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Biomedical subjects

David Gozal

Publications and source records attributed to David Gozal.

139 records · Page 8Linked to original sources
PubMed2002

Obstructive sleep apnea and the prefrontal cortex: towards a comprehensive model linking nocturnal upper airway obstruction to daytime cognitive and behavioral deficits.

Obstructive sleep apnea (OSA) is accompanied by significant daytime cognitive and behavioral deficits that extend beyond the effects of sleepiness. This article outlines a causal model by which to understand these psychological effects among OSA patients. The model proposes that sleep disruption and blood gas abnormalities prevent sleep-related restorative processes, and further induce chemical and structural central nervous system cellular injury. This, in turn, leads to dysfunction of prefrontal regions of the brain cortex (PFC), manifested behaviorally in what neuropsychologists have termed 'executive dysfunction'. Executive dysfunction is proposed to markedly affect the functional application of cognitive abilities, resulting in maladaptive daytime behaviors. The proposed model (1) accounts for the specific psychological phenotype associated with OSA, (2) accommodates developmental components in this phenotype, (3) bridges between physical and psychological phenomena, (4) suggests mechanisms by which the nocturnal disorder might have effects on daytime functioning, (5) is empirically testable, (6) generates unique research hypotheses, and (7) has practical implications. The model is intended to act as a catalyst for future research and as a preliminary guide for clinicians.

Adaptation, Psychological↗
PubMed2002

Proteomic analysis of CA1 and CA3 regions of rat hippocampus and differential susceptibility to intermittent hypoxia.

The CA1 and CA3 regions of the hippocampus markedly differ in their susceptibility to hypoxia in general, and more particularly to the intermittent hypoxia that characterizes sleep apnea. Proteomic approaches were used to identify proteins differentially expressed in the CA1 and CA3 regions of the rat hippocampus and to assess changes in protein expression following a 6-h exposure to intermittent hypoxia (IH). Ninety-nine proteins were identified, and 15 were differentially expressed in the CA1 and the CA3 regions. Following IH, 32 proteins in the CA1 region and only 7 proteins in the more resistant CA3 area were up-regulated. Hypoxia-regulated proteins in the CA1 region included structural proteins, proteins related to apoptosis, primarily chaperone proteins, and proteins involved in cellular metabolic pathways. We conclude that IH-mediated CA1 injury results from complex interactions between pathways involving increased metabolism, induction of stress-induced proteins and apoptosis, and, ultimately, disruption of structural proteins and cell integrity. These findings provide initial insights into mechanisms underlying differences in susceptibility to hypoxia in neural tissue, and may allow for future delineation of interventional strategies aiming to enhance neuronal adaptation to IH.

Animals↗
PubMed2002

Behavioural and neurocognitive implications of snoring and obstructive sleep apnoea in children: facts and theory.

The pathophysiology of obstructive sleep apnoea (OSA), a common condition in children, is poorly understood. While adenotonsillar hypertrophy is certainly a major contributor, other factors are needed for OSA to develop. OSA has been associated with substantial morbidities primarily affecting cardiovascular and neurobehavioural systems which may not be completely reversed with appropriate treatment. This paper reviews the available information and attempts to provide the rationale for early diagnosis and treatment of OSA in children.

Child↗
PubMed2002

Intravenous sedation: an adjunct to enable orthodontic treatment for children with disabilities.

Intravenous (i.v.) sedation has become established as an important and preferred alternative to general anaesthesia (GA), in order to overcome difficulties in patient management encountered in the delivery of routine dental treatment of the disabled. However, its potential for the delivery of orthodontics for this group has never been exploited. The present pilot study describes the use of i.v. sedation with propofol to enable the performance of certain complex orthodontic and surgical procedures, which require strict control of the oral environment for prolonged periods, in a group of 10 of the most-difficult-to-manage disabled patients. The use of i.v. sedation provided a satisfactory management modality in these patients, who had previously been referred for GA. The parents reported complete satisfaction and general agreement that the same modality would again be welcomed. I.v. sedation significantly reduces the use of GA and makes treatment more readily available to a larger number of disabled patients.

Adolescent↗
PubMed2002

Familial dysautonomia: deep sedation and management in endoscopic procedures.

