Occult hepatitis B viral DNA in liver carcinomas from a region with a low prevalence of chronic hepatitis B infection.

Occult hepatitis B is defined by the presence of hepatitis B viral (HBV) DNA in the serum or liver in persons lacking hepatitis B surface antigen (HBsAg) in the serum. A high prevalence of occult HBV has been reported in hepatocellular carcinoma (HCC) from Asia, but little information is available on the prevalence of occult HBV in HCC from regions with a low prevalence of typical chronic hepatitis B infection. In a retrospective study, 19 cases of primary liver cancer were investigated for the presence of occult HBV DNA by amplification of the surface, core, and X gene. In addition, HBV copy numbers were quantitated by real time polymerase chain reaction, genotyped, and samples tested for covalently closed circular HBV DNA, which is a marker of active viral replication. Occult HBV was found in three of 19 cases (16%). Genotyping was successful in two cases, both of which were genotype A. HBV DNA copy numbers were low, all less than 10 copies/microg liver DNA. No closed circular HBV DNA was detected. Thus, in this study occult HBV was of genotype A and was found in a low percentage of cases of HCC and was associated with low tissue HBV DNA copy numbers and no detectable evidence for viral replication.

Kidney transplantation in young children: should there be a minimum age?

The optimal age for transplantation in children with end-stage renal disease remains controversial. Many centers have adopted a policy of waiting until such children reach a certain minimum age or weight, maintaining them on chronic dialysis until then. Their policy is based on historical data showing inferior graft survival in very young children. We feel that with proper donor selection and recipient care, comparable results can be achieved in very young age groups. We herein present our results with kidney transplantation in children <1 year old. Between 1 January 1984 and 31 December 1999, we performed 321 kidney transplants in children < or =13 years at the University of Minnesota. We analyzed our results in three age groups: <1 year (n=30), 1 through 4 years (n=122), and 5 through 13 years (n=169). We found no significant differences in patient or graft survival rates between the three groups. Almost all our infant (<1 year) recipients underwent primary transplants from living donors (LDs). However, even when we compared results only of primary LD transplants between the three groups, we found no significant differences. To date, all our infant recipients are alive and well, 24 (80%) with a functioning original graft. Causes of the 6 graft losses were chronic rejection (n=3), vascular thrombosis (n=2), and recurrent disease (n=1). Infants had significantly lower incidences of acute and chronic rejection compared with older recipients, but a tendency to higher incidences of delayed graft function and vascular thrombosis. Infants had significant increases in weight post transplant: the mean standard deviation score rose from -2.8 pre transplant to -0.2 by age 5 years and to +1.8 by age 10 years. The improvement in height was less marked: the mean standard deviation rose from -3.2 pre transplant to -1.6 by age 5 years and to -1.4 by age 10 years. Kidney transplant results in very young children can be comparable to those in older children. There need be no minimum age for performing a kidney transplant. The timing of the transplant should not be based on age or size alone.

Pharmacokinetics of FK506 after intravenous and oral administration in patients awaiting renal transplantation.

The authors examined the safety and pharmacokinetics of FK506, a new hepatically metabolized immunosuppressant, after single-dose intravenous (i.v.) infusion (20 micrograms.kg(-1) x 4 hours-1) and oral (80 micrograms/kg) administration in six nondialysis patients, aged 27 to 53 years, with chronic renal failure awaiting transplantation. A two-period, randomized, crossover study protocol was used with blood samples drawn for 72 hours after each dose and a washout period of 4 days. Whole-blood FK506 levels were determined using a standard, two-step, nonspecific enzyme immunoassay. There were no significant changes in vital signs, EKG, or complete laboratory test battery for any patient during the entire study period. No side effects were noted after i.v. or oral FK506 dosing. Mean +/- SD distribution half life was 0.9 +/- 0.2 hours, elimination half life (t1/2 beta) 33 +/- 8 hours, total body clearance (CL) 2.4 +/- 1.1 L/hour, and bioavailability 14 +/- 12%. There was no significant correlation between serum creatinine (Cr) and CL (r = 0.36) or between Cr and t1/2 beta (r = -0.30). It was found that FK506 is incompletely and erratically absorbed after oral administration and is rapidly distributed outside the blood compartment after IV dosing. An extended sampling period seems necessary to accurately characterize the slow elimination phase of FK506.

Kidney transplantation in patients with type I diabetes: 26-year experience at the University of Minnesota.

With current immunosuppressive protocols, 1- and 6-year graft survival is similar in diabetic and nondiabetic kidney transplant recipients. Living-donor transplant recipients have significantly better outcome. Death with function and chronic rejection remain the 2 predominant causes of graft loss for diabetic recipients. Compared with national statistics on diabetic patient survival on dialysis, our data suggest that transplantation is the treatment of choice for diabetic patients with end-stage renal disease.

Neurodevelopmental outcome and school performance of very-low-birth-weight infants at 8 years of age.

The neurodevelopmental outcome and school performance of 50 appropriate for gestational age (AGA) and 33 small for gestational age (SGA) very-low-birth-weight (VLBW) infants, compared to a control group (41 Term infants) were assessed at 8 years of age. The incidence of major handicaps among AGA and SGA/VLBW infants respectively, was 16% and 6%. No major handicap was found in the control group. The incidence of neurodevelopmental abnormalities (NDA) among AGA's (40%) and SGA's (57.6%) compared with the control group (31.7%) was found to be significantly higher. School failure occurred more frequently among VLBW infants (22.9%) and was related in children with NDA--and more particularly among AGA's--to the presence of language disorders or associated NDA. Evaluation of the consequences of NDA and school problems for later academic and professional achievement now requires further follow-up studies.

Neurodevelopmental abnormalities in preschool children with high perinatal risk. Prognostic value and consequences on education at 8 years of age.

Two groups of 41 children with high perinatal risk were studied. All children of the study group (SG) had neurodevelopmental abnormalities (NDA) at the age of 5 years, without major handicap. The control group (CG) consisted of 41 children matched for sex, neonatal pathology, birthweight, gestational age and socioeconomic status, without NDA at 5 years. In the SG 85.4% of the children had persistent NDA at school age. In the CG 36.6% of the children presented NDA, but less severe than those of the SG. The SG children had more often associated NDA than those of the CG. The outcome of NDA diagnosed at preschool age and the results of psychometric tests are described. Associated NDA or a borderline IQ, with emotional and behavioral problems, have a gloomy school prognosis. 46.3% of the children in the SG had major schooling problems and 12.2% of children in the CG. These results show the possibility to detect children at risk of school achievement problems before school entrance; they might be useful in counselling and preventing behavioral and educational difficulties.