Biomedical subjects

Claude Gaultier

Publications and source records attributed to Claude Gaultier.

30 records · Page 2Linked to original sources

PubMed2003

Exclusion of RNX as a major gene in congenital central hypoventilation syndrome (CCHS, Ondine's curse).

Congenital central hypoventilation syndrome (CCHS) is a rare condition for which segregation analyses have suggested genetic factors. The respiratory phenotype of Rnx knock-out mice together with the Rnx expression at the brainstem level prompted us to consider the RNX gene as a candidate for CCHS in human. The screening of the RNX gene in a series of 25 patients with CCHS did not reveal any significant nucleotide variation. We therefore conclude that RNX is not a major gene for CCHS in human.

DNA↗

PubMed2003

Neonatal exposure to 65% oxygen durably impairs lung architecture and breathing pattern in adult mice.

STUDY OBJECTIVE: To test the hypothesis that exposure to hyperoxia during the postnatal period of rapid alveolar multiplication by septation would cause permanent impairments, even with moderate levels of hyperoxia. DESIGN: We exposed mouse pups to 65% O(2) (hyperoxic mice) or normoxia (normoxic mice) during their first postnatal month, and we analyzed lung histology, pulmonary mechanics, blood gas, and breathing pattern during normoxia or in response to chemical stimuli in adulthood, when they reached 7 to 8 months of postnatal age. RESULTS: Hyperoxic mice had fewer and larger alveoli than normoxic mice (number of alveoli per unit surface area of parenchyma, 266 +/- 62/mm(2) vs 578 +/- 77/mm(2), p < 0.0001) [mean +/- SD], the cause being impaired alveolarization (radial alveolar count, 5.8 +/- 0.2 in hyperoxic mice vs 10.5 +/- 0.5 in normoxic mice, p < 0.0001). Respiratory system compliance was higher in hyperoxic mice (0.098 +/- 0.006 mL/cm H(2)O) than in normoxic mice (0.064 +/- 0.006 mL/cm H(2)O, p < 0.016). Baseline tidal volume (VT) and breath duration (TTOT]) measured noninvasively by whole-body plethysmography were larger in hyperoxic mice than in normoxic mice (VT, + 15%, p < 0.01; TTOT, + 12%, p < 0.01). Despite these impairments, blood gas, baseline minute ventilation E, and E responses to hypoxia and hypercapnia were normal in hyperoxic mice, compared with normoxic mice. CONCLUSION: Hyperoxic exposure during lung septation in mice may cause irreversible lung injury and breathing pattern abnormalities in adulthood at O(2) concentrations lower than previously thought. However, ventilatory function and body growth were preserved, and ventilatory function showed no major abnormalities, at least at rest, despite early oxygen-induced injuries.

Animals↗

PubMed2002

Pulmonary function tests in preschool children with cystic fibrosis.

Pulmonary function tests have rarely been assessed in preschool children with cystic fibrosis (CF). The objective of this multicenter study was to compare pulmonary function in 39 preschool children with CF (height, 90-130 cm; 16 homozygous Delta F508) and in 79 healthy control children. Functional residual capacity (helium dilution technique) and expiratory interrupter resistance (Rint(exp)) (interrupter technique) were measured. As compared with control children, children with CF had significantly higher Rint(exp), expressed as absolute values and as Z-scores (1.05 +/- 0.36 versus 0.80 +/- 0.20 kPa.L(-1). second, p < 0.0001; and 1.31 +/- 1.72 versus 0.19 +/- 0.97, p < 0.0001), and significantly lower specific expiratory interrupter conductance (1.29 +/- 0.34 versus 1.63 +/- 0.43 kPa(-1). second, p < 0.0001). The effect of the bronchodilator salbutamol on Rint(exp) was not significantly different between children with CF and control children. Rint(exp) Z-scores were significantly higher in children with CF who were exposed to passive smoke (n = 8) (p < 0.03). Children with CF and with a history of respiratory symptoms (n = 31) had significantly higher functional residual capacity Z-scores (p < 0.02) and lower specific expiratory interrupter conductance Z-scores (p < 0.04). Genotype did not influence the data. We conclude that Rint(exp) and functional residual capacity measurements may help to follow young children with CF who are unable to perform reproducible forced expiratory maneuvers.

