Determination of natural and depleted uranium in urine at the ppt level: an interlaboratory analytical exercise.

An analytical exercise was initiated in order to determine those procedures with the capability to measure total uranium and uranium (238U/235U) isotopic ratios in urine samples containing >0.02 microg U kg-1 urine. A host laboratory prepared six identical sets of twelve synthetic urine samples containing total uranium in the range of 25 to 770 ng U kg-1 urine and with 238U/235U isotopic ratios ranging from 138 (100% NU) to 215 (51% DU). Sets of samples were shipped to five testing laboratories (four based in Canada and one based in Europe). Each laboratory utilized one of the following analytical techniques: sector field inductively coupled plasma mass spectrometry (ICP-SF-MS), quadrupole inductively coupled plasma mass spectrometry (ICP-Q-MS), thermal ionization mass spectrometry (TIMS), and instrumental/delayed neutron activation analysis (I/DNAA), in their analyses.

An examination of uranium levels in Canadian forces personnel who served in the Gulf War and Kosovo.

A uranium bioassay program was conducted involving 103 active and retired Canadian Forces personnel. The total uranium concentrations in each of two 24-h urine collections were analyzed separately at independent commercial laboratories by inductively coupled plasma mass spectrometry (ICP-MS) and by instrumental neutron activation analysis (INAA). The mean and median concentrations were determined to be 4.5 ng L(-1) and 2.8 ng L(-1), respectively, from ICP-MS and 17 ng L(-1) and 15 ng L(-1), respectively, from INAA. The total uranium concentrations were sufficiently low so that isotopic (238U:235U ratio) assays could not be performed directly from urine samples. Isotopic assays were performed on hair samples from 19 of the veterans participating in the testing. The isotopic hair assays were scattered around the natural 238U:235U ratio of 137.8, ranging from 122 +/- 21 to 145 +/- 16 (1sigma). Due to concern expressed in the media over possible depleted uranium exposure and long-term retention in bone, a single bone sample (vertebrate bone marrow) from a deceased member of the Canadian Forces was also analyzed for total uranium content and isotopic ratio by ICP-MS. The sample was shown to have 16.0 +/- 0.3 microg kg(-1) uranium by dry weight and a 238U:238U isotopic ratio of 138 +/- 4, consistent with natural uranium.

Thoracotomy for persistent bronchopleural fistula in the very low birth weight infant.

Although conservative treatment is appropriate for most very low birth weight infants with bronchopleural fistulas, early surgical closure may improve survival in properly selected patients. We report our experience with successful surgical closure in 3 consecutive neonates weighing <800 g.

Academic outcome in long-term survivors of pediatric liver transplantation.

Fifty long-term (3-9 year) survivors of pediatric liver transplantation were assessed using IQ, achievement, and school history measures. Forty-seven of these children had been evaluated before transplantation on intellectual measures, with mean scores for the group found to be in the low average range. At follow-up evaluation, the scores remained in the low average range on all intellectual measures; performance on academic tests was also within the low average range. Thirteen children (26%) were classified as having learning problems based on discrepancies between intellectual and academic function, but only five of them (38%) had received special education services. Nine of the children (18%) had IQ scores less than 70. Academic outcome did not relate to diagnosis, time between diagnosis and transplantation, age at time of transplantation, or average levels of cyclosporin A. Careful assessment and appropriate special education services are indicated to optimize the educational outcome of children who survive liver transplantation.

Epstein-Barr virus PCR correlated with viral histology and serology in pediatric liver transplant patients.

Epstein-Barr virus (EBV)-associated illnesses in posttransplant patients are difficult to diagnose. Attempts to aid in the diagnosis of such illnesses using the polymerase chain reaction (PCR) analysis for EBV have met with variable success due to the potential exquisite sensitivity of the assay. We have designed a relatively insensitive EBV PCR assay and compared the results with objective evidence of EBV activity including serologic response and in situ hybridization for the EBV genome. Eighty-five specimens from 65 patients were analyzed by the EBV PCR using DNA from whole blood. EBV serologic evaluation was done on 53 of the samples and in situ hybridization for EBV (EBER-1 mRNA) on 46 paired liver biopsies. Of 85 samples, 25 (29%) were positive for EBV using the PCR assay. Intensity of amplification was graded 0.5-1+ (weak) to 3+ (strong). Using these criteria, 19 EBV PCR-positive samples were graded 0.5-1+, 5 were graded 2+, and 1 was graded 3+. Of the moderate to strongly positive samples (2+ or 3+), five of six had two or more EBER-1-positive cells in the liver biopsies. Of the remaining 40 liver biopsies with either negative or weak positive PCR results, 3 had only single cells positive for EBER-1; the remainder were negative. In addition, PCR-positive results correlated with increasing EBV anti-early antigen antibody (P = .005) and viral capsid antigen IgG immunoglobulin G VCA (P = .05) EBV-positive results using the PCR assay correlated with objective evidence for increased EBV burden in children after liver transplantation. These preliminary data suggest that this PCR test may be useful to help guide immunosuppressive therapy in the posttransplant patient. Further evaluation using larger numbers of patients will be necessary to confirm this.

