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Biomedical subjects

B A Meyer

Publications and source records attributed to B A Meyer.

14 recordsLinked to original sources

The effect of fetal sepsis on umbilical cord blood gases.

The relationship between fetal sepsis and acid-base status is unknown. We hypothesized that in utero sepsis would result in fetal metabolic acidemia. In a retrospective study during a 38-month period, the acid-base status at birth of neonates with in utero sepsis, documented by positive blood cultures, was reviewed. Compared with term neonates, preterm neonates had a 22-fold increase in the risk of bacteremia at birth. In spite of this increased risk of sepsis, there was no significant alteration in arterial pH in preterm septic neonates when compared with preterm controls. Fetal sepsis at term was accompanied by a statistically significant reduction in arterial pH (7.21 +/- 0.07) compared with controls (7.26 +/- 0.06, p less than 0.05). When controlled for other variables, the decrease in arterial pH at term was correlated with an increased duration of labor (7.3 +/- 0.7 in controls vs 10.8 +/- 0.9 hours in neonates with sepsis, p less than 0.05). The classic predictors of chorioamnionitis were found to be poor prognostic indicators of fetal bacteremia. Fetal sepsis at term is associated with a deterioration in the fetal acid-base status and a prolongation of labor.

Acid-Base Equilibrium

The effect of preterm birth on umbilical cord blood gases.

Apgar scores are used routinely to assess early neonatal status, but are less accurate in the preterm neonate because of developmental immaturity. Attention has been directed to umbilical cord gases as a method of neonatal evaluation. Using a retrospective chart review of all viable preterm births (24-36 weeks' gestation) between January 1986 and December 1989, we tabulated the umbilical cord gas indices of these infants. Fetuses with lethal congenital anomalies and those with abnormal heart rate tracings on admission were excluded from the data base, leaving 1872 infants. Cord arterial blood gas values were available for analysis in 74.4% of cases and cord venous gas values in 81.8%. The mean (+/- standard deviation [SD]) arterial and venous umbilical cord blood gas values for the preterm infants, were, respectively: pH, 7.26 +/- 0.08 and 7.33 +/- 0.07; oxygen pressure, 19.0 +/- 7.9 and 29.2 +/- 9.7 mmHg; carbon dioxide pressure, 53.0 +/- 10.0 and 43.4 +/- 8.3 mmHg; bicarbonate, 24.0 +/- 2.3 and 22.8 +/- 2.1 mEq/L; and base excess, -3.2 +/- 2.9 and -2.6 +/- 2.5 mEq/L. Acidemia was defined statistically as 2 SDs or more below the population mean. The incidence of 5-minute Apgar scores below 7 in the preterm infants was 8.5% and within this group, 17.8% were acidemic (arterial pH 7.10 or lower). More than 82% of neonates with 5-minute Apgar scores less than 7 had normal umbilical cord blood gases. There was no significant difference in umbilical arterial blood gas values between preterm infants and 1924 term deliveries at our institution between 1986-1988.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid-Base Equilibrium

The metabolic clearance rate of epinephrine in the fetus of the diabetic ewe.

Delayed organ maturation is a characteristic of the fetus of the diabetic mother with poor glucose control. We hypothesized that the ovine fetal catecholamine maturation sequence would be delayed in the fetus of the diabetic ewe. Twelve pregnant ewes were rendered glucose intolerant by the administration of streptozocin at 85 to 95 days' gestation. Maternal diabetic status was verified with fasting blood glucose assessments. The fetal metabolic clearance rate of epinephrine was determined at 126 to 140 days' gestation by the constant infusion of 0.1 micrograms epinephrine per kilogram estimated fetal weight per minute. Fetal arterial blood gas values, lactate, glucose, and insulin levels were measured before infusion; after 20, 30, and 40 minutes of epinephrine infusion; and 15, 30, and 60 minutes after cessation of infusion. Fetal plasma glucose rose significantly from a control level of 42.1 +/- 8.2 to 64.6 +/- 5.9 mg/dl during the epinephrine infusion (p less than 0.05). Fetal insulin levels increased from a baseline of 9.2 +/- 2.6 microIU/ml to 32.4 +/- 18.0 in the recovery period (p less than 0.05), and lactate levels similarly rose from 36.4 +/- 4.8 to 52.2 +/- 8.2 mg/dl (p less than 0.05). The plasma epinephrine production rates did not vary significantly between fetuses less than 135 and greater than 135 days' gestation (15.4 +/- 1.5 vs 13.9 +/- 2.0 ng/min, p greater than 0.5). The fetal metabolic clearance rate of epinephrine at early gestations (less than 135 days) was similar to that of the fetus of the nondiabetic ewe (35.3 +/- 3.4 vs 28.0 +/- 4.3 ml/min/kg, p greater than 0.2). However, at later gestations (greater than 135 days) the fetus of the diabetic ewe did not have the increase in the metabolic clearance rate previously published for the control fetus (32.0 +/- 4.6 vs 133.7 +/- 41.7 ml/min/kg, p less than 0.05). These data appear to indicate an absence in the maturation of the metabolic clearance rate of epinephrine in the fetus of the diabetic ewe. The observed alteration in the metabolic clearance rate of epinephrine of the fetus of the diabetic ewe could potentially impair the response to stress.

