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Biomedical subjects

David Gozal

Publications and source records attributed to David Gozal.

At least 91 records · Page 5Linked to original sources
PubMed2004

Epidemiologic survey of 196 patients with congenital central hypoventilation syndrome.

This study examined the cross-sectional medical and social characteristics of children diagnosed with congenital central hypoventilation syndrome (CCHS). A detailed questionnaire was mailed to all families with a child with CCHS who are affiliated with a family network or support group. The questionnaire response rate was >75% (n=196). Mean age was 10.22 years +/- 6.6 years (SD) (range, 0.4-38 years), with a 1:1 sex ratio. Multisystem involvement was almost universal among the cohort, with Hirschsprung's disease (HD) present in 16.3%; 61.7% of the children had a tracheotomy, but 14.3% were never tracheotomized, with 77 subjects (39.3%) not having a tracheostomy tube at time of survey. Respiratory support approaches varied but clearly reflected the trend towards earlier and more widespread transition to noninvasive ventilatory modalities. Significant developmental problems were noted, but attendance in regular classes occurred in the majority. Significant deficiencies in routine periodic evaluation and management were reported. In addition, the presence of CCHS was associated with a significant financial and psychosocial burden to the families. In conclusion, a comprehensive survey of 196 CCHS children and their families revealed a cross-sectional picture of substantial medical and psychosocial complexities associated with this disorder, and pointed out substantial inadequacies in routine preventive care that appear to impose stress on the families. The emerging trend of earlier transition to noninvasive ventilatory support warrants future studies. Implementation of recommended guidelines for diagnosis and multidisciplinary follow-up of CCHS should ultimately ameliorate the long-term outcome of this lifelong condition.

Adolescent↗
PubMed2004

A pediatric sedation/anesthesia program with dedicated care by anesthesiologists and nurses for procedures outside the operating room.

OBJECTIVE: To examine the performance of a pediatric sedation team working according to a specific protocol and to assess parental satisfaction with the service. STUDY DESIGN: A descriptive observational study of all procedures performed by the sedation team (comprising sedation-trained pediatric intensive care nurses and dedicated anesthesiologists) in a university hospital over 6 years. Data collected included demographics, procedure and location, sedation staff present, sedation failure, drugs used, requirements for escalation of sedation, complications, and parental satisfaction. RESULTS: Sedation was provided for 8760 procedures in 5554 children. The sedation nurse started 1769 (20%) procedures using triclofos sodium and required the assistance of the anesthesiologist in 115 (6.5%) cases. The remaining 6991 (80%) cases were performed by the anesthesiologist, predominantly using propofol (in 72.5% of cases). No cases were deferred as a result of insufficient sedation. Adverse events were recorded in 153 (1.7%) children. Of these, 132 (86%) were mild decreases in oxygen saturation. Three children were not discharged as a result of oversedation. Feedback indicated that 95% of parents were very satisfied with the sedation service. CONCLUSION: A dedicated sedation team using a written protocol provides a service with minimal case cancellation, zero sedation failure, very good safety, and excellent parental satisfaction.

Adolescent↗
PubMed2004

Nitric oxide synthase and intermittent hypoxia-induced spatial learning deficits in the rat.

Intermittent hypoxia (IH) during sleep induces significant neurobehavioral deficits in the rat. Since nitric oxide (NO) has been implicated in ischemia-reperfusion-related pathophysiological consequences, the temporal effects of IH (alternating 21% and 10% O(2) every 90 s) and sustained hypoxia (SH; 10% O(2)) during sleep for up to 14 days on the induction of nitric oxide synthase (NOS) isoforms in the brain were examined in the cortex of Sprague-Dawley rats. No significant changes of endothelial NOS (eNOS) and neuronal NOS (nNOS) occurred over time with either IH or SH. Similarly, inducible NOS (iNOS) was not affected by SH. However, increased expression and activity of iNOS were observed on days 1 and 3 of IH (P < 0.01 vs. control; n = 12/group) and were followed by a return to basal levels on days 7 and 14. Furthermore, IH-mediated neurobehavioral deficits in the water maze were significantly attenuated in iNOS knockout mice. We conclude that IH is associated with a time-dependent induction of iNOS and that the increased expression of iNOS may play a critical role in the early pathophysiological events leading to IH-mediated neurobehavioral deficits.