Percutaneous transhepatic endoscopic electrohydraulic lithotripsy of biliary tract calculi after orthotopic liver transplantation.

The development of biliary tract calculi after orthotopic liver transplantation presents a unique clinical problem. Previously described techniques for removing biliary stones by shock wave lithotripsy, litholytic therapy with oral bile acids, and endoscopic mechanical extraction may be ineffective or contraindicated in liver transplant patients. For this reason, percutaneous transhepatic electrohydraulic lithotripsy (EHL) was performed using an 11 French flexible ureteroscope in two pediatric patients who developed biliary tract calculi following orthotopic liver transplant. There were no complications and postoperative follow-up over 4 years has been uneventful. To our knowledge, these represent the first reported cases of percutaneous transhepatic endoscopic EHL to fragment biliary tract stones in a transplanted liver, which for us has been a safe and effective therapeutic option.

Epstein-Barr virus-associated leiomyosarcomas in liver transplantation recipients. Origin from either donor or recipient tissue.

BACKGROUND: Leiomyosarcoma, a mesenchymal malignancy with smooth muscle differentiation, is extremely rare in children. Immunosuppression, due to either antirejection medication in organ transplantation recipients or human immunodeficiency virus infection (HIV), appears to constitute a predisposition. METHODS: Two cases of leiomyosarcoma in pediatric liver transplantation recipients were investigated and compared clinically with respect to site of origin and course of the disease and pathologically by routine histology and electron microscopy, by forensic DNA methodology for origin from donor or recipient tissue, and by EBER-1 in situ hybridization for evidence of latent Epstein-Barr virus (EBV) infection. RESULTS: A 9-year-old male developed a high grade, poorly differentiated leiomyosarcoma in his allografted liver 2 years after transplantation, and despite antineoplastic chemotherapy, he died of metastatic disease. The genotype of his tumor indicated an origin from allografted tissue. A 12-year-old female had a low grade retroperitoneal leiomyosarcoma involving the superior mesenteric vein. After resection, she remained disease free without chemotherapy. The genotype of her tumor indicated an origin from native tissue. In both tumors, latent EBV infection was documented. CONCLUSIONS: Neoplastic smooth muscle proliferation in immunosuppressed liver transplantation recipients is analogous to the more common posttransplantation lymphoproliferative disorder in involving transformation of either engrafted donor tissue or recipient tissue elsewhere in the body, in displaying a wide spectrum of histologic differentiation, grade and clinical behavior, and in exhibiting evidence of latent EBV infection.

A survey of psychosocial adaptation in long-term survivors of pediatric liver transplants.

We assessed 41 children and adolescents who had received liver transplants at least 4 years ago, for social, behavioral, and emotional adaptation; physical function; and family stress. We compared their level of adaptive functioning to published data from chronically ill and medically well children. On many measures, transplant recipients had equivalent levels of function to the comparison groups. However, 6- to 11-year-old patients showed mild social and scholastic deficits. Patients' parents report less negative impact of the illness on the family than do parents of other chronically ill children. A listing of medication side effects and the degree to which they are problematic was obtained.

Use of distal splenorenal shunt in children referred for liver transplant evaluation.

Variceal bleeding remains a common cause of morbidity for children with both intrahepatic and extrahepatic portal hypertension. Occasionally, patients referred for liver transplant evaluation have significant variceal bleeding, despite adequate synthetic liver function. During a 7-year period, 322 children were referred for liver transplant evaluation. Six underwent distal splenorenal shunt surgery after evaluation. There were four boys and two girls. The average age was 11 +/- 4 years, and the average weight was 39 +/- 15 kg. The etiology of variceal bleeding was intrahepatic portal hypertension in five (1 biliary atresia, 2 chronic hepatitis, 2 congenital hepatic fibrosis) and extrahepatic portal vein thrombosis in one. Two patients had no previous attempts at sclerotherapy (one because of an abnormality in platelet function, the other because of extensive gastric varices), and four had multiple previous sclerotherapy treatments. No patient had preoperative encephalopathy. Three cases were Child's class A, and three were Child's class B. Preoperative evaluation of the portasystemic system was performed with magnetic resonance (MR) imaging or splenoportography. All patients underwent a distal splenorenal shunt procedure, four of whom also had splenopancreatic disconnection. One patient required 100 mL of blood replacement, and five required no blood. The average length of hospital stay was 9.8 +/- 2.2 days. Postoperative complications were minimal. All patients are alive, without recurrent gastrointestinal bleeding or encephalopathy, and they have patent shunts, which was confirmed by MR or Doppler ultrasound at a mean of 25 +/- 20 months after shunt surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

