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Biomedical subjects

W H Tooley

Publications and source records attributed to W H Tooley.

At least 19 recordsLinked to original sources

Outcome of very-low-birth-weight infants exposed to beta-sympathomimetics in utero.

In this study we examined neonatal and early childhood outcomes after intrauterine exposure to beta-sympathomimetic agents on infants with birth weights less than or equal to 1500 gm. The hospital courses and anthropomorphic, developmental, and neurologic development of 201 infants exposed to one or more beta-sympathomimetic agents (isoxsuprine, 33; ritodrine, 70; terbutaline, 43; combination, 55) were analyzed and compared with those of 130 control infants of similar birth weight. One hundred and seventy-seven infants had follow-up to 1 year of age, 101 to age 3, and 58 to age 4. When treatments consisting of a single beta-sympathomimetic or no treatment were compared, there were no statistically significant overall differences found in growth and development or in most of the short-term measures of infant well-being. However, significant overall differences with no evidence of confounding by time-related effects were found for the following; mortality, none greater than terbutaline; maximum positive inspiratory pressure when respiratory distress syndrome was present, none greater than terbutaline; neonatal trauma, terbutaline greater than ritodrine. Other differences were found in conjunction with evidence of time-related confounding, or within specific time intervals. It should be noted that these differences are not necessarily due to effects of the different treatments, as the data are observational.

Female

Initial clinical trial of EXOSURF, a protein-free synthetic surfactant, for the prophylaxis and early treatment of hyaline membrane disease.

EXOSURF is a protein-free surfactant composed of 85% dipalmitoylphosphatidylcholine, 9% hexadecanol, and 6% tyloxapol by weight. A single dose of 5 mL of EXOSURF per kilogram body weight, which gave 67 mg of dipalmitoylphosphatidylcholine per kilogram body weight, or 5 mL/kg air was given intratracheally in each of two controlled trials: at birth to neonates 700 through 1350 g (the prophylactic trial, n = 74) or at 4 to 24 hours after birth to neonates greater than 650 g who had hyaline membrane disease severe enough to require mechanical ventilation (the rescue trial, n = 104). In both studies, time-averaged inspired oxygen concentrations and mean airway pressures during the 72 hours after entry decreased significantly (P less than .05) in the treated neonates when compared with control neonates. Thirty-six percent of the treated neonates in the rescue study had an incomplete response to treatment or relapsed within 24 hours, suggesting the need for retreatment in some neonates. In the rescue trial, risk-adjusted survival increased significantly in the treated group. There were no significant differences in intracranial hemorrhages, chronic lung disease, or symptomatic patent ductus arteriosus between control and treated infants in either trial.

Administration, Inhalation

Stridor and gastroesophageal reflux in infants.

A relation was found between persistent stridor and gastroesophageal reflux in seven infants, aged 6 weeks to 6 months. Stridor began at 11 days to 2 months of age, and four of the seven infants had transient hypercarbia on at least one occasion before study. Only one had a history of frequent vomiting; three had recurrent pneumonia. Midesophageal pH, chest and abdominal movement, exhaled carbon dioxide partial pressure, and heart rate of six of the infants were recorded for 4 to 12 hours as they slept. Esophageal pH of the seventh infant was recorded for 24 hours. In the six completely studied infants, there were persistent increases of greater than 10 mm Hg in exhaled carbon dioxide level (three infants), of greater than 10 breaths per minute in respiratory rate (four infants), and in retractions and stridor (six infants) 5 to 20 minutes after onset of reflux. Stridor improved with medical management in 48 hours (five of five infants) and disappeared in 3 weeks (three of five infants) to 2 months (one of five infants). One of these medically treated infants subsequently was treated by Nissen gastric fundoplication because of a recurrence of persistent and severe stridor. Three infants had antireflux surgery, and in two of these stridor disappeared in 48 hours. In the third infant stridor disappeared 3 weeks after surgery. Based on this experience, reflux occasionally causes stridor, probably because of acute inflammation of the upper airway. If structural anomalies are ruled out, infants with severe stridor should be examined for gastroesophageal reflux.

Esophagus

Neonatal status and hearing loss in high-risk infants.

