Uncommon phenotype for a codon 178 mutation of the human PrP gene.
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Biomedical subjects
Publications and source records attributed to C Gaultier.
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We used a placebo-controlled standardized protocol to define the dose-response relationship to the beta-adrenergic bronchodilator salbutamol (albuterol) in 10 ventilator-dependent premature infants at a postnatal age of 13.3 +/- 4.9 days. Passive respiratory system resistance and compliance were measured at baseline and 10 minutes after administration of salbutamol via a metered-dose inhaler and spacer device. Salbutamol caused a significant dose-related response with a 33% mean decrease in respiratory system resistance (p less than 0.05) and a 67% mean increase in respiratory system compliance (p less than 0.001). In seven and six patients, respectively, 100 micrograms of salbutamol caused significant improvement in resistance and compliance; 200 micrograms was required in the remainder, but one patient had no improvement in compliance. Oxygen saturation increased linearly with the increase in compliance. In 7 of the 10 infants, the duration of action of 200 micrograms of salbutamol on the following day was 3 hours. We conclude that bronchodilator treatment may be useful in the management of ventilator-dependent neonates with respiratory distress syndrome.
Sleep related increases in respiratory resistive loads in infants and children may or may not be associated with complete obstruction, i.e. obstructive apneas. Nevertheless, important clinical symptoms, both nocturnal and diurnal, may be present and should be taken into consideration. A thorough investigation must be performed to select the most appropriate therapy.
This study was designed to determine the cardiac, respiratory, and arousal responses to an esophageal acid infusion test in near-term infants free from neurological, gastroesophageal, and cardiopulmonary disease at time of testing during active sleep. Eight infants (gestational age 28-37.5 weeks, postconceptional age 36-40 weeks) were tested. Using standardized procedures and timing, we compared the cardiac, respiratory and arousal responses during a control period and during distal esophageal saline and acid infusion periods. The duration of each of these periods was 5 min. The pH of the acid infusion was 2.2. We found that this mild distal esophageal acid infusion test induced significant prolongation of the interval between successive electrocardiogram R waves compared with control and saline infusion periods (806.5 +/- 145.7 ms, 478.8 +/- 49.4 ms, and 468.8 +/- 37.2 ms, respectively; p less than 0.01) and of the duration of the respiratory cycle (2.9 +/- 0.7 s, 1.5 +/- 0.3 s, and 1.5 +/- 0.2 s, respectively; p less than 0.01). Esophageal acid infusion elicited significant electroencephalogram (EEG) arousal responses. The number of the EEG arousals was significantly increased during the acid period as compared with control and saline infusion periods (2.9 +/- 1.4, 0.5 +/- 0.5, and 0.4 +/- 0.5, respectively; p less than 0.01). Total arousal duration was significantly increased during acid as compared with control and saline infusion periods (42 +/- 17.5 s, 4.5 +/- 5.1 s, and 3.5 +/- 5.0 s, respectively; p less than 0.01). We conclude that distal esophageal acid stimulation elicits significant cardiac, respiratory, and EEG arousal responses in near-term infants during active sleep.
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The aim of this study was to reappraise the effects of maternal meperidine administration on breathing pattern during the first hours of life taking into account the state of alertness. Because breathing instability is more pronounced during active sleep, we hypothesized that meperidine administration might create a greater risk for respiratory instability during active sleep, the prominent sleep state in newborns. We studied eight full-term, healthy newborns whose mothers had received a continuous i.v. infusion of meperidine (81 +/- 9 mg) that was terminated 5.5 +/- 2.1 h before delivery. These infants were compared with a control group of eight full-term newborns whose mothers did not receive any opioids. In both groups, all babies were delivered vaginally after a normal labor and had Apgar scores of 9 or 10 at 1 and 5 min. Neonatal gastric secretion and maternal venous and umbilical venous blood were sampled at delivery for determination of meperidine concentration. From 60 to 300 min after delivery, behavioral sleep states and thoracic and abdominal movement as well as transcutaneous arterial oxygen saturation (SaO2) were monitored continuously. The number of apneic spells lasting more than 3 s during 100 min of recording and the percentage of time with SaO2 below 90% in each sleep state were recorded. During quiet sleep, all respiratory variables were similar in both groups. During active sleep, there were significantly more apneic episodes (37.1 +/- 25.1 versus 11.2 +/- 13.9) and a higher percentage of time with SaO2 less than 90% (14.3 +/- 16.7% versus 1.3 +/- 1.5%) in the meperidine group than in the control group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
