We have developed a micro-injection technique to deliver recombinant adenovirus and AAV to mouse fetuses at day 15 after conception. Several routes of delivery, including injections to the amniotic fluid, the front limb, the placenta, the liver, and the retro-orbital venus plexus, were tested using an E1-deleted recombinant adenovirus (Ad.CBlacZ) or a recombinant adeno-associated virus (AAV.CMVlacZ) carrying a ␤-galactosidase (lacZ) gene. Injection of Ad.CBlacZ into the amniotic cavity led to transgene expression in the skin and in the digestive tract of the fetuses. Injection of Ad.CBlacZ in the front limb resulted in LacZ expression in all major muscle groups around the injection site and at low levels in the liver. The other three routes of delivery, ie intraplacental, intra-hepatic and retro-orbital injections of Ad.CBlacZ, all led to lacZ expression predominantly in the liver. Further studies revealed a maximal tolerant dose

SummaryAt 0-3 days of age the plasma ammonium concentration in full term appropriate for gestational age (AGA) infants was (mean 2 SEM) 27.5 & 0.5 pM; a value similarlo that reported * in adults. Ammonium levels in low birthweight AGA and SGA groups were 47.0 + 2.0 p M and 45.1 r 3.3 p M respectively; significantly elevated (P < 0.001) as compared to the full term group. These increased ammonium levels persisted at 3-5 weeks of age. Associated with the hyperammonemia was a significant (P < 0.01) decrease in plasma a-ketoglutarate concentration:11.8 r 1.0 pM, in the low birthweight AGA as compared to 20.7 r 0.6 p M in the full term AGA infants. There was an inverse linear correlation between ~l a s m a concentrations of ammonium and a-ketoglutarate r = -0.86, P < 0.001. Urinary orotate excretion was significantly elevated (P < 0.05) in low birthweight AGA infants. There was no difference in the plasma concentrations of glutamine, glutamate, or alanine among the various groups. Hyperammonemia was not associated with neurologic dysfunction. SpeculationThere is a greater accumulation of ammonium in low birthweight as compared to full term infants. This may be a consequence of a developmental delay of one or more of the enzymes required for urea synthesis. Alternatively, the hyperammonemia may be related to arginine andlor ornithine diversion out of the cycle and incomplete repletion of ornithine from glutamate via the A'-pyrroline-5-carboxylate pathway.were measured once or twice a week on capillary blood during the first 2 months of life. Plasma a-ketoglutarate concentration and urinary orotate excretion were also measured at 0-3 days of age in 30 infants. Plasma ammonium determinations were performed within 30 min of blood drawing using a cation exchange resin, AS previobsly described (3). The normal adult range is 15-33 pM. Glutamine (18), glutamate (4), alanine (30), and a-ketoglutarate (16) were measured by modifications of enzymatic fluorometric techniques, allowing capillary plasma to be used. Urinary orotate was measured by the method of Goldstein et al. (11). A neurologic examination as described by Prechtl and Beintema (20) was performed on the low birthweight infants at 0-3 days of age. RESULTSThe full term group consisted of 25 males (22 were black) and 27 females (25 were black); the low birthweight groups consisted of 14 males (11 were black) and 22 females (20 were black).Birthweights of the groups were (mean + SEM): full term 3261 + 59 g, low birthweight SGA 1848 + 185 g, and low birthweight AGA 1963 + 79 g. Gestational age in the groups were (mean + SD): full term AGA 39 + 1.5 weeks, low birthweight SGA 37 + 3 weeks and low birthweight AGA 33 + 2.5 weeks. All infants received a proprietary milk formula (Similac) containing 1.5 g protein/100 ml, 18 parts bovine whey protein to 82 parts bovine caseins. Mean protein intake was similar in all groups at 3-5 weeks of age (3.0 g/kg/day) and was higher in the full term group during the first 3 days of life (1.7 compared to 1.2 &kg/ day). At 0-3 days of age,...

We studied promotions at Johns Hopkins University School of Medicine to determine whether clinician-teachers are less likely to be promoted or are promoted later in life than researchers and whether those who are promoted have more articles published than those who are not promoted. Over a five-year period, 93 percent of candidates for the rank of associate professor and 79 percent of the candidates for the rank of professor were promoted. There were no significant differences between clinical and research faculty members in terms of the probability that they would be promoted or their age at promotion to either associate professor or professor. Despite these findings, the responses to a questionnaire indicated that former faculty members perceived clinician-teachers as less likely than researchers to be promoted. Those who were promoted had had about twice as many articles published in peer-reviewed journals as those who were not promoted. We recommend improved counseling of medical school faculty members and more extensive discussion of the criteria for promotion and the chances of academic success.