In utero gene transfer and expression: a sheep transplantation model

Retroviral-mediated gene transfer was used to insert a Neo R gene into fetal sheep hematopoietic cells obtained by exchange transfusion from lambs in utero. After gene transfer the cells were returned to the donor fetus. The lambs were examined after birth for the presence of a functioning Neo R gene. Of ten analyzable animals, six were positive for G418 resistant progenitor cells (CFU-Mix, CFU-C, BFU-E, CFU-E). Two animals were studied for extended periods of time: 8 and 24 months. Each has demonstrated a pattern wherein positive periods are interspersed with times when there were no detectable G418-resistant cells. We conclude that retroviral-mediated gene transfer can be used to insert genes into early progenitor cells of fetal sheep in utero and that the animals can continue to demonstrate blood cells expressing the gene for more than 2 years after birth. This is a US government work. There are no restrictions on its use.     

Pediatric experience with intradialytic parenteral nutrition and supplemental tube feeding

Good nutrition is necessary to maximize the potential for growth and development in the pediatric age-group, but children, like adults with chronic renal failure and end-stage renal disease, may be anorectic and eat poorly. Infants and adolescents are at special risk because of the intense demands of growth during the first 2 years of life and again during puberty. Neurodevelopment is also adversely affected by poor nutrition, especially in infants. Approximately two-thirds of pediatric dialysis patients are treated with chronic peritoneal dialysis, which results in significant protein losses in the dialysis effluent that can contribute to protein-calorie malnutrition. Meeting the nutritional needs of pediatric patients usually requires supplemental sources, such as intradialytic parenteral nutrition (IDPN) or tube feeding. Little is known about the effectiveness or desirability of IDPN in pediatric patients. More studies, especially of amino acid-based dialysis fluids for chronic peritoneal dialysis, need to be done before making IDPN a standard for pediatrics. Supplemental nasogastric or gastrostomy tube feedings have been very successful in maintaining and improving growth in infants, but no studies are available to evaluate their success in older children and adolescents. Recombinant growth hormone therapy, in addition to good nutrition and control of other growth factors such as acidosis, renal osteodystrophy, and chronic volume depletion, may be necessary for most growth-retarded children with chronic renal failure to achieve normal adult height.