Animals

Streptozocin-induced diabetes mellitus in the pregnant ewe.

To evaluate the effects of streptozocin on maternal pancreatic beta-cell function, we administered the agent to 14 pregnant ewes at 85 to 90 days' gestation on two occasions, 4 days apart. Intravenous glucose tolerance tests were performed before the initial administration, before the second dose, and 4 weeks after the final dose of streptozocin. There was a significant elevation in maternal fasting blood glucose (82 +/- 8.1 mg/dl before streptozocin and 102.6 +/- 6.8 mg/dl after streptozocin, p less than 0.05). Five late-gestation ewes were used as controls, and a significant elevation in fasting plasma glucose levels was found in the streptozocin-treated animals (71.4 +/- 7.1 mg/dl control vs 102.6 +/- 6.8 mg/dl after streptozocin, p less than 0.05). The glucose tolerance test curves showed a significant elevation 4 weeks after streptozocin compared with before streptozocin (p less than 0.05). The maternal insulin response to streptozocin demonstrated a loss of the second-phase insulin response to the glucose load after one dose of streptozocin and loss of the first phase after two doses. The fetuses of the streptozocin-treated ewes showed a significant elevation in plasma glucose level compared with that of controls (13.3 +/- 0.8 mg/dl, n = 5) vs 42.1 +/- 8.1 mg/dl, n = 10; p less than 0.05, control vs streptozocin, respectively). There was a consistent trend to fetal hyperinsulinemia in the fetuses of the streptozocin-treated ewes, although this did not achieve statistical significance (3.3 +/- 0.8 microIU/ml, n = 5 vs 9.6 +/- 2.5 microIU/ml, n = 10; p = 0.06, control vs streptozocin, respectively). The fetal insulin/glucose ratio was preserved in the streptozocin-treated ewes. Comparison of fetal weights between the control and diabetic ewes showed a significant increase in fetal weight in the fetuses of diabetic ewes (3280 +/- 46 gm in control fetuses vs 3710 +/- 54 gm in diabetic fetuses, p less than 0.05). The alterations in the maternal glucose and insulin response resulting from streptozocin-induced pancreatic beta-cell destruction combined with elevations in fetal glucose, insulin, and weight provides a large animal model suitable for investigation of gestational diabetes in pregnancy.

Animals

Evaluation of phenazopyridine hydrochloride as a tool in the diagnosis of premature rupture of the membranes.

This is a prospective study to determine whether a maternal orally administered azo dye, phenazopyridine hydrochloride, would cross into amniotic fluid, and thus be of potential aid in the diagnosis of rupture of the membranes. Based on anecdotal experience, we hypothesized that this compound would cross the placenta and be excreted in the fetal urine, causing discoloration of the amniotic fluid. Ten patients with uncomplicated pregnancies undergoing elective amniocentesis for obstetric indications received an oral dose of 400 mg of phenazopyridine hydrochloride 4 hours prior to the procedure. Amniotic fluid was also available from five control patients who did not receive phenazopyridine hydrochloride. The typical orange-to-red discoloration of the urine was seen in all study patients, indicating ingestion of the dye. None of the ten patients had evidence of the azo dye in their amniotic fluid by visual inspection or by spectrophotometric absorbance. After the amniotic fluid samples were acidified, the presence of the azo dye was visually demonstrable, and spectrophotometry confirmed measurable concentrations (mean +/- SE: 13.08 +/- 0.72 micrograms/ml). We conclude that although phenazopyridine hydrochloride does cross the placenta into the fetal compartment, its presence causes a visual and spectrophotometric change in the color of amniotic fluid only when the normal basic pH of amniotic fluid is acidified.

Amniotic Fluid

Placental thromboxane and prostacyclin production in an ovine diabetic model.

We hypothesized that streptozocin-induced ovine diabetes would cause alterations in the placental production of thromboxane and prostacyclin. With a tissue incubation technique, we examined the placental production of thromboxane and prostacyclin in cotyledons from seven normal near-term ewes (127 +/- 3 days' gestation) and six streptozocin-induced diabetic ewes (125 +/- 3 days' gestation). Diabetic status was verified with serial fasting blood glucose assessments. Placental tissue was incubated in Dulbecco's modified Eagle's medium for 48 hours at 37 degrees C with 95% oxygen and 5% carbon dioxide. Samples were collected at 0, 1, 2, 4, 8, 20, 32, and 48 hours. Radioimmunoassay of the stable metabolites thromboxane B2 and 6-keto-prostaglandin F1 alpha were used to determine thromboxane and prostacyclin production, respectively. Placental thromboxane production was reduced in diabetic animals when compared with control animals (5.63 +/- 2.81 vs 7.32 +/- 1.37 pg/mg per hour, respectively; p less than 0.05). Prostacyclin production was also significantly reduced in the diabetic placentas compared with control placentas (11.44 +/- 4.06 vs 16.29 +/- 4.59 pg/mg per hour, respectively; p less than 0.05). We conclude that the ovine placenta produces thromboxane and prostacyclin. The ovine thromboxane production rate is comparable to that of the human placenta but the prostacyclin production rate is approximately two to three times higher. The observed decrease in the placental production of thromboxane and prostacyclin may reflect an adverse effect of hyperglycemia directly on eicosanoid production or indirectly through decreased placental cellular proliferation.

