The Bloxsom air lock: a historical perspective.

In 1950, Allan P. Bloxsom (1901-1991), a pediatrician at the St Joseph Hospital in Houston, introduced his positive pressure oxygen air lock (AL) for the delivery room resuscitation of the asphyxiated newborn. The infant's entire body was placed into a cylindrical steel chamber that was tightly sealed and infused with warmed humidified 60% oxygen. The positive pressure within the AL was cycled between 1 and 3 lb/in(2) at 1-minute intervals to simulate the intrauterine pressures during the second stage of labor. Bloxsom developed the AL device in response to his hypothesis that the contractions of labor help to "condition: the infant for extrauterine survival. Parmalee said that the AL "certainly locks the infant up, safe from meddlesome and unintelligent treatment." When clear plastic versions of the AL became commercially available, it received widespread use in delivery rooms and newborn nurseries throughout the United States. In 1953, Apgar and Kreiselman produced apnea in adult dogs using pentobarbital and a muscle relaxant, and found that the AL device was unsuccessful with the oxygenation and ventilation of the animals. In 1954, Townsend in Rochester, New York, reported on his experience with the AL in 150 premature infants. He concluded that the AL should be "more accurately referred to as an oxygenator" and that, "the truly apneic infant cannot be maintained in a acyanotic state by the AL." The AL was finally subjected to the scrutiny of a randomized, controlled clinical trial that was published in 1956. Reichelderfer and Nitowski at Johns Hopkins randomized 171 infants to receive care in the AL or in an Isolette. Routine resuscitation, including positive pressure ventilation, was administered, as needed, to both study groups before placement into the AL or Isolette (Air Shields Inc, Hatboro, PA). They did not find any differences in the outcomes of the 2 study groups. By the mid 1950s, new information linking oxygen therapy and retrolental fibroplasia, led to a rapid decline in the use of the AL, even before the publication of the randomized trial.

Kenneth Harrison Uttley (1901-1972). Historian to the diseases of Antigua, British West Indies

Dr Kenneth Harrison Uttley (1901-1972) served as the Chief Medical Officer in Antigua, British West Indies, from 1955 until 1966. During this time, Dr. Uttley personally reviewed and tabulated an island-wide governmental demographic database of all births, deaths and causes of death during the preceding 100 years. This database was the result of a Compulsory Birth and Death Registration Ordinance enacted as one of several Colonial Poor Laws in 1856. His efforts resulted in the publication of a total of 30 papers in American and British medical journals. Many of these papers reviewed historical demographic trends in births, fertility rates, neonatal deaths, infant mortality and early childhood mortality rates. Others focussed on the historical epidemiology of specific diseases such as neonatal tetanus, leprosy, tuberculosis and malaria. This is the first complete bibliographical account of Uttley's contributions to the history of diseases in the West Indies in general and Antigua in particular. Dr Uttley also served as an ordained priest in the Anglican Church and, upon retirement from the Colonial Medical Services, returned to England to serve as the Vicar of Purton, Oxfordshire.

Concentration-dependent, temperature-dependent non-Newtonian viscosity of lung surfactant dispersions.

The bulk shear viscosities of aqueous dispersions of lavaged calf lung surfactant (LS) and its chloroform:methanol extract (CLSE) were measured as a function of concentration, shear rate and temperature. At 10-mg phospholipid per milliliter, dispersions of LS and vortexed CLSE in 0.15 M NaCl (saline) had low viscosities near 1 cp over a range of shear rates from 225 to 1125 s(-1). Lung surfactant viscosity increased with phospholipid concentration and became strongly non-Newtonian with higher values at low shear rates. At 37 degrees C and 40 mg/ml, LS and vortexed CLSE in saline had viscosities of 38 and 34 cp (77 s(-1)) and 12 and 7 cp (770 s(-1)), respectively. Viscosity values for LS and CLSE were dependent on temperature and, at fixed shear, were lower at 23 degrees C than at 37 or 10 degrees C. Hysteresis was also present in viscosity measurements depending on whether shear rate was successively increased or decreased during study. Addition of 5 mM Ca(2+) at 37 degrees C markedly reduced CLSE viscosity at all shear rates and decreased LS viscosity at low shear rates. Dispersion by sonication rather than vortexing increased the viscosity of CLSE at fixed shear, while synthetic phospholipids dispersed by either method had low, relatively Newtonian viscosities. The complex viscous behavior of dispersions of LS and CLSE in saline results from their heterogeneous aggregated microstructure of phospholipids and apoproteins. Viscosity is influenced not only by the aggregate surface area under shear, but also by phospholipid-apoprotein interactions and aggregate structure/deformability. Similar complexities likely affect the viscosities of biologically-derived exogenous surfactant preparations administered to patients in clinical surfactant therapy.

