Karen A. Waters
University of Sydney
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Featured researches published by Karen A. Waters.
Pediatric Research | 1999
Karen A. Waters; Brian Meehan; Jing-Qi Huang; Roy A. Gravel; Jean Michaud; Aurore Côté
Although evidence shows that victims of sudden infant death syndrome (SIDS) suffer repetitive episodes of hypoxemia, only subtle abnormalities have been found in their brains by light microscopy. The aim of the present study was to determine whether apoptosis, a form of cell death that can be triggered by hypoxemia and that leaves no scarring detectable by light microscopy, would be present in hypoxia-sensitive brain regions of SIDS victims. We looked for the presence of apoptosis with an in situ end-labeling method that detects DNA fragmentation. We studied 29 SIDS victims who were age-matched to nine control cases. We found significant neuronal apoptosis in 79% of the SIDS cases: 55% of the cases positive in the hippocampus and 96% positive in the brainstem. Whereas the distribution of apoptosis in the hippocampus was in hypoxia-sensitive subregions, the distribution in the brainstem was mostly in dorsal nuclei, including those involved with sensation in the face and position of the head (nucleus of the spinal trigeminal tract and vestibular nuclei). The control cases showed no significant apoptosis in the hippocampus and a mild degree in the brainstem in three cases. Our results indicate the occurrence of an acute insult at least several hours before death, an insult from which the infants had apparently recuperated. This suggests that SIDS victims suffered repeated apoptosis resulting in significant neuronal damage and, thus, functional loss in key brain regions. The involvement of specific nuclei in the brainstem may be linked to the fact that prone sleeping is a significant risk factor for SIDS. Enhanced neuronal death by apoptosis may thus have major implications for understanding the sequence of events leading to SIDS.
The Journal of Pediatrics | 1998
Karen A. Waters; Patricia A. Forbes; Angela Morielli; Cindy Hum; Augustin M. O'Gorman; Olivier Vernet; G. Michael Davis; Ted L. Tewfik; Francine Ducharme; Robert T. Brouillette
BACKGROUND Although patients with myelomeningocele and the Chiari II malformation are known to have sleep apnea and respiratory control deficits, the prevalence, types, severities, and associations of sleep-disordered breathing (SDB) have not been adequately defined. METHODS A cross-sectional study of our myelomeningocele clinic population was undertaken to correlate polysomnographic results with historical data and findings from magnetic resonance imaging of the Chiari malformation, pulmonary function results, and nocturnal pulse oximetry. RESULTS A questionnaire survey of symptoms was available for 107 of 109 children (98% of the clinic population), and 83 patients agreed to undergo overnight polysomnography. Breathing during sleep was classified as normal in 31 cases (37%), mildly abnormal in 35 cases (42%), and moderately/severely abnormal in 17 cases (20%). Among the 17 patients with moderately/severely abnormal SDB, 12 patients had predominantly central apneas and 5 had predominantly obstructive apnea. Patients with a thoracic or thoracolumbar myelomeningocele, those who had previously had a posterior fossa decompression operation, those with more severe brain-stem malformations, and those with pulmonary function abnormalities were more likely to have moderately/severely abnormal SDB, relative risks (95% confidence intervals) 9.2 (2.9 to 29.3), 3.5 (1.3 to 8.9), 3.0 (0.9 to 10.5), and 11.6 (1.6 to 81.3), respectively. Failure of obstructive SDB to resolve after adenotonsillectomy in four patients suggested abnormal control of pharyngeal airway patency during sleep. Nocturnal pulse oximetry accurately predicted moderately/severely abnormal SDB with a sensitivity of 100% and a specificity of 67%. CONCLUSIONS The pathogenesis of SDB in patients with myelomeningocele involves the functional level of the spinal lesions, congenital and acquired brainstem abnormalities, pulmonary function abnormalities, disorders of upper airway maintenance, and sleep state. Polysomnography and nocturnal pulse oximetry should be performed in high-risk patients to detect and classify SDB.
Neurology | 2007
Helen Young; A. Lowe; Dominic A. Fitzgerald; C. Seton; Karen A. Waters; E. Kenny; Linda S. Hynan; Susan T. Iannaccone; Kathryn N. North; Monique M. Ryan
Objective: To assess the effect of institution of noninvasive ventilation (NIV) on clinical outcome and quality of life (QOL) in a cohort of children with severe neuromuscular disorders. Methods: We reviewed records and obtained clinical data from the year prior to commencing NIV and annually thereafter. Data obtained included diagnosis, patient symptoms, mortality, NIV adverse effects, pulmonary function tests, polysomnographic data, length of hospitalizations, and health care costs. Patients and parents completed questionnaires assessing QOL with NIV and recalling QOL before NIV. Results: Fourteen of 17 (82%) suitable patients were enrolled. Follow-up ranged from 6 to 84 months (median 30). Symptoms of daytime sleepiness (p = 0.003) and headache (p = 0.046) improved after initiation of NIV. Sleep quