In silico predicted transcriptional regulatory control of steroidogenesis in spawning female fathead minnows (Pimephales promelas).

Oocyte development and maturation (or oogenesis) in spawning female fish is mediated by interrelated transcriptional regulatory and steroidogenesis networks. This study integrates a transcriptional regulatory network (TRN) model of steroidogenic enzyme gene expressions with a flux balance analysis (FBA) model of steroidogenesis. The two models were functionally related. Output from the TRN model (as magnitude gene expression simulated using extreme pathway (ExPa) analysis) was used to re-constrain linear inequality bounds for reactions in the FBA model. This allowed TRN model predictions to impact the steroidogenesis FBA model. These two interrelated models were tested as follows: First, in silico targeted steroidogenic enzyme gene activations in the TRN model showed high co-regulation (67-83%) for genes involved with oocyte growth and development (cyp11a1, cyp17-17,20-lyase, 3ß-HSD and cyp19a1a). Whereas, no or low co-regulation corresponded with genes concertedly involved with oocyte final maturation prior to spawning (cyp17-17α-hydroxylase (0%) and 20ß-HSD (33%)). Analysis (using FBA) of accompanying steroidogenesis fluxes showed high overlap for enzymes involved with oocyte growth and development versus those involved with final maturation and spawning. Second, the TRN model was parameterized with in vivo changes in the presence/absence of transcription factors (TFs) during oogenesis in female fathead minnows (Pimephales promelas). Oogenesis stages studied included: PreVitellogenic-Vitellogenic, Vitellogenic-Mature, Mature-Ovulated and Ovulated-Atretic stages. Predictions of TRN genes active during oogenesis showed overall elevated expressions for most genes during early oocyte development (PreVitellogenic-Vitellogenic, Vitellogenic-Mature) and post-ovulation (Ovulated-Atretic). Whereas ovulation (Mature-Ovulated) showed highest expression for cyp17-17α-hydroxylase only. FBA showed steroid hormone productions to also follow trends concomitant with steroidogenic enzyme gene expressions. General trends predicted by in silico modeling were similar to those observed in vivo. The integrated computational framework presented was capable of mechanistically representing aspects of reproductive function in fish. This approach can be extended to study reproductive effects under exposure to adverse environmental or anthropogenic stressors.

Outcome of infants with bronchopulmonary dysplasia who receive extracorporeal membrane oxygenation therapy.

BACKGROUND/PURPOSE: Extracorporeal membrane oxygenation (ECMO) is an accepted therapy for acute respiratory failure but more recently has been used in infants with bronchopulmonary dysplasia (BPD) and superimposed acute pulmonary insults. The purpose of this study was to review the outcomes of such infants. METHODS: Charts of infants at The Children's Hospital of Philadelphia (CHOP) who had a diagnosis of BPD before ECMO were reviewed. In addition, to obtain survival data in a larger population, the Extracorporeal Life Support Organization (ELSO) Registry was searched for infants with BPD before ECMO. RESULTS: Of 204 patients who received noncardiac ECMO at CHOP, 9 had BPD before ECMO. Of 7 survivors, 4 were still ventilator dependent at 9 to 39 months of corrected age. Developmentally, 4 had significant global delays, whereas 3 had significant language and motor delays with average to mildly delayed cognitive abilities. The ELSO Registry search showed 76 patients with BPD before ECMO, with a 78% survival. CONCLUSIONS: The survival rate of infants with BPD who receive ECMO is comparable to, or better than, the survival rates in most other ECMO populations. However, there appears to be a high risk of severe pulmonary and neurodevelopmental sequelae.

How students nurses see home healthcare nurses today.

Students in an associate degree nursing program participated in observational home healthcare experiences. By observing the interactions between the client/family and the home healthcare nurse, these students noted crucial differences between the delivery of acute and home care nursing. Their observations can be helpful to practicing home care nurses who serve as their role models and to orientation coordinators and faculty members who teach home care nursing to novices.

Adverse neurodevelopmental outcome after extracorporeal membrane oxygenation among neonates with bronchopulmonary dysplasia.

