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Biomedical subjects

V Chernick

Publications and source records attributed to V Chernick.

At least 19 recordsLinked to original sources

Efficacy of salbutamol and ipratropium bromide in decreasing bronchial hyperreactivity in children with cystic fibrosis.

A proportion of patients with cystic fibrosis (CF) suffer from increased airway hyperreactivity but their response to bronchodilators is variable. Adrenergic agents may produce an increase, no change or a decrease in forced expiratory volume in 1 second (FEV1). We hypothesized that the variable response might be related to poor aerosol distribution caused by the presence of secretions. Therefore, in 11 children with CF and airway hyperreactivity the influence of pretreatment with either 0.9% saline, salbutamol, or ipratropium bromide on the methacholine challenge test was evaluated in a double-blind, randomized, cross-over study. FEV1 (mean +/- S.E.) did not change following pretreatment with saline, salbutamol, or ipratropium (1.64 +/- 0.22, 1.63 +/- 0.16 and 1.67 +/- 0.19, respectively). All patients demonstrated airway hyperreactivity with a PC20 below 8 mg/mL (geometric mean, 0.41 mg/mL) after saline pretreatment. Salbutamol inhalation significantly increased the PC20 to 1.24 mg/mL (P less than 0.01), but ipratropium bromide was found to be even more effective than salbutamol (PC20 = 7.37 mg/mL) (P less than 0.0001). We conclude that the variable response to bronchodilator is not secondary to impaired aerosol distribution since ipratropium bromide effectively blocked the response to methacholine. The improvement in PC20 without a change in baseline FEV1 following salbutamol suggests that the adrenergic agent altered the contractile mechanism of smooth muscle.

Adolescent

Response to inhaled bronchodilators and nonspecific airway hyperreactivity in children with cystic fibrosis.

We tested the hypothesis that children with CF who have a significant response to bronchodilator (BD) would respond positively to standard methacholine (Mch) challenge. Our objective was to correlate the response to BD with the concentration that produced a 20% fall (PC20) in forced expiratory volume in 1 second (FEV1). We studied 22 patients (12 males), aged 10.5 +/- 0.7 years (mean +/- SE), with a Shwachman-Kulczycki score 82 +/- 2.6 and baseline FEV1 of 80 +/- 4.5% predicted. Baseline expiratory flows, static lung volumes, and airway resistance were measured before and 30 min after inhaled salbutamol. On a separate day, within 2 weeks, a Mch challenge was given, with doubling concentrations from 0.03 to 8.0 mg/mL. A positive challenge was defined as a PC20 less than or equal to 2.0 mg/mL, and a positive response to BD as a greater than 6% of FEV1 increase. Mch challenge yielded 17 responders (R) with a PC20 of 0.5 +/- 0.1 mg/mL, and 5 nonresponders (NR) with a PC20 of 8.8 +/- 2.9 mg/mL. Baseline FEV1 was 77 +/- 5.3% predicted in R compared to 89 +/- 6.3% in NR (P = less than 0.001). History of springtime rhinitis was positive in 9/17 R and 2/5 NR. No significant correlation was found between baseline FEV1 and PC20, or between change in FEV1 post-BD and PC20. A greater than 6% increase in FEV1 was seen in 14/17 R (83% sensitivity) and in none of the 5 NR (100% specificity). In R, 8/17 patients had baseline FEV1 less than 80% predicted, compared to 1/5 in NR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Maturation of steady-state CO2 sensitivity in vagotomized anesthetized lambs.

