Historical evidence for the origin of teaching hospital, medical school and the rise of academic medicine.

Historical progression and the development of current teaching hospitals, medical schools and biomedical research originated from the people of many civilizations and cultures. Greeks, Indians, Syriacs, Persians and Jews, assembled first in Gondi-Shapur during the Sasanian empire in Persia, and later in Baghdad during the Golden Age of Islam, ushering the birth of current academic medicine.

Avicenna (AD 980 to 1037) and the care of the newborn infant and breastfeeding.

A brief historical review of medicine during the fourth century Islamic civilization or eleventh century AD in Persia or Iran was undertaken with its focus on Avicenna. A physician-philosopher, named Ibn Sina or Avicenna (980 to 1037), followed and further expanded the tradition of western philosophy and medicine by Aristotle, Hippocrates and Galen. Avicenna, a physician, philosopher, astrologist, anatomist, pharmacologist, ethicist and poet wrote, the Canon of Medicine, the most comprehensive medical textbook of its time. This important textbook was extensively used in European medical schools for centuries after Avicenna's death. In the Canon of Medicine, a chapter is dedicated to the care of the newborn infant dealing with hygiene, breastfeeding and upbringing of the child.

Biochemical changes in prostanoids and cerebral expression of cyclooxygenase (COX)-1 and COX-2 during morphine sulfate infusion in the newborn piglet .

To examine the biochemical regulation of morphine sulfate (MS) on prostanoid synthesis, conscious newborn piglets received a bolus dose of 100 microg/kg followed by a continuous infusion dose of 100 microg/kg/h. The control group received equivalent volume bolus and continuous infusion of 5% dextrose. Blood samples were drawn from the femoral artery and sagittal sinus vein before, during and after infusion for measurement of prostanoids. The expression of mRNAs encoding cyclooxygenases (COX)-1 and -2 in the brainstem, thalamus, cortex, and cerebellum of the newborn piglets were also examined. Systemic PGE2 levels declined substantially during and post MS infusion (p < 0.01), whereas sagittal sinus vein PGE2 levels increased following the bolus dose (p < 0.01) and at 4 h of continuous infusion (p < 0.01). MS infusion did not affect systemic 6-ketoPGF1alpha levels, however, in the cerebral circulation 6-ketoPGF1alpha levels increased 146% (p < 0.01) following the bolus dose and remained elevated throughout the infusion and post infusion times. Systemic TxB2 levels increased transiently at 4 h (p < 0.01) and sagittal sinus vein TxB2 increased at 0.5 and 1 h (p < 0.01) during continuous infusion. RT-PCR assays revealed a 1.5- (p < 0.001) to 4-fold (p < 0.001) increased expression of COX-1 mRNA in the MS-infused brain samples. In contrast, no differences in COX-2 mRNA were detected between the groups. These data imply that MS may have significant effects on prostanoid synthesis in the newborn. The data further show that the MS-induced prostanoid responses appear to be mediated via COX-1.

Biochemical and molecular endothelin responses to morphine sulfate infusion in conscious newborn piglets.

