Glucocorticoids and the respiratory distress syndrome.
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Biomedical subjects
Publications and source records attributed to J W Johnson.
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In the present study, we sought to assess the clinical efficacy of the optical density of amniotic fluid at 650 nm (A650) to predict lung maturity in the human fetus. The A650 of 113 samples of amniotic fluid obtained from 16 to 45 weeks' gestation was determined. Mature values (A650 greater than or equal to 0.11) were not observed until 35 weeks' gestation but were always present after 39 weeks' gestation. In those infants delivered within 48 hours of amniocentesis, the absence rates of respiratory distress syndrome were the same with a mature lecithin/sphingomyelin (L/S) ratio (97.9%) and a mature A650 (97.3%). However, immature values in both tests were poor prognosticators of respiratory distress syndrome, with a rate of 37.5% with the immature L/S ratio and 15.8% with the immature A650. A mature A650 may be substituted for the L/S ratio, but an immature A650 is less reliable. In addition, we found that differences in centrifugation altered the A650 value, whereas exposure to light and cold storage did not.
Six patients with the congenital anomaly, pancreas divisum, and recurrent acute pancreatitis were treated surgically. The diagnostic triad of multiple episodes of abdominal pain with elevated serum amylase and identification of the anomaly by ERCP was present uniformly. Sphincteroplasty of the ampulla of Vater and ductoplasty of the accessory papilla were performed in five patients. One patient had sphincteroplasty only due to failure to identify the accessory duct. Two patients eventually required major pancreatic resection for pain relief. Three additional patients were identified and managed nonoperatively. Data of 44 patients with surgically treated pancreas divisum have been collected from the literature. Review of these patients indicates that dual sphincteroplasty or dorsal ductoplasty are the two most frequently employed procedures and appear to give good results.
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In a retrospective review of 697 postterm pregnancies we attempted to validate three tests used to identify the fetus at increased risk: the 24-hour urinary estrogen per gram creatinine (E/Cr), the nonstress test (NST) and the contraction stress test (CST). Using the corrected perinatal mortality rate (PMR) among term pregnancies (0.23%) as a standard for comparison, we found the PMRs among postterm patients with negative screening tests to be as follows: 0.23% with normal E/Crs, 0.65% with negative CSTs (not significantly different) and 2.4% with reactive NSTs (p less than 0.005). When we used intrapartum fetal distress as a standard for comparison, the E/Cr exhibited the highest sensitivity (88%) whereas those of the CST and NST were much lower (7-10%). The specificities were 63%, 98% and 92%, respectively. From this retrospective study the E/Cr appears to be of most assistance in identifying fetuses at increased risk, the CST is of intermediate assistance, and the NST is of least assistance.
Despite the absence of verifiable indications, routine circumcision of the male neonate remains one of the most common surgical procedures in the United States. A sample of obstetric clinic patients in a large urban hospital was tested to determine whether spoken educational intervention would reduce the rate of circumcision. The results showed that the rate was lowered significantly (94.4% circumcised in the control group versus 72% circumcised in the study group). Nevertheless, the majority of the study mothers requested circumcision for their sons despite the educational intervention, suggesting the presence of strong social motives. The authors conclude that many mothers in this population chose circumcision because of inadequate medical information or strong social motives. Both must be addressed if the rate of elective circumcision is to be reduced.
Previous investigations of the effect of glucocorticoids on fetal lung development have suggested that changes in lung structural properties may be of greater functional significance than changes in lung surfactant. In this study we examined the mechanism of the glucocorticoid-induced change in lung structure and compared it with the changes that occur during normal development. Rhesus monkeys (Macaca Mulatta) were treated with betamethasone prior to 133 days gestational age and then delivered by cesarian section either at 133 days or near term at 160 days. Our results show that normal fetal lung development over the last month of gestation occurs with a 45% increase in lung dry weight and a 56% increase in the maximal air volume per gram lung (Vmax/g). The immediate effect of the steroid was to cause a similar percentage increase in Vmax/g but no increase in lung weight. In fact, there were significant decreases in lung weight at both 133 and 160 days in the treated animals. In addition, we found no significant changes in the mean alveolar size either with normal development or with the steroid treatment. We thus conclude that in the rhesus monkey, the lung maturation process involves both an increase in lung mass and an increase in the number of alveoli per gram of that mass. The betamethasone treatment results in accelerated recruitment of alveoli coupled with impaired growth of lung tissue.