Animals↗
PubMed2004

Developmental and metabolic implications of the hypoxic ventilatory response.

This review explores the evidence to support the leading hypothesis that the metabolic response to hypoxia early in life provides the pathophysiological basis for the metabolic syndrome. Hypoxia is a frequent occurrence during early development and induces a state of energy depletion that triggers a wide range of 'metabolic' responses to preserve homeostasis. Recent interest in the sequelae of energy depletion through hypoxic mechanisms has grown, particularly because of demonstrated links with ensuing metabolic abnormalities and increased risk for future cardiovascular disease. The 'metabolic syndrome' refers to the combination of obesity, hyperinsulinaemia, dyslipidaemia and hypertension in adults. The metabolic responses to energy depletion during early development provide explanations for some of the mechanisms that ultimately lead to serological features of metabolic dysfunction in children with sleep-disordered breathing. Thus, the acute compensatory response of energy conservation to hypoxia during early development at the cellular, serological and whole organism levels suggests that the metabolic abnormalities that develop later in life may in fact originate very early in life; in other words, constitute early life antecedents of adult disease. Evidence regarding the circumstances under which responses to hypoxia become maladaptive will be discussed, with a focus on chronic conditions and those associated with intermittent respiratory dysfunction such as sleep-disordered breathing.

Humans↗
PubMed2004

Psychiatric symptoms in children with insomnia referred to a pediatric sleep medicine center.

BACKGROUND AND PURPOSE: To assess the frequency and nature of clinical and psychiatric symptoms in children referred to a pediatric sleep center for evaluation of insomnia. PATIENTS AND METHODS: A retrospective chart review of all children referred to the pediatric sleep medicine was conducted. Children presenting exclusively with sleep initiation and/or maintenance problems underwent a structured clinical psychiatric interview and their parents completed the behavioral assessment system for children (BASC), pediatric symptom checklist, the clinical attention problem scale and a detailed sleep questionnaire. RESULTS: Twenty-three of 46 children (50%) with persistent insomnia had a professional diagnosis of another psychiatric disorder. In the remaining 50%, although parents denied any previous psychiatric history, 40% displayed psychiatric symptoms as documented by psychometric measures and clinical interview. A significant positive correlation was observed between depressive BASC score and sleep onset latency and an inverse correlation was present with REM sleep latency. CONCLUSION: The vast majority of children presenting with persistent insomnia exhibit clinical symptoms of an accompanying psychiatric disorder, suggesting that comprehensive psychometric assessments are warranted in this population.

Attention Deficit Disorder with Hyperactivity↗
PubMed2004

Sleep in children with psychiatric disorders.

Although the exact nature of sleep disturbances present in children with psychiatric disorders has not been studied extensively, it is apparent that children with significant emotional and behavioral problems are more likely to experience sleep difficulties. Children with sleep-related issues that are limited to bedtime can be managed effectively with specific cognitive-behavioral interventions. Children with more pervasive anxiety (eg, PTSD or OCD, mood disorders such as major depression or bipolar disorder, or neurodevelopmental disabilities such as autism) require a more exhaustive evaluation, and most of them also need sleep problems to be managed by sleep professionals using combinations of psychotherapeutic and pharmacologic approaches.

Child↗
PubMed2004

Neurocognitive dysfunction and sleep in children: from human to rodent.

Sleep disturbance in children, whether because of poor sleep hygiene or sleep-related breathing disorders, is associated with significant behavioral and neurocognitive deficits. The mechanisms by which sleep disturbance contributes to the daytime manifestations are unclear, although it seems that sleep fragmentation and intermittent hypoxia are important. The long-term outcome for children with untreated diseases leading to sleep disruption is currently unknown. Increased awareness and early identification and treatment of conditions that lead to altered sleep should yield improved neurocognitive outcomes in affected children.

Animals↗
PubMed2004

Snoring and obstructive sleep apnoea in children: why should we treat?