The biochemical and molecular endothelin-1 (ET-1) responses to high dose morphine sulfate infusion were studied in conscious newborn piglets (n = 6) that received a loading dose of 100 micrograms/kg over 5 min followed by a continuous i.v. infusion dose of 100 micrograms.kg-1.h-1 for 4 h. The control group (n = 6) received equivalent volume loading and infusion doses of 5% dextrose. Blood samples were drawn serially from the femoral artery and sagittal sinus vein before (0), during (30 min, 1, 2, 3, and 4 h), and post (1 and 2 h) infusion. Five micrograms of total RNA obtained from brainstem tissue homogenates was analyzed by reverse transcriptase--polymerase chain reaction (RT-PCR). The amounts of mRNA encoding ET-1, and endothelin receptor subtypes ETA and ETB, were semiquantitated using densitometric scanning. Morphine infusion resulted in elevated respiratory rate and mean arterial blood pressure, with no effect on arterial pH, Po2, and O2 saturation. Compared with the control group, morphine induced significant elevations in plasma ET-1 levels following the bolus dose (systemic: 13.2 +/- 3.6 vs. 8.6 +/- 2.2 pg/mL, p < 0.05; sagittal sinus vein: 13.7 +/- 3.4 vs. 8.2 +/- 0.9 pg/mL, p < 0.01). These effects lasted up to 2 h after discontinuation of morphine infusion (systemic: 14.5 +/- 3.4 to 18.7 +/- 5.7 pg/mL vs. 7.5 +/- 0.8 to 9.4 +/- 3.2 pg/mL, p < 0.05 to p < 0.01; sagittal sinus vein: 14.8 +/- 2.7 to 17.6 +/- 2.8 pg/mL vs. 7.5 +/- 1.4 to 9.4 +/- 3.4 pg/mL, p < 0.05 to p < 0.01). The RT-PCR assay showed a twofold (p < 0.02) upregulation in ET-1 and a threefold (p < 0.007) upregulation in ETA receptor mRNA expression in the brainstem of morphine-treated animals. In contrast, there was a threefold (p < 0.0001) downregulation of the ETB receptor mRNA expression. The rapid and sustained elevations in systemic arterial and sagittal sinus venous ET-1 levels suggest a role for ET-1 in the morphine-induced excitatory responses observed in newborn piglets. Upregulation of ETA receptors and downregulation of ETB receptors in the brainstem with high doses of morphine may indicate possible effects on cerebral vascular tone.

Pharmacodynamic effects and pharmacokinetic profile of continuous infusion fentanyl in newborn piglets.

The objective of this study was to determine hemodynamic effects and pharmacokinetic profiles of fentanyl with continuous infusion in 1- to 3-day-old newborn piglets. The piglets (n = 6) were administered a loading dose of fentanyl at 30 microg/kg i.v. over 15 min followed by a continuous i.v. infusion at 10 microg/kg/h for 6 h. The control group (n = 8) received equivalent volume bolus and infusion of 5% dextrose. Blood samples were obtained serially from systemic circulation and sagittal sinus vein for measurement of plasma fentanyl, pH and blood gases. Plasma fentanyl achieved steady state levels by 30 min of infusion both in the systemic (202.7 +/- 39.1 ng/ml) and sagittal sinus vein (136.7 +/- 20.7 ng/ml). Fentanyl caused a transient increase in respiratory rate at 2 h. Heart rate was significantly elevated at 30 min and 6 h during infusion but systemic and sagittal sinus vein blood pressure remained unchanged. Systemic and sagittal sinus vein PO2 were significantly decreased from 2 through 6 h of infusion. Compared to the control group, there was a 56% (p < 0.01) decrease in sagittal sinus vein O2 content at 30 min of infusion, an effect which lasted up to 6 h (47%, p < 0.01). Fractional O2 extraction by the brain increased significantly at 30 min (26%, p < 0.01) and remained elevated throughout the infusion time (22%, p < 0.05 at 6 h). Brain fractional O2 extraction increased as a function of brain fractional fentanyl extraction (r2 = 0.40, p < 0.001). Mean clearance was estimated as 56.2 +/- 13.7 ml/kg/h (range 43.5-76.9 ml/kg/h), mean volume of distribution at steady state was 1.29 +/- 0.6 liters/kg (range 0.78-2.15 liters/kg) and the mean half-life was 15.7 +/- 5.7 h (range 9.4-22.5 h). These data suggest that increased systemic oxygen may be necessary to maintain normal cerebral oxygen extraction during fentanyl anesthesia/analgesia.

Multicenter controlled clinical trial of high-frequency jet ventilation in preterm infants with uncomplicated respiratory distress syndrome.

