Teaching teamwork during the Neonatal Resuscitation Program: a randomized trial.

OBJECTIVE: To add a team training and human error curriculum to the Neonatal Resuscitation Program (NRP) and measure its effect on teamwork. We hypothesized that teams that received the new course would exhibit more teamwork behaviors than those in the standard NRP course. STUDY DESIGN: Interns were randomized to receive NRP with team training or standard NRP, then video recorded when they performed simulated resuscitations at the end of the day-long course. Outcomes were assessed by observers blinded to study arm allocation and included the frequency or duration of six team behaviors: inquiry, information sharing, assertion, evaluation of plans, workload management and vigilance. RESULT: The interns in the NRP with team training group exhibited more frequent team behaviors (number of episodes per minute (95% CI)) than interns in the control group: information sharing 1.06 (0.24, 1.17) vs 0.13 (0.00, 0.43); inquiry 0.35 (0.11, 0.42) vs 0.09 (0.00, 0.10); assertion 1.80 (1.21, 2.25) vs 0.64 (0.26, 0.91); and any team behavior 3.34 (2.26, 4.11) vs 1.03 (0.48, 1.30) (P-values <0.008 for all comparisons). Vigilance and workload management were practiced throughout the entire simulated code by nearly all the teams in the NRP with team training group (100% for vigilance and 88% for workload management) vs only 53 and 20% of the teams in the standard NRP. No difference was detected in the frequency of evaluation of plans. CONCLUSION: Compared with the standard NRP, NRP with a teamwork and human error curriculum led interns to exhibit more team behaviors during simulated resuscitations.

Response of placental vasculature to high glucose levels in the isolated human placental cotyledon.

We report the effect of high glucose infusion on vascular resistance in isolated human placental cotyledons perfused with Krebs-Ringer-bicarbonate solution containing 80 mg/dl (4.4 mmol/L), 160 mg/dl (8.8 mmol/L), or 320 mg/dl (17.6 mmol/L) D-glucose (n = 6). Placental vascular resistance remained constant during 25-minute perfusion periods with 80 mg/dl followed by 160 mg/dl glucose solution. Subsequent perfusion with 320 mg/dl glucose produced a significant increase in placental vascular resistance. Placentas were also studied in which the placental cotyledon was sequentially perfused for 25-minute periods with solutions containing glucose at 80 mg/dl followed immediately by 320 mg/dl (n = 5). Placental vascular resistance remained constant throughout perfusion with 80 mg/dl glucose solution but increased significantly after beginning perfusion with 320 mg/dl glucose. We conclude that the increase in placental vascular resistance appears to be a function of the high glucose level rather than the duration of glucose perfusion.

Bladder injury and uroascites from umbilical artery catheterization.

Umbilical artery catheterization in the newborn can lead to perforation of the bladder or urachal remnant with extravasation of urine into the peritoneal cavity. We present a case of such an injury that led to uroascites and respiratory distress. This injury usually requires prompt surgical repair for resolution.

Ontogeny of ovine fetal liver and kidney plasma membrane insulin receptors and fetal growth.

This investigation was performed to define certain characteristics of insulin-receptor interaction during the last 2 months of gestation in fetal sheep liver and kidney. Twenty-one sheep carrying a total of 46 fetuses were sacrificed at various gestational ages from 94 days to term; fetal and maternal livers and kidneys were analyzed by a radioreceptor assay for insulin binding characteristics. Specific binding of insulin to partially purified ovine fetal liver and kidney plasma membranes increased as gestation approached term, at which time specific binding was two- to fourfold greater to fetal than to maternal tissues. Associated with increased specific binding were late gestational increases in affinity of insulin for receptors in both fetal liver and kidney and an earlier increase in insulin receptor concentration in fetal kidney. These observations in fetal sheep liver and kidney are similar to reported observations in other species. However, the increase in specific binding of insulin to male fetal liver membranes was exponential; in contrast, there was no apparent increase in specific binding to female fetal liver membranes during the gestational interval surveyed. Both the weights and the vertebral column lengths of these fetuses were shown by multivariate analysis to be significantly affected by the interaction between specific binding of insulin and fetal sex. However, in 30 additional sheep fetuses we observed no difference between male and female fetuses in the increase with time in liver glycogen content. The lack of sex difference in this postreceptor event is consonant with the demonstrated dissociation between liver insulin receptors and glycogen synthesis in the late fetal rat. Our observations suggest that late gestational differences between male and female sheep fetuses in insulin specific binding to liver and, possibly, to other tissues such as cartilage, muscle, and/or fat, that are coupled to postreceptor events may account for differences in fetal growth between the sexes.

Effects of ovine maternal hyperglycemia on fetal regional blood flows and metabolism.