To assess the accuracy of the respiratory inductive plethysmograph (RIP) during sleep in obese patients with obstructive sleep apnea (OSA), we monitored 13 patients with OSA during wakefulness and nocturnal sleep with simultaneous measurements of tidal volume from RIP and integrated airflow. Patients wore a tightly fitting face mask with pneumotachograph during wakefulness and sleep. Calibrations were performed during wakefulness prior to sleep and compared with subsequent wakeful calibrations at the end of the study. Patients maintained the same posture during sleep (supine, 11; lateral, two) as during calibrations. There were no significant differences in calibrations before sleep and after awakening. The mean error in 13 patients undergoing RIP measurements of tidal volume during wakefulness was -0.7 +/- 3.4 percent while that during sleep was 2.1 +/- 14.9 percent (p < 0.001). The standard deviation (SD) of the differences between individual breaths measured by RIP and integrated airflow was 9.8 +/- 5.5 percent during wakefulness and 25.5 +/- 18.6 percent during sleep (p < 0.001). During both wakefulness and sleep, errors in RIP tidal volume were not significantly correlated with body mass index. In 12 patients with at least 10 percent time in each of stages 1 and 2 sleep, SD was greater in stage 2 sleep compared with wakefulness and stage 1 (p < 0.001). In three patients who manifested all stages of sleep, SD was greater in REM sleep than in wakefulness and all stages of non-REM sleep (p < 0.001). In three patients who manifested all stages of sleep, SD was greater in REM sleep than in wakefulness and all stages of non REM sleep (p < 0.001). This was associated with paradoxic motion of the rib cage in two patients during REM. We conclude that, despite increased errors in individual breath measurements during sleep, more marked during stages 2 and REM sleep, RIP is clinically useful to measure ventilation quantitatively in obese patients with sleep apnea. The criterion of a decrease of 50 percent in tidal volume assessed by RIP is appropriate to define hypopneas in such patients.
The accuracy of the Radiometer OSM3 oxymeter for measurement of fetal haemoglobin (HbF) in infants was investigated, and compared to one of the standard reference methods using alkali electrophoresis of haemoglobin. Blood samples of 37 infants with different gestational (27-41 weeks) and postnatal (1-198 days) ages were analysed. The two methods gave very close results but a significant mean difference (range -4.5-16.5%). However, agreement between the two methods was judged clinically acceptable (95% limits of agreement -7.5-15.5%). A rapid determination of HbF percentage, using OSM3, is an important determinant for correct assessment of oxygen saturation in newborn infants in intensive care units.
Fourteen fluoro pyrimidine-4-ones, four fluoro bispyrimidine-4-ones and two fluoro pyrimidine-4-ones with fused ring have been prepared. The reactivity of the carbonyl group of two pyrimidine-4-ones phosphorus oxychloride was studied. The 4-chloro pyrimidines reacted with ammonia or morpholine giving 4-substituted pyrimidines. Eight compounds are evaluated for their anti-inflammatory and anti-convulsivant properties: they were found to be weakly active against oedema and three of them protected rats form tonic convulsions.
Hypoxia enhances bronchial responsiveness in sheep and dogs and we recently reported a similar effect in asthmatic subjects. Activation of a reflex arc due to stimulation of peripheral chemoreceptors has been suggested to explain this finding. We evaluated the contribution of carotid body chemoreceptors to hypoxia-induced bronchial responsiveness in conscious sheep. Incremental concentrations of aerosolized methacholine were given to each of seven sheep ventilated successively (in a random order) with a normoxic and a hypoxic gas mixture (15% O2 in N2), both before and after peripheral surgical chemodenervation. Hypoxia alone did not affect lung mechanics in intact or chemodenervated animals. Bronchial responsiveness to methacholine was significantly increased by hypoxia in intact sheep, as compared to chemodenervated sheep. We conclude that hypoxia has a stimulating effect on bronchial responsiveness in awake sheep similar to that seen in human patients with asthma. This increased responsiveness may be mediated by hypoxic stimulation of carotid body chemoreceptors, which in turn may influence the nervous control of airway calibre.