Preterm and term deliveries were analyzed at The Johns Hopkins Hospital from January 1, 1976, through December 31, 1977, to determine maternal infection risks associated with premature rupture of the membranes (PROM). Gravidas who delivered preterm infants demonstrated an increased incidence of endometritis with or without PROM. The risk of endometritis attributable solely to PROM was insignificant compared with the risk attributable to preterm delivery. These findings implicate infection in the mechanism of preterm labor, with or without PROM.
In previous studies, we noted that treatment of pregnant rhesus monkeys with betamethasone resulted in a marked increase in fetal lung distensibility. The purpose of the present study was to determine whether these changes persisted during subsequent in utero development. Pregnant rhesus monkeys were treated with 2 mg of betamethasone intramuscularly from day 120 to day 133 and underwent delivery by cesarean section one month later. The treated fetuses were found to have smaller lungs (-31%; p less than 0.005), and lower alveolar stability (-14%; p less than 0.025) than the control fetuses. Additional findings included smaller weights for the brain (p less than 0.01), liver, pancreas, and heart (p less than 0.05). Smaller adrenal (p less than 0.025) and larger pituitary weights (p less than 0.05) and lower plasma corticoid concentrations (p less than 0.001) indicated long-standing adrenal insufficiency in the treated fetuses. These persistent sequelae caution the indiscriminate and prolonged use of these potent glucocorticoids during pregnancy.
Of 438 snakes in a zoologic collection, 35 died during a 3-month period; all were members of the family Viperidae. Clinical signs consisted of gaping of the mouth followed within 1 day by convulsions. All necropsied animals had a mucoid exudate throughout the respiratory tract. Histologic evaluation of lung revealed evidence of interstitial pneumonia, with occasional eosinophilic intracytoplasmic inclusions in epithelial cells. A paramyxo-like virus, isolated in viper heart cells from lung tissue, was observed by electron microscopy to be budding from cell membranes. The virus hemagglutinated chicken red blood cells at 5 C, and antibody titers were assayed by hemagglutination inhibition. In a random survey of 22 snakes from the zoologic collection, antibody titers to the virus ranged from 1/20 to 1/2,560.
Steady-state fluorescence polarization (FP) of 1,6-diphenyl-1,3,5-hexatriene (DPH) in monkey and human amniotic fluid was studied over a wide range of gestational ages. In both of these systems, the fluorescence polarization decreased with advancing gestational age. In the monkey, these measurements were correlated with both biochemical and physiologic parameters of lung function, including maximal lung volume, alveolar stability, percentage of disaturated phosphatidylcholine in lung homogenate, and lecithin/sphingomyelin ratio of amniotic fluid. Fluorescence polarization values correlated well with the lung disaturated phosphatidylcholine content expressed as a percentage of phosphatidylcholine, thus suggesting that the fluorescent probe interacts with a fraction of the amniotic fluid which is closely related to development of the pulmonary surfactant. system. Comparison of monkey and human amniotic fluid fluorescence polarizations showed a greater anisotropy of DPH in the monkey fluid at all stages of gestation, thereby indicating a greater microviscosity in monkey pulmonary surfactant.