Neurophysiologic and behavioral assessments of auditory function were performed on 224 very low birth weight (less than or equal to 1500 gm) infants requiring intensive care in the nursery. The subjects were studied prospectively from 36 weeks to 4 years of age, as available for follow-up. To classify them according to their neonatal status, we applied a principal components analysis to a number of variables representative of the extent of illness and of patient care in early postnatal life. The subjects were then divided into neonatal status quartiles and evaluated for hearing outcome. All those with sensorineural hearing loss fell exclusively into the lowest neonatal status quartile. Sensorineural hearing loss was statistically associated (1) with greater amounts of furosemide administration for longer durations and in combination with aminoglycoside antibiotics and (2) with more episodes of low pH, hypoxemia, or both, higher total bilirubin levels, and substantially lower neonatal status scores. Birth weight, gestational age, highest creatinine level, Apgar score, and aminoglycosides alone were not systematically related to hearing capacity. Subjects in the lowest neonatal status quartile also had a considerably higher incidence of middle ear disorders, characterized by elevated thresholds and prolonged auditory brain stem-response latencies reflective of conductive hearing loss. We conclude that protracted illness and its associated treatment, independently of specific diagnostic categories, constitute important risk factors for permanent hearing loss and for transient hearing loss in early life.

Aminoglycosides

Developmental outcome following posthemorrhagic hydrocephalus in preterm infants. Comparison of twins discordant for hydrocephalus.

The mental development and neurologic outcome of four sets of preterm twins, in whom one infant within each pair developed posthemorrhagic hydrocephalus during the neonatal period, were assessed. Each hydrocephalic infant presented with signs of increased intracranial pressure and required placement of a ventriculoperitoneal shunt. Three of the four hydrocephalic infants required revision or replacement of the shunt during the first year. The four nonhydrocephalic infants had normal neurologic outcomes. All four hydrocephalic infants had some neurologic abnormalities on follow-up examination. Neurologic abnormalities were transient in one infant and persistent in three others, each of whom showed evidence of mild right hemiparesis. Within each twin pair, developmental rates and mental test scores were strikingly similar throughout infancy and early childhood. Two of the twin pairs have undergone psychological assessments at 8 and 11 years of age. Relatively lower IQ scores were obtained for the hydrocephalic child in each twin pair at these ages.

Cerebral Hemorrhage

Antenatal prediction of graduated risk of hyaline membrane disease by amniotic fluid foam test for surfactant.

We measured amniotic fluid surfactant by the semiquantitative foam stability test within 24 hours before delivery of 410 infants, 64 of whom developed HMD diagnosed by standard criteria. When surfactant titers were ranked in eight categories, they predicted graded risks of HMD. On this basis we defined five "risk groups" with significantly different incidences of HMD (I = 0.5%; II = 10%; III = 25%; IV = 41%; V = 79%). Infants in Groups I and II were heavier and more mature than those in Groups III to V. However, among infants of equivalent GA or birth weight, the incidence of HMD still correlated significantly with the foam test results. Within each risk group the incidence of HMD was equal among infants delivered by vagina and by cesarean section, slightly greater among males than females, and inversely proportional to GA. In Group V the incidence of HMD was 100% among infants at less than 33 weeks' GA. We used this relationship to devise a system that improved prediction of HMD by combining the foam test results with GA.

Amniocentesis

Tracheal fluid in fetal lambs: spontaneous decrease prior to birth.

We studied tracheal fluid (TF) production in 14 fetal lambs: 6 controls, 6 receiving atropine on 1 or more of the last 7 days before birth, and 2 with bilateral section of the cervical vagosympathetic trunk. A cannula diverted all TF into an intrauterine bag; we collected TF intermittently and measured its volume. All ewes delivered spontaneously at 128-150 days' gestation. TF production decreased before birth in all fetuses except one control. TF production decreased before birth in all fetuses except one control. TF production did not correlate with fetal arterial blood gas tensions, hematocrit, or plasma proteins. In controls only, TF production correlated with fetal arterial pH (P less than 0.02); however, the pH range was small and the correlation has questionable physiological significance. For all fetuses, TF production during the 7 days before birth correlated inversely with the plasma cortisol concentration of 48 h previously (n = 36; r = -0.603; P less than 0.001). We conclude a) TF production in fetal lambs decreases before spontaneous term or preterm labor; b) this decrease is not affected by atropine or by section of the cervical vagosympathetic trunk; and c) the decrease in TF production may be related to increased secretion of cortisol.

Animals

Skin surface carbon dioxide tension in sick infants.

Skin surface PCO2 (PSCO2) was measured at 44 C in 17 sick infants using a Radiometer surface PCO2 electrode. Values obtained for PSCO2 were compared with simultaneous values for arterial PCO2 (PaCO2). PSCO2 was found to be linerarly related to PaCO2 by a regression line with a slope 1.37. PaCO2 could be predicted from PSCO2 to within 6 torr in all instances. The relationship was not affected by the patient's gestational age, postnatal age, weight, or blood pressure. This electrode is a valuable clinical tool in the management of sick infants.