Airway Resistance↗

PubMed2002

beta 2 nicotinic acetylcholine receptor subunit modulates protective responses to stress: A receptor basis for sleep-disordered breathing after nicotine exposure.

Nicotine exposure diminishes the protective breathing and arousal responses to stress (hypoxia). By exacerbating sleep-disordered breathing, this disturbance could underpin the well established association between smoking and the increased risk of sudden infant death syndrome. We show here that the protective responses to stress during sleep are partially regulated by particular nicotinic acetylcholine receptors (nAChRs). We compared responses of sleeping wild-type and mutant mice lacking the beta2 subunit of the nAChR to episodic hypoxia. Arousal from sleep was diminished, and breathing drives accentuated in mutant mice indicating that these protective responses are partially regulated by beta2-containing nAChRs. Brief exposure to nicotine significantly reduced breathing drives in sleeping wild-type mice, but had no effect in mutants. We propose that nicotine impairs breathing (and possibly arousal) responses to stress by disrupting functions normally regulated by beta2-containing, high-affinity nAChRs.

Animals↗

PubMed2002

Use of nasal cannula for detecting sleep apneas and hypopneas in infants and children.

We evaluated tolerance of nasal cannula (NC) by 14 infants (median age, 2.6 months) and 16 children (median age, 5.5 years) with suspected obstructive sleep apnea syndrome and compared the efficacy of the NC with that of a nasobuccal thermistor in detecting obstructive apneas (OA) and obstructive hypopneas (OH) on polysomnography traces. The relationship between cannula flow and esophageal pressure was assessed in six patients. Time spent with an uninterpretable flow signal was longer when using a cannula than when using a thermistor in infants (p < 0.05) and children (p < 0.01), and it was longer in the younger patients (p < 0.05). Among the 650 OA-OH detected by either method, only 38% were detected by both, and 58% were detected by the cannula and missed by the thermistor, so that the apnea-hypopnea index was higher with cannula than with thermistor in each age group (p < 0.01). More hypopneas than apneas were detected by the cannula and missed by the thermistor (p < 0.001). Out-of-phase thoracic and abdominal motions and/or changes in the end-tidal CO(2) signal shape were associated with 86% of OH identified by cannula. In the six patients whose esophageal pressure was measured, all respiratory events identified using a cannula were associated with increased "airway resistance." Thus, the NC is more likely than the thermistor to detect OA and OH in infants and children, and this superiority is particularly marked for hypopneas.

Adolescent↗

PubMed2002

Ventilatory responses to hypercapnia and hypoxia in heterozygous c-ret newborn mice.

The c-ret proto-oncogene encodes a tyrosine-kinase receptor involved in survival and differentiation of neural crest cell lineages. Previous studies have shown that homozygous c-ret-/- mice die soon after birth and have impaired ventilatory responses to hypercapnia. Heterozygous c-ret +/- mice develop normally, but their respiratory phenotype has not been described in detail. We used whole-body flow plethysmography to compare baseline breathing and ventilatory and arousal responses to chemical stimuli in unrestrained heterozygous c-ret +/- newborn mice and their wild-type c-ret +/+ littermates at 10-12 h of postnatal age. The hyperpnoeic and arousal responses to hypoxia and hypercapnia were not significantly different in these two groups. However, the number and total duration of apnoeas and periodic breathing episodes were significantly higher in c-ret +/- than in c-ret +/+ pups during hypoxia and post-hypoxic normoxia. These results are further evidence that respiratory control at birth is heavily dependent on genes involved in the neural determination of neural crest cells.

Animals↗

PubMed2002

Pre/postbronchodilator interrupter resistance values in healthy young children.