OBJECTIVE: The relationship between bronchopulmonary dysplasia (BPD) and neurodevelopmental outcome after extracorporeal membrane oxygenation (ECMO) has not been extensively reported. We compared the outcomes in a large series of infants with and without BPD after ECMO. STUDY DESIGN: Hospital charts and follow-up records of 145 infants treated with ECMO (1985 through 1990) were reviewed. Complete long-term respiratory and follow-up outcome data were available in 64 infants. BPD occurred in 17 survivors; the remaining 47 did not have BPD. RESULTS: Babies with BPD were more likely to have had respiratory distress syndrome. Mean (+/- SD) age at ECMO initiation was later for the BPD group (127+/-66 vs 53+/-39 hours, p < 0.001), and the duration of ECMO treatment was longer (192+/-68 vs 119+/-53 hours, p < 0.001). Bayley Scales of Infant Development scores at <30 months were lower in infants with BPD (p < 0.001), as were three of four Mullen Scales of Early Learning scores (> or = 30 months, p < 0.001 or p = 0.01). At 57+/-16 months 11 (64%) patients with BPD had mild neurologic disabilities, and 3 (18%) had severe disabilities. At a similar age (53+/-16 months, p = NS) 16 (34%) patients without BPD had mild disabilities, whereas 2 (4%) had severe disabilities (p < 0.01). CONCLUSIONS: The occurrence of BPD after ECMO is associated with adverse neurodevelopmental outcome. Patients with BPD after ECMO merit close long-term follow-up.

Pulmonary sequelae in infants treated with extracorporeal membrane oxygenation.

The decision to place an infant on extracorporeal membrane oxygenation (ECMO) is based on predictions of expected morbidity and mortality. One unknown factor is the relationship between pre-ECMO pulmonary dysfunction and on barotrauma and post-ECMO pulmonary sequelae. To determine whether placement of infants on extracorporeal membrane oxygenation (ECMO) early is associated with less subsequent pulmonary dysfunction than placing infants on EMCO later, we evaluated pulmonary function in 25 neonates prior to ECMO, when the infants had come off EMCO, and at the time of nursery discharge. Pulmonary resistance (R) and compliance (CL) were determined by a pneumotachograph and esophageal manometry, and functional residual capacity (FRC) was determined by a helium dilution method. Maximal expiratory flow (VmaxFRC) was determined by thoracic compression at the time of discharge. Infants were assigned to an early ECMO group (< 36 hours of age, n = 12), or a late ECMO group (> 36 hours of age, n = 13). When first evaluated, the early group had a higher oxygenation index than the late group (mean value, 63 versus 48), but initial pulmonary function measurements were not different between the two groups. In the early group mean CL increase from 0.20 to 0.36 ml/cmH2O/kg, FRC increased from 7 to 20 ml/kg, and mean R decreased from 107 to 61 cmH2O/L/sec between the initial study and immediately after ECMO. In the late group, only FRC increased from a mean of 8 to 20 ml/kg. CL and FRC increased from post-ECMO to discharge in both groups (mean CL from 0.36 to 0.76 ml/cmH2O/kg in the early group, and from 0.30 to 0.79 in the late group). Mean FRC increased from 20 to 26 ml/kg in the early group, and from 20 to 25 ml/kg in the late group. VmaxFRC was lower in the late than the early group at discharge (mean, 1.14 versus 1.58 L/sec; P < 0.05). While both groups of infants had minimal pulmonary dysfunction at discharge, the infants placed on ECMO early had evidence of slightly less airway dysfunction despite a higher initial oxygenation index than the infants placed on ECMO late.

Setting roller pump occlusion with the transonic HT109 flowmeter.

Setting the occlusion of a roller pump may be facilitated using the TRansonic HT109 Ultrasonic Flowmeter (Transonic Systems, Inc. Ithaca, NY) with non-invasive transducer. The process addresses the need to set occlusion quickly and accurately before initiation of extracorporeal membrane oxygenation (ECMO). This can be performed with the circuit tubing before blood prime and does not require opening the fluid filled ECMO apparatus to air. The principle is based on the fact that fluid flow through the tubing will change with roller occlusion. Using the Transonic flowmeter, a pre determined (partially occlusive) setting can be achieved by first determining the point of total occlusion, then decreasing occlusion a small percentage from this maximum (i.e., total) occlusion. Clinical application in 35 neonatal ECMO cases has shown the practice to be safe, reliable, and efficient.

