Robert D. Guthrie

Testosterone treatment for micropenis during early childhood

Low-dosage, short-term, systemic testosterone therapy resulted in enlargement of micropenis to normal penile size for age in 4, XY boys under 3 years of age. Each patient was given 25 mg. of intramuscular Depo-Testosterone every three weeks for three months. Acceleration of linear growth and osseous maturation was transient, returning toward a normal rate after the therapy. Parental acceptance of the results was favorable, and virilizing side effects other than enlargement of the penis were minimal. The decision to utilize this mode of treatment should obviously be approached with caution.

A Proposed Neuropathological Basis for Learning Disabilities in Children Born Prematurely

This study aimed at providing understanding of the etiology and mechanisms responsible for the learning and behavioral disabilities in the increasing numbers of survivors of neonatal intensive care units who develop MBD/LD‐type (minimal brain dysfunction, learning disabilities) complications. The brains of 16 premature infants who died within the first month of life were studied by microscopic examination. Significant neuropathological findings in gray‐matter and white‐matter were found in many areas, including both superficial cortical and deep basal brain structures. These lesions are postulated to be precursors to later LD and MBD syndromes in infants who survive, such that similar lesions of varying severity correlate with varying degrees of brain dysfunction. Premature infants who survive are known from other studies to be high‐risk candidates for LD‐and MBD‐type developmental disabilities.

HYPOXIC VENTILATORY RESPONSE IN THE NEWBORN MONKEY

Summary: The hypoxic ventilatory response was determined in twelve unanesthetized newborn monkeys, Macaca nemestrina, Measurements of blood gases and ventilation were made during normoxia and hypoxia at the postnatal ages of 2, 7, and 21 days, Data were collected during quiet sleep. The infant monkey demonstrated a definite but transient hyperventilatory response following exposure to a Fi02 of 0.12 or 0.14 on the second day of life. Baseline ventilation increased 15% (Fi02 = 0.14) and 28% (Fi02 0.12) after 1 minute of hypoxia; p. 0.05 in both instanes. Return to baseline ventilation occurred between 3 and 5 minutes after hypoxic stimulus onset. This biphasic response to hypoxia converted to an adult-like, sustained hyperventilation during the ensuing three weeks of postnatal maturation. Episodes of periodic breathing and/or apnea were noted to occur during the induced hypoxemia. These data demonstrate that the infant subhuman primate has a ventilatory response to hypoxia that is similar to that of the human infant and is an excellent model for the study of the maturation of the respiratory control system.Speculation: The mechanisnis involved i n the unique neonatal response to hypoxia have not been elucidated. In light of current evidence, direct suppression of respiratory center output by an inhibitor seems the most likely possibility.However, adverse alterations in pulmonary mechanics brought on by the hypoxia itself or fatigue of the carotid body remain viable alternatives.

1017 TIME OF INITIATION OF CPAP IN HMD

The effects of the time of application of CPAP on the mortality and morbidity of HMD were examined in 36 infants in 3 weight groups (<1200, 1201-1800 and ≥1801 gms). Infants were randomly assigned by weight group to early (E) or late (L) CPAP by nasal prongs when PaO2≤50 mgHg while breathing in FIO2=0.4 or 0.7, respectively. Results are shown below:There were no differences in mortality, need for artificial ventilation, time spent in an FIO2>0.3 or >0.7 or in the incidence of air leak or chronic lung disease. Eleven of nineteen infants assigned to late CPAP never required an FIO2≥0.7 and did not receive CPAP. The present study suggests that the early application of CPAP offers no measurable advantage over the late application of CPAP in the treatment of mild HMD.

