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Biomedical subjects

V Chernick

Publications and source records attributed to V Chernick.

At least 37 records · Page 2Linked to original sources

Development of the EEG between 30 and 40 weeks gestation in normal and alcohol-exposed infants.

A total of 441 newborn infants with gestational ages between 30 and 40 weeks had EEG studies between 36 and 48 hours after birth. Their mothers had either abstained from alcohol during pregnancy or had ingested alcohol in one of four categories: occasional, moderate, binge or frankly alcoholic. The power of the EEG, using linear regression analysis, was significantly higher among infants of mothers in the occasional, binge and alcoholic categories than among infants of abstainers. Developmental changes in the EEGs of binge-drinking mothers were even more striking than in those of the offspring of the alcoholic mothers. These results indicate that fetal exposure to alcohol interferes with normal maturation of the brain as early as 30 weeks gestation. Furthermore, exposure to frequent high quantities of alcohol may be even more harmful to the fetal brain than continuous chronic exposure.

Brain

The effect of chronic biphrenectomy on lung growth and maturation in fetal lambs. Morphologic and morphometric studies.

Three fetal lambs underwent phrenic nerve section between Days 99 and 104 of gestation, and 2 twins of the experimental animals underwent sham operation at the same time. When they were killed at 135 to 137 days of gestation, the experimental animals had lower specific lung weights (g/kg) and lung volumes (ml/kg) and had delayed lung development by subjective microscopy. Light microscopic morphometry showed significantly less volume proportion of potential gas-exchanging air spaces, less parenchyma, and more gas-exchanging wall. Scanning electron microscopy confirmed these findings and also showed that the transition zone between conducting and gas-exchanging areas was less sharp in the experimental animals, attributed to diminished alveolarization of distal conducting airways. Transmission electron microscopy, together with morphometry, showed a diminished maturation of alveolar Type II cells, with fewer osmiophilic lamellar bodies and more glycogen. The number of mesenchymal-Type II cell interconnections was not altered. Maturation of bronchiolar epithelium was not affected, and mesenchymal-epithelial connections were not observed. We conclude that bilateral phrenic nerve section not only diminishes lung growth, but also diminishes intrauterine maturation of the alveolar well. Maturation of bronchiolar epithelium may not be affected by fetal respiration.

Animals

Maternal alcohol ingestion and the incidence of respiratory distress syndrome.

The risk of respiratory distress syndrome in infants born to mothers with varying quantities of alcohol intake during pregnancy was assessed. In infants less than 37 weeks' gestation, there was a decreasing incidence of respiratory distress syndrome with increasing maternal alcohol consumption (p less than 0.02). In addition, in infants less than 37 weeks' gestation, maternal alcohol ingestion was associated with a decreased risk of respiratory distress syndrome even when adjusted for other factors such as smoking, gestational age, birth weight, Apgar score, and sex of the infant. It is suggested that maternal alcohol ingestion enhances the maturation of the fetal lung.

Alcohol Drinking

A novel analysis of fetal breathing.

We have analyzed a variety of approaches in assessing fetal breathing parameters (VT, TI, Ttot, VT/TI, VI) in eight fetal sheep during a control period and during stimulation with 6 and 9% CO2. By using conventional analysis of data blocks varying from 100 to 1500 breaths, several different conclusions could be reached regarding the respiratory response to hypercapnia: stimulation, depression, or no change in all parameters studied. A new analysis based on piecewise linear regression used as a data grouping technique indicated that a simple mean +/- SD of the individual parameters was an inappropriate description of normal or stimulated fetal breathing. Based on tests for homogeneity of regressions of VT on TI for a completely random design, it is concluded that an estimate of fetal respiratory drive is only described adequately by two to four regression regimes. These regimes, estimated from the regression technique, could be combined to give a weighted mean value based on the proportion of time they were present. Using this new approach and an analysis of variance, we found (i) that frequency and VI were similar between animals during control and hypercapnia, (ii) that breathing frequency decreased during hypercapnia, and (iii) a positive relationship between VT and TI.

Animals

Maturation of spontaneous fetal diaphragmatic activity and fetal response to hypercapnia and hypoxemia.