Documented home apnea monitoring: effect on compliance, duration of monitoring, and validation of alarm reporting.

The objectives of this study were to: (1) measure patient compliance with monitoring, (2) validate parental reports of alarms at home, (3) examine monitoring duration, and (4) compare documented monitor records with the traditional pneumogram to evaluate patients for monitor discontinuation. During the 1-year period from January through December, 1992, 114 infants were followed up with documented monitoring. Simultaneously, 113 infants were followed up with conventional monitors. Infants were premature, or victims of apparent life-threatening episodes (ALTE), or siblings of SIDS victims. Monitors recorded all episodes of apnea greater than 15 seconds and bradycardia less than 80 beats per minute. All families were contacted biweekly by telephone. Downloads were performed at regular intervals. Monitor downloads were compared with simultaneous pneumograms to assess the accuracy of a long-term, intermittent event-recording system versus short-term (6- to 12-hour) continuous recording. All families were highly compliant with the use of home monitoring. Although Caucasian families used the monitors more often than non-Caucasian families, all groups used the monitor > 75% of the time. True episodes were verified in 38% of patients by monitor downloads. Only 7.4% of all recorded events were true events. Of the real events, 51.2% were apneas of 16-20 seconds. No significant differences were found in overall duration of monitoring between documented and nondocumented monitors. In the premature infants, the duration of monitoring was significantly reduced in those infants found to have no true episodes over those with real events at home. Readmission for ALTE was reduced in infants with documented monitors. Premature infants without events were monitored an average of 24 fewer days (P = 0.03). Computerized monitor downloads were found to be equally, if not more, sensitive than pneumograms in evaluating infants for monitor discontinuation. Documented monitoring offers a viable alternative to traditional monitoring and pneumograms in assisting clinicians and families in evaluating their infant's progress. By accurately assessing compliance, distinguishing true from false alarms, and decreasing the need for pneumograms, these devices provide valuable information to clinicians and families.

Developmental changes in renal artery blood flow velocity during the first three weeks of life in preterm neonates.

Changes in color Doppler imaging measurements of renal artery blood flow velocity have been reported previously during fetal life and during the first week postnatally in term and preterm infants. This study reports longitudinal, developmental changes in renal artery and aortic blood flow velocities occurring postnatally, from birth to day 1 of life, at 1 week, and at 2 to 3 weeks of age in 14 premature babies (mean gestation, 30 +/- 4 (SD) weeks; birth weight, 1.45 +/- 0.57 kg), and identified by means of color Doppler imaging and pulsed Doppler spectral analysis. Results indicate that a significant increase in renal artery systolic blood flow velocity occurs within the first week of life (from 40 +/- 3 (SEM) cm/sec at birth or on day 1, to 53 +/- 3 cm/sec on day 7, to 51 +/- 4 cm/sec on day 14 to 21; repeated-measures analysis of variance, p = 0.004), concurrently with a significant increase in abdominal aortic blood flow velocities, both systolic (from 40 +/- 4 at birth or on day 1, to 70 +/- 8 on day 7, to 76 +/- 8 cm/sec on day 14 to 21; p <0.001) and diastolic (from 4 +/- 2 at birth or on day 1, to 11 +/- 2 on day 7, to 11 +/- 2 cm/sec on day 14 to 21; p = 0.00 1). Systemic blood pressure did not increase concomitantly during the some period. Neither the presence of respiratory distress syndrome or patent ductus arteriosus nor treatment with indomethacin altered developmental increases in observed renal artery blood flow velocities. The presence of an umbilical artery catheter in the high thoracic position in five infants, however, created turbulence at the level of the renal arteries, significantly increasing renal artery systolic flow velocity from 32 +/- 4 to 44 +/- 5 cm/sec (p = 0.009) and increasing renal resistive index from 0.90 +/- 0.03 to 0.96 +/- 0.04 (p = 0.046). These results suggest that renal artery blood flow velocity increases during the first postnatal week in preterm infants and is likely related to increases in aortic blood flow velocity and reduction in renal vascular resistance.