University of Wisconsin preservation solution compared with Euro Collins preservation solution in pediatric liver transplantation.

Orthotopic liver transplantation has become the accepted treatment for end-stage liver disease in children. To evaluate the efficacy of the University of Wisconsin (UW) preservation solution in pediatric liver transplantation, a group of 34 livers preserved with UW solution was compared in a nonrandomized fashion with a historical control group of 34 livers preserved with Euro Collins (EC) solution. Primary graft nonfunction did not occur in either group. Both groups were similar with respect to age, sex, weight, diagnosis, severity of the recipient's condition, donor condition at harvest, donor/recipient blood type match, and immunosuppressive management. The UW group had a significantly higher bilirubin, AST, ALT, and GGT during the first week after transplantation when compared with the EC group but no significant differences were noted after the ninth post-transplant day. No differences were noted when the groups were compared as to surgery time (9.1 v 8.4 hours), blood volumes replaced (1.8 v 2.0), number of ICU days (5.0 v 6.5), total number of infections per graft (1.0 v 0.8), total hospital days (31 v 30), and hospital cost ($134,000 v $126,000). The total preservation time was improved from 7 hours (range, 3.2 to 9.9) in the EC group to 13.9 hours (range, 6.9 to 22.3) in the UW group (P < .001). UW solution allows a significant increase in cold ischemic time in liver transplantation when compared with EC. This increase in preservation time resulted in no detrimental effect when compared with EC and potentially led to milder episodes of rejection in the postoperative period.

Hepatic artery thrombosis in children with liver transplants: false-positive findings at Doppler sonography and arteriography in four patients.

OBJECTIVE: Patency of the hepatic artery in patients with liver transplants is evaluated with duplex Doppler sonography. In many centers, loss of an arterial waveform in the liver hilum is an indication for immediate arteriography to confirm the presence of hepatic artery thrombosis. We describe the findings in four children with liver transplants in whom occlusion of the graft artery was erroneously suggested by findings on duplex Doppler sonography and angiography. MATERIALS AND METHODS: We describe four patients 14-26 months old who had undergone liver transplant 9 days to 9 weeks earlier. The patients were critically ill with sepsis and hypotension. Duplex Doppler sonography was performed by interrogation of the hepatic artery in the liver hilum and parenchyma. When loss of an arterial waveform in the hilum was identified, angiography was performed immediately. Angiography consisted of aortography in all patients and selective celiac or superior mesenteric angiography in three patients. Autopsy was performed in all patients. RESULTS: Duplex Doppler sonography showed loss of arterial waveforms in the liver hilum in all patients; intrahepatic arterial waveforms were absent in three. The hepatic artery was not opacified at arteriography, but all patients had a patent hepatic artery at autopsy. Postmortem hepatic histology showed massive hepatic necrosis in three patients--necrosis without rejection in two and necrotizing vasculitis associated with severe rejection in one. The fourth patient had minor hepatic parenchymal injury. CONCLUSION: We conclude that failure to show flow in the hepatic artery with duplex Doppler sonography and arteriography is not necessarily indicative of arterial thrombosis. A low-flow nonocclusive phenomenon caused by massive hepatic necrosis or systemic hypotension may not be distinguishable from arterial occlusion.

Cognitive patterns in school-age children with end-stage liver disease.

Although children with end-stage liver disease (ESLD) have been found to have cognitive delays, the relationship between patterns of cognitive function and diagnostic category, age of onset, duration and severity of disease has not been assessed before transplantation. Verbal and performance IQ (VIQ, PIQ) scores and scores on Bannatyne's cognitive factors for 43 children with ESLD were compared with those of 15 control children with cystic fibrosis (CF) and with existing normative data. Children with biliary atresia had deficits in PIQ, spatial and sequential scores. Children with alpha-1 antitrypsin deficiency did not differ significantly from CF controls but did show deficits compared with normative data. Children with onset of disease in the first year of life had deficits on all cognitive measures compared with both control groups. In contrast, children with later onset differed from the normative population only on VIQ and the acquired knowledge factor. In multiple regression analyses, duration of disease and indexes of liver dysfunction combine to predict cognitive scores. These preliminary findings suggest that children with early onset of liver disease are at high risk for cognitive impairment.