The maturation of the respiratory sensitivity to CO2 was studied in three groups of anesthetized (ketamine, acepromazine) lambs 2-3, 14-16, and 21-22 days old. The lambs were tracheostomized, vagotomized, paralyzed, and ventilated with 100% O2. Phrenic nerve activity served as the measure of respiration. The lambs were hyperventilated to apneic threshold, and end-tidal PCO2 was raised in 0.5% steps for 5-7 min each to a maximum 7-8% and then decreased in similar steps to apneic threshold. The sinus nerves were cut, and the CO2 test procedure was repeated. Phrenic activity during the last 2 min of every step change was analyzed. The CO2 sensitivity before and after sinus nerve section was determined as change in percent minute phrenic output per Torr change in arterial PCO2 from apneic threshold. Mean apneic thresholds (arterial PCO2) were not significantly different among the groups: 34.8 +/- 2.08, 32.7 +/- 2.08, and 34.7 +/- 2.25 (SE) Torr for 2- to 3-, 14- to 16-, and 21- to 22-day-old lambs, respectively. After sinus denervation, apneic thresholds were raised in all groups [39.9 +/- 2.08, 40.9 +/- 2.08, and 45.3 +/- 2.25 (SE) Torr, respectively] but were not different from each other. CO2 response slopes did not change with age before or after sinus nerve section. We conclude that carotid bodies contribute to the CO2 response during hyperoxia by affecting the apneic threshold but do not affect the steady-state CO2 sensitivity and the central chemoreceptors are functionally mature shortly after birth.

Anesthesia

Analysis of respiratory neuronal activity in fetal sheep.

We developed a new method to monitor fetal medullary respiratory neurons utilizing a two-stage approach. At 129-133 days of gestation, sheep were anesthetized, and a window was placed over the area of the fourth ventricle. After a recovery period of 3-5 days, the fetus was exteriorized into a saline bath under maternal spinal anesthesia, and the head was connected rigidly to a stereotaxic frame. Microelectrodes were inserted into the area of the nucleus tractus solitarius during rapid-eye-movement sleep, and extracellular recordings of 223 respiratory neurons were analyzed: 76% were inspiratory, 9% expiratory, and 15% phase spanning, as classified by visual and computer correlation to diaphragmatic activity. More detailed analysis of 100 neurons was done to assess the respiratory component (eta 2) by use of a modification of the method developed by Orem and Dick (J. Neurophysiol, 50: 1098-1107, 1983). With use of cohorts of 25 breaths, fetal respiratory neurons were found to frequently change their phase relationship to diaphragmatic activity. The eta 2 statistic of fetal respiratory neurons was not a stable characteristic but changed over time. This could be a reflection of an immature central respiratory system before birth or the lack of major sensory inputs.

Animals

A controlled trial of synthetic surfactant in infants weighing 1250 g or more with respiratory distress syndrome. The American Exosurf Neonatal Study Group I, and the Canadian Exosurf Neonatal Study Group.

BACKGROUND: Surfactant-replacement therapy is now recognized as a life-saving and safe intervention in small premature infants, but there is little evidence concerning its risks and benefits in larger premature infants. METHODS: We conducted a placebo-controlled, blinded trial in 1237 infants with respiratory distress who were enrolled at 23 hospitals in the United States and 13 hospitals in Canada. At entry all the infants weighed at least 1250 g, were receiving mechanical ventilation, and had a ratio of arterial to alveolar oxygen tension below 0.22. The initial dose of either the synthetic surfactant (Exosurf, 5 ml per kilogram of body weight) or air (the placebo) was administered less than 24 hours after birth, with a second dose given 12 hours later. A total of 614 infants were assigned to receive surfactant, and 623 to receive placebo. RESULTS: Fewer infants in the surfactant group than in the placebo group died before 28 days of age or survived at 28 days with bronchopulmonary dysplasia (7 percent vs. 12 percent, P = 0.002). In the first 28 days of life, there were fewer deaths due to respiratory distress syndrome in the surfactant group (1 percent vs. 3 percent, P = 0.043), lower overall neonatal mortality (4 percent vs. 7 percent, P = 0.04), and a lower incidence of bronchopulmonary dysplasia (3 percent vs. 6 percent, P = 0.008). There was also a significantly lower incidence of pulmonary air leaks, intraventricular hemorrhage, patent ductus arteriosus, seizures, hypotension, and pulmonary hypertension in the surfactant group. The infants treated with surfactant were weaned from oxygen and mechanical ventilation significantly sooner than those given placebo, and they less often required high-frequency ventilation or extracorporeal membrane oxygenation. The primary side effect observed more frequently among the infants who received surfactant treatment was pulmonary hemorrhage (six infants vs. one infant, P = 0.055). CONCLUSIONS: In infants weighing at least 1250 g at birth who have respiratory distress syndrome, treatment with two doses of synthetic surfactant improves survival and reduces perinatal morbidity.

Birth Weight

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