Investigation of fatigue failure of S-65-HL "Super Tygon" roller pump tubing.

A failure analysis was performed on Norton S-65-HL Tygon tubing. Fatigue testing was performed on four sizes of this tubing, and essentially showed how the tubing wears out. A dynamic "life hours to failure" test, which was performed on the 3/8" internal diameter (ID) size, quantified when the tubing ruptured. Based on results of laboratory testing and the institution's clinical extracorporeal membrane oxygenation (ECMO) experience, a reasonable life expectancy for the 3/8" S-65-HL Tygon size was determined for use in this institution's neonatal ECMO system. An understanding of the expected performance of roller pump tubing-an integral component of the ECMO system-is imperative to providing safe, effective extracorporeal life support.

Prognosis with preoperative pulmonary function and lung volume assessment in infants with congenital diaphragmatic hernia.

OBJECTIVES: To determine whether fatal pulmonary hypoplasia, as assessed by functional residual capacity (FRC), can be distinguished from other reversible causes of respiratory failure in infants with congenital diaphragmatic hernia (CDH). METHODS: In the present study, 25 term neonates having CDH without other anomalies (mean birth weight +/- SD, 3.25 +/- 0.50 kg) were enrolled prospectively into a protocol evaluating pulmonary function. Lung compliance (CL) and FRC were measured before diaphragmatic repair and compared with the highest oxygenation index (OI) and lowest PaCO2, also obtained preoperatively. Pulmonary function assessment was repeated after diaphragm repair on postoperative days 3 and 7. CL was determined by esophageal manometry and pneumotachography, and FRC was determined by helium dilution. RESULTS: Fifteen infants (60%) survived to hospital discharge. Eighteen (72%) required extracorporeal membrane oxygenation (ECMO) for support, and of these, 8 (44%) survived. PaCO2 was similar preoperatively in infants grouped as survivors without ECMO, survivors with ECMO, and nonsurvivors. In nonsurvivors (all of whom received ECMO), the preoperative OI was significantly higher (51 +/- 21), CL was less (0.11 +/- 0.04 mL/cm of water per kg), and FRC was smaller (4.5 +/- 1.0 mL/kg) than in the survivors who required ECMO (26 +/- 18, 0.18 +/- 0.08 mL/cm of water per kg, and 12 +/- 5 mL/kg, respectively), as well as in the survivors without ECMO, (6 +/- 2, 0.32 +/- 0.16 mL/cm of water per kg, and 15.8 +/- 4 mL/kg, respectively). The group surviving with ECMO had a higher OI than the infants surviving without ECMO. All nonsurviving infants had FRCs of less than 9.0 mL/kg preoperatively. In contrast, only 2 of the 15 survivors had preoperative FRCs less than 9 mL/kg. CONCLUSIONS: The results of this study suggest that preoperative assessment of FRC may predict fatal pulmonary hypoplasia in most infants with CDH.

The timing of SIDS deaths in premature infants in an urban population.

Previous reports have demonstrated that premature infants are at greatly increased risk for sudden infant death syndrome (SIDS). Although only 9% of infants are born at less than 36 weeks' gestation, 20% of SIDS victims are former premature infants. The objective of this study was to characterize the time course of SIDS in premature infants and to determine why SIDS occurs at such a high rate in this patient population. A database of all cases of SIDS in Philadelphia from 1987 through 1991 was used to establish the time course for SIDS deaths in term and preterm infants. Gestational age was established by Dubowitz exam. To evaluate distinctly different age groups, infants from 32-36 weeks were excluded from analysis. Age at death and postconceptional age of death were compared for both groups. Data are described in weeks (mean +/- SEM), and analyzed using unpaired t-test and log-rank test to compare survival rate between term and preterm infants. A significant difference (P < 0.01) was noted in age at death of term versus preterm infants. No difference was found in postconceptional age of death. The survival rates were also different (P < 0.001). Preterm infants showed a much wider distribution in age of death from SIDS. The term infants followed the classic SIDS curve. By 32 weeks' postnatal age, 95% of all SIDS had taken place in the term group, but only 75% in the preterm group. The age at death for SIDS differs in the preterm infant.(ABSTRACT TRUNCATED AT 250 WORDS)

Infant sleep position following new AAP guidelines. American Academy of Pediatrics.

