Karen Waters
The University of Sydney, Medicine, Faculty Member
Background: The emergence of acute-onset functional neurological symptoms, the focus of this study, is one of three stress responses related to immunisation. This case–control study documents the experience of 61 young people with past or... more
Background: The emergence of acute-onset functional neurological symptoms, the focus of this study, is one of three stress responses related to immunisation. This case–control study documents the experience of 61 young people with past or current functional neurological disorder (FND) in relation to the COVID-19 vaccination program in Australia. Methods: Information about the young person’s/parent’s choice and response pertaining to COVID-19 vaccination was collected as part of routine clinical care or FND research program follow-up. Results: 61 young people treated for FND (47 females, mean age = 16.22 years) and 46 healthy controls (34 females, mean age = 16.37 years) were included in the study. Vaccination rates were high: 58/61 (95.1%) in the FND group and 45/46 (97.8%) in the control group. In the FND group, 2 young people (2/61, 3.3%) presented with new-onset FND following COVID-19 vaccination; two young people with resolved FND reported an FND relapse (2/36, 5.56%); and two y...
Research Interests:
Objective To determine the practices of neonatologists in managing high-risk neonates believed to be at risk of sleep disordered breathing (SDB). Design An electronic web-based questionnaire assessing awareness of and current practices... more
Objective To determine the practices of neonatologists in managing high-risk neonates believed to be at risk of sleep disordered breathing (SDB). Design An electronic web-based questionnaire assessing awareness of and current practices for managing neonates predisposed to SDB with conditions like craniofacial anomalies, neuromuscular disorders or airway problems was emailed to 232 neonatologists and neonatal fellows working in Australia and New Zealand (NZ). Additionally, neonatologists were approached directly during the annual Australia and NZ perinatal conference in 2019. Results 93 neonatologists (40%) responded to the survey. The majority (85%) of the respondents stated that there were no written protocols/criteria for sleep consultation in their unit. We found considerable variations in the threshold for performing tests including oximetry or referring for polysomnography. Most respondents would perform oximetry before referring for a sleep consultation. However, the duration ...
Research Interests:
Adenotonsillectomy forms part of first-line management for pediatric obstructive sleep apnea (OSA). In nonrandomized studies of preschool-aged children, it is associated with postoperative weight gain. Being overweight or obese in... more
Adenotonsillectomy forms part of first-line management for pediatric obstructive sleep apnea (OSA). In nonrandomized studies of preschool-aged children, it is associated with postoperative weight gain. Being overweight or obese in childhood is a predictor of cardiovascular and metabolic disease in later life. Using longitudinal data from a multicenter randomised controlled trial, we assessed the impact of adenotonsillectomy on growth trajectory in preschool-aged children with mild-moderate OSA. Secondary aims were to assess the influence of social factors and baseline polysomnography parameters on growth trajectory. A total of 190 children (aged 3–5 years) with obstructive apnea hypopnea index ≤10 were randomly assigned to early (within 2 months) or routine (12-month wait) adenotonsillectomy. Anthropometry and polysomnography were performed at baseline, 12-month and 24-month timepoints for 126 children. Social risk factors were recorded using a questionnaire. Baseline characteristic...
Research Interests:
OBJECTIVES: It remains uncertain whether treatment with adenotonsillectomy for obstructive sleep apnea in children improves cognitive function. The Preschool Obstructive Sleep Apnea Tonsillectomy and Adenoidectomy study was a prospective... more
OBJECTIVES: It remains uncertain whether treatment with adenotonsillectomy for obstructive sleep apnea in children improves cognitive function. The Preschool Obstructive Sleep Apnea Tonsillectomy and Adenoidectomy study was a prospective randomized controlled study in which researchers evaluated outcomes 12 months after adenotonsillectomy compared with no surgery in preschool children symptomatic for obstructive sleep apnea. METHODS: A total of 190 children (age 3–5 years) were randomly assigned to early adenotonsillectomy (within 2 months) or to routine wait lists (12-month wait, no adenotonsillectomy [NoAT]). Baseline and 12-month assessments included cognitive and behavioral testing, medical assessment, polysomnography, and audiology. The primary outcome was global IQ at 12-month follow-up, measured by the Woodcock Johnson III Brief Intellectual Ability (BIA). Questionnaires included the Pediatric Sleep Questionnaire, Parent Rating Scale of the Behavioral Assessment System for Ch...
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
To validate the Sonomat against polysomnography (PSG) metrics in children and to objectively measure snoring and stertor to produce a quantitative indicator of partial upper airway obstruction that accurately reflects the pathology of... more
To validate the Sonomat against polysomnography (PSG) metrics in children and to objectively measure snoring and stertor to produce a quantitative indicator of partial upper airway obstruction that accurately reflects the pathology of pediatric sleep-disordered breathing (SDB). Simultaneous PSG and Sonomat recordings were performed in 76 children (46 male, age 5.8 ± 2.8, BMI = 18.5 ± 3.8 kg/m2). Sleep time, individual respiratory events and the apnea/hypopnea index (AHI) were compared. Obstructed breathing sounds were measured from the unobtrusive non-contact experimental device. There was no significant difference in total sleep time (TST), respiratory events or AHI values, the latter over-estimated by 0.3 events hr-1 by the Sonomat. Poor signal quality was minimal and gender, BMI, and body position did not adversely influence event detection. Obstructive and central events were classified correctly. The number of runs and duration of snoring (13 399 events, 20% TST) and stertor (5...