The interrupter technique estimates flow resistance. It entails occlusion of the airways during tidal breathing while flow and mouth pressure are recorded. This noninvasive technique is easy to use in young children. The aim of the present study was to measure inspiratory and expiratory interrupter resistance (Rint(insp), Rint(exp)) before and after bronchodilator administration in young healthy white children. We designed a multicenter study using a standardized procedure for Rint measurements. Centers in five French cities studied 91 children (48 boys and 43 girls; height, 92 to 129 cm; mean age 5.3 +/- 1.4 years). Mean values were not significantly different for Rint(insp) and Rint(exp) (0.78 +/- 0.21 versus 0.78 +/- 0.20 KPa x L(-1) x second). However, the difference between Rint(insp) and Rint(exp) decreased significantly with age and being positive before 5 years and negative later on (p < 0.02). Rint(insp) and Rint(exp) decreased significantly with height (Rint(insp) [KPa x L(-1) x second] = 2.289 - 1.37. 10(-2) x H [cm], Rint(exp) [KPa. L(-1) x second] = 2.021 - 1.12.10(-2) x H [cm]; p < 0.001). Bronchodilator (salbutamol) administration significantly decreased Rint(insp) and Rint(exp) (p < 0.001). Bronchodilator-induced changes (% of predicted values) in mean Rint(insp) and mean Rint(exp) were -15% (95% confidence interval, -46 to +15%) and -12% (95% confidence interval, -46 to +22%), respectively. Sex did not affect pre- or postbronchodilator values. Data from the present study may prove useful for testing lung function in young children with respiratory disorders who failed to cooperate with forced expiratory maneuvers.

Airway Resistance↗

PubMed2002

Depression of hypoxic arousal response in adolescent mice following antenatal vasoactive intestinal polypeptide blockade.

Late-gestation blockade of vasoactive intestinal polypeptide (VIP) activity in pregnant mice produces discrete morphological abnormalities in the somatosensory cortex of offspring. We investigated the functional implications of this lesion on the behavioural arousal response to moderate hypoxia. Pregnant mice received twice-daily injections of 200 microl saline (control), or saline + 50 microg VIP antagonist (anti-VIP) on embryonic days 17 and 18. Offspring were studied unrestrained at 6-7 weeks after birth, in a bias-flow whole-body plethysmograph during behavioural quiet sleep. Arousal was defined by movement (MVT) lasting > or =1 s. Hypoxic ventilatory (HVR) and arousal responses were measured during a 5 min exposure to 10 % O(2)-3 % CO(2) (hypoxia); peripheral chemoreflex drive was estimated by transient hyperoxia administered at rest and end-hypoxia (Dejours-type test). MVTs increased in all mice during hypoxia, but in anti-VIP mice: (a) MVT onset was delayed (174 +/- 90 vs. 108 +/- 59 s from the start of hypoxia, anti-VIP vs. control; P = 0.008); and (b) MVTs were less frequent, and total MVT time in hypoxia was less (8 +/- 7 vs. 15 +/- 9 %; P = 0.03). The HVR, and peripheral drive at rest and end-hypoxia were comparable in control and anti-VIP mice. In conclusion, a significant arousal deficit was evident in anti-VIP mice. This was not associated with obviously deranged peripheral or brainstem-mediated responses to hypoxia during sleep. This may signal a general deficit in the way hypoxic distress is monitored and processed, and arousal initiated and sustained in these mice.

Animals↗

PubMed2002

Comparison of the hyperoxic test and the alternate breath test in infants.

Peripheral chemoreceptor function has been tested using either the hyperoxic test (HT), which decreases minute ventilation (V E) by causing physiologic chemodenervation, or the alternate breath test (ABT), which induces V E alternations by delivering rapid hypoxic stimuli through breath-by-breath alternations in fractional inspired O(2) between normoxia (0.21) and hypoxia (0.15). No previous studies have compared ventilatory responses to both tests in the same infants. We hypothesized that the V E decrease during HT would be significantly related to V E alternations during ABT. Eighteen infants (postnatal age 21 +/- 14 d) underwent two 30-s HTs and two ABTs (quiet sleep, face mask, and pneumotachograph; mass spectrometry measurement of inspired and expired O(2) and CO(2) fractions; and breath-by-breath analysis). The tests were done in random order. Decreases in V E and mean inspiratory flow (tidal volume over inspiratory time, VT/TI) during HTs were significantly correlated to their respective percentage coefficients of alternation during ABTs (r = 0.69 and 0.70, respectively, p < 0.01). Principal components analysis showed that the V E and VT/TI decreases during HTs were due chiefly to a fall in VT, whereas V E and VT/TI alternations were ascribable to alternations in both VT and TI. Intraindividual coefficients of variation of V E changes were significantly lower during HTs than during ABTs. We conclude that (1) ventilatory responses to HT and ABT are significantly correlated despite differences in the mechanisms of the V E changes; (2) the better reproducibility of the V E response to HT as compared with ABT may be an advantage in clinical practice.