Comparison of the abdominal muscle response to CO2 rebreathing in rapid-eye-movement (REM) and non-REM (NREM) sleep was performed in healthy premature infants near full term. Eight subjects were studied at a postconceptional age of 40 +/- 1.6 (SD) wk (range 38-43 wk) during spontaneous sleep. Sleep stages were defined on the basis of electrophysiological and behavioral criteria, and diaphragmatic and abdominal muscle electromyographic activity was recorded by cutaneous electrodes. The responses to CO2 were measured by a modified Read rebreathing technique. The minute ventilation and diaphragmatic and abdominal muscle electromyographic activities were calculated and plotted against end-tidal CO2 partial pressure. Both the ventilatory and diaphragmatic muscle responses to CO2 decreased from NREM to REM sleep (P less than 0.05). Abdominal muscles were forcefully recruited in response to CO2 rebreathing during NREM sleep. In REM sleep, abdominal muscle response to CO2 was virtually absent or decreased compared with NREM sleep (P less than 0.05). We conclude that 1) the abdominal muscles are recruited during NREM sleep in response to CO2 rebreathing in healthy premature infants near full term and 2) the abdominal muscle recruitment is inhibited during REM sleep compared with NREM sleep, and this REM sleep-related inhibition probably contributes to the decrease in the ventilatory response to CO2 rebreathing in REM sleep.
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The influence of sleep on cardiac function in severe bronchopulmonary dysplasia was assessed in five children 1.5 to 5 years of age. Left and right ventricular ejection fractions (LVEF and RVEF) were investigated by equilibrium radionuclide ventriculography in five children undergoing polygraphic monitoring during the different states of alertness: wakefulness, nonrapid eye movement sleep, and rapid eye movement sleep. Intraobserver and interobserver LVEF and RVEF measurement reproducibility was high. During quiet, supine wakefulness, LVEF was normal, but RVEF was low. During sleep, a decrease in both LVEF and RVEF, expressed as a percentage of the awake value, was marked in the two children with the most nocturnal desaturation and longest duration of paradoxic rib cage motion during inspiration. It is concluded that radionuclide ventriculography can be easily performed during sleep in children and can provide useful information regarding right ventricular function during sleep in children with severe bronchopulmonary dysplasia.
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Sleep apnea syndrome and systemic hypertension are frequently associated but their causal relationship is unclear. We compared the oscillations of systemic blood pressure and heart rate during polysomnography in 8 normotensive subjects (2 females) and 5 hypertensive (supine awake blood pressure: 165 +/- 7/96 +/- 5 mmHg) without treatment. Their ages (normotensive: 52.1 +/- 11.0 yrs, hypertensive: 51.2 +/- 6.4 yrs) and body mass indices (32.6 +/- 9.6 kg/m2 vs 33.2 +/- 5.2 kg/m2 respectively) were not statistically different. Systemic blood pressure was continuously monitored by a non invasive digital plethysmography (Finapres). Both groups had similar respiratory events indices (normotensive: 45.2 +/- 18.1/hr, hypertensive: 48.4 +/- 20.5/hr) and minimal oxygen saturations (79.4 +/- 9.1% vs 82.4 +/- 7.0% respectively). During apneas in slow-wave sleep were observed the minimal values for systolic and diastolic pressures which were significantly higher in hypertensive than in normotensive (138.2 +/- 9.6/83.2 +/- 16.1 mmHg vs 105.9 +/- 11.1/60.5 +/- 10.9 mmHg respectively). During resumption of ventilation maximal blood values were recorded which were also higher in hypertensive than in normotensive (185.0 +/- 13.8/113.2 +/- 21.5 mmHg vs 155.9 +/- 19.8/88.7 +/- 17.1 mmHg respectively) (p less than 0.05). Although absolute variations of blood pressure were similar, relative changes in systolic pressure were significantly higher in normotensive (p less than 0.05). Maximal heart rate was 76.8 +/- 6.2 bpm in normotensive and 76.6 +/- 3.9 bpm in hypertensive during resumption of ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)
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Pulmonary function was evaluated in both infancy and childhood in the same 19 prematurely born infants, who required mechanical ventilation (MV) during the neonatal period. Results of our patients were compared with those of control subjects. Upon first evaluation, we found that lung resistance (RL) was significantly elevated (24.85 +/- 6.06 vs. 17.77 +/- 2.39 cmH2O/L/s; P less than 0.01). The mean value of dynamic lung compliance (CLdyn) was low, but the difference compared to controls did not reach significance. From infancy to childhood, elevated RL persisted (9.33 +/- 2.51 vs. 6.52 +/- 1.52 cm H2O/L/s; P less than 0.01), and the decrease of CLdyn became significant (46.86 +/- 12.84 vs. 59.34 +/- 15.68 mL/cmH2O; P less than 0.05). In addition, maximum flow at functional residual capacity was significantly decreased (0.824 +/- 0.284 vs. 1.215 +/- 0.358 L/s; P less than 0.01); whereas pulmonary diffusing capacity for carbon monoxide was similar in the patients (7.62 +/- 2.16 mL/min/mm Hg) and in the controls (8.38 +/- 1.6). Pulmonary dysfunction following premature birth, respiratory distress, and prolonged MV may not resolve from infancy to childhood.