OBJECTIVES: Familial dysautonomia is a rare genetic disorder that affects the development of the central nervous system, causing GI dysfunction. Because of an improved prognosis, elective surgical procedures are more common and present a unique problem to the anesthesiologist. All patients reported in the literature underwent these interventions under general anesthesia in the operating theater. We report our preliminary experience with deep sedation in the endoscopy room in patients with this rare syndrome. METHODS: Four girls (7-16 yr old) underwent percutaneous endoscopic gastrostomy insertion and/or endoscopic retrograde cholangiopancreaticography. Preprocedure management consisted of adequate hydration and anxiolysis. Intraprocedure management consisted of stabilization of an erratic autonomic nervous system. Midazolam (0.1-0.2 mg/ kg) was administered i.v. before the procedure. Deep sedation was accomplished with propofol i.v. (0.5-1 mg/kg) and maintained with a propofol drip (50-100 microg/kg/min). Recovery was managed in the gastroenterology unit of our facility. RESULTS: Body temperature, ventilation, heart rate, blood pressure, oxygen saturation, and end-tidal CO2 were stable during the endoscopies. The patients regained consciousness at the end of the endoscopy and were able to drink or to eat as normal. Pain that could precipitate a crisis was present in two patients and was successfully treated with a simple analgesic. No other complications occurred. CONCLUSION: This rare genetic disorder presents unique management problems to the anesthesiologist, resulting in morbidity and mortality when general anesthesia is used. Our patients received appropriate management before endoscopy, and we performed the procedure under deep sedation. No complications occurred. We are thus confident that deep sedation in the endoscopy suite is safe in this rare syndrome.

Adolescent↗
PubMed2002

Gasping and autoresuscitation in the developing rat: effect of antecedent intermittent hypoxia.

Gasping is a critically important mechanism for autoresuscitation and survival during extreme tissue hypoxia. Evidence of antecedent hypoxia in sudden infant death syndrome suggests that intermittently occurring hypoxic episodes may modify gasping and autoresuscitation. To examine this issue, an intermittent hypoxia (IH) profile consisting of alternating room air and 10% O(2)-balance N(2) every 90 s was applied to pregnant Sprague-Dawley rats (IHRA; n = 50) and to pups after a normal pregnancy (RAIH; n = 50) as well as to control pups (RARA; n = 50). At postnatal day 5, pups were exposed to 95% N(2)-5% CO(2), and gasping and the ability to autoresuscitate were assessed. Compared with RARA, IHRA- and RAIH-exposed pups had a reduced number of gasps, decreased overall gasp duration, and were less likely to autoresuscitate on introduction of room air to the breathing mixture during the last phase of gasping (P < 0.001 vs. RARA). We conclude that both prenatal and early postnatal IH adversely affect gasping and related survival mechanisms.

Air↗
PubMed2002

Impaired spatial learning and hyperactivity in developing rats exposed to intermittent hypoxia.

Obstructive sleep apnea (OSA) is a frequent medical condition and is associated with cognitive impairments in adults and with hyperactivity and decreased school performance in children. In an adult rodent model, intermittent hypoxia (IH), such as occurs in OSA, is associated with neurodegenerative changes in the hippocampus and cortex and with spatial learning deficits. Because a unique developmental window of neural vulnerability to IH is present, we hypothesized that exposure to IH throughout the vulnerable ages would result in increased behavioral impairments in the juvenile rat. Rat pups were therefore exposed to either room air or IH beginning at postnatal (PN) d 10 until PN d 30. Learning and memory were assessed via a standard place-training version of the Morris water maze beginning at PN d 25. Locomotor activity was assessed on PN d 29 and 30. Pups exposed to IH displayed significant spatial learning impairments, and exposed male rats but not female rats displayed increased locomotor activity in the open field. Collectively, these findings indicate that exposure to IH at an age that corresponds to the peak incidence of OSA in children induces substantial learning impairment and gender-dependent behavioral hyperactivity in the juvenile rat. We postulate that this novel experimental model may allow for future exploration of mechanisms underlying the neurobehavioral deficits of children with OSA.

Adolescent↗
PubMed2002

Effect of supplemental oxygen on sleep architecture and cardiorespiratory events in preterm infants.