Frequent and loud snoring is a very frequent condition in prepubertal children affecting approximately 10% of all 2-8 year old children. If polysomnographical evaluations are performed in these snoring children, approximately 10% will be diagnosed with obstructive sleep apnoea (OSA). The pathophysiology of OSA in children is still poorly understood. Indeed, while adenotonsillar hypertrophy is certainly a major contributor to OSA, other factors need to be implicated for OSA to develop. In recent years, it has become apparent that OSA and snoring are not as innocuous as previously thought. Indeed, epidemiological and pre-post treatment analyses have identified substantial morbidities that primarily affect cardiovascular and neurobehavioural systems, namely pulmonary hypertension, systemic elevation of arterial blood pressure, nocturnal enuresis, reduced somatic growth, behavioural problems that resemble attention deficit-hyperactivity disorder, as well as learning and cognitive deficits. These problems are associated with marked increases in healthcare-related costs. More importantly, if timely diagnosis and intervention are not implemented, some of these morbid complications may not be completely reversible, leading to long-lasting residual consequences.

Behavior↗
PubMed2004

OK-432 therapy for cervical lymphangioma.

OBJECTIVE: To describe our experience with sclerosing treatment of lymphangiomas in the head and neck region by intralesional injections of OK-432. STUDY DESIGN: Case series. METHODS: Patients with the diagnosis of a macrocystic-type cervical lymphangioma were treated by one to three intralesional injections of OK-432 (0.01 mg of OK-432/1 mL of lymphangioma fluid, up to a maximum of 0.2 mg in the first injection and 0.3 mg in the second or third injections). All injections were performed under ultrasound guidance. Children were injected under sedation. RESULTS: Eleven patients were treated with injections of OK-432: 7 children and 4 adults. They were followed up for a period of 5 to 68 (mean 30) months. Eight (73%) patients had complete or subcomplete resolution of the lymphangioma after one or two injections. In three (27%) cases, no response was obtained (2 cases) or the lymphangioma recurred (1 case) after two to three injections. In two cases, surgical excision was performed. There was no evidence of fibrosis around the cysts. There were no complications to OK-432 injections. CONCLUSION: Intralesional injection of OK-432 is an effective treatment modality for macrocystic-type lymphangiomas in the head and neck region. It has no complications, and surgical excision in case of failure is not compromised by fibrosis. Sclerosing of macrocystic-type lymphangiomas with OK-432 should therefore be considered before surgical excision.

Adult↗
PubMed2004

New concepts in abnormalities of respiratory control in children.

PURPOSE OF REVIEW: Respiratory control disorders such as apnea of prematurity, apparent life-threatening events, sudden infant death syndrome, and central hypoventilation are relatively frequent conditions in the pediatric age range and are associated with substantial morbidity and mortality. The explosion of technological breakthroughs in biology and medicine has facilitated our understanding of the fundamental mechanisms that govern the development of brain regions underlying respiratory control functions. RECENT FINDINGS: Recent critically important discoveries encompass the identification of neurons that constitute the central respiratory rhythm generator in the brainstem, the conceptual framework allowing for many neurons located in multiple strategic regions within the brain to coordinate central chemosensitivity, the discovery of long-term and short-term plasticity in hypoxic ventilatory regulation, and the recent uncovering of specific gene mutations in children affected with congenital central hypoventilation syndrome. SUMMARY: While the developmental aspects of control breathing are only now being actively explored in the context of our current understanding, it is likely that such efforts will yield important novel approaches to the clinical and pharmacologic management of these disorders in the near future.

Humans↗
PubMed2004

The effect of fasting practice on sedation with chloral hydrate.