OBJECTIVE: To test the hypothesis that high-frequency jet ventilation (HFJV) will reduce the incidence and/or severity of bronchopulmonary dysplasia (BPD) and acute airleak in premature infants who, despite surfactant administration, require mechanical ventilation for respiratory distress syndrome. DESIGN: Multicenter, randomized, controlled clinical trial of HFJV and conventional ventilation (CV). Patients were to remain on assigned therapy for 14 days or until extubation, whichever came first. Crossover from CV to HFJV was allowed if bilateral pulmonary interstitial emphysema or bronchopleural fistula developed. Patients could cross over to the other ventilatory mode if failure criteria were met. The optimal lung volume strategy was mandated for HFJV by protocol to provide alveolar recruitment and optimize lung volume and ventilation/perfusion matching, while minimizing pressure amplitude and O2 requirements. CV management was not controlled by protocol. SETTING: Eight tertiary neonatal intensive care units. PATIENTS: Preterm infants with birth weights between 700 and 1500 g and gestational age <36 weeks who required mechanical ventilation with FIO2 >0.30 at 2 to 12 hours after surfactant administration, received surfactant by 8 hours of age, were <20 hours old, and had been ventilated for <12 hours. Outcome Measures. Primary outcome variables were BPD at 28 days and 36 weeks of postconceptional age. Secondary outcome variables were survival, gas exchange, airway pressures, airleak, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and other nonpulmonary complications. RESULTS: A total of 130 patients were included in the final analysis; 65 were randomized to HFJV and 65 to CV. The groups were of comparable birth weight, gestational age, severity of illness, postnatal age, and other demographics. The incidence of BPD at 36 weeks of postconceptional age was significantly lower in babies randomized to HFJV compared with CV (20.0% vs 40.4%). The need for home oxygen was also significantly lower in infants receiving HFJV compared with CV (5.5% vs 23.1%). Survival, incidence of BPD at 28 days, retinopathy of prematurity, airleak, pulmonary hemorrhage, grade I-II IVH, and other complications were similar. In retrospect, it was noted that the traditional HFJV strategy emphasizing low airway pressures (HF-LO) rather than the prescribed optimal volume strategy (HF-OPT) was used in 29/65 HFJV infants. This presented a unique opportunity to examine the effects of different HFJV strategies on gas exchange, airway pressures, and outcomes. HF-OPT was defined as increase in positive end-expiratory pressure (PEEP) by >/=1 cm H2O from pre-HFJV baseline and/or use of PEEP of >/=7 cm H2O. Severe neuroimaging abnormalities (PVL and/or grade III-IV IVH) were not different between the CV and HFJV infants. However, there was a significantly lower incidence of severe IVH/PVL in HFJV infants treated with HF-OPT compared with CV and HF-LO. Oxygenation was similar between CV and HFJV groups as a whole, but HF-OPT infants had better oxygenation compared with the other two groups. There were no differences in PaCO2 between CV and HFJV, but the PaCO2 was lower for HF-LO compared with the other two groups. The peak inspiratory pressure and DeltaP (peak inspiratory pressure-PEEP) were lower for HFJV infants compared with CV infants. CONCLUSIONS: HFJV reduces the incidence of BPD at 36 weeks and the need for home oxygen in premature infants with uncomplicated RDS, but does not reduce the risk of acute airleak. There is no increase in adverse outcomes compared with CV. HF-OPT improves oxygenation, decreases exposure to hypocarbia, and reduces the risk of grade III-IV IVH and/or PVL.

Comparative efficacy of exosurf and survanta surfactants on early clinical course of respiratory distress syndrome and complications of prematurity.

OBJECTIVES: To determine the comparative efficacy of Exosurf Neonatal and Survanta surfactants on the early course of respiratory distress syndrome (RDS), arterial blood gases, ventilatory support, outcome morbidity rate, and complications of prematurity and RDS. STUDY DESIGN: Medical records from 203 premature newborn infants undergoing mechanical ventilation for respiratory distress syndrome, and who received up to four rescue doses of either Exosurf or Survanta, were retrospectively reviewed. RESULTS: All groups were comparable for birth weight and gestational age. Although the two randomized groups were similar in severity of RDS based on fraction of inspired oxygen (FIO2) and ventilatory support, a significantly greater improvement in respiratory function as evidenced by FIO2, mean airway pressure, alveolar-arterial partial pressure of oxygen difference, and oxygen index, was observed in the Survanta group from 12 hours (p < 0.05) through 48 hours (p < 0.01). Comparison of outcome morbidity rate by gestational age showed a higher occurrence of retinopathy of prematurity (p < 0.02) among the older infants (28 to 32 weeks) who were treated with Exosurf. CONCLUSION: Survanta exerted a significantly faster response in the early clinical course of RDS compared with Exosurf. However, no difference in the impact on eventual respiratory outcome was observed. We therefore conclude that both surfactants are effective for the treatment of RDS.