EFFECTS OF SLEEP STATE ON THE VENTILATORY RESPONSE TO INHALED CO 2 IN THE NEONATAL PRIMATE

Sleep state and an altered CO2 response have been implicated in the pathophyeiology of idiopathic apnea of prematurity and the Sudden Infant Death Syndrome. In order to examine the effect of sleep on CO2 sensitivity, the steady state ventilatory response to inhaled CO2 was determined in gestationally timed Macaca nemestrina at 7 and 21 days of age. Tidal volume (VT) and respiratory frequency (f) were measured in premature (gestational age = 143-150 days) and term (gestational age = 165-169 days) animals in the awake (Aw), REM and NREM states following CO2 inhalation. Sleep state was determined from simultaneous recordings of sleep electroencephalograms. Data presented is the slope of the ventilatory response, ±SE, cc/Kg.min mmHg PICO2 on day 7.There were no differences among the slopes of the CO2 response curves plotted against PICO2 or PaCO2 in the Aw, REM or NREM states in premature or term animals at postnatal ages 1 or 7 days. During CO2 breathing a large increase in VT and a small increase in f was observed in each state in both premature and term animals at each postnatal age. There were no differences in the %ΔVT/Kg. mmHg PICO2 or %Δf/Kg.mmHg PICO2 in REM compared to NREM sleep. Sleep state does not influence the CO2 sensitivity of the premature or term monkey between 1 and 3 weeks of age.

1697 ROLE OF ENDOGENOUS OPIATES IN CO2 SENSITIVITY IN THE NEWBORN PRIMATE

Recent reports indicate that naloxone will shorten the duration of primary apnea following asphyxia (Ped.Res. 14:357, 1980) and prevent the secondary depression of ventilation during hypoxia in the newborn rabbit (Ped.Res.14:643, 1980). Previous authors have shown the CO2 sensitivity in the newborn increases with postnatal maturation (J.A.P. 41:41, 1976; J.A.P. 48:347, 1980). To determine whether endorphins depress CO2 sensitivity in the immediate newborn period, five newborn M. nemestrina were studied on day 2-3 and again on day 19-21. VE/Kg and PO.2 were measured in duplicate trials in tracheotomized animals during steady state hyperoxia (FiO2=1.0), then again at 5-7 minutes of hyperoxic hypercapnia (FiO2=0.96, FiCO2=0.04). Naltrexone was given IV at a dose of 0.1 mg/kg and the trials were repeated.Values are mean ± S.E.M. Statistical analysis by paried t test. These results suggest that endogenous opiates do not influence the hyperoxic hypercapnic response in the newborn subhuman primate and confirm recent reports in adult humans (Am.Rev.Resp. Dis.121:1045,1980).

969 SLEEP STATE AND MATURATION OF CO2 SENSITIVITY IN THE PREMATURE PRIMATE

Sleep apnea and altered CO2 sensitivity have been implicated in the pathophysiology of SIDS. To investigate the hypothesis that sleep state and postnatal maturation influence minute ventilation and steady state CO2 sensitivity, 7 healthy premature M. nemestrina were studied serially in the first 3 weeks of life. VE/Kg in room air, 2,3,4, and 5% CO2 was measured via nasal wrongs and hot wire anemometer and arterial gases were sampled in 3 animals after a steady state was attained. Sleep state was assessed from EEG, EOG, EMG and respiratory pattern.Baseline VE/Kg and VT/Kg increased and f decreased in REM and NREM sleep with increasing postnatal age (p<.05), but there were no differences in VE/Kg between the 2 states at each age. VE/Kg increased following inhalation of CO2 in each state at each postnatal age, but there were no significant differences in CO2 sensitivity between NREM and REM sleep. In NREM sleep CO2 sensitivity increased progressively with increasing postnatal age (p<.025) whereas in REM sleep this maturational increase in slope was not observed (p>.4). The CO2 ventilatory response curve shifted to the left in both states with increasing age.These results suggest that there is a sleep state specific difference in postnatal maturation of CO2 sensitivity - a progressive increase in NREM sleep and no significant change in REM sleep. Failure of this normal maturational increase in NREM sleep may be important to the pathophysiology of SIDS.