude that liver transplantation for end-stage alcohol-related cirrhosis provides excellent results and that resource utilization appears to be equivalent to that for patients undergoing transplantation for non-alcohol-related cirrhosis.

Liver transplant for fulminant hepatic failure.

Fulminant hepatic failure is a challenging indication for liver transplantation because of associated multiple organ failure, profound neurologic abnormalities and coagulopathy. Sixteen patients have undergone emergent orthotopic liver transplantation for this indication at the University of Michigan, Ann Arbor, Michigan. Despite the associated problems, patient survival (68.2% at 2 years), intra-operative blood product utilization and duration of surgery were comparable to patients receiving liver transplants for other indications. All patients experienced complete recovery from preoperative neurologic abnormalities. Recurrent viral hepatitis did occur but did not result in allograft loss. For selected patients, orthotopic liver transplantation is excellent therapy for patients presenting with fulminant hepatic failure.

Uncertainty analysis of the water balance technique for measuring seepage from animal waste lagoons.

Water balance measurements can be used to estimate seepage rates from animal waste lagoons and earthen storages. This method requires detailed measurements of depth changes and cumulative evaporation during 5- to 10-d periods. Quantifying the uncertainty surrounding the measurements is crucial if data from seepage tests are used to determine if lagoons are meeting engineering specifications and operating within regulatory guidelines. Uncertainty analyses, using a 95% confidence interval, were applied to field data collected during studies of animal waste lagoons in Kansas and Oklahoma. Changes in depth were measured with float-based recorders and evaporation was estimated from meteorological observations. Results showed that rate changes in depth could be measured to within +/-0.28 mm d(-1) or better when wind speeds at the start and end of the test were less than 4 m s(-1). Uncertainty in evaporation was the most significant factor affecting the seepage estimate, and surface temperature and relative humidity were the main sources of imprecision in the evaporation calculations. Evaporation could be estimated to within 10 to 20%, with the largest uncertainty occurring during windy conditions. Uncertainty in the calculated seepage rate increased as evaporation increased. When evaporation rates are low (e.g., <4 mm d(-1)), seepage can be estimated to within +/-0.5 mm d(-1) with 95% confidence. A precision of +/-0.25 mm d(-1) is possible when research-grade instruments are deployed under favorable weather conditions. A measurement duration of 5 d is adequate for most water balance tests. In many cases, precision of the water balance technique will be sufficient in determining if a working lagoon is within regulatory guidelines.

The relation between dimensions of normal and pathological personality and childhood maltreatment in incarcerated boys.

The relation between subtypes of maltreatment and dimensions of personality and personality pathology was investigated in a representative sample of 142 incarcerated Dutch male juveniles. Normal personality dimensions were assessed with the Big Five Inventory, the Dimensional Assessment of Personality Pathology-Basic Questionnaire for Adolescents was used to measure pathological personality dimensions, and the Childhood Trauma Questionnaire was used to assess childhood maltreatment. The five maltreatment subtypes were found to be differentially and uniquely related to the normal and pathological personality dimensions in juvenile delinquents. The association between the abusive subtypes and Emotional Dysregulation depended on the co-occurrence of neglect. It was concluded that subtypes of maltreatment are distinctively related to dimensions of personality and personality pathology, possibly due to specific gene-environment interactions. Further research on this interplay is needed to be able to recognize genetic vulnerability. Early identification of children at risk could aid to limit the long-term consequences of maltreatment.