Kenneth Harrison Uttley (1901-1972). Historian to the diseases of Antigua, British West Indies.

Dr Kenneth Harrison Uttley (1901-1972) served as the Chief Medical Officer in Antigua, British West Indies, from 1955 until 1966. During this time, Dr. Uttley personally reviewed and tabulated an island-wide governmental demographic database of all births, deaths and causes of death during the preceding 100 years. This database was the result of a Compulsory Birth and Death Registration Ordinance enacted as one of several Colonial Poor Laws in 1856. His efforts resulted in the publication of a total of 30 papers in American and British medical journals. Many of these papers reviewed historical demographic trends in births, fertility rates, neonatal deaths, infant mortality and early childhood mortality rates. Others focussed on the historical epidemiology of specific diseases such as neonatal tetanus, leprosy, tuberculosis and malaria. This is the first complete bibliographical account of Uttley's contributions to the history of diseases in the West Indies in general and Antigua in particular. Dr Uttley also served as an ordained priest in the Anglican Church and, upon retirement from the Colonial Medical Services, returned to England to serve as the Vicar of Purton, Oxfordshire.

Early dexamethasone-attempting to prevent chronic lung disease.

BACKGROUND: We previously demonstrated improved survival and early outcomes in a pilot trial of 2 doses of intravenous dexamethasone for infants with surfactant-treated respiratory distress syndrome. (1) A multicenter, randomized, double-blind trial was undertaken to confirm these results. METHODS: Infants <30 weeks' gestation were eligible if they had respiratory distress syndrome, required mechanical ventilation at 12 to 18 hours of age, and had received at least 1 dose of exogenous surfactant. Infants were excluded if sepsis or pneumonia was suspected or if congenital heart disease or chromosomal abnormalities were present. A total of 384 infants were enrolled-189 randomized to dexamethasone (.5mg/kg birth weight at 12-18 hours of age and a second dose 12 hours later) and 195 to an equal volume of saline placebo. RESULTS: No differences were found in the dexamethasone versus placebo groups, respectively, regarding the primary outcomes of survival (79% vs 83%), survival without oxygen at 36 weeks' corrected gestational age (CGA; both 59%), and survival without oxygen at 36 weeks' CGA and without late glucocorticoid therapy (46% vs 44%). No significant differences between the groups in estimates from Kaplan-Meier survival analyses were found for median days on oxygen (50 vs 56 days), ventilation (20 vs 27 days), days to regain birth weight (15.5 vs 14 days), or length of stay (LOS; 88 vs 89 days). Infants given early dexamethasone were less likely to receive later glucocorticoid therapy for bronchopulmonary dysplasia during their hospitalization (27% vs 35%). No clinically significant side effects were noted in the dexamethasone group, although there were transient elevations in blood glucose and blood pressure followed by a return to baseline by study day 10. Among infants who died (40 vs 33), there were no differences in the median days on oxygen, ventilation, nor LOS. However, in survivors (149 vs 162), the following were observed: median days on oxygen 37 versus 45 days, ventilation 14 versus 19 days, and LOS 79 versus 81 days, for the dexamethasone versus placebo groups, respectively. CONCLUSIONS: This dose of early intravenous dexamethasone did not reduce the requirement for oxygen at 36 weeks' CGA and survival was not improved. However, early dexamethasone reduced the use of later prolonged dexamethasone therapy, and among survivors, reduced the median days on oxygen and ventilation. We conclude that this course of early dexamethasone probably represents a near minimum dose for instituting a prophylactic regimen against bronchopulmonary dysplasia.