Research Interests:
IQ deficits are linked to even mild obstructive sleep apnoea (OSA) in children. Although OSA is commonly first diagnosed in the pre-school age group, a randomised trial is still needed to assess IQ outcomes after adenotonsillectomy in the... more
IQ deficits are linked to even mild obstructive sleep apnoea (OSA) in children. Although OSA is commonly first diagnosed in the pre-school age group, a randomised trial is still needed to assess IQ outcomes after adenotonsillectomy in the pre-school age-group. This randomised control trial (RCT) will primarily determine whether adenotonsillectomy improves IQ compared to no adenotonsillectomy after 12 months, in preschool (3-5 year-old) children with mild to moderate OSA. This protocol is for an ongoing multi-centred RCT with a recruitment target of 210 subjects (105 in each arm). Children age 3-5 years with symptoms of OSA, are recruited through doctor referral, at the point of referral to the Ear Nose and Throat (ENT) services. Screening is initially with a questionnaire (Paediatric Sleep Questionnaire, PSQ) for symptoms of obstructive sleep apnoea (OSA). Where questionnaires are positive (suggestive of OSA) and ENT surgeons recommend them for adenotonsillectomy, they are invited t...
Research Interests: Pediatrics, Intelligence, Clinical Trial, Australia, Medicine, and 15 moreNeurocognitive, Neurocognition, Humans, Child, Obstructive sleep apnea, Female, Male, New Zealand, Incidence, Adenoidectomy, Polysomnography, Pre school, Child preschool, Adenotonsillectomy, and Paediatrics and reproductive medicine
Research Interests: Biology, Immunohistochemistry, Neuropathology, Medicine, In Situ Hybridization, and 15 moreHumans, Female, Brainstem, Male, Infant, Sudden Infant Death Syndrome, Clinical Sciences, Analysis of Variance, Neurosciences, Case Control Studies, Glutamate Receptor, Brain stem, NMDA receptor, Cell count, and reverse transcriptase polymerase chain reaction
Sleep is considered an important time of healing and restoration during illness. The primary aim of this study was to determine the prevalence of self-reported sleep disturbance in children admitted to a tertiary children's hospital... more
Sleep is considered an important time of healing and restoration during illness. The primary aim of this study was to determine the prevalence of self-reported sleep disturbance in children admitted to a tertiary children's hospital with a variety of medical diagnoses. Parents of children admitted to the hospital, aged between 1 and 18 years, were asked to complete a sleep diary during one night of their child's hospital stay. Children older than 12 years were asked to complete a diary independently. Descriptive statistics were used to summarise the data. Overall, 107 children were surveyed for one hospital inpatient night. The overall prevalence of poor sleep was 52.3%. The wide age range and variety of diagnosis limited further detailed analysis of specific causes of this problem. Poor sleep prior to admission was the strongest predictor of poor sleep in hospital suggesting that these children already had an underlying sleep problem. Unprompted awakenings were predominantl...
Research Interests:
Research Interests:
The purpose of this review is to provide guidelines for the use of oral appliances (OAs) for the treatment of snoring and obstructive sleep apnoea (OSA) in Australia. A review of the scientific literature up to June 2012 regarding the... more
The purpose of this review is to provide guidelines for the use of oral appliances (OAs) for the treatment of snoring and obstructive sleep apnoea (OSA) in Australia. A review of the scientific literature up to June 2012 regarding the clinical use of OAs in the treatment of snoring and OSA was undertaken by a dental and medical sleep specialists team consisting of respiratory sleep physicians, an otolaryngologist, orthodontist, oral and maxillofacial surgeon and an oral medicine specialist. The recommendations are based on the most recent evidence from studies obtained from peer reviewed literature. Oral appliances can be an effective therapeutic option for the treatment of snoring and OSA across a broad range of disease severity. However, the response to therapy is variable. While a significant proportion of subjects have a near complete control of the apnoea and snoring when using an OA, a significant proportion do not respond, and others show a partial response. Measurements of baseline and treatment success should ideally be undertaken. A coordinated team approach between medical practitioner and dentist should be fostered to enhance treatment outcomes. Ongoing patient follow-up to monitor treatment efficacy, OA comfort and side effects are cardinal to long-term treatment success and OA compliance.