OBJECTIVE: To investigate the effect of low-flow supplemental oxygen (SupOx) on sleep architecture and cardiorespiratory events in asymptomatic preterm infants. METHODS: An overnight polysomnographic evaluation was conducted prospectively in 23 premature infants who were born at 30.0 +/- 3.2 (standard deviation) weeks' gestational age and studied at 38.1 +/- 4.4 weeks' postconceptional age. Infants were free of any adverse events, including cardiorespiratory monitor alarms in the nursery for at least 1 week before the study. Infants received room air (RA) or SupOx via nasal cannula at 0.25 L/min. RESULTS: Quiet sleep density was increased during SupOx (33.3 +/- 10.8% vs 26.6 +/- 10.0% total sleep time [TST] in RA), and a reciprocal decrease in active sleep density was observed (61.5 +/- 11.1% vs 68.4 +/- 9.9% TST in RA). No differences in sleep efficiency emerged (69.7 +/- 10.6% SupOx vs 69.7 +/- 8.8% RA). SupOx elicited significant decreases in apnea index (3.8 +/- 2.4 events/h vs 11.1 +/- 6.4 events/h in RA) and in the percentage of time spent in periodic breathing (1.8 +/- 2.9% vs 6.7 +/- 8.9% in RA). In addition, SupOx decreased the frequency of bradycardic events (0.3 +/- 0.8 events vs 2.5 +/- 0.03 events in RA) and improved overall oxygen saturation (98.7 +/- 1.1% vs 96.4 +/- 2.2%). No changes in alveolar ventilation, as derived from end-tidal CO2 measurements, was detected (38.6 +/- 5.8 mm Hg in SupOx vs 38.4 +/- 5.4 mm Hg in RA). CONCLUSIONS: Asymptomatic preterm infants exhibit frequent and potentially clinically adverse cardiorespiratory events when assessed in the sleep laboratory. Administration of SupOx to these infants is associated with an increase in the overall duration and percentage TST spent in quiet sleep with reciprocal changes in active sleep. In addition, improvement in respiratory stability is observed with the use of low-flow SupOx, as evidenced by a decrease in apnea, periodic breathing, and bradycardia, without adverse effects on alveolar ventilation.

Administration, Intranasal↗
PubMed2002

Severe hypersomnolence after pituitary/hypothalamic surgery in adolescents: clinical characteristics and potential mechanisms.

OBJECTIVES: After resection of hypothalamic/pituitary tumors, children are at risk for development of hormonal deficiencies, obesity, and hypersomnolence. However, the prevalence and pathophysiology of these complications are unclear. The purpose of this study was to assess the prevalence and severity of hypersomnolence in children after resection of pituitary tumors and to study the potential factors that contribute to this sleepiness if present. We further hypothesized that decrements in orexin levels may contribute to the sleepiness. METHODS: Six children who underwent hypothalamic/pituitary surgery were identified. Five of these patients and 5 matched control subjects underwent overnight polysomnography followed by a multiple sleep latency test. Children who had a primary sleep disorder (eg, obstructive sleep apnea) underwent treatment and were restudied subsequently (n = 2). Blood levels of pituitary hormones were measured. Blood and cerebrospinal fluid (CSF) were drawn from 4 patients and 3 control subjects to measure orexin levels. RESULTS: Endocrine control was appropriate in all children. Although patients had longer sleep duration but similar sleep efficiency than control subjects, relatively severe daytime somnolence was present (mean sleep latency: 10.3 +/- 5.3 minutes vs 26.2 +/- 1.1 minute in control subjects). Sleepiness did not correlate with body mass index or age. Furthermore, serum and CSF orexin levels did not differ between patients and control subjects. CONCLUSIONS: Severe daytime sleepiness is frequent among children who undergo pituitary/hypothalamic surgery and does not seem to result from inappropriate cortisol or thyroxine replacement, disturbed nocturnal sleep, or low levels of orexin in the serum or CSF. We therefore speculate that other, unidentified neurohormonal mechanisms may mediate the excessive sleepiness of these patients.

Adolescent↗
PubMedDate not supplied

Melatonin in children and adolescents with insomnia: a retrospective study.

Effectiveness and tolerability of melatonin was assessed in 32 children (mean age 9.6 +/- 4.5 years) with chronic sleep initiation and sleep maintenance problems treated naturalistically in a pediatric sleep medicine center. Children received melatonin for an average of 2.1 +/- 2.0 months at a final average dose of 2.0 +/- 1.2 mg administered 1 hour before bedtime. Twenty-nine (90.6%) children exhibited partial improvement to complete resolution of their sleep problems as measured by sleep latency time and number of awakenings reported by parents. Thus, melatonin may be effective, safe, and well tolerated in the treatment of chronic insomnia in children.

Administration, Oral↗
PubMedDate not supplied

Clinical and parental assessment of sleep in children with attention-deficit/hyperactivity disorder referred to a pediatric sleep medicine center.

Frequently reported sleep problems in children with attention deficit-hyperactivity disorder (ADHD) referred to a pediatric sleep medicine center were assessed and compared with objective sleep assessments. A retrospective review of 97 children with ADHD (mean age of 8.3+/-3.0 years) was conducted. Polysomnography in 69 children revealed periodic limb movement disorder (PLMD) in 36% and sleep-disordered breathing in 7%, while actigraphy uncovered substantial variability in sleep schedules of 16 patients. Although parental subjective sleep complaints were verified by objective sleep assessments in a small proportion of cases, PLMD and night-to-night variability in sleep patterns were common.

Adolescent↗