Lipid intolerance in neonates receiving dexamethasone for bronchopulmonary dysplasia.

BACKGROUND: We hypothesized that dexamethasone induces hypertriglyceridemia (triglyceride levels >2.82 mmol/L [250 mg/dL]) and increases free fatty acid (FFA) levels and that steroid-induced hypertriglyceridemia is associated with hyperinsulinemia and elevated FFA levels. OBJECTIVE: To study the effect of dexamethasone sodium phosphate on lipid metabolism in neonates receiving intravenous lipids. DESIGN: A prospective cohort study with patients serving as their own controls. SETTING: Neonatal Intensive Care Unit, Children's Hospital at Strong, Rochester, NY. METHODS: All neonates younger than 29 weeks' gestational age at birth receiving 3 g/kg per day of intravenous lipids who were to start dexamethasone therapy for bronchopulmonary dysplasia were eligible. Exclusion criteria included neonates with active infection, prior hypertriglyceridemia, bleeding manifestations, recent surgery, thyroid medication, and human recombinant insulin intravenous infusion therapy. Ten neonates were studied. Blood was drawn for triglyceride, FFA, and insulin assays before initiating and at 1, 2, 3, and 5 days after starting dexamethasone therapy. On day 3, dexamethasone dosage was decreased as per protocol. Intravenous lipid intake was kept constant. Statistical analysis was done using a paired t test. RESULTS: Six of 10 neonates reached a state of hypertriglyceridemia (95% confidence interval, 26.2%-87.8%). The mean average increase in triglycerides, insulin, and FFA levels in neonates receiving 3 g/kg per day of intravenous lipids after initiation of dexamethasone therapy was 0.75 mmol/L (66.6 mg/dL) (P=.007), 127 pmol/L (P = .006), and 47.5 micromol/L (P = .65), respectively. Six neonates who developed hypertriglyceridemia had significantly elevated mean peak FFA levels (918.3 micromol/L) prior to developing hypertriglyceridemia compared with 4 neonates (mean peak FFA levels, 380.2 micromol/L) who had triglyceride levels lower than 2.82 mmol/L (250 mg/dL) (P = .002). CONCLUSION: We conclude that dexamethasone induces hypertriglyceridemia in the presence of hyperinsulinemia and increased FFA levels.

Comparison of two strategies for surfactant prophylaxis in very premature infants: a multicenter randomized trial.