Arteries

Stimulation of breathing movements in fetal sheep by inhibitors of prostaglandin synthesis.

We studied the effects of inhibitors of prostaglandin synthesis on fetal breathing movements on 17 occasions in 11 lambs (gestational age 125-141 days). We gave 12 h infusions of sodium mechlofenamate (8.6-22.2 mg.kg-1) in 13 studies and indomethacin (21.8-38.8 mg.kg-1) in four studies. Results were similar with both agents and did not correlate with drug dosage. There were no changes in fetal arterial blood pressure, pH or blood gas tensions. We assessed fetal breathing movements by measurements of tracheal pressure for a control period of 224 h prior to and 208 h during the infusion of inhibitors of prostaglandin synthesis; their administration caused a marked stimulation of fetal breathing movements judged from the following four variables: (1) incidence of fetal breathing movements increased from 38.4 to 69.2% of the time (P < 0.001); (2) average amplitude of change in tracheal pressure during fetal breathing movements increased from 4.1 to 6.0 torr (P < 0.01); (3) maximal amplitude of change in tracheal pressure during fetal breathing movements increased from 8.8 to 13.4 torr (P < 0.01); and (4) the duration of the longest continuous episode of fetal breathing movements increased from 37 to 229 min (P < 0.05). Two fetuses had electrocorticogram (ECoG) recordings. In control periods, fetal breathing movements occurred only during low voltage, high frequency ECoG activity; however, during infusions of inhibitors of prostaglandin synthesis, fetal breathing movements occurred also during high voltage, low frequency ECoG activity. We conclude that inhibitors of prostaglandin synthesis stimulate fetal breathing movement in fetal sheep. These results suggest that a component of the prostaglandin system is a factor which inhibits breathing movements during fetal life.

Animals

Clinical limitations and advantages of transcutaneous oxygen electrodes.

We investigated the clinical use and limitations of the transcutaneous oxygen electrode described by Huch, Lübbers and Huch in 30 sick infants. One hundred and fifty-nine measurements of arterial oxygen tension (PaO2) and transcutaneous oxygen tension (tcPO2) were made. During the comparisons, arterial blood pressures, heart rate thoracic impedance were continuously recorded, skin axillary and environmental temperatures, hematocrit and skin thickness were measureed and the degree of peripheral perfusion noted. Despite a wide range of these variables, values of tcPO2 and PaO2 were similar (slope 0.963). Two groups of infants were identified in whom tcPO2 was lower than PaO2. These were infants receiving an intravascular infusion of tolazoline and infants with mean arterial blood pressures more than 2.5 s.d. below the predicted average value. Both of these situations represent extreme alterations in peripheral blood flow and give important information regarding the limitations of the method. Less extreme alterations in flow caused by mild hypotension, hypothermia, anemia, radiant warmers, and bilirubin lights did not adversely affect the transcutaneous PO2--arterial PO2 correlation. Advantages of transcutaneous oxygen monitoring over more conventional monitoring methods were assessed. We conclude that the transcutaneous oxygen electrode is safe, is easy to use, has few limitations and provides data which can help improve the management of most sick infants.

Blood Gas Analysis

Transcutaneous oxygen tension in sick infants.

The clinical usefulness of the transcutaneous O2 electrode was investigated in 30 sick infants; 159 simultaneous measurements of arterial PO2 and transcutaneous PO2 were made. During the comparisons, arterial blood pressure, heart rate, and thoracic impedance were continuously recorded, and skin axillary and environmental temperatures and hematocrit were noted. Despite a wide range of arterial blood pressure and hematocrits, arterial PO2 and transcutaneous PO2 were similar (slope, 0.963), except for 2 groups of sick infants. Some infants with severe, persistent pulmonary hypertension who were receiving an intravascular infusion of tolazoline and infants with mean arterial blood pressures more than 2.5 SD less than the predicted average had values for transcutaneous PO2 that were lower than PO2. The surface O2 electrode is safe and relatively easy to use and provides data that can help in the management of most sick infants.

Blood Pressure

Radioimmunoassay of pulmonary surface-active material in the tracheal fluid of the fetal lamb.

We measured pulmonary surfactant antigen by radioimmunoassay and phospholipid by lipid phosphorus assay in fluid collected during 12-hour periods from the trachea of lambs in utero between 102 and 147 days of gestation. Both phospholipid and antigen were detectable at 114 days and were present at low concentrations until 137 days. The concentrations then increased rapidly and reached 5- to 10-fold higher concentrations before parturition. The ratio of lipid phosphorus to antigen increased approximately 5-fold as the lungs passed from canalicular to alveolar architecture and approximated the adult ratio only during the alveolar stage of development.

Animals