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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

Relationship between response to inhaled salbutamol and methacholine bronchial provocation in children with suspected asthma.

Fifty children (27 females, 23 males) ages 6-15 years who were referred for evaluation of suspected asthma had baseline FEV1 and FEF25-75 of greater than or equal to 80% and FEF50 greater than or equal to 70% of predicted values. All had these tests repeated on the same day, after inhaling salbutamol. On a subsequent day PC-20 (methacholine) was determined as an index of bronchial hyperreactivity (BH). Fourteen age-matched healthy children (6 females, 8 males) were studied in a similar manner. There was no significant relationship between the PC20 and the change in FEF25-75 or FEF50 following salbutamol. There was a negative correlation between the initial FEV1 (% predicted) and the percent change in FEV1 following salbutamol (P less than 0.01). An increase in FEV1 of greater than 6% occurred in 7/12 (58.3%) patients with PC20 less than or equal to 0.25 mg/mL (Group I); in 7/24 (29.2%) patients with PC20 = 0.26-2.0 mg/mL (Group II); in only 1/14 (7.1%) patients with PC20 greater than 2.1 mg/mL (Group III) and in none of those asymptomatic (control) children with PC20 greater than 8.0 mg/mL (Group IV). All subjects who had a change in FEV1 greater than 6% after salbutamol had a PC20 less than 8 mg/mL and this test detected the majority of patients with severe BH. However, although the sensitivity of the test was 100%, the predictive value was only 36%. We conclude that in the presence of a normal baseline FEV1 a change of greater than 6% following salbutamol inhalation is indicative of bronchial hyperreactivity.

Administration, Inhalation

Sleep quality in children with asthma treated with theophylline or cromolyn sodium.

The effect of theophylline and cromolyn sodium on sleep was studied in 10 children with asthma who were 10 to 17 years of age (mean 13.5 +/- 2.4 years). Theophylline or cromolyn sodium was taken for 14 days in a double-blind, crossover, placebo-controlled trial. Theophylline blood levels before sleep were 10.2 +/- 4 micrograms/ml during the theophylline period. There was no difference in pulmonary function between the two periods. Theophylline did not disrupt sleep as measured by sleep latency, total sleep time, sleep efficiency, movement time, microarousals, and arousals. Apneic episodes (greater than or equal to 10 seconds) were of central origin and less frequent during the theophylline period (p less than 0.05). Arterial oxygen desaturation (greater than 5% decrease from baseline saturation when awake) was less frequent during the theophylline treatment (p less than 0.05). We conclude that theophylline treatment of the children's asthma did not disrupt sleep and appeared to have a protective effect in regard to apnea, hypopnea, and arterial oxygen saturation.

Adolescent

Fetal breathing and development of control of breathing.

Technical advances during the last several decades have greatly facilitated research into fetal physiology and behavior, specifically fetal breathing (FB). Breathing movements have been demonstrated in the fetuses of every mammalian species investigated and appear to be part of normal fetal development. In this review we focus on the methods of measuring FB and on some of the problems associated with these measurements and their interpretation. We also review fetal behavior, the role of the peripheral and central chemoreceptors in spontaneous FB, the fetal respiratory response to hypercapnia and hypoxia, and the transition to continuous breathing at birth. It is clear that in many ways the control of breathing movements in utero differs from that after birth. In particular, inhibitory influences are much more prominent before than after birth. Possibly this is due to the unique fetal situation, in which conservation of energy may be more important than any advantage breathing activity imparts to the fetus.

Animals

Effect of theophylline on lung function tests, sleep quality, and nighttime SaO2 in children with cystic fibrosis.