INTRODUCTION: Previous trials of surfactant therapy in premature infants have demonstrated a survival advantage associated with prophylactic therapy as an immediate bolus, compared with the rescue treatment of established respiratory distress syndrome. The optimal strategy for prophylactic therapy, however, remains controversial. When administered as an endotracheal bolus immediately after delivery, surfactant mixes with the absorbing fetal lung fluid and may reach the alveoli before the onset of lung injury. This approach, however, causes a brief delay in the initiation of standard neonatal resuscitation, including positive pressure ventilation, and is associated with a risk for surfactant delivery into the right main stem bronchus or esophagus. As an alternative approach, surfactant prophylaxis may be administered in small aliquots soon after resuscitation and confirmation of endotracheal tube position. Although this strategy has substantial logistical advantages in clinical practice, its efficacy has not been established. OBJECTIVE: The purpose of this study was to determine whether the established benefits of the immediate bolus strategy for surfactant prophylaxis could still be achieved using a postventilatory aliquot strategy after initial standard resuscitation and stabilization. DESIGN: Multicenter randomized clinical trial with patients randomized before delivery to immediate bolus or postventilatory aliquot therapy. PARTICIPANTS: Inborn premature infants delivered to mothers at an estimated gestational age of 24[0/7] to 28[6/7] weeks. INTERVENTIONS: Those infants who were randomized to the immediate bolus strategy were intubated as rapidly as possible after birth, and a 3-mL intratracheal bolus of calf lung surfactant extract (Infasurf) was administered before the initiation of positive pressure ventilation. Those infants who were randomized to the postventilatory aliquot strategy received standard resuscitation measures with intubation by 5 minutes of age, if not required earlier. At 10 minutes after birth, 3 mL of surfactant was administered in 4 divided aliquots of 0.75 mL each. Patients in both groups were eligible to receive up to three additional doses of surfactant as rescue therapy in the neonatal intensive care unit, if needed. OUTCOME MEASURES: The primary outcome variable was survival to discharge to home. Secondary variables included neonatal complications and requirement for oxygen therapy at 36 weeks' postmenstrual age. RESULTS: Among three centers, 651 infants were enrolled and randomized before delivery. Survival to discharge to home was similar for the two strategies for surfactant therapy as prophylaxis: 76% for the immediate bolus group and 80% for the postventilatory aliquot group. In a secondary analysis, the rate of supplemental oxygen administration at 36 weeks' postmenstrual age was 18% for the immediate bolus group and 13% for the postventilatory aliquot group. CONCLUSIONS: Survival to discharge to home was similar with immediate bolus and postventilatory aliquot strategies for surfactant prophylaxis. Because of its logistical advantages in the delivery room and its beneficial effects on prolonged oxygen requirements, we recommend the postventilatory aliquot strategy for surfactant prophylaxis of premature infants delivered before 29 weeks' gestation.

School-age follow-up of prophylactic versus rescue surfactant trial: pulmonary, neurodevelopmental, and educational outcomes.

BACKGROUND: Exogenous surfactant replacement has improved survival and reduced pulmonary complications of prematurity. Improved early outcomes for infants of <30 weeks' gestation treated with a strategy of prophylactic versus rescue surfactant, if needed, were demonstrated in a multicenter, randomized trial conducted between 1985 and 1988. We reevaluated a subset of survivors from this trial to determine the pulmonary and neurodevelopmental outcomes at school age. METHODS: At 4.5 to 8 years of age, all survivors from one of the three centers were located, and 96% were evaluated. The original randomization included stratification by center and followed an intention-to-treat methodology in assessing the efficacy of prophylactic versus rescue treatment with surfactant. The follow-up test battery included a health-assessment questionnaire, spirometry, 88% saturation test, neurologic examination, and the McCarthy Scales of Children's Abilities (MSCA) and the Conners' Parent Rating Scale-48. Educational achievement was determined by school class placement and teachers' reports of achievement. RESULTS: Of the 192 children originally enrolled, 154 survived. Evaluations were performed on 148 of these infants. An abnormal pulmonary history was found in 45 (30%) of the children: 16 (22%) in the prophylactic group and 29 (39%) in the rescue group. Formal pulmonary function was evaluated in 81 children; 29 (78%) in the prophylactic group and 33 (75%) in the rescue group were considered abnormal. No significant differences were found between the two groups on either cognitive or motor subscales of the MSCA, the Conners' Parent Rating Scale-48, the neurologic examination, the education services received in school, or the teacher ratings of below-average academic performance. Intelligence scores measured on the MSCA were low-normal for both groups. Some level of educational assistance was being provided to 72 (49%) of the cohort studied, and both groups had below average educational performance and increased needs for educational assistance. CONCLUSIONS: Prophylactic surfactant administration to infants of <30 weeks' gestation was associated with fewer long-term clinical pulmonary complications than assignment to rescue administration. Formal pulmonary testing at school age did not reveal significant differences between treatment groups in those infants who could be tested. There also were no group differences found on neurologic, cognitive, behavioral, or educational assessments at school age.

School-age follow-up of a single-dose prophylactic surfactant cohort.