OBJECTIVE: This report examines the response of families to the American Academy of Pediatrics June 1992 recommendation that healthy term infants be put to sleep on their back or side to decrease the risk of sudden infant death syndrome. Parents at two clinics and private practices were interviewed to ascertain sleep position practices. METHODS: Parents of infants from 1 to 6 months of age who were in the waiting room for a well-child visit were eligible for study. A total of 760 interviews were conducted using a closed-ended questionnaire. Parents were asked about sleep position, positional changes during sleep, and factors that influenced their decision to position their infant prone, side, or supine. Interviews were conducted from September 1993 through April 1994. This interval was divided into two equal, 4-month time intervals. Sleep practices were compared during the first and second time periods. Differences between practice and clinic groups were measured. Groups were compared using the chi-square test, with results considered significant at P < .05. RESULTS: The number of infants placed side or supine for sleep increased significantly since the inception of the study, from 38.1% to 59.1%. Despite this increase, parents reported that the impetus for changing position came from family or the media, rather than from health professionals. Initially, the proportion of infants in private practices placed side or supine was greater than that of clinic patients. That difference disappeared by the end of the study. Prone positioning continued to be more prevalent in the 3- to 6-month-old infants than in the 1- to 3-month-old group. The majority of infants at all ages awoke in the same position that they were put to sleep. CONCLUSIONS: Side and supine positioning for sleep increased in all socioeconomic groups. A small number of infants placed side or supine for sleep are found prone on awakening. Health professionals need to increase their role in providing sleep position guidance. As the proportion of the population positioning their infants side or supine for sleep increases, it should be possible to examine the effect on the sudden infant death syndrome rate.

Risk factors for bronchopulmonary dysplasia after extracorporeal membrane oxygenation.

OBJECTIVE: To determine risk factors for the development of bronchopulmonary dysplasia (BPD) after treatment with extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective case-control study. SETTING: Tertiary care level 3 neonatal intensive care unit. PARTICIPANTS: Seventy-three newborns treated with ECMO for severe respiratory failure during a 5-year period, who survived until day of life 28, and who did not have pulmonary hypoplasia as the initial cause for respiratory failure. INTERVENTIONS: None. MAIN OUTCOME MEASURE: The presence of BPD after treatment with ECMO, which was defined as oxygen and/or ventilatory requirements at day of life 28, with characteristic abnormalities seen on chest x-ray film. RESULTS: The age at ECMO initiation was significantly greater for patients with BPD compared with patients without BPD (mean +/- SD, 135 +/- 68 hours vs 50 +/- 37 hours; P < .001). There was an 11.5-fold increased risk for the development of BPD if ECMO was initiated at greater than 96 hours of age. The primary diagnosis of respiratory distress syndrome imparted a 5.2-fold increased risk for the development of BPD. Patients with BPD required ECMO significantly longer than patients without BPD (203 +/- 73 hours vs 122 +/- 51 hours; P < .001). CONCLUSION: These results demonstrate that delayed use of ECMO in treating neonatal respiratory failure is associated with an increased risk for the development of BPD and a longer duration of ECMO therapy.

Pulmonary function testing in the critically ill neonate, Part III: Case studies.

Accurate monitoring of respiratory status is of vital importance for the bedside nurse caring for the critically ill neonate. Pulmonary function testing can be utilized to effectively diagnose and quantitate lung disease in infants. Data obtained can be integrated into the nursing assessment and facilitate appropriate nursing interventions. The case studies provided in Part III of this series illustrate the utility of such testing in neonates with a range of illnesses and different diagnostic and therapeutic dilemmas. Case study one is an infant with chronic lung disease complicated by bronchospasm, case study two is an infant with bronchomalacia, and case study three demonstrates fine tuning of the ventilator in an infant with respiratory distress syndrome. Every study describes the usefulness of pulmonary function testing on a specific patient, each with different pulmonary pathology. These case studies, and the discussion in parts I and II of this series, illustrate the value of integrating pulmonary function data with ongoing clinical assessment to optimize the care of the sick or convalescing neonate. Tests ordered on a routine and/or as-needed basis will provide detailed information on the infant's pulmonary status that may be readily available at the infant's bedside. The neonatal nurse's involvement in requesting, performing, and interpreting these tests may enhance the treatment of the infant in intensive care.