Combined effects of antenatal corticosteroids and surfactant supplementation on the outcome of very low birth weight infants.

Antenatal corticosteroids in preterm pregnancy may result in the reduction of the incidence of respiratory distress syndrome (RDS) and neonatal mortality. It is well known that postnatal use of surfactant in very low birth weight (VLBW) infants with RDS results in decreased neonatal morbidity and mortality. To evaluate the additive beneficial effects of combined antenatal corticosteroids and postnatal use of rescue surfactant on the outcome of VLBW infants, we retrospectively reviewed 286 maternal/infant charts of preterm infants with gestational ages 23 to 32 weeks and birth weights 501 to 1500 gm who were born at our institution from 1991 through 1994. Of the 87 (30%) infants who were treated with corticosteroids before birth, 41 (47%) had RDS, and of the 199 (70%) infants who were not treated with corticosteroids before birth, 162 (81%) had RDS (p < 0.001). The infants who had RDS and who were treated with corticosteroids before birth had a decreased incidence of pulmonary air leaks and a decreased need for diuretic therapy. In addition, they had a significant reduction in O2 requirement and ventilator settings as reflected by FIO2, mean airway pressure, ventilator rate, O2 index, and A-aDO2 before they received the first dose of rescue surfactant (p < 0.05 to p < 0.01) in contrast to other VLBW infants who had RDS and who were not treated with corticosteroids before birth. We conclude that antenatal corticosteroid therapy in threatened premature labor combined with the use of postnatal rescue surfactant is associated with a decreased incidence of RDS and may be beneficial for reducing the severity of RDS and improving the eventual outcome of VLBW infants.

Effects of continuous infusion fentanyl citrate on cerebrovascular and systemic prostanoids in postsurgical newborn piglets.

BACKGROUND: Newborns admitted to the intensive care unit undergo multiple painful procedures. Fentanyl citrate (FC) is one of the most commonly used drugs for pain relief in the newborn. Although it has been reported that one of the biological effects of fentanyl is hemodynamic stability, the response of systemic and/or cerebrovascular prostanoids to FC infusions have not been studied. METHODS: To examine the effects of continuous intravenous (IV) infusion of FC on systemic and cerebrovascular prostanoid concentrations, two groups of spontaneously breathing newborn piglets (1-3 days old) were studied. The study group (n = 6) and the control group (n = 8) were respectively given a loading dose of 30 micrograms/kg IV over 15 minutes, immediately followed by a continuous IV infusion of 10 micrograms/kg/hr for 6 hours, or a placebo (PB) solution of 5% dextrose in a similar fashion. Cerebrospinal fluid (0.5 mL) from cisterna magna puncture and blood samples (1.0 mL) from the sagittal sinus vein and carotid artery were collected serially before and after FC or PB infusion for drug and PG determinations. FC was measured by high pressure liquid chromatography (HPLC), and the prostanoids were measured using enzyme immunoassay (EIA) kits. RESULTS: FC infusion induced marked elevations in 6-ketoPGF1 alpha (300%, p < 0.001) and TXB2 (150%, p < 0.001) at 30 minutes, and remained elevated up to 2 hours of infusion. In addition, systemic 6-ketoPGF1 alpha increased by 180% (p < 0.001) and PGE2 concentrations fell dramatically at 30 minutes (87%, p < 0.001) and did not return to normal levels during the infusion time (83% to 81%, p < 0.001 to p < 0.01). CSF 6-ketoPGF1 alpha and TXB2 levels increased by 152% and 80%, respectively (p < 0.001), but PGE2 decreased by 76% (p < 0.001), at 6 hours of infusion. An inverse relationship existed between FC, and sagittal sinus PGE2 levels (r = 0.46, p < 0.03) and systemic PGE2 levels (r = 0.602, p < 0.02). CONCLUSION: The data suggest FC is rapidly transported across the blood brain barrier and the effects on cerebrovascular prostanoids, particularly PGE2 is rapid and prolonged. PGE2 appears to be the primary responsive prostanoid. The magnitude of the response, as evidenced by the early and sharp reductions in systemic and cerebrovascular concentrations, suggest vasoconstriction, with possible adverse effects on organ blood flow and metabolic activity. However, further studies are required to evaluate the effects on organ blood flow and metabolism.