Research Interests:
Ventilatory responses (VRs) were measured via a sealed face mask and pneumotachograph in 30 unsedated, mixed-breed miniature piglets at 12.6 ± 2.3 days of age ( day 1) and then repeated after seven daily 24-min exposures to 10% O2-6% CO2... more
Ventilatory responses (VRs) were measured via a sealed face mask and pneumotachograph in 30 unsedated, mixed-breed miniature piglets at 12.6 ± 2.3 days of age ( day 1) and then repeated after seven daily 24-min exposures to 10% O2-6% CO2 [hypercapnic hypoxia (HH)]. Arterial blood was sampled at baseline, after 10 min of exposure, and after 10 min of recovery. VRs included hypoxia (10% O2 in N2), hypercapnia (6% CO2 in air), and HH (10% O2-6% CO2-balance N2). Treatment groups ( n = 10 each) were exposed to 24 min of HH from day 2 to 8 as sustained HH (24 min of HH and then 24 min of air) or cyclic HH (4 min of HH alternating with 4 min of air). Day 1 and 9data were compared in treatment and control groups. After cyclic HH, respiratory responses to CO2 were reduced during hypercapnia and during HH ( P < 0.001 vs. control for minute ventilation in both). In both treatment groups, time to peak minute ventilation was delayed in hypoxia ( P = 0.02, ANOVA), and response amplitude was in...
Research Interests:
To determine whether stimulus frequency affects physiological compensation to an intermittent respiratory stimulus, we studied piglets (n = 43) aged 14.8 +/- 2.4 days. A 24-min total hypercapnic hypoxia (HH) (10% O(2)-6% CO(2)-balance... more
To determine whether stimulus frequency affects physiological compensation to an intermittent respiratory stimulus, we studied piglets (n = 43) aged 14.8 +/- 2.4 days. A 24-min total hypercapnic hypoxia (HH) (10% O(2)-6% CO(2)-balance N(2) = HH) was delivered in 24-, 8-, 4-, or 2-min cycles alternating with air. Controls (n = 10) breathed air continuously. Minute ventilation and temperature were not different between the 2-min and 24-min groups, with neither different from controls during recovery. Piglets exposed to 8-min cycles had ventilatory stimulation, whereas those exposed to 4-min cycles had significant depression of ventilation. Despite this, piglets in these intermediate intermittent HH (IHH) groups (8- and 4-min cycles) showed more severe acidosis and attenuated temperature changes (P < 0.001 and P < 0.01 for pH and temperature vs. 24 min, respectively). Cycle time affected the ability of young piglets to tolerate IHH. More severe respiratory acidosis developed when...
Research Interests: Biology, Medicine, Biological Sciences, Anoxia, Circadian Rhythm, and 15 moreAnimals, Anesthesia, Applied Physiology, Periodicity, Respiration, Body Temperature, Respiratory System, Swine, Gases, Acidosis, Respiratory Mechanics, Hypercapnia, Arteries, Respiratory acidosis, and Medical and Health Sciences
Research Interests: Hypoxia, Medicine, Habituation, Anoxia, Obstructive sleep apnea, and 15 moreAnimals, Anesthesia, Behavior change, Arousal, Intermittent hypoxia, Analysis of Variance, Postnatal development, Clinical Study, Blood gas analysis, Apnea, Hypercapnia, Pulmonary ventilation, Outcome measure, Asphyxia, and Medical and Health Sciences
Research Interests: Neuroscience, Biology, Medicine, Brain, Humans, and 15 moreAnoxia, Nicotine, Animals, Cell Death, Central Nervous System, Early development, Animal Model, Brain Ischemia, Sudden Infant Death Syndrome, Newborn Infant, Oxygen, Neurosciences, Biochemistry and cell biology, Hypercapnia, and NMDA receptor
ABSTRACT Il semble que les victimes de mort subite du nourrisson (MSN) ont ete exposees a des episodes repetes d&#39;hypoxemie (evidence anatomopathologique). L&#39;objectif de notre etude est de determiner s&#39;il y a... more
ABSTRACT Il semble que les victimes de mort subite du nourrisson (MSN) ont ete exposees a des episodes repetes d&#39;hypoxemie (evidence anatomopathologique). L&#39;objectif de notre etude est de determiner s&#39;il y a evidence de lesions neuropathologiques recentes chez les victimes de mort subite (MSN et autres causes). Toutes les autopsies ont ete realisees dans un centre pediatrique et ont inclus l&#39;examen histologique du cerveau par un neuropathologiste. Un diagnostic de MSN a ete porte chez 129 des 149 cas revus. Les cas de survie prolongee suivant une reanimation ont ete exclus. Chez 27 % des MSN et chez 60 % des autres cas (p Document Type: Abstract DOI: http://dx.doi.org/10.1016/S0929-693X(97)83402-1 Publication date: July 1, 1997 $(document).ready(function() { var shortdescription = $(&quot;.originaldescription&quot;).text().replace(/\\&amp;/g, &#39;&amp;&#39;).replace(/\\, &#39;&lt;&#39;).replace(/\\&gt;/g, &#39;&gt;&#39;).replace(/\\t/g, &#39; &#39;).replace(/\\n/g, &#39;&#39;); if (shortdescription.length &gt; 350){ shortdescription = &quot;&quot; + shortdescription.substring(0,250) + &quot;... more&quot;; } $(&quot;.descriptionitem&quot;).prepend(shortdescription); $(&quot;.shortdescription a&quot;).click(function() { $(&quot;.shortdescription&quot;).hide(); $(&quot;.originaldescription&quot;).slideDown(); return false; }); }); Related content In this: publication By this: publisher In this Subject: Pediatrics By this author: Cote, A. ; Waters, K. ; Michaud, J. GA_googleFillSlot(&quot;Horizontal_banner_bottom&quot;);
We use issues that arose in the management of a 4-year old girl with a congenital myopathy to consider the tension between respecting the choices and decisions of the child's parents and applying clinical practice guidelines that... more
We use issues that arose in the management of a 4-year old girl with a congenital myopathy to consider the tension between respecting the choices and decisions of the child's parents and applying clinical practice guidelines that emphasise minimising risk to the child. This case raises the issue of when it is reasonable to override parents' choice of management options.