The effect of theophylline (T) was studied in 12 children with cystic fibrosis (CF) (seven males and five females) aged 7 to 17 yr (mean, 11.8 +/- 2.8). T or placebo (P) was taken for 10 days in a double-blind, crossover controlled trial. During Nights 9 and 10 of each study period, the subjects slept in a sleep laboratory, where complete polysomnographs were recorded. Patients were subdivided according to T blood levels above or below 10 micrograms/ml: five children had a mean serum T of 11.7 +/- 1.6 micrograms/ml (Group 1), and seven patients had serum T levels of 6.7 +/- 1.5 micrograms/ml (Group 2). There was no difference in pulmonary function between the two periods, but Group 2 had significantly better baseline lung function (p less than 0.01). During sleep while on T, Group 1 had a higher mean SaO2 (93.1 +/- 0.3% T versus 90.7 +/- 0.3% P; p less than 0.0001), less time with a decrease greater than 5% in SaO2 from baseline (43.7 +/- 7.9 min T versus 85.8 +/- 7.9 min P; p less than 0.01), and a lower heart rate (HR), (77.9 +/- 5.1 bpm T versus 86.1 +/- 4.2 bpm P; p less than 0.01). Group 2 did not show differences in these parameters. T significantly disrupted sleep as measured by sleep efficiency and total wake time independently of serum level (p less than 0.01). There was no significant effect of T on the incidence of apnea, hypopnea, or body movements during sleep.(ABSTRACT TRUNCATED AT 250 WORDS)

Child

Prediction of subsequent motor and mental retardation in newborn infants exposed to alcohol in utero by computerized EEG analysis.

In a prospective, blinded study 38 infants of mothers with varying quantities of alcohol ingestion during pregnancy had an EEG at 40 weeks post conceptional age. Bayley Development Tests were administered between 1.5 and 10 months of age. The total power of the EEG during REM sleep was inversely related to subsequent motor development (r = -0.51, F = 13.1, p less than 0.0008) whereas the total power of the EEG during quiet sleep was inversely related to subsequent mental development (r = 0.61, F = 24.4, p less than 0.0001). In alcohol exposed babies EEG abnormalities were present even in the absence of fetal alcohol syndrome (FAS). In 16 older children born to abstainers or alcoholic mothers similar results were obtained. Thus, the power of the EEG during REM and quiet sleep at birth appears to be a sensitive index of alcohol effects on the fetal brain and may be used to predict future motor and mental development.

Alcohol Drinking

Influence of naloxone on fetal breathing and the respiratory response to hypercapnia.

The effect of naloxone on fetal breathing and the respiratory sensitivity to CO2 was tested on chronically prepared fetal lambs on days one and four post-surgery. After a control period the fetus was challenged with hypercapnia for 10 min and after another control period 9 mg naloxone was administered to the fetus followed by another CO2 test 15 min later. An index of fetal breathing (Veq), tidal volume (VT) and frequency of breathing (f) was determined from tracheal pressure deflections and from the integrated diaphragmatic EMG, expressed as power of diaphragmatic activity per min. Naloxone consistently caused fetal arousal but the duration was variable. The respiratory response to naloxone was also variable and not statistically different from control. The respiratory sensitivity to CO2 (% delta Veq/Torr delta PaCO2 or % delta Diaph. Power/min/Torr delta PaCO2) was not changed by naloxone on either day. We conclude that endorphins do not have a significant direct role in the fetal respiratory response to CO2 but may be involved in the control of state.

Animals

Control of organ blood flow in fetal sheep during normoxia and hypoxia.

The role of peripheral chemoreceptors in the circulatory adaptation to hypoxia and the effects of rapid-eye-movement (REM) and non-REM (NREM) sleep and breathing activity on organ blood flow were assessed in fetal sheep. Blood flow was measured with isotope-labeled microspheres on intact, vagotomized (VX), and sinoaortic-denervated (SAD) fetuses. Denervation did not change the biventricular cardiac output (Biv. CO) or organ blood flows during normoxia. In intact fetuses the blood flow was increased during hypoxemia in brain, adrenals, and heart but not in kidneys, skeletal muscles, or placenta. The increase in organ blood flow during hypoxemia was reduced in the VX group and even more in SAD fetuses, but in the latter group, blood flow was still increased in mid-brain, medulla, pons, skeletal muscles, and heart. Sleep states per se did not significantly affect the blood flow to any organs tested. However, the Biv. CO and blood flow to all organs except kidneys and adrenals was increased during fetal breathing in REM sleep. We conclude that 1) during moderate hypoxemia both aortic and carotid bodies plus an additional mechanism are involved in redistributing fetal blood flow, and 2) changes in organ perfusion during REM sleep are due to concomitant fetal breathing.