The electromyogram (EMG) of the diaphragm, lateral rectus, and nuchal and hindlimb muscles were studied during spontaneous activity and during hypercapnia or hypoxemia in eight fetal sheep from 0.5 to 0.8 gestation (73-128 days). At the earliest gestational age, diaphragmatic EMG activity was mainly tonic and associated with tonic activity of somatic muscles. The stimulus for the diaphragmatic activity originated centrally. Brief periods of a rapid-eye-movement (REM) state characterized by phasic lateral rectus and diaphragmatic activity and absence of nuchal activity were recognized. Furthermore, from 0.5 to 0.7 gestation onward, activity of all muscles increased. Thereafter increased specificity of activity in relation to the apparent REM and non-rapid-eye-movement (NREM) state occurred. With maturation, phasic diaphragmatic activity increased at the expense of tonic activity. The most striking effect of maturation on apnea was a greater proportion of apnea lasting greater than 1 min, but the total duration of apnea as a percent of a total recording remained unchanged. The quantitative response to hypercapnia during maturation was independent of the pattern of spontaneous diaphragmatic activity. Hypercapnia at 0.5 gestation changed the pattern of diaphragmatic EMG activity from mainly tonic to phasic. Thus the central chemoreceptors and appropriate neuronal pathways are present and functional as early as 0.5 gestation. Hypercapnia at 0.5 gestation caused a shift in diaphragmatic EMG power to lower frequencies similar to that found during control conditions in the older fetus. This might suggest that during maturation there is increased recruitment of phrenic motoneurons. Hypoxemia abolished tonic somatic activity at 0.5 gestation and decreased phasic diaphragmatic activity at more advanced gestational ages. Therefore the central inhibitory mechanisms of hypoxemia are developed by 0.5 gestation.

Animals

The effect of maternal CO2 breathing on lung development of fetuses in the rabbit. Morphologic and morphometric studies.

We have examined male fetuses from rabbits exposed from Day 21 to Day 28 of gestation to 8% CO2 for 8 h each day. Fetuses of CO2-exposed mothers weighed less and had lungs that weighed less but when expressed per unit body weight were unchanged. Distended lung volumes were greatly increased in the CO2 group. Light microscope morphometry showed more mature lungs with increased volume proportion of air spaces, decreased air-space wall, and decreased nonparenchyma in CO2-exposed animals. Individual air-spaces were larger, gas exchanging surface area was increased, air-space walls were thinner, and higher ratios of mature to immature crests were found. Electron microscope morphometry showed decreased glycogen in alveolar Type II cells and increased volume proportion of lamellar bodies in the CO2 group. Type II cells were more cuboidal. We interpret these changes to represent increased tissue and cellular maturation in fetuses whose mothers breathed CO2. We speculate that the changes were brought about by increased fetal respiration, which may cause increased stretch and distention of the lung. Alternative mechanisms are discussed.

Animals

Is bronchiolitis in infancy an antecedent of chronic lung disease in adolescence and adulthood?

Acute bronchiolitis in infancy appears to be associated with persistence of wheezing or subsequent asthma in later life. Chest imaging techniques have demonstrated persistent structural lung damage such as atelectasis, bronchiectasis, and obliterative bronchiolitis among survivors of the more severe forms of bronchiolitis. In addition, in a significant number of survivors without demonstrable structural damage, pulmonary function studies have revealed a spectrum of disturbances including air-trapping, reduced air flow at low lung volumes, hypoxemia (all indicating disease in the small airways), and bronchial hyperreactivity. However, it has not yet been proven definitively whether the relationship between severe bronchiolitis in infancy and chronic obstructive lung disease is causal or noncausal. Further prospective clinical studies are needed to resolve this question.

Acute Disease

Cystic fibrosis in the adolescent and adult.

Modern comprehensive therapy for CF now allows the survival of patients into adulthood. In addition, more patients are being diagnosed for the first time in adolescence or early adulthood. As a result, over 20% of all CF patients are aged 18 years or older. The clinical and radiologic features of the older patients differ from those of pediatric patients and are discussed in this article. However, as with the pediatric patients, chronic lung disease remains the major cause of morbidity and is, almost uniformly, the cause of death in adolescent and adult CF. The plain chest radiograph remains a vital tool not only for diagnosis but as a simple method for establishing a baseline at diagnosis and quantifying serial changes as the patient ages.

Adolescent

Stimulation of fetal breathing activity by beta-adrenergic mechanisms.