Chronic snoring (≥4 nights per week) is not benign. Otherwise healthy children with chronic snoring and evidence of adenotonsillar hypertrophy can be referred directly for adenotonsillectomy. Snoring children... more
Chronic snoring (≥4 nights per week) is not benign. Otherwise healthy children with chronic snoring and evidence of adenotonsillar hypertrophy can be referred directly for adenotonsillectomy. Snoring children &amp;amp;amp;amp;amp;amp;lt;30 months or with significant medical comorbidities should be referred for specialist sleep evaluation. Older children with intermittent snoring or without significant medical comorbidities can be managed with a combination of medical and surgical interventions listed herein.
Tracheostomy decannulation in the paediatric patient is usually considered when there is resolution or significant improvement in the original indication for the tracheostomy. The child&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s... more
Tracheostomy decannulation in the paediatric patient is usually considered when there is resolution or significant improvement in the original indication for the tracheostomy. The child&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s cardiorespiratory function needs to be optimized and assessment of the readiness for decannulation is generally by endoscopic evaluation to confirm airway patency and vocal cord mobility. Functional airway assessment procedures include downsizing the tracheostomy, adding fenestration, speaking valves and capping the tracheostomy tube. Few objective measures have been demonstrated to accurately predict the likelihood of successful decannulation. This study aims to evaluate the usefulness of polysomnography (PSG) with a capped tracheostomy tube, as an adjunct to airway endoscopy and traditional decannulation procedures, to predict decannulation outcome. A retrospective review was conducted for patients who underwent &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;capped&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; PSG prior to a trial of tracheostomy decannulation at the Sydney Children&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Hospitals Network. The charts were reviewed for clinical data and PSG results. 30 children with a total of 40 PSG reports were included in this study. There was a statistically significant difference in mean oxygen saturation, minimum oxygen saturation, total apnoea/hypopnoea index, desaturations &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;3%, and desaturations &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;3% index between those that had successful decannulation compared to failed decannulation. The measures with the greatest significance, and therefore, the best predictors of decannulation outcome were total apnoea/hypopnoea index (3.35events/h vs. 18.5events/h, p=0.004) and desaturation events (20.33 events vs. 192 events, p=0.001). PSG with a capped tracheostomy tube is a useful, objective tool to complement endoscopy and functional airway assessment in the consideration of decannulation in the paediatric population.
Research Interests:
Non-invasive ventilation (NIV) in children has become an increasingly common modality of breathing support where pressure support is delivered through a mask interface or less commonly through other non-invasive interfaces. At this time,... more
Non-invasive ventilation (NIV) in children has become an increasingly common modality of breathing support where pressure support is delivered through a mask interface or less commonly through other non-invasive interfaces. At this time, NIV is considered a first-line option for ventilatory support of chronic respiratory insufficiency associated with a range of respiratory and sleep disorders. Previous reviews on the effectiveness, complications and adherence to NIV treatment have lacked systematic methods. The purpose of this scoping review is to provide an overview of the evidence for the use of long-term NIV in children. We will use previously established scoping methodology. Ten electronic databases will be searched to identify studies in children using NIV for longer than 3 months outside an intensive care setting. Grey literature search will include conference proceedings, thesis and dissertations, unpublished trials, reports from regulatory agencies and manufacturers. Two rev...
We recently showed that orexin expression in sudden infant death syndrome (SIDS) infants was reduced by 21% in the hypothalamus and 40-50% in the pons compared to controls. Orexin maintains wakefulness/sleeping states, arousal and... more
We recently showed that orexin expression in sudden infant death syndrome (SIDS) infants was reduced by 21% in the hypothalamus and 40-50% in the pons compared to controls. Orexin maintains wakefulness/sleeping states, arousal and rapid-eye-movement sleep; abnormalities for which have been reported in SIDS. This study examined the effects of two prominent risk factors for SIDS, intermittent hypercapnic hypoxia (IHH) (prone-sleeping), and chronic nicotine exposure (cigarette-smoking), on orexin A/B (OxA/OxB) expression in piglets. Piglets were randomly assigned to 5 groups: saline-control (n=7), air-control (n=7), nicotine (2mg/kg/day[14 days]) (n=7), IHH (6-minutes 7%O2 /8%CO2 oscillated with air, 4x) (n=7) and combination nicotine/IHH (N+IHH) (n=7). OxA/OxB was quantified in the central tuberal hypothalamus [dorsal medial hypothalamus (DMH), perifornical area (PeF), lateral hypothalamus (LH)] and in the dorsal raphe, locus coeruleus of the pons. Nicotine and N+IHH exposures signifi...