Fetal combined ventricular output (CVO) and regional distribution of blood flow were measured in 12 ewes in late gestation by the radiolabeled microsphere method. Three sets of determinations were made in sequence beginning with a control study and repeating the measurements after the ewe had received intravenous glucose at 0.35 g X min-1 for 90 min and again after the ewe had received glucose at 0.85 g X min-1 for a second 90-min period. Maternal whole blood glucose concentrations were 2.98 +/- 0.18 (means +/- SE), 10.43 +/- 0.45, and 21.59 +/- 0.90 mM during the respective study periods. Fetal CVO did not change during maternal hyperglycemia; however, it was redistributed, with a decrease in umbilical blood flow to the placenta from 43.5% of CVO to 31.9 and 30.8%, respectively. The fetal carcass, heart, intestines, kidneys, liver, and adrenals each received increased percent CVO; these increases equaled the decrease in placental blood flow. Fetuses became hypoxemic and developed a mixed acidemia during induced maternal hyperglycemia, but oxygen delivery to the heart, brain, and kidneys was unchanged. These observations indicate that maternal hyperglycemia results in previously unsuspected fetal cardiovascular responses.

Decreases in ovine fetal cartilage sulfate uptake and serum sulfate during gestation.

In vitro assays for [35S]sulfate uptake by ovine fetal costal cartilage were used to assess gestational changes in cartilage metabolism. Addition of 20% normal human serum to the incubation medium increased fetal cartilage [35S]sulfate incorporation into glycosaminoglycans. Both basal and human serum-stimulated uptakes of [35S]sulfate by fetal sheep cartilage decreased from midgestation to full term. The incremental response in [35S]sulfate uptake that was stimulated by human serum decreased as gestation proceeded to full-term. Fetal serum sulfate concentration decreased logarithmically during gestation, raising the possibility that cartilage sulfate uptake might become substrate limited as full term is approached. Perfusion of seven late gestation sheep fetuses for 7 days with Na2SO4 to achieve serum sulfate concentrations similar to those observed earlier in gestation resulted in a 33% increase in mean cartilage [35S]sulfate uptake compared with that of control twin fetuses, but uptake was not increased to values that occurred spontaneously earlier in gestation. These results suggest that the decreasing rate of [35S]sulfate uptake by fetal cartilage during the last half of gestation is associated only minimally with decreasing serum sulfate levels and is most consistent with intrinsic change in resting chondrocyte metabolism during gestation.

Contraplacental hypogastrinemic effect of gastrin infusion in sheep.

Infusion of gastrin, G-17I, at 0.4 microgram/min into either the maternal or fetal venous circulation of six late gestation sheep was associated with increases in serum gastrin concentration in the infused circulation and reciprocal decreases in the serum gastrin concentration in the other circulation (contraplacental) that perfused the placenta. Pentagastrin infusion at 0.4 microgram/min was associated with an increase in C-terminal specific gastrin immunoreactivity in both the infused and the contraplacental circulations. These observations suggest that biologically active fragments of gastrin, but not the intact molecule, may cross the ovine placenta. An alternative explanation for our results is that gastrin infusion into either the maternal or fetal circulation which perfuses the placenta may result in the release of an inhibitor (i.e., somatostatin) into the other circulation. Of broad importance, these observations indicate that although intact polypeptide hormones may not traverse the placenta, their concentrations in maternal and fetal sera may not be as independent as previously believed. Serum gastrin half-life values in late gestation sheep fetuses, lambs, and ewes were determined to be 13.7 +/- 1.9, 16.7 +/- 2.6, and 15.2 +/- 2.8 min, respectively. These similar values indicate that the relatively high serum gastrin concentrations observed in near-term sheep fetuses are not the result of prolonged half-life in the fetus.

Umbilical glucose and lactate extractions during maternal hyperglycemia in sheep.

Umbilical glucose and lactate extractions were determined in previously instrumented pregnant ewes into some of which D-glucose was infused to produce graded levels of maternal hyperglycemia as great as 20 mM. While fetal arterial glucose concentration continued to increase linearly as a function of maternal arterial glucose concentration during maternal hyperglycemia, the umbilical venoarterial difference in blood glucose concentration did not, and umbilical glucose extraction approached a plateau at approximately 0.063 mmol X min-1 X kg fetus-1 at maternal glucose concentrations greater than approximately 8 mM. The observed plateau in glucose extraction is consistent with saturation at high maternal glucose concentrations of the carrier mechanism for transport of glucose from the maternal to the fetal aspects of the trophoblast. The observed value of the plateau in umbilical extraction of glucose is slightly less than the maximum extraction predicted from previously published equations for this species, but the maternal blood glucose concentration at which the observed maximum occurred agrees closely with the value predicted by those equations. Umbilical lactate extraction, 0.031 +/- 0.021 mmol X min-1 X kg fetus-1, was independent of maternal arterial blood glucose and lactate concentrations and was independent of umbilical glucose extraction.

Effect of maternal serum insulin on umbilical extraction of glucose and lactate in fed and fasted sheep.