Experiments were done on chronically prepared fetal lambs, 125-135 days gestation, to test the effects of various catecholamines on fetal breathing (FB) as well as the influence of isoproterenol on the fetal respiratory response to hypoxemia. Bolus injections of epinephrine, norepinephrine, and isoproterenol (5-20 micrograms) were administered via the lingual artery or femoral or jugular vein during periods of FB activity or apnea. The effects of epinephrine and norepinephrine on FB were variable and not statistically significant. Isoproterenol produced a significant increase in FB, frequency of breathing, and mean inspiratory effort, when infused during rapid-eye-movement (REM) sleep but it failed to induce FB during non-rapid-eye-movement (NREM) sleep. The positive response during REM sleep was absent following pretreatment with 3-5 mg propranolol and after bilateral section of the sinus nerves. The effect of hypoxia on FB was tested before and during constant infusion of isoproterenol (1 microgram/min iv). A reduction of the fetal arterial PO2 by 3-10 Torr produced the characteristic depression of FB in either situation. These results indicate that the fetal carotid body chemoreceptors can reflexly stimulate FB under certain circumstances but that their effectiveness is limited by more powerful inhibitory mechanisms such as those operative during NREM sleep and hypoxemia.

Adrenergic beta-Agonists

Effects of hypercapnia and hypoxemia on fetal breathing after decortication.

The effects of hypercapnia and hypoxemia on breathing movements were studied in 12 chronically decorticated fetal sheep, 127-140 days gestation. The fetal state of consciousness was defined in terms of activity of the lateral rectus and nuchal muscles. Arterial blood pressure was monitored. Fetal breathing was determined by integrated diaphragmatic electromyogram (EMG) and analyzed in terms of inspiratory time (TI), expiratory time (TE), electrical equivalent of tidal volume (EVT), breath interval (TT), duty cycle (TI/TT), mean inspiratory flow equivalent (EVT/TI), and instantaneous ventilation equivalent (EVT/TT). Fetal breathing occurred only during episodes of rapid-eye movements, and the response to hypercapnia consisted of an increase in EVT, TI, EVE, and EVT/TI and a decrease in the coefficient of variation of all measured parameters. Induction of hypoxia during episodes of spontaneous fetal breathing produced a decrease in the rate of breathing and an increase in EVT and TI with no change in the variability of all parameters studied. Since similar responses to hypercapnia and hypoxemia are seen in the intact fetus, we conclude that the cerebral cortex has no obvious effect on the chemical control of fetal breathing.

Animals

Interference of cardiovascular sounds with phonopneumography in children.

We have used fast Fourier transform and power spectra analysis to determine possible interference of cardiovascular sounds with the analysis of breath sounds in children. Ten normal children, 8 to 13 yr of age, were studied with sound transducer over midprecordium, right upper lobe, and right lower lobe along with simultaneously recorded ECG and air flow. Detection of R-waves facilitated sampling of sound segments at defined flow rates, with inclusion or exclusion of heart sounds. Measurements during breath-holding and without heart sounds served as baseline values. Heart sounds were only slightly attenuated over the right upper lobe. There was a considerable overlap in the power spectra of heart and breath sounds, mainly in frequencies below 100 Hz. Analysis of low-frequency components of normal breath sounds requires sampling during parts of the cardiac cycle that are free of cardiovascular sounds.

Adolescent

The effect of anticholinergic treatment on postexertional wheezing in asthma studied by phonopneumography and spirometry.

Postexertional wheezing is an important clinical sign of nonspecific airway hyperreactivity. We have studied wheezing after exercise in 6 asthmatic subjects, 13 to 20 yr of age, using spectral analysis of recorded tracheal sounds. Automated spectral characterization was used to measure wheezing as a proportion of respiratory time. Anticholinergic treatment with ipratropium bromide (Atrovent) was compared with placebo to investigate effects on postexertional wheezing, and pulmonary function was compared with the result of respiratory sound analysis. Atrovent did not abolish exercise-induced bronchospasm but improved preexercise lung function and thereby caused a parallel upward shift in the response curves. Wheezing after Atrovent was significantly less, later in onset, and mainly expiratory at 20 min after exercise. Wheezing as a percentage of total respiratory time correlated well with FEV1, Vmax50, and SGaw. Analysis of respiratory sounds and automated quantification of wheezing may be a useful complementary test of bronchial obstruction in asthma.