Research Interests:
Matrix assisted laser desorption/ionisation imaging mass spectrometry (MALDI-IMS) has not previously been utilised to examine sudden infant death syndrome (SIDS). This study aimed to optimise MALDI IMS for use on archived... more
Matrix assisted laser desorption/ionisation imaging mass spectrometry (MALDI-IMS) has not previously been utilised to examine sudden infant death syndrome (SIDS). This study aimed to optimise MALDI IMS for use on archived formalin-fixed-paraffin-embedded human infant medulla tissue (n=6, controls; n=6, SIDS) to evaluate differences between multiple nuclei of the medulla by using high resolution IMS. Profiles were compared between SIDS and age/sex matched controls. LC-MALDI identified 55 proteins based on 321 peptides across all samples; 286 peaks were found using IMS, corresponding to these 55 proteins that were directly compared between controls and SIDS. Control samples were used to identify common peptides for neuronal/non-neuronal structures allowing identification of medullary regions. In SIDS, abnormal expression patterns of 41 peptides (p≤0.05) corresponding to 9 proteins were observed; these changes were confirmed with immunohistochemistry. The protein abnormalities varied a...
Research Interests:
Postnatal exposure to cigarette smoke during infancy is associated with increased number of respiratory illnesses, impaired pulmonary function, and the occurrence of Sudden Infant Death Syndrome (SIDS). It is also associated with reduced... more
Postnatal exposure to cigarette smoke during infancy is associated with increased number of respiratory illnesses, impaired pulmonary function, and the occurrence of Sudden Infant Death Syndrome (SIDS). It is also associated with reduced cognitive functioning and attention deficits in childhood. Nicotine, the major neurotoxic component of cigarette smoke, induces its actions by binding to nicotinic acetylcholine receptors (nAChR). Using a piglet model of postnatal nicotine exposure, we studied the immunohistochemical expression of nAChR subunits α2, α3, α4, α5, α7, α9, β1 and β2 in the brainstem medulla and the hippocampus, given the role of these structures in cardiorespiratory control and cognition, respectively. We compared piglets exposed postnatally to 2mg/kg/day nicotine for 14 days (n=14: 7 males: 7 females) to controls (n=14: 7 males: 7 females). In the hippocampus, decreased expression was seen for α3 in CA1 (p=0.017), α9 in CA1 (p<0.001) and CA2 (p<0.001), β1 in CA1 ...
Research Interests:
Orexin neuropeptides (OxA and OxB) and their receptors (OX1R and OX2R) are involved in maintenance of sleep and wakefulness, and are regulated by various environmental stimuli. We studied piglets, in the early neonatal period, exposed to... more
Orexin neuropeptides (OxA and OxB) and their receptors (OX1R and OX2R) are involved in maintenance of sleep and wakefulness, and are regulated by various environmental stimuli. We studied piglets, in the early neonatal period, exposed to 48-min of intermittent hypercapnic hypoxia (IHH; 7% O2/8% CO2) alternating with air. Three groups of 13-14 day-old piglets with IHH exposure of 1-day (1D-IHH) (n=7), 2-days (2D-IHH) (n=7) and 4-days (4D-IHH) (n=8) were compared to controls (exposed only to air, n=8). Immunoreactivity of OxA and OxB was studied in the piglet hypothalamic regions of the dorsomedial hypothalamus (DMH), perifornical area (PeF) and lateral hypothalamic area (LH). Results showed that after 1D- and 2D-IHH, total OxA and OxB expression decreased by 20% (p≤0.005) and 40% (p<0.001), respectively. After 4D-IHH, the decrease in OxA and OxB was 50% (p<0.001). These findings indicate that a chronic IHH exposure induces greater changes in orexin neuropeptide expression than ...
Research Interests:
Research Interests:
To assess effects of anesthesia and opioids, we studied 13 children with obstructive sleep apnea (OSA, age 4.0 +/- 2.2 yr, mean +/- SD) and 24 age-matched control subjects (5.8 +/- 4.0 yr). Apnea indexes of children with OSA were 29.4 +/-... more
To assess effects of anesthesia and opioids, we studied 13 children with obstructive sleep apnea (OSA, age 4.0 +/- 2.2 yr, mean +/- SD) and 24 age-matched control subjects (5.8 +/- 4.0 yr). Apnea indexes of children with OSA were 29.4 +/- 18 h-1, median 30 h-1. Under inhalational anesthetic, closing pressure at the mask was 2.2 +/- 6.9 vs. -14.7 +/- 7.8 cmH2O, OSA vs. control (P < 0.001). After intubation, spontaneous ventilation was 115.5 +/- 56.9 vs. 158.7 +/- 81.6 ml x kg-1 small middle dot min-1, OSA vs. control (P = 0.02), despite elevated PCO2 (49.3 vs. 42.1 Torr, OSA vs. control, P < 0.001). Minute ventilation fell after fentanyl (0.5 microg/kg iv), with central apnea in 6 of 13 OSA cases vs. 1 of 23 control subjects (P < 0.001). Consistent with the finding of reduced spontaneous ventilation, apnea was most likely when end-tidal CO2 exceeded 50 Torr during spontaneous breathing under anesthetic. Thus children with OSA had depressed spontaneous ventilation under anest...