Breath Tests↗

PubMed2002

Ventilatory control in newborn mice prenatally exposed to cocaine.

Infants born to mothers who used cocaine during pregnancy are at increased risk for neonatal death and respiratory impairments. Confounding factors such as multiple substance abuse make it difficult to isolate the effects of cocaine. We used a murine model to test the hypothesis that prenatal cocaine exposure may impair ventilatory responses to chemical stimuli in newborns. Seventy-two pregnant mice were randomly assigned to three groups: cocaine (COC), saline (SAL), and untreated (UNT). COC and SAL mice received subcutaneous injections of either 20 mg/kg of cocaine or a saline solution twice a day from gestational days 8-17. Ventilation (V'(E)) and tidal volume (V(T)), both divided by body weight, and breath duration (T(TOT)) were measured using whole-body plethysmography in freely moving COC (n = 47), SAL (n = 123), and UNT (n = 93) pups on postnatal day 2.The comparison between SAL and UNT pups showed significant differences in baseline breathing and in V'(E) responses to hypoxia, suggesting that maternal stress caused by injections affected the development of ventilatory control in pups. Baseline T(TOT) was significantly longer in COC than in SAL pups. V'(E) responses to hypoxia were significantly smaller in COC than in SAL pups (+27 +/- 35% vs. +38 +/- 25%), but V'(E) responses to hypercapnia were similar (29 +/- 15% vs. 25 +/- 23%).Thus, breathing control was impaired by prenatal cocaine exposure, possibly because of abnormal development of neurotransmitter systems, such as the dopamine and serotonin systems.

Animals↗

PubMed2002

Abnormal esophageal motility in children with congenital central hypoventilation syndrome.

BACKGROUND & AIMS: Congenital central hypoventilation syndrome, an unexplained disorder of the central control of breathing that may reflect widespread dysfunction of brainstem structures, is regarded as a form of neuro cristopathy. Because swallowing-induced peristalsis is centrally controlled and depends on neural crest-derived esophageal innervation, we looked for esophageal dysmotility in patients with congenital central hypoventilation syndrome. METHODS: Seven patients without dysphagia or any other upper gastrointestinal tract symptoms were studied prospectively (5 girls and 2 boys; median age, 14 years; range, 11-18 years). They were compared with 7 age- and sex-matched controls. Esophageal manometry was performed using a low-compliance infusion system and the station pull-through technique. At least 10 wet swallows were analyzed in each subject. RESULTS: Pressure wave propagation was abnormal in all 7 patients (median percentage of swallows propagated, 18%, and range, 0-66; controls, 90% and 80-100; P < 0.001). Lower esophageal sphincter relaxation was abnormal in 5 patients (patients, 73% and 53-100; controls, 95% and 90-100; P = 0.01). In 2 patients, lower esophageal sphincter pressure was above the 95th percentile of control values. CONCLUSIONS: These abnormalities are strong evidence of lower esophageal dysfunction in congenital central hypoventilation syndrome. We speculate that the underlying mechanism may be dysfunction of the central structures that control swallowing.

Adolescent↗

PubMed2002

Sleep organization is unaffected by caffeine in premature infants.

We performed 10-hour polysomnographic recordings in 15 neurologically normal and clinically stable 33- to 34-week postmenstrual age (PMA) neonates, 10 of whom had been treated >3 days with once-per-day oral caffeine citrate (5 mg/kg) given at approximately 2 PM. We analyzed (a) the usual sleep-wake variables, including wakefulness, active sleep, quiet sleep, and indeterminate sleep expressed as the number of episodes, duration, and percentage of total sleep time; (b) the duration and order of variable modifications during transitions between the main active sleep and quiet sleep states; and (c) the characteristics of morning data (before caffeine) compared with evening data (after caffeine). We found no significant differences between the controls and the infants receiving maintenance caffeine.

Caffeine↗