Transduction of primitive human marrow and cord blood-derived hematopoietic progenitor cells with adeno-associated virus vectors.

We evaluated the capacity of adeno-associated virus (AAV) vectors to transduce primitive human myeloid progenitor cells derived from marrow and cord blood in long-term cultures and long-term culture-initiating cell (LTC-IC) assays. Single-colony analyses showed that AAV vectors transduced CD34(+) and CD34(+)38(-) clonogenic cells in long-term culture. Gene transfer was readily observed in LTC-ICs derived from 5-, 8-, and 10-week cultures. Recombinant AAV (rAAV) transduction was observed in every donor analyzed, although a wide range of gene transfer frequencies (5% to 100%) was noted. AAV transduction of LTC-ICs was stable, with week-8 and -10 LTC-ICs showing comparable or better transduction relative to week-5 LTC-ICs. Fluorescence in situ hybridization (FISH) analyses performed to determine the fate of AAV vectors in transduced cells showed that 9% to 28% of CD34(+) and CD34(+)38(-) cells showed stable vector integration as evidenced by chromosome-associated signals in metaphase spreads. Comparisons of interphase and metaphase FISH suggested that a fraction of cells also contained episomal vector at early time points after transduction. Despite the apparent loss of the episomal forms with continued culture, the number of metaphases containing integrated vector genomes remained stable long term. Transgene transcription and placental alkaline phosphatase (PLAP) expression was observed in CD34(+), CD34(+)38(-) LTC-ICs in the absence of selective pressure. These results suggest that primitive myeloid progenitors are amenable to genetic modification with AAV vectors.

Elective induction versus spontaneous labor: a retrospective study of complications and outcome.

OBJECTIVE: This retrospective study was undertaken to identify whether electively induced labor places the mother or her fetus at increased risk as compared with her spontaneous labor cohort. STUDY DESIGN: This study compares the labor, delivery, and fetal outcome of 253 parturients in which labor was electively induced with 253 matched controls who began labor spontaneously. All patients were delivered at Huntington Memorial Hospital in Pasadena, California, during the calendar year 1990. The patients were between 37 and 41 weeks' gestation and had no medical or obstetric conditions necessitating induction. The cases and controls were matched for age group, parity, gestational age, and delivering obstetrician. RESULTS: Epidural anesthesia was used in 83.8% of patients in the induction group versus 55.7% in the spontaneous group. Patients with labor induced had a shorter first stage of labor. Meconium staining was found significantly more often in the spontaneous group than in the induced group (16.2% vs 6.7%). This contributed to a greater rate of neonatal consultations in the spontaneous labor group. Although cesarean section rates between the two groups were similar, nulliparous patients in the induction group with an estimated Bishop score of less than or equal to 5 had a 50% cesarean section rate. Iatrogenic prematurity was not encountered. No differences existed between the two groups with respect to intrapartum maternal complications, fetal complications, or postpartum complications. CONCLUSIONS: When compared with spontaneous labor, elective induction of labor at term does not appear to pose an increased risk to the mother or her fetus in a carefully selected patient population. However, elective induction of labor in a nulliparous patient with an unfavorable cervix should be discouraged.