Changes in cerebrospinal fluid and cerebrovascular endothelin concentrations during hypotension and hypertension in newborn piglets with induced sterile meningitis.

The effects of sterile meningitis on endothelin-1 (ET-1) and big ET-1 concentrations during hypotension and hypertension were studied in the cerebrospinal fluid and plasma of newborn piglets. Cerebrospinal fluid was obtained via cisterna magna puncture, and blood was obtained from the sagittal sinus vein and left subclavian artery. The study group consisted of 14 newborn piglets injected with 0.5 mL heat-killed group B streptococcus (GBS) (10(9) colony forming unit (cfu) equivalents), into the right cerebral lateral ventricle; the control group consisted of 10 newborn piglets injected with sterile normal saline, in a similar fashion. Hypotension (mean arterial blood pressure (MABP) 20-59 mmHg; 1 mmHg = 133.3 Pa) and hypertension (MABP 110-140 mmHg) were induced 1.5-2 h apart in random sequence in each animal, by inflating balloon-tipped catheters placed at the aortic root and descending aorta, respectively. Cerebral blood flow (CBF) was measured using radiolabeled microspheres, 15 min before and after injection of GBS or saline (normotension), during the hypotension and hypertension episodes, and during recovery normotension, immediately prior to cerebrospinal fluid and blood sampling. ET-1 and big ET-1 concentrations (pg/mL) were measured using radioimmunoassay kits. The combined effect of induced sterile meningitis and induced hypotension resulted in a significant rise in the concentration of cerebrospinal fluid ET-1 (control, 5.1 +/- 0.1; GBS, 9.3 +/- 0.2 pg/mL; p < 0.01), cerebrospinal fluid big ET-1 (control, 0; GBS, 18.1 +/- 2.7 pg/mL; p < 0.01), and sagittal sinus (cerebrovascular) big ET-1 (control, 15.5 +/- 4.2; GBS, 47.5 +/- 9.6 pg/mL; p < 0.01). In contrast, the combined effect of induced sterile meningitis and induced hypertension resulted in a marked elevation in cerebrovascular ET-1 concentrations (control, 9.5 +/- 0.9; GBS, 28.5 +/- 6.1 pg/mL; p < 0.01), with no significant change in cerebrospinal fluid concentrations. In addition, cerebrovascular production of ET-1 increased dramatically during hypertension in the GBS group (control, 0; GBS, 161.7 +/- 13.2 pg.min-1.100 g-1; p < 0.001), and was maintained during the recovery period (133.7 +/- 10.8 pg.min-1.100 g-1). Cerebrovascular ET-1 concentrations correlated significantly with total CBF and MABP in both groups of animals (control, r = 0.49, p < 0.002; GBS, r = 0.64, p < 0.0001), but the response was of a much greater magnitude in the GBS group. There was an inverse relationship between cerebrovascular big ET-1 concentrations and total CBF (r = -0.53, p < 0.0001) and MABP (r = -0.71, p < 0.0001) in the GBS group. In the MABP range of 60-110 mmHg a positive relationship was observed between cerebrovascular ET-1 concentrations and cerebral vascular resistance, in the control group only (r = 0.59, p < 0.002). The combined insult of induced sterile meningitis and induced hypotension or hypertension may be associated with increased cerebrovascular ET-1 and (or) big ET-1 concentrations. Changes in these vasoactive agents may contribute to pressure passivity of CBF in the newborn with meningitis.

Effect of group B streptococcal meningitis on retinal and choroidal blood flow in newborn pigs.