Pulmonary function testing in the critically ill neonate, Part II: Methodology.

Pulmonary function testing is an important diagnostic tool in neonatal intensive care. These tests provide a detailed assessment of an infant's pulmonary status that can be used in several ways: to monitor the progression of lung disease, to streamline ventilator management, and to assess the infant's response to new treatments, such as surfactant replacement therapy or bronchodilators. In some settings, these tests are performed by specially trained nurses, and the results are available immediately for planning nursing care. This relatively noninvasive and low-risk assessment can be performed on all infants, whether on mechanical ventilation or breathing spontaneously. A comprehensive pulmonary function evaluation can be performed at the bedside in less than 60 minutes and is generally well tolerated. In this article, the determination of pulmonary "vital signs" tidal volume, minute ventilation, respiratory rate, pulmonary compliance, resistance, resistive work of breathing, and functional residual capacity-are discussed. The esophageal balloon technique for measuring dynamic pulmonary mechanics and energetics, as well as the helium dilution technique for measuring functional residual capacity, are described.

Continued pulmonary recovery observed after discontinuing extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation (ECMO) is a valuable therapy for the treatment of reversible lung disease in neonates. Associated with this treatment, however, are risks for complications that increase with the duration of therapy. We evaluated alveolar-arterial oxygen tension difference P(A-a)O2 pulmonary compliance (CL), and functional residual capacity (FRC) in 20 infants immediately after ECMO was discontinued, and again 24 hours thereafter. We measured CL by pneumotachography and esophageal manometry and FRC by helium dilution. Mean (+/- SEM) values for CL and FRC increased (CL from 0.28 +/- 0.02 to 0.35 +/- 0.03 mL/cmH2O)/kg and FRC from 18.6 +/- 1.4 to 22.2 +/- 1.1 mL/kg; P < 0.05), and P(A-a)O2 and the oxygenation index (OI) decreased (200 +/- 19 to 169 +/- 14 mm Hg and 6.9 +/- 0.44 to 5.4 +/- 0.5, respectively; P < 0.02), over the 24 hour period following ECMO. Nineteen of 20 infants experienced improvement in at least two of these parameters. Improvements were found to be greatest in the infant with the worst lung function immediately after discontinuing ECMO, and in the ten infants who had not received pancuronium bromide for inducing skeletal muscle paralysis, following decannulation from ECMO. These data indicate that improvement in lung function following ECMO will generally continue over the 24 hour period following the termination of cardiopulmonary bypass, and that borderline pulmonary status may not preclude discontinuation of bypass therapy.

Pulmonary function testing in the critically ill neonate, Part I: An overview.

Respiratory insufficiency, a frequent problem encountered by the critically ill neonate, has many etiologies. Pulmonary function testing can effectively diagnose, quantify, and qualify the dysfunction so as to better define a prognosis and guide appropriate therapy. Recent advances in computer-assisted technology and miniaturization of equipment now allow simple, reproducible, and rapid neonatal pulmonary function assessment at the bedside. The indications for, and benefits of, pulmonary function testing vary with gestation, age, and clinical condition of the infant. The overall description of the pulmonary function profile is discussed in this article. The general questions and approaches utilized for routine testing, the initial pulmonary function profile, and evaluation of the acutely ill infant and that of the convalescing preterm are addressed. The expertise of the intensive care nurse is invaluable in ensuring that safe, accurate, and reproducible data are obtained. The nurse can then use the data to alter the infant's care plan and to determine the necessity and timing for retesting. Specific information on methodology and examples of specific tests are given in related articles (Parts II, Vol. 13 No. 2 and III, Vol. 13 No. 4, respectively). A complete knowledge of pulmonary function assessment is important for any nurse caring for critically ill neonates.