Research Interests:
Research Interests:
Research Interests:
STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by repeated episodes of upper-airway obstruction during sleep leading to significant hypercapnic hypoxic conditions. These conditions are associated with increased levels of... more
STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by repeated episodes of upper-airway obstruction during sleep leading to significant hypercapnic hypoxic conditions. These conditions are associated with increased levels of proinflammatory cytokines (including interleukin [IL]-6, tumor necrosis factor [TNF]-alpha, and C-reactive protein [CRP]) and subsequent increased cardiovascular risk. It is unclear whether hypercapnic hypoxia itself causes inflammatory perturbations.DESIGN: We evaluated circulating IL-6, TNF- a and CRP in a piglet model of infant OSA, following exposure to acute intermittent hypercapnic hypoxia (IHH). Study groups comprised of treatment (n = 8) and control (n = 8) groups. Treatment was two 90-minute sessions of IHH with arterial blood sampled before and after each IHH session.MEASUREMENTS AND RESULTS: IL-6, TNF-alpha and CRP levels were measured before and after IHH treatment sessions. Results showed an increase in IL-6 following the first session of IHH that was neither sustained, nor repeated, during a subsequent exposure. Using mixed-modelling, TNF-alpha changed between time points and groups. There were no changes in CRP over the duration of the study.CONCLUSION: These results suggest that acute hypoxia causes a transient increase in IL-6 levels and has implications for the pathogenesis of increased cardiovascular disease in OSA, especially in childhood.
Research Interests:
Research Interests: Psychopharmacology, Fear, Cognition, Long Term Potentiation, Attention, and 22 moreNeurochemistry, Face recognition (Psychology), Prefrontal Cortex, In Situ Hybridization, Dopamine, Hippocampus, Learning and Memory, Cues, Animals, Object Recognition, Male, Acetylcholine, Amygdala, Fear conditioning, Norepinephrine, mRna expression levels, Cognitive impairment, Rats, Operant Conditioning, Medial Prefrontal Cortex, Piperidines, and Dorsal hippocampus
The most important risk factors currently identified for the sudden infant death syndrome (SIDS) are prone sleeping and cigarette smoke exposure. In this study, we investigated the neuropathological sequelae of these risk factors by... more
The most important risk factors currently identified for the sudden infant death syndrome (SIDS) are prone sleeping and cigarette smoke exposure. In this study, we investigated the neuropathological sequelae of these risk factors by exposing piglets to intermittent hypercapnic-hypoxia (IHH) and/or nicotine (nic) in the early postnatal period. Our hypothesis was that either nic or IHH exposure could increase neuronal cell death, and that combined exposure (nic+IHH) would be additive. Four exposure patterns were studied: controls (n=14), IHH (n=10), nic (n=14), and nic+IHH (n=14). All groups had equal gender ratios. Nic exposure via an implanted osmotic minipump commenced within 48 h of birth and continued until age 13-14 days when animals were killed and brains collected. A total of 48 min of hypercapnic-hypoxia was delivered on the day immediately prior to killing in a pattern comprising 6 min of HH (8% O(2), 7% CO(2), balance N(2)) alternating with 6 min of air. Immunohistochemistry was performed to identify neurons positive for active caspase-3 and DNA fragmentation (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, TUNEL) in seven nuclei of the caudal medulla. Staining quantification showed that: 1. IHH induced neuronal death (increased both TUNEL and casapse-3) in more brainstem nuclei than nicotine. 2. Females were more severely affected by IHH than males. 3. Where IHH and nicotine were combined, TUNEL expression was approximately 5% less than IHH alone, but changes in caspase-3 were variable. We conclude that acute exposure to IHH in the postnatal period is more neurotoxic than exposure to nicotine alone. Combined exposure to IHH and nicotine produced variable responses with some results suggesting that nicotine can be neuroprotective. These results indicate that environmental insults attributable to prone sleeping can produce neurotoxic sequelae in SIDS, with some regional specificity in the response. However, no consistent relationship is evident when combining the two insults.