Animals

Effect of terfenadine on the response to exercise and cold air in asthma.

To assess the role of histamine as a mediator in the response to exercise and isocapnic hyperventilation of cold air (IHCA) in asthma, we studied nine asthmatic subjects, age 13 to 25 years. All had exercise induced asthma (EIA) and positive responses to IHCA. Baseline lung function was measured before standardized challenges with histamine, exercise and IHCA. On separate days, these tests were repeated 3 h after a single oral dose of 120 mg terfenadine (TF). Histamine responsiveness decreased significantly, with a provocative concentration, producing a greater than or equal to 20% fall in FEV1 (PC20), of 1.1 +/- 0.8 mg/ml (mean +/- SEM) before and 12.0 +/- 4.9 mg/ml after the antihistamine. EIA was significantly less after TF, with 53 +/- 5% mean maximal falls in FEV1 from baseline before, and 29 +/- 9% after treatment (P less than 0.01, paired t-test). In contrast, the effect of TF on the response to IHCA was insignificant, with mean maximal falls of 45 +/- 7% in FEV1 before, and 41 +/- 7% after treatment. There was a correlation between PC20 and lowest FEV1 (% predicted) for EIA (r = 0.56, P less than 0.05), but not for IHCA (r = 0.34, NS). This study indicates a role of histamine as a mediator in EIA but not in IHCA, supporting different mechanisms for both stimuli.

Adolescent

Normal lung growth following antenatal dexamethasone treatment for respiratory distress syndrome.

Antenatal steroid therapy reduces the incidence of respiratory distress syndrome (RDS) in premature infants. However, animal studies showed a decrease in lung cell number and lower lung weights in fetal rabbits exposed to hydrocortisone. This prompted us to measure flows and lung volumes (by spirometry and helium-dilution method) in children greater than 6 years who were part of a study by the Collaborative Group on Antenatal Steroid Therapy. The effect of antenatal steroids on subsequent pulmonary function had not previously been studied. Of the 158 children originally enrolled before birth, a total of 8 dexamethasone (DEX)- and 11 placebo-treated children were still local residents and fulfilled the criteria of the study (gestational age, 28-34 weeks; DEX/placebo treatment 1-7 days before delivery). Mean heights and weights were normal with no significant differences between the groups. Pulmonary function tests showed no differences in lung volumes or expiratory flows between the children whose mothers had received antenatal DEX and those who had received placebo. These results indicate no adverse effect of antenatal DEX on subsequent lung volumes and expiratory flows in childhood.

Child

Clinical trial of naloxone in birth asphyxia.

To determine whether endogenous opiates play a role in the pathogenesis of perinatal asphyxia, a blinded clinical trial of naloxone, a competitive opiate receptor blocker, was undertaken in infants with low 1-minute Apgar scores. Of 85 infants with 1-minute Apgar score 0 to 3, 44 received an injection of naloxone (approximately 0.4 mg/kg) and 41 received saline solution. In 108 infants with 1-minute Apgar score 4 to 6, 54 received naloxone and 54 saline solution. In neither group was there a significant effect of naloxone on respiratory frequency or heart rate up to 30 minutes after injection, nor at 24 hours of age. In both groups active muscle tone of upper and lower limbs was increased by naloxone, a response that may not be beneficial in the face of inadequate oxygen delivery to vital organs. We conclude that naloxone at this dose had no readily apparent benefit in the resuscitation of the asphyxiated newborn infant.

Adult

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