Adolescent

Response to cold air hyperventilation in normal and in asthmatic children.

To assess the sensitivity of isocapnic hyperventilation with cold air in detecting airway hyperreactivity in asthmatic children, we studied 13 asthmatic patients (mean age 11.1 years) and 10 normal children. Cold air challenge consisted of 4 minutes of moderate hyperventilation plus another 4 minutes of maximal hyperventilation, both with subfreezing air (-16 degrees to -18 degrees C). Exercise and IHCA tests were done within 5 days and in random sequence. Mean (+/- SE) maximal % delta FEV1 after IHCA was 27 +/- 5.1% in the asthmatic children vs 4.5 +/- 1.2% in the normal subjects (P less than 0.01), even though there were no significant differences in the maximal minute ventilation equivalent between the two groups. Mean maximal % delta FEV1 after exercise was 31.7 +/- 5.6 in the asthmatic group. There was no difference in the sensitivity of the exercise and IHCA tests to detect bronchospasm in asthmatic children. Airway obstruction after IHCA was sharp and brief: maximal at 3 minutes after challenge, and back to 10% of baseline after 11 minutes. In seven asthmatic children the refractoriness to cold air and exercise was studied by repeating each test within 30 minutes; all seven showed significant refractoriness to exercise, and six showed no refractoriness to IHCA. We conclude that exercise and cold air-induced bronchospasm have different physiologic mechanisms, and that cold air testing can be used as a routine challenge to identify airway hyperreactivity in children.

Adolescent

Hypercapnia alters sleep state pattern.

Mild hypercapnia in the adult animal does not affect sleep pattern but more severe hypercapnia in the fetus increases the duration of REM sleep. Adult male rats were exposed daily for 2-3 h sessions at random to 6, 7, and 8% CO2 or room air. Breathing CO2 caused a 60% increase in sleep onset latency, a 28% decrease in sleep duration, but no change in percent time spent in REM. However, the duration of REM sleep episodes increased by 30%. Thus, in both fetal and adult animals severe hypercapnia appears to have a similar effect on sleep pattern.

Analysis of Variance

Naloxone reduces decrease in ventilation induced by hypoxia in newborn infants.

The mechanism responsible for the decrease in ventilation during breathing of low fractional concentration of inspired O2 in the newborn infant is poorly understood. The present study tested the hypothesis that endogenous opiates account for this ventilatory decrease. Eleven healthy newborn infants breathed 15% O2, balance N2 for 5 min following an injection of saline and following an injection of naloxone. Neither injection caused a change in minute ventilation (VE) or ventilatory pattern when the infants were breathing room air. However, the decreased ventilation during hypoxia following naloxone was significantly less than that following saline. VE dropped about 14% following saline but only about 4% following naloxone. However, the adult ventilatory response to hypoxemia, i.e., a relatively sustained increase in VE, was not attained. Naloxone had no influence on the occurrence of periodic breathing during hypoxemia. Thus in the healthy full-term newborn infant, endogenous opiates account only for a part of the decreased ventilation during hypoxemia.

Humans

Indomethacin-induced fetal breathing: mechanism and site of action.

The mechanism and site of action of indomethacin-induced fetal breathing (FB) was investigated in 26 chronically prepared fetal lambs. Indomethacin, which preferentially blocks prostaglandin production, was infused into the fetal circulation in two stages, 60 mg in 10 min and 60 mg over 7 h. Indomethacin stimulated sleep-state independent FB that was greatly reduced or abolished by infusions of prostaglandin E2 (PGE2). Infusions of nordihydroguaiaretic acid, which preferentially blocks the synthesis of leukotrienes, had no consistent effect on either fetal sleep or breathing activity when administered alone or after indomethacin. This suggests that the characteristic FB induced by indomethacin is due to inhibition of prostaglandin synthesis (PGE2) and not due to an overproduction of leukotrienes. The indomethacin effect on FB was observed in all fetuses tested including those deprived of peripheral chemoreceptor function, vagotomy, decortication, or spinal cord section at the T1 level. Complete constriction of the ductus arteriosus for many hours had no effect on FB. We conclude that inhibition of PGE2 synthesis stimulates FB by a central mechanism other than the cortex.

Animals