Research Interests: Neuroscience, Psychology, Hypoxia, Immunohistochemistry, Apoptosis, and 21 moreNicotine, Female, Animals, Male, Cell Death, Risk factors, Caspase, Ion, Sex Factors, Analysis of Variance, Time Factors, Swine, PBS, Risk Factors, Somatic Cell Count, Neurosciences, Nts, Hypercapnia, TUNEL, Terminal Deoxynucleotidyl Transferase, and DNA fragmentation
Research Interests: Cognitive Science, Biology, Hypoxia, Immunohistochemistry, Apoptosis, and 24 moreMedicine, Brain, Anoxia, NHS, Nicotine, Female, Animals, Male, Risk factors, IHC, TrkB, Ion, Gcms, Swine, PBS, Risk Factors, Recombinant Proteins, Cell Survival, Neurosciences, Nts, NIC, Hypercapnia, Cell Growth, and Brain stem
The role of the N-methyl-D-aspartate (NMDA) receptor in cell death was evaluated in the piglet brainstem after exposure to intermittent hypercapnic hypoxia (IHH). Study groups comprised controls (n=6) and piglets exposed to IHH on 2 (n=6)... more
The role of the N-methyl-D-aspartate (NMDA) receptor in cell death was evaluated in the piglet brainstem after exposure to intermittent hypercapnic hypoxia (IHH). Study groups comprised controls (n=6) and piglets exposed to IHH on 2 (n=6) or 4 (n=5) successive days prior to euthanasia. All piglets had the caudal medulla evaluated at 13-14 days of age using double immunohistochemistry for TUNEL and the NMDA receptor 1 (NR1) subunit. The percent of TUNEL positive neurons amongst NR1 (% TUN in NR1) and non-NR1 neurons (% TUN in non-NR1) was determined in eight nuclei. After 2 days of IHH, %TUN in NR1 was increased in the dorsal motor nucleus of the vagus (DMNV, P=0.007) and the inferior olivary nucleus (ION, P=0.05). After 2 days IHH, %TUN in non-NR1 neurons was increased in the lateral reticular nucleus (LRt, P=0.05), nucleus of the solitary tract (NTS, P=0.004) and gracile nucleus (P=0.05). After 4days IHH, the increase of %TUN in NR1 was sustained in the ION (P=0.05), while %TUN in non-NR1 neurons was sustained in NTS (P=0.04) and LRt (P=0.006). Daily IHH exposure induces neuronal death within NR1 and non-NR1 neurons, but the neuronal phenotype is consistent within affected brainstem nuclei. Involvement of the NMDA receptor tended to occur in nuclei with higher basal NR1 expression, and thus occurred in nuclei relevant to cardiorespiratory function. We speculate that IHH exposures, such as occurs during obstructive apnea or facial entrapment in prone sleeping during infancy, can induce abnormalities of cardiorespiratory control.
Research Interests:
Nasal continuous positive airways pressure (nCPAP) is recommended in children for the treatment of obstructive sleep apnoea which persists following adenotonsillectomy. Nasal CPAP was successfully used in the palliative care of two... more
Nasal continuous positive airways pressure (nCPAP) is recommended in children for the treatment of obstructive sleep apnoea which persists following adenotonsillectomy. Nasal CPAP was successfully used in the palliative care of two severely disabled children with upper airway obstruction as an alternative to tracheostomy. Nasal CPAP resulted in the correction of obstructive apnoea in sleep, with the added benefit of sleep consolidation and fewer nocturnal arousals requiring parental attendance. There was also an unexpected benefit of reduced airway problems in the awake state in these children. Nasal CPAP is an effective form of treating upper airway obstruction for palliative care in association with other major disabilities.
Research Interests:
Infants at risk of sudden infant death syndrome (SIDS) have been shown to have dysfunctional sleep and poor arousal thresholds. In animal studies, both these attributes have been linked to impaired signalling of the neuropeptide orexin.... more
Infants at risk of sudden infant death syndrome (SIDS) have been shown to have dysfunctional sleep and poor arousal thresholds. In animal studies, both these attributes have been linked to impaired signalling of the neuropeptide orexin. This study examined the immunoreactivity of orexin (OxA and OxB) in the tuberal hypothalamus (n = 27) and the pons (n = 15) of infants (1-10 months) who died from SIDS compared to age-matched non-SIDS infants. The percentage of orexin immunoreactive neurons and the total number of neurons were quantified in the dorsomedial, perifornical and lateral hypothalamus at three levels of the tuberal hypothalamus. In the pons, the area of orexin immunoreactive fibres were quantified in the locus coeruleus (LC), dorsal raphe (DR), laterodorsal tegmental (LDT), medial parabrachial, dorsal tegmental (DTg) and pontine nuclei (Pn) using automated methods. OxA and OxB were co-expressed in all hypothalamic and pontine nuclei examined. In SIDS infants, orexin immunoreactivity was decreased by up to 21 % within each of the three levels of the hypothalamus compared to non-SIDS (p ≤ 0.050). In the pons, a 40-50 % decrease in OxA occurred in the all pontine nuclei, while a similar decrease in OxB immunoreactivity was observed in the LC, LDT, DTg and Pn (p ≤ 0.025). No correlations were found between the decreased orexin immunoreactivity and previously identified risk factors for SIDS, including prone sleeping position and cigarette smoke exposure. This finding of reduced orexin immunoreactivity in SIDS infants may be associated with sleep dysfunction and impaired arousal.
Research Interests:
The brainstem has been a focus in Sudden Infant Death Syndrome (SIDS) research for 30 years. Physiological and animal model data show that cardiorespiratory, sleep, and arousal mechanisms are abnormal after exposure to SIDS risk factors... more
The brainstem has been a focus in Sudden Infant Death Syndrome (SIDS) research for 30 years. Physiological and animal model data show that cardiorespiratory, sleep, and arousal mechanisms are abnormal after exposure to SIDS risk factors or in infants who subsequently die from SIDS. As the brainstem houses the regulatory centres for these functions, it is the most likely site to find abnormalities. True to this hypothesis, data derived over the last 30 years shows that the brainstem of infants who died from SIDS exhibits abnormalities in a number of major neurotransmitter and receptor systems including: catecholamines, neuropeptides, acetylcholinergic, indole amines (predominantly serotonin and its receptors), amino acids (predominantly glutamate), brain derived neurotrophic growth factor (BDNF), and some cytokines. A pattern is emerging of particular brainstem nuclei being consistently affected including the dorsal motor nucleus of the vagus (DMNV), nucleus of the solitary tract (NT...