This study reports the school-age developmental and health status of a preventilatory surfactant cohort. The sample consisted of 39 surviving subjects (21 experimental and 18 controls) born at 25 to 29 weeks gestation who were studied at 6 and 12 months and 5 to 7 years of age. At 6- and 12-month follow-ups, the cohort was functioning close to the population normative mean. Although cognitive and motor assessments at school age also showed no group differences, 8 of 19 (42%) in the surfactant group and 9 of 17 (53%) in the normal saline group attained a McCarthy General Cognitive Index score of < or = 84 (abnormal range). On the Connors' Parental Questionnaire, both groups scored high on the Learning Disability Subscale. The surviving cohort at 5 to 7 years had no identified long-term sequelae due to surfactant therapy, yet both groups were at risk for neurodevelopmental and educational morbidity.

In utero adrenal hemorrhage associated with fetal distress, subsequent transient neonatal hypertension, and a nonfunctioning ipsilateral kidney.

We present an unusual case of in utero adrenal hemorrhage associated with fetal distress. This case was further complicated by transient neonatal hypertension that resolved spontaneously and a nonfunctioning ipsilateral kidney. We discuss the possible underlying pathophysiology.

Feeding premature infants while low umbilical artery catheters are in place: a prospective, randomized trial.

OBJECTIVE: The objective of this prospective, randomized clinical trial was to test the hypothesis that there is no difference in the frequency of feeding problems and necrotizing enterocolitis between a group of premature infants who received early enteral feedings while low umbilical artery catheters (LUACs) were in place, and a late group who were not fed until 24 hours after removal of LUACs. PATIENTS AND METHODS: Twenty-nine premature infants (born at 28.5 +/- 3.0 SD weeks of gestational age) who were in stable condition received early enteral feedings at a median of 2 days while a LUAC was in place; 31 infants (born at 28.6 +/- 2.7 SD weeks of gestational age) received late enteral feedings at a median of 5 days of age, 24 hours after the removal of the LUAC. Feeding complications and interventions and nutritional characteristics were recorded prospectively. RESULTS: There were no differences in the baseline perinatal characteristics of the two groups. The incidence of gastric residua and the incidence of abdominal distention were the same in both groups. The early feeding group had significantly fewer percutaneous central venous catheters, evaluations for sepsis, and episodes of receiving nothing by mouth while a gastric suction tube was in place. Infants in the early group received parenteral alimentation-lipid emulsion infusions for a median of 13 days versus 30 days for the late-fed group (p = 0.0028 by Wilcoxon test). There were two cases of necrotizing enterocolitis in the early group versus four cases in the late group. CONCLUSIONS: Premature infants in stable condition who receive enteral feedings while LUACs are in place do not have an increased incidence of feeding problems compared with infants who do not receive enteral feedings until 24 hours after removal of LUACs.

Developmental disabilities related education, technical assistance, and research activities in developing nations.

Few resources are available to identify principles, benefits, and pitfalls concerning international exchanges among professionals in the developmental disabilities field. In the present paper different models for international activities in mental retardation and developmental disabilities were described. Several principles were articulated that characterize successful international programs. These principles were illustrated in a descriptive case study of an international exchange and technical assistance project conducted between a University Affiliated Program and a developing nation.

High-frequency jet ventilation and surfactant treatment of newborns with severe respiratory failure.

Twenty-eight newborn infants (birthweight, 2.4 +/- 1.1 kg; gestational age, 34.6 +/- 6.1 weeks) with respiratory distress syndrome (RDS), meconium aspiration syndrome, or pneumonia who deteriorated in spite of optimal conventional mechanical ventilation (CMV) and exogenous surfactant therapy were treated with high-frequency jet ventilation (HFJV) and continued surfactant therapy. For enrollment, infants had to have a limited response to surfactant therapy and conventional ventilation, and meet clinical criteria that confirmed clinical deterioration and severity of illness. Study infants had received exogenous calf lung surfactant extract (CLSE) and conventional ventilation prior to the start of HFJV at 46.3 +/- 8.2 hours of age. Patients initially responded to HFJV alone with significant improvement in several respiratory variables, but deteriorated subsequently and receive additional doses of exogenous surfactant on HFJV. Exogenous surfactant and HFJV resulted in significant and sustained improvement in several respiratory variables. Only ten patients deteriorated to meet criteria for a second surfactant dose on HFJV, and two patients received a third dose. Twenty-five of the 28 patients studied survived (89%). No patients received extracorporeal membrane oxygenation or were discharged home on oxygen. The results of this pilot study suggest that the combination of HFJV and exogenous surfactant replacement may be effective in treating infants with more severe respiratory failure, and indicate the need for more extensive controlled investigations.