OBJECTIVES: Infants undergo various painless imaging procedures frequently. Mild sedation is required in such cases to reduce anxiety as well as to ensure optimal performance of the procedure. The most frequently used sedative as a single drug is chloral hydrate. The issue of preprocedural fasting is a subject of contention. The purpose of this study was to assess the effect of the American Academy of Pediatrics (AAP)/American Society of Anesthesiology (ASA) fasting practice guidelines on the efficacy and success of the sedation with chloral hydrate. METHODS: The sedation records of 200 infants from 2 hospitals who underwent auditory brainstem response for evaluation of hearing loss were evaluated retrospectively. In the first hospital (group A), strict nulla per os (NPO) guidelines were followed in accordance with the guidelines published by the AAP/ASA, whereas in the second hospital (group B), no fasting period was required. All children were premedicated with chloral hydrate. We evaluated the sedation failure rate, total dose of chloral hydrate needed, adverse effects, overall sleep time, and time to discharge. RESULTS: The average fasting period as expected was significantly longer in group A patients than in group B patients (5.7 +/- 1.7 vs. 2 +/- 0.2 hours; P < 0.001). Group A patients demonstrated a significantly higher failure rate to achieve sedation with the first dose of chloral hydrate compared with group B patients (21% vs.11%; P = 0.03), hence needing higher doses (83 +/- 31 vs. 61 +/- 21 mg/kg; P < 0.01), and were sedated for longer periods (103 +/- 42 vs. 73 +/- 48 minutes; P < 0.001) and discharged later. No difference was found in the adverse effect rate. CONCLUSION: Fasting was associated with an increased failure rate of the initial sedation. As a consequence, an increased total dose of chloral hydrate was required inducing a prolonged sedation time. Presumably, this is a result of the fact that a hungry child is irritable and therefore more difficult to sedate.

Adolescent↗
PubMed2004

Neurobehavioral correlates of sleep-disordered breathing in children.

The effects of sleep-disordered breathing (SDB) on neurobehavioral function were examined in two matched groups of children from the general population. Thirty-five children with polysomnographically confirmed SDB were matched for ethnicity, age, gender, maternal educational attainment, and maternal smoking, to healthy children with no evidence of SDB. Children with SDB had significantly lower mean scores on the Differential Ability Scales for General Conceptual Ability (similar to IQ) and for the Non-verbal Cluster. On the neuropsychology assessment battery (NEPSY), children with SDB scored significantly lower than the control group on the attention/executive function domain and two subtests within that domain, one measuring visual attention and the other executive function. In addition, children with SDB scored significantly lower than the controls on one subtest from the NEPSY language domain: Phonological Processing. This subtest measures phonological awareness, a skill that is critical for learning to read. No differences in behavior, as measured by the Child Behavior Checklist (CBCL) or the Conners' Parent Rating Scale, were found between the two groups. Using a novel algorithm to assess sleep pressure, we found that children with SDB were significantly sleepier than controls. Furthermore, total arousal index was negatively correlated with neurocognitive abilities, suggesting a role for sleep fragmentation in pediatric SDB-induced cognitive dysfunction.

Aptitude↗
PubMed2004

Platelet-activating factor receptor-deficient mice are protected from experimental sleep apnea-induced learning deficits.

Intermittent hypoxia (IH) during sleep, a hallmark of sleep apnea, is associated with neurobehavioral impairments, regional neurodegeneration and increased oxidative stress and inflammation in rodents. Platelet-activating factor (PAF) is an important mediator of both normal neural plasticity and brain injury. We report that mice deficient in the cell surface receptor for PAF (PAFR-/-), a bioactive mediator of oxidative stress and inflammation, are protected from the spatial reference learning deficits associated with IH. Furthermore, PAFR-/- exhibit attenuated elevations in inflammatory signaling (cyclo-oxygenase-2 and inducible nitric oxide synthase activities), degradation of the ubiquitin-proteasome pathway and apoptosis observed in wild-type littermates (PAFR+/+) exposed to IH. Collectively, these findings indicate that inflammatory signaling and neurobehavioral impairments induced by IH are mediated through PAF receptors.

Animals↗
PubMed2004

Whole-body hypoxic preconditioning protects mice against acute hypoxia by improving lung function.