6-Ketoprostaglandin F1 alpha

Hemodynamic effects of leukotriene C4 in ovine fetus.

Leukotrienes are synthesized during pregnancy and produce cardiovascular effects in adults. We hypothesized that leukotriene C4 would cause vasoconstriction in the fetus and placenta. Eight near-term, unanesthetized ovine fetuses were studied before and after infusion of 10 micrograms leukotriene C4 (LTC4) into the fetal vena cava. Cardiovascular monitoring of maternal and fetal arterial pressures and heart rates was performed. Fetal blood flows were measured by the radioactive-microsphere technique. Sustained elevations in systolic and diastolic blood pressure and decreased fetal heart rate began by 1 min and returned to baseline by 30 min. Arterial pH fell from 7.33 +/- 0.01 to 7.29 +/- 0.01 at 15 min (P less than 0.05) and to 7.29 +/- 0.01 at 30 min (P less than 0.05), with a significant increase in base deficit from 0.7 +/- 0.7 to 3.5 +/- 0.7 at 15 min (P less than 0.05) and to 2.9 +/- 1.0 at 30 min (P less than 0.05). Fetal PO2 and PCO2 were unchanged. Significant decreases in blood flow and resistance were seen in the umbilical placental circulation as well as in fetal skeletal muscle and intestine. Blood flow and resistance were unchanged in the renal and adrenal vascular beds. Fetal administration of LTC4 caused no changes in maternal cardiovascular parameters. These findings represent the first in vivo studies of the effects of a lipoxygenase metabolite on fetal-placental blood flow.

Animals

The effect of magnesium sulfate tocolysis on the fetal biophysical profile.

The biophysical profile has proved to be a valuable tool for the assessment of fetal well-being, independent of gestational age. Magnesium sulfate is commonly used as a tocolytic agent, yet relatively little is known about its effects on the biophysical activities of the fetus. To investigate the effects of magnesium sulfate on the biophysical profile, we performed serial studies on patients who received tocolytic therapy with this agent because of preterm labor. A total of 16 women with 22 fetuses at 26 to 34 weeks' gestation in spontaneous preterm labor were studied. An initial biophysical profile was performed at the time of admission, and a second examination was performed when maternal serum magnesium levels reached 6 to 8 mg/dl. On admission all fetuses had reactive nonstress test results and 21 of 22 (95%) demonstrated sustained fetal breathing movements. With magnesium sulfate tocolysis, 50% of fetuses had nonreactive nonstress test results, and only 4 of 22 (18%) demonstrated sustained fetal breathing movements. Fetal tone, gross body movements, and amniotic fluid volume were found to be unaffected by magnesium sulfate tocolysis.

Adult

Lactation and phenylketonuria.

Many young women who were diagnosed as having phenylketonuria (PKU) during routine neonatal screening and effectively treated during childhood are now of childbearing age. Recent reports suggest that maternal dietary therapy instituted before conception may improve the likelihood of a successful pregnancy and normal offspring. However, it is not known whether the intake of phenylalanine (phe) should be restricted during lactation. While phe levels in breast milk from women with PKU are markedly elevated, to our knowledge serum phe levels have not been measured in nursing newborn infants of PKU mothers. The present case report describes the pregnancy and early lactation of a mother with PKU, including serial measurements of serum phe levels in her offspring while being breast-fed.

Adult

Activity level of mother's usual occupation and low infant birth weight.

Previous studies of the effect of mother's employment on infant birth weight have shown mixed results. This study was designed to explore the relationship between activity level of a woman's occupation and her risk of delivering a low-birth-weight infant. Using 1981 state of Washington birth certificate records, the authors selected 5,822 subjects. Case subjects were women who had delivered infants weighing 2,500 g or less; controls were those who had delivered normal-weight infants. Women were grouped into five activity levels based on their usual occupation. No association was detected between activity level of mother's usual occupation and delivery of a low-birth-weight infant. These data suggest that active work is not associated with an increased risk of having a low-birth-weight baby.

Adult

A student teaching module: physician errors.

The subject of physician errors which harm patients was presented in an Introduction to Clinical Medicine (ICM) course for first-year medical students at the University of Washington in 1986. Students read specified articles, attended a faculty panel discussion, and participated in small discussion groups. One year after the session, students were surveyed. Most of the students found the reading materials provocative and appreciated the opportunity to discuss a subject they think about often. Of the respondents, 88% believed the topic should continue to be included in the first-year ICM course. The results suggest that the first year of medical school is an appropriate time to begin to discuss the fallibility of physicians and how physician errors are handled.

Curriculum