Research Interests:
During sleep changes in central and peripheral neurological pathways and muscle tone result in unique vulnerabilities in the respiratory system. Abnormalities of the respiratory system that are not apparent in wakefulness can become... more
During sleep changes in central and peripheral neurological pathways and muscle tone result in unique vulnerabilities in the respiratory system. Abnormalities of the respiratory system that are not apparent in wakefulness can become evident during particular sleep states, making overnight polysomnography (PSG) a valuable diagnostic indicator of the source as well as the severity of the abnormality. In this review these respiratory disorders are grouped according to whether they are attributable to upper airway collapse, poor gas diffusion or inadequate ventilation (respiratory effort). Inadequate ventilation may be secondary to abnormal respiratory drive (control) or to inadequate pulmonary muscle function. As a diagnostic tool, overnight PSG can help distinguish whether the origin of the disorder is central or peripheral on the basis of which sleep state is associated with greatest abnormality. The most common treatment interventions include supplemental oxygen, continuous positive...
Research Interests:
Apnea and arousal are modulated with sleep stage, and swallowing may interfere with respiratory rhythm in infants. We hypothesized that swallowing itself would display interaction with sleep state. Concurrent polysomnography and... more
Apnea and arousal are modulated with sleep stage, and swallowing may interfere with respiratory rhythm in infants. We hypothesized that swallowing itself would display interaction with sleep state. Concurrent polysomnography and measurement of swallowing allowed time-matched analysis of 3,092 swallows, 482 apneas, and 771 arousals in 17 infants aged 1-34 wk. The mean rates of swallowing, apnea, and arousal were significantly different, being 23.3 +/- 8.5, 9.4 +/- 8.8, and 15.5 +/- 10.6 h(-1), respectively (P < 0.001 ANOVA). Swallows occurred before 25.2 +/- 7.9% and during 74.8 +/- 6.3% of apneas and before 39.8 +/- 6.0% and during 60.2 +/- 6.0% of arousals. The frequencies of apneas and arousals were both strongly influenced by sleep state (active sleep > indeterminate > quiet sleep, P < 0.001), whether or not the events coincided with swallowing, but swallowing rate showed minimal independent interaction with sleep state. Interactions between swallowing and sleep state...
Research Interests:
Animal studies have shown that decreased orexin expression changes sleep regulation with normal aging. This study examined orexin A and B expression in the tuberal hypothalamus in infants (0-1 year; n = 8), children (4-10 years; n = 7),... more
Animal studies have shown that decreased orexin expression changes sleep regulation with normal aging. This study examined orexin A and B expression in the tuberal hypothalamus in infants (0-1 year; n = 8), children (4-10 years; n = 7), young adults (22-32 years; n = 4), and older (48-60 years; n = 7) adults. Neuronal expression was defined by the percentage positive orexin immunoreactive (Ox-ir) neurons in the whole tuberal hypothalamus, and in the dorsal medial (DMH), perifornical, and lateral hypothalamus. In addition, the number of Ox-ir neurons/mm(2), regional distribution, and co-localization were examined. Within the whole tuberal hypothalamic section, there was a 23% decrease in the percentage of Ox-ir neurons between infants and older adults (p < 0.001), and a 10% decrease in older compared with younger adults (p = 0.023). These changes were confined to the DMH and/or perifornical hypothalamus. There was a 9%-24% decrease in Ox neurons/mm(2) in adults compared with infan...
Research Interests:
Identification of disease-associated proteins is critical for elucidating CNS disease mechanisms and elaborating novel treatment strategies. It requires post-mortem tissue analysis which can be significantly affected by the collection... more
Identification of disease-associated proteins is critical for elucidating CNS disease mechanisms and elaborating novel treatment strategies. It requires post-mortem tissue analysis which can be significantly affected by the collection process, post-mortem intervals (PMIs), and storage conditions. To assess the effect of time and storage conditions on brain protein stability, SELDI-TOF-MS protein profiles were assessed in rat frontal cortex, caudate-putamen, hippocampus and medulla samples collected after various PMIs (0, 6, 12, 24, 48, and 72 h) at 4 °C or at room temperature (RT) storage. Regions of interest were isolated from cryosections (tissue apposition, TA), or micropunched from cryosections apposed on filter paper (paper apposition, PA), and applied onto an NP20 ProteinChip array. Protein alterations, while greater at RT than at 4 °C, were detected at 6h then differentially evolved in the various brain regions, with greater alterations in the caudate-putamen (60%) and the cortex (48%). Overall, our sensitive analytical method allowed unveiling of different patterns of protein susceptibility to PMI and to storage temperature in the various brain regions. Some protein peaks were altered in all brain regions and may potentially serve as markers of the PMI status of the brain, or for reference values when studying new proteins. Changes in disease-related proteins within post-mortem samples can be greatly affected by PMI and storage conditions, particularly when studying fragile and/or low abundant protein/peptides in tissues sampled from the caudate-putamen and neocortex.