In 18 chronically instrumented pregnant ewes in late gestation, umbilical extractions of glucose and lactate were determined before and during the continuous infusion of ovine insulin, 0.25 mU/kg . min, into one uterine artery. Studies were conducted in both well-nourished and fasting ewes. Exogenous insulin increased the umbilical extraction of glucose without altering the umbilical extraction of lactate over the range of concentrations of maternal blood glucose encountered in the fed and fasted states. Moreover, the efflux of lactate into the uterine venous circulation in two additional ewes was not altered by the administration of insulin. These studies support the hypothesis that maternal circulating insulin binds to insulin receptors on the microvillous brush border of the placenta to effect an increase in the carrier-mediated transfer of glucose rather than cause an intraplacental decrease in the catabolism of glucose to lactate. The results suggest that, as maternal levels of blood glucose and serum insulin spontaneously rise in concert over the physiologic range, both factors may contribute to the increasing umbilical extraction of glucose. Furthermore, these observations raise the possibility that decreased binding of insulin by placental insulin receptors, which is reported to occur in placentas from diabetic women, may be accompanied by a relatively decreased umbilical uptake of glucose for a given maternal concentration of glucose, but not of lactate.

Plasma alpha-fetoprotein concentrations in pregnant cows exposed to Sarcocystis cruzi, Campylobacter fetus, or Aspergillus fumigatus.

Bovine alpha-fetoprotein (AFP) was determined in maternal plasma, using radioimmunoassay in an attempt to detect and monitor fetal distress in pregnant cows. Plasma from pregnant cows in the 4th to 5th month of the gestation which had been exposed to Sarcocystis cruzi, Campylobacter fetus, or Aspergillus fumigatus was used. Plasma AFP concentrations were determined at intervals from before the cows were exposed until they had aborted or calved. The plasma AFP concentration of the exposed pregnant cattle remained at 6.5 +/- 5.0 mg/ml until 24 to 48 hours before abortion or parturition, when the value increased to 25.0 +/- 8.0 ng/ml. This pattern was similar for cattle exposed to each of the infective agents. Unlike in persons, rats, or monkeys, fetal-maternal transfer of AFP seems to be minimal in cows even with inflammation or necrosis of the placentome, Thus, changes in AFP concentrations in bovine plasma cannot be used as a diagnostic tool for fetal distress or fetal death.

Ontogeny of tissue and serum gastrin concentrations in fetal and neonatal sheep.

We investigated the perinatal ontogenic changes in ovine serum and tissue gastrin concentration. Fetal and maternal serum gastrin levels in serums obtained from indwelling catheters in the fetal and maternal circulations and tissue gastrin levels were assessed by radioimmunoassay and immunohistochemistry. Fetal serum gastrin concentration was undetectable until the 107th day of gestation and significantly increased to levels surpassing maternal values. Neonatal serum hormone concentration continued to rise, reaching a peak during the 4th postnatal wk and decreasing after the 4th wk coincident with weaning. Maternal serum gastrin concentration did not vary during pregnancy and did not correlate with fetal serum gastrin levels. Fetal abomasal and duodenal gastrin concentrations and abomasal G-cell number increased in parallel with the developmental alterations in fetal serum hormone levels during gestation. The developmental increase in abomasal gastrin concentration was not associated with a shift in the molecular form of the hormone. These findings support the hypothesis that circulating gastrin in the fetus is of fetal origin.

Hydrolysis of dipeptides by human and ovine placentas.

Human and ovine placental tissue homogenates were assayed for dipeptidase activity in vitro. Glycyl-L-leucine, L-leucyl glycine, glycyl-L-lysine, and L-lysyl glycine were hydrolyzed by placental homogenates. The pH optimum for the reaction was 8.0. The relationship between enzyme activity and concentration was linear for placental homogenate concentrations between 0.01 and 0.10 mg protein/ml of reaction mixture. Enzyme activities were 1.92 +/- 0.12 (S.E.) micromoles/min/mg protein for hydrolysis of glycyl-L-leucine, 0.34 +/- 0.06 (S.E.) micromoles/min/mg protein for hydrolysis of glycyl-L-lysine by human placenta, and 2.79 +/- 0.80 micromoles/min/mg protein and 0.41 +/- 0.25 micromoles/min/mg protein, respectively, by ovine placenta. The infusion of glycyl-L-leucine into the uterine artery of unstressed catheterized pregnant ewes yielded increased concentrations of both component amino acids in uterine venous blood and of leucine in umbilical venous blood.

Effects of fasting on uterine blood flow and substrate uptake in sheep.

Twelve chronically instrumented late-gestation ewes fasted for 5 days were found to have a 25% decrease in total uterine blood flow and a 20% decrease in placental blood flow. Cardiac output was unchanged but was redistributed, as measured by radiolabeled microspheres, in a pattern similar to that produced by catecholamines. Fasting also was associated with hypoglycemia and altered whole blood amino acid concentrations. Uterine uptakes of glucose, oxygen, essential amino acids and glutamine, an important uterine and fetal nutrient, were decreased significantly during fasting. The increased hepatic blood flow and decreased arterial concentrations of glucogenic amino acids observed during fasting are consistent with a redistribution of maternal cardiac output to support maternal hepatic gluconeogenesis at the expense of nutrient supply to the gravid uterus.