A comparison of surfactant as immediate prophylaxis and as rescue therapy in newborns of less than 30 weeks' gestation.

BACKGROUND: Exogenous pulmonary surfactants are administered into the trachea either to prevent respiratory distress syndrome in premature infants or to treat it. In a randomized, multicenter trial, we compared the results of surfactant therapy initiated as prophylaxis with the results of rescue therapy with surfactant. METHODS: Before birth, 479 infants with an estimated gestational age of less than 30 weeks were randomly assigned to receive surfactant as prophylaxis (n = 235) or rescue therapy (n = 244). The infants in the prophylaxis group received a 90-mg intratracheal dose of an exogenous calf-lung surfactant extract at the time of delivery, whereas the infants in the rescue-therapy group received 90 mg of the surfactant several hours after delivery if the fractional inspiratory oxygen concentration was at least 0.40 or if the mean airway pressure was at least 0.686 kPa (7 cm of water), or both. Infants in both groups received additional doses of surfactant at intervals of 12 to 24 hours if these criteria were met. RESULTS: The proportion of infants surviving until discharge to their homes was significantly higher in the prophylaxis group than in the rescue-therapy group (88 vs. 80 percent, P = 0.028). This difference was due primarily to the longer survival of very premature infants (less than or equal to 26 weeks' gestation) in the prophylaxis group than in the rescue-therapy group (75 vs. 54 percent, P = 0.006). According to proportional-hazards regression analysis, the distribution of survival times was better for all infants in the prophylaxis group (P = 0.007) and for the subgroup of infants in the prophylaxis group who were delivered at 26 weeks' gestation or earlier (P = 0.0048). Infants in the prophylaxis group who were delivered at 26 weeks' gestation or earlier had a lower incidence of pneumothorax than similar infants in the rescue-therapy group (7 vs. 18 percent, P = 0.03). CONCLUSIONS: We found a significant advantage to the administration of the initial dose of surfactant as prophylaxis rather than as rescue therapy in very premature infants.

Surfactant treatment of full-term newborns with respiratory failure.

Surfactant inactivation has been shown to be a significant factor in animal models of lung injury and may also be important in some forms of respiratory failure in full-term newborns. Fourteen full-term newborns with respiratory failure associated with pneumonia (7 patients) and meconium aspiration syndrome (7 patients) were treated with 90 mg/kg of a calf lung surfactant extract, given intratracheally up to every 6 hours for a maximum of four doses. The group mean fraction of inspired oxygen (FI02) before treatment was 0.99 +/- 0.01 SEM, and the mean airway pressure (MAP) was 14.6 +/- 1.0 cm H2O. Patients showed significant improvement in oxygenation after initial surfactant treatment, with the arterial-alveolar oxygenation ratio (a/A ratio) rising from 0.09 +/- 0.01 before surfactant treatment to 0.22 +/- 0.05 by 15 minutes (P = .03) and remaining improved for 6 hours. The oxygenation index, incorporating MAP as well as oxygen variables, also improved significantly from 26.2 +/- 3.1 to 11.2 +/- 1.7 at 15 minutes (P less than .001), with improvement sustained for more than 6 hours. Chest radiographs were blindly scored from 0 (normal) to 5 (severe opacification), and these improved with marginal significance after initial surfactant treatment (from 2.9 +/- 0.2 to 2.5 +/- 0.2, P = .05).(ABSTRACT TRUNCATED AT 250 WORDS)