Survival in severe hypoxia such as occurs in high altitude requires previous acclimatization, which is acquired over a period of days to weeks. It was unknown whether intrinsic mechanisms existed that could be rapidly induced and could exert immediate protection on unacclimatized individuals against acute hypoxia. We found that mice pretreated with whole-body hypoxic preconditioning (WHPC, 6 cycles of 10-min hypoxia-10-min normoxia) survived significantly longer than control animals when exposed to lethal hypoxia (5% O2, survival time of 33.2 +/- 6.1 min vs. controls at 13.8 +/- 1.2 min, n = 10, P < 0.005). This protective mechanism became operative shortly after WHPC and remained effective for at least 8 h. Accordingly, mice subjected to WHPC demonstrated improved gas exchange when exposed to sublethal hypoxia (7% O2, arterial blood Po2 of 49.9 +/- 4.2 vs. controls at 39.7 +/- 3.6 Torr, n = 6, P < 0.05), reduced formation of pulmonary edema (increase in lung water of 0.491 +/- 0.111 vs. controls at 0.894 +/- 0.113 mg/mg dry tissue, n = 10, P < 0.02), and decreased pulmonary vascular permeability (lung lavage albumin of 7.63 +/- 0.63 vs. controls at 18.24 +/- 3.39 mg/dl, n = 6-10, P < 0.025). In addition, the severity of cerebral edema caused by exposure to sublethal hypoxia was also reduced after WHPC (increase in brain water of 0.254 +/- 0.052 vs. controls at 0.491 +/- 0.034 mg/mg dry tissue, n = 10, P < 0.01). Thus WHPC protects unacclimatized mice against acute and otherwise lethal hypoxia, and this protection involves preservation of vital organ functions.

Acute Disease↗
PubMed2004

Differential expression of cysteinyl leukotriene receptors 1 and 2 in tonsils of children with obstructive sleep apnea syndrome or recurrent infection.

BACKGROUND: Recurrent tonsillitis and sleep apnea are the major indications for tonsillectomy in children. We hypothesized that the recurrent vibration in the upper airway of snoring children would promote inflammatory changes in the tonsillar tissue and would lead to the up-regulation of cysteinyl leukotriene (LT) receptors (Rs). OBJECTIVE: To assess the expression patterns of the human LT-Rs in children undergoing tonsillectomy, and compare those patterns in children having recurrent throat infections (RIs) and children with obstructive sleep apnea syndrome (SA). METHODS: Tonsillar tissue from 17 children with SA and 13 with RIs was subjected to quantitative polymerase chain reaction using specific primers for LT1-R and LT2-R, and to immunohistochemistry and Western blotting for protein expression of LT1-R and LT2-R. RESULTS: Messenger RNA encoding for the expression of LT1-R and LT2-R was detected in the tonsils of all children. Immunoblots revealed significantly higher expressions of LT1-R and LT2-R in the tonsils of children with SA. The topographic pattern of both receptors differed among the tonsils of children with SA and RI. CONCLUSION: LT1-R and LT2-R are expressed in pediatric tonsillar tissue, are more abundant in SA patients, and demonstrate a specific topographic pattern of expression. These findings suggest that an inflammatory process involving LT expression and regulation occurs in children with SA.

Child↗
PubMed2004

Plasma C-reactive protein levels among children with sleep-disordered breathing.

INTRODUCTION: Levels of C-reactive protein (CRP), an important serum marker of inflammation with major implications for cardiovascular morbidity and atherogenesis, are elevated among adult patients with sleep-disordered breathing (SDB). We hypothesized that elevated CRP plasma levels would also be present among children with SDB. METHODS: Eighty-one children (mean age: 9.3 +/- 3.7 years) underwent polysomnographic evaluations. Samples for plasma CRP level and lipid profile determinations were drawn the next morning. RESULTS: Because plasma CRP levels were not normally distributed in this cohort, logarithmic transformation was applied. Log plasma CRP levels were significantly higher in the SDB group (obstructive apnea/hypopnea index [AHI] of > or =5), compared with the mild SDB group (AHI of > or =1 and <5) and the control group (AHI of <1). Significant positive correlations were found between log CRP levels and AHI (r =.53) and arousal index (r =.28), whereas an inverse correlation was found between the lowest nocturnal arterial oxygen saturation and log CRP levels (r = -.47). These correlations persisted after exclusion of outliers. Moreover, 94% of the children with elevated log CRP levels reported excessive daytime sleepiness and/or learning problems, compared with 62% of the children with normal log CRP levels. CONCLUSIONS: Plasma CRP levels were increased among some children with SDB and were correlated with AHI, arterial oxygen saturation nadir, and arousal index measures. These changes were particularly prominent among children who were sleepy or presented with neurobehavioral complaints. The intermittent hypoxemia and sleep fragmentation of SDB may underlie inflammatory responses, the magnitude of which may ultimately lead to the cardiovascular, cognitive, and behavioral morbidities of SDB.

Analysis of Variance↗