A 40-month retrospective review of 677 postterm pregnancies was undertaken to determine the usefulness of 24-hour urinary estrogen per gram of creatinine (E/Cr) in monitoring such pregnancies. The cutoff value between normal and low E/Cr values was chosen at the tenth percentile (18 mg/gm). The corrected perinatal mortality rate (PMR) in post-term pregnancies with normal E/Cr was 0.23% (1/426) and was not different from that at term (0.23%; 4/1,775). However, in post-term pregnancies with low E/Cr, the corrected PMR was 9.2% (4/43), representing a 40-fold increase (P less than 0.001). The incidence of fetal distress was also significantly higher in patients with low E/Cr (57%) than in those with normal E/Cr (5.5%; P less than 0.001). It was worrisome to note that three of four stillborn infants had antepartum fetal heart testing within 4 days, which indicated fetal well-being. The E/Cr appears to be a reliable test for identifying those postterm pregnancies at risk that might benefit from obstetric intervention.
Using the rhesus monkey as an animal model we measured several indices of fetal lung maturation including pressure-volume characteristics and phospholipid concentrations and correlated them with the absorbance of amniotic fluid at 650 nm (A650). Those parameters, which are indicative of the presence of surfactant (i.e., deflation stability, lecithin-sphingomyelin ratio, lung phosphatidylcholine, as well as disaturated phosphatidylcholine), correlate significantly with the amniotic fluid A650, even after correction for gestational age. Maximal lung volume changes, thought to be reflective of alterations in tissue forces, did not correlate with A650. These data in the rhesus fetus indicate that the A650 reflects pulmonary surfactant characteristics independent of gestational age. Accordingly, this test may prove to be an accurate predictor of the risk of the respiratory distress syndrome.
A type-and-screen procedure was established whereby obstetric patients with no complications would be tested for ABO, Rh, and unexpected antibody. If the antibody screen was negative, cross matches would not be performed. Type and screen could be converted in 20 minutes to cross match, or type-specific blood would be immediately available. Our initial results with type and screen demonstrated 65.5% utilization but 399 cross matches were done for 17 transfusions (cross match/transfusion ratio of 17.6/1). The protocol was changed so that all nonbleeding patients would be typed and screened. A total of 503 of the next 563 patients (89.3%) were typed and screened; cross matches provided 33 transfusions (cross match/transfusion ratio of 4.9/1). An estimated 964 cross matches were eliminated with cost savings of $14,460 in 3 months. We concluded that the type-and-screen procedure is an effective tool in reducing the cross match/transfusion ratio and in lowering costs in obstetric patients with no compromise in patient care, even in high-risk patients.
The purpose of this prospective, nonconcurrent study was to determine whether maternal hypoglycemia, as measured by a 3-hour glucose tolerance test, is associated with pregnancies resulting in growth-retarded infants. Our results demonstrate that maternal hypoglycemia is significantly associated with intrauterine growth retardation other than the low birth weight type and that the 3-hour glucose tolerance test is an effective early screening test in detecting pregnancies at risk of fetal growth retardation.
The sinusoidal fetal heart rate pattern has been reported to be an indication of fetal compromise. In this review of 31 cases, drawn from a total of 559 monitored cases of normal and at-risk women, only one resulted in poor outcome, and this was attributable to a difficult breech delivery. An association with administration of analgesics is confirmed. The sinusoidal fetal heart rate pattern does not appear to be uniformly associated with fetal distress. Its presence should be an indication for meticulous assessment of other electrocardiographic, biochemical, or clinical evidence of fetal status.
Glucocorticoids are reported to accelerate fetal lung development, whereas insulin is alleged to interfere with this effect of glucocorticoids. A paradox exists, however, in that glucocorticoids also induce hyperinsulinemia. The purpose of this study was to explore the interrelationships of betamethasone, hyperinsulinemia, and hyperglycemia to fetal lung maturation. In this rhesus preparation, maternal betamethasone administration produced an alarming increase in maternal and fetal plasma insulin values. A significant increase in total lung volumes also occurred, but lung surfactant properties (as measured by amniotic fluid lecithin/sphingomyelin concentrations, lung alveolar deflation stability, and lung phosphatidylcholine concentrations) remained unchanged. These findings are consistent with the following hypotheses: (1) Betamethasone-induced hyperinsulinemia impairs acceleration of surfactant production but does not negate increases in maximum lung volume; (2) betamethasone-induced increases in maximum lung volume occur through mechanisms other than alveolar surfactant alterations.