PURPOSE: To assess the effect of group B streptococcal (GBS) meningitis on retinal blood flow (RetBF) and choroidal blood flow (ChBF) autoregulation in sedated newborn piglets (1 to 5 days of age). METHODS: Fourteen study animals injected with 0.5 ml heat-killed GBS (10(9)) were compared to 10 control animals injected with 0.5 ml saline. The site of injection for both groups was the cerebral lateral ventricles. RetBF and ChBF were measured by radioactive microspheres (141Ce, 51Cr, 113Sn, 85Sr, 95Nb, 46Sc) over a mean arterial blood pressure (MABP) range of 20 to 150 mm Hg. Hypertension and hypotension were induced 2 hours apart in random sequence on each animal by inflating balloon-tipped catheters placed at the descending aorta and the aortic root, respectively. RetBF and ChBF were measured 15 minutes before and after injection of GBS or saline (baseline) and during hypotension or hypertension. RESULTS: Fifth-order polynomial regression analyses of RetBF and ChBF (ml/100 g per minute) versus MABP showed that in control animals, blood flows were constant at MABP of 60 to 110 mm Hg for RetBF and was pressure passive above and below these ranges. However, no autoregulation was observed for ChBF throughout the MABP range. In contrast, RetBF of GBS-treated animals increased with increasing blood pressure throughout range of MABP studied, and absence of autoregulation was maintained in the choroid. Vascular resistance (mm Hg/ml per minute/100 g) increased as MABP was raised to maintain constant flow and was correlated linearly with MABP at 60 to 110 mm Hg (r = 0.6682, P = 0.0003) in RetBF of control animals but not in GBS-treated animals (r = -0.291, P = NS). Vascular resistance did not change with MABP for ChBF of control animals (r = -0.264, P = NS) but decreased as MABP was raised in GBS-treated animals (r = -0.548, P < 0.0001). GBS did not alter oxygen delivery, which varied directly with MABP in control animals (RetBF: r = 0.74, P < 0.001; ChBF: r = 0.68, P < 0.001) and in GBS-treated animals (RetBF: r = 0.55, P < 0.001; ChBF: r = 0.68, P < 0.001). CONCLUSION: Group B streptococcal meningitis significantly impairs eye blood flow autoregulation and may contribute to increased risk of retinal damage in infants with meningitis.

Ascorbic acid concentrations in umbilical cord veins and arteries of preterm and term newborns.

Ascorbic acid (AA) is a powerful antioxidant required for the defense against oxidative stress. At present it is not known whether AA may play a role in the developmental process of the fetus. We therefore determined the relationship of AA levels between the umbilical cord vein (UCV) and umbilical cord artery (UCA) of preterm ( < 37 weeks of gestation) and term ( > or = 37 weeks of gestation) infants and compared those levels to matched maternal venous AA levels. We also assessed the association between UCV plasma AA levels with birth weight and gestational age by measuring AA in 88 UCV plasma samples and 58 UCA plasma samples obtained from newborn infants ranging in gestational age from 24 to 42 weeks and birth weight from 675 to 5,020 g, by high pressure liquid chromatography. Maternal venous samples were collected at the time of delivery. The mean UCV plasma AA levels (mg/dl) were significantly lower in the preterm group than in the term group (0.43 +/- 0.59 and 1.16 +/- 0.97, respectively; p < 0.002); however, the mean UCA plasma AA levels did not differ between the groups. In contrast, mean maternal venous plasma AA levels of the preterm group (1.33 +/- 0.62) were significantly higher than those of the mothers in the term group (0.72 +/- 0.69; p < 0.01). A direct correlation was found between UCV levels and birth weight (r = 0.23, p < 0.05), and UCV levels and gestational age (r = 0.23, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal administration of granulocyte colony-stimulating factor improves neonatal rat survival after a lethal group B streptococcal infection.

Maternally administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been shown to cross the placenta and induce a peripheral neutrophilia and increases in the marrow and spleen neutrophil storage pools in fetal and newborn rats. In the present study, we have used this model system to investigate the efficacy of prenatally administered rhG-CSF on neonatal defense to a lethal challenge with Group B-beta hemolytic Streptococcus (GBS). Pregnant rats were injected with rhG-CSF twice daily beginning 6 days before parturition. At birth, all pups were infected with a dose of GBS that is lethal for 90% of infected pups (LD90). Survival was monitored daily for 5 days. Survival of infected pups from saline-treated mothers beyond 60 hours after infection was 10%. No difference in survival was observed among pups from mothers treated 2 and 4 days before parturition. In contrast, we determined that survival was 82.5% among infected pups from mothers treated for 6 days before parturition with rhG-CSF. Our results demonstrate that maternal administration of rhG-CSF augments neonatal defenses against a lethal bacterial challenge.

Adrenal responsiveness in very-low-birth-weight infants treated with dexamethasone.