Portal vein stenosis complicating liver transplantation in children: percutaneous transhepatic angioplasty.

Portal vein stenosis complicating orthotopic liver transplantation in children is uncommon. The authors report their early experience with transhepatic portal vein angioplasty in the treatment of portal vein stenosis in this setting. The technique was used in two children (aged 2 and 6 years) who had undergone liver transplantation for biliary atresia 15 and 42 months earlier, respectively. Both patients presented with chronic anemia and intermittent gastrointestinal bleeding. The diagnosis of portal vein stenosis was confirmed at fine-needle splenoportography. Access to the portal venous system was gained by means of a transhepatic approach. Low-profile angioplasty balloon catheters were used to dilate anastomotic strictures of the portal vein in both children. At the end of the procedure, the tract within the liver was occluded with gelatin sponge pledgets. Both procedures were technically successful and caused no complications, and in both patients gastrointestinal bleeding ceased.

An approach to ABO-incompatible liver transplantation in children.

Survival in ABO-incompatible (ABO-I) liver transplantation has been reported to be between 40% and 60%. Management techniques have included routine immunosuppression as well as prophylactic antilymphoblast globulin, pre- and posttransplant plasmapheresis (PLPH), and splenectomy. Over a 6-year period, 155 orthotopic liver transplants were performed in 139 pediatric patients. Seven children received an ABO-I allograft. In the latter transplants, immunosuppression consisted of triple-drug therapy (cyclosporine A, prednisone, and azathioprine) along with prospective double-volume PLPH for ABO titers (IgA and IgM) greater than or equal to 1:8. Splenectomy was not performed on any patient. One patient was refractory to PLPH and was treated with a hemofiltration system using an immunoadsorption cartridge with synthetic A group antigen. The overall survival for patients receiving ABO-I allografts was 57% (4/7), with a 67% (4/6) graft survival in those patients treated with PLPH. The graft survival for patients treated with prospective PLPH and MALG was 60% (3/5). There was a 60% incidence of rejection in those patients treated with prospective PLPH and these episodes were all mild (steroid bolus only). While ABO-I transplantation is a reasonable option in the emergency setting, further study is necessary before it should be routinely used to increase the general donor organ pool in pediatric liver transplantation.

Emotional adaptation in children after liver transplantation.

The emotional adaptation of 25 children who had undergone successful liver transplantation at least 1 year previously was evaluated and compared with that of a control group of 26 children with diabetes mellitus, matched for age, gender, and socioeconomic status, and with reported normative values. With the use of parent- and self-report measures, emotional adaptation was assessed in terms of behavioral adjustment (Child Behavior Checklist), depressive experiences (Children's Depression Inventory), anxiety (State-Trait Anxiety Inventory for Children), and self-concept (Piers-Harris Children's Self-concept Scale). Similar variables were also assessed by a projective personality measure (Rorschach). We found minimal differences in emotional adjustment between liver transplant and diabetic groups; on self-report measures, the adjustment of those with liver transplants was as good as, or better than, that of normative samples. However, on other tests, children with transplants differed from normative samples. On projective measures, liver transplant recipients had an increased number of depressive experiences, situationally related internal distress, and a greater tendency toward negative self-focus and evaluation. We conclude that in pediatric liver transplant recipients, behavioral and emotional adjustment is as good as in children with another chronic illness; in comparison with physically well children, the transplant recipients have subtle signs of emotional difficulties.

Neuropsychological function in young children who have undergone liver transplantation.

Presented neuropsychological data from 20 patients between the ages of 4 and 9 years, who had undergone liver transplantation at least 12 months prior to study participation, and compared them to a control group of 20 children with cystic fibrosis. The liver transplant group showed deficits in VIQ, PIQ, visual-spatial and abstraction/reasoning skills, but not in alertness/concentration, motor, or sensory-perceptual functions. On motor and sensory-perceptual tests, no differences were found in direction of lateralization of deficits. Visual-spatial deficits found in this study sample are similar to those found in adults with end-stage liver disease and in a previous report of an overall older group of children following liver transplantation. However younger children have greater evidence of generalized impairment and VIQ deficits which have not been found in older groups. Findings are discussed in relation to possible etiology, location of brain damage, and clinical implications.