This study was designed to investigate the effect of steroid administration in ill premature neonates. Twenty high-risk very-low-birth-weight (VLBW) infants [birth weight (BW) < or = 1,300 g] with a mean BW 948 +/- 220 g, gestational age (GA) 27 +/- 1.7 weeks underwent 1-hour ACTH (Cortrosyn) stimulation tests and determination of 17-hydroxyprogesterone (17OHP)/dehydroepiandrosterone sulfate (DHEAS) at 23.6 +/- 15.9 days poststeroid treatment for bronchopulmonary dysplasia (BPD)/airway obstruction. Metyrapone tests were also obtained in 18 infants. Baseline (nonsteroid-exposed) values for pre-/post-ACTH cortisol, 17OHP, DHEAS, and pre-/post-metyrapone compound S values were obtained in 5 infants. Eight of 18 (44%) infants had evidence of secondary (hypothalamic-pituitary) adrenal suppression based on abnormal metyrapone tests. No difference was found in BW, GA, time on O2 or AV, steroid dose/kg, or neonatal/postneonatal mortality between the suppressed and nonsuppressed groups. Two of 4 infants with borderline ACTH tests had subnormal compound S levels postmetyrapone. No relationship was found between steroid dose/kg and cortisol response post-ACTH. Additionally, corrected GA was not related to change in cortisol, 17OHP, and DHEAS pre-/post-ACTH. Two infants exhibited recovery of adrenal suppression documented by repeated metyrapone testing at 63 and 186 days poststeroid treatment. In conclusion, this study documents the apparent high incidence of secondary adrenal suppression in VLBW infants treated with dexamethasone. Clinical significance of these findings deserves further investigation.

Multicenter controlled trial comparing high-frequency jet ventilation and conventional mechanical ventilation in newborn infants with pulmonary interstitial emphysema.

One hundred forty-four newborn infants with pulmonary interstitial emphysema were stratified by weight and severity of illness, and randomly assigned to receive treatment with high-frequency jet ventilation (HFJV) or rapid-rate conventional mechanical ventilation (CV) with short inspiratory time. If criteria for treatment failure were met, crossover to the alternate ventilatory mode was permitted. Overall, 45 (61%) of 74 infants met treatment success criteria with HFJV compared with 26 (37%) of 70 treated with CV (p less than 0.01). Eighty-four percent of patients who crossed over from CV to HFJV initially responded to the new treatment, and 45% ultimately met success criteria on HFJV. In contrast, only 9% of those who crossed over from HFJV to CV responded well to CV (p less than 0.01), and the same 9% ultimately met success criteria (p less than 0.05). Therapy with HFJV resulted in improved ventilation at lower peak and mean airway pressures, as well as more rapid radiographic improvement of pulmonary interstitial emphysema, in comparison with rapid-rate CV. Survival by original assignment was identical. When survival resulting from rescue by the alternate therapy in crossover patients was excluded, the survival rate was 64.9% for HFJV, compared with 47.1% for CV (p less than 0.05). The incidence of chronic lung disease, intraventricular hemorrhage, patent ductus arteriosus, airway obstruction, and new air leak was similar in both groups. We conclude that HFJV, as used in this study, is safe and is more effective than rapid-rate CV in the treatment of newborn infants with pulmonary interstitial emphysema.

Significance of anti-A and anti-B isohemagglutinins in cord blood of ABO incompatible newborn infants: correlation with hyperbilirubinemia.

Transcutaneous bilirubin index measurements (TcBI) were determined in ABO-incompatible term white newborn infants who had an indirect Coombs' test for detection of ABO incompatibility (ABO test) performed on cord blood. Serial transcutaneous measurements in the first 72 hours of life in 63 ABO test positive (group I) and 31 ABO test negative (group II) infants were compared with a control group of 109 term ABO compatible infants (group III). During the first phase of this study, the accuracy of TcBI was confirmed in 33 infants who had serum bilirubin determinations demonstrating a correlation coefficient of r = 0.93 between the jaundice meter index reading and total serum bilirubin. Determination of total serum bilirubin using TcBI did not show any statistically significant differences when groups I, II, and III were compared for maximum serum bilirubin values. These results reveal that a positive ABO test does not increase the predictive value of hyperbilirubinemia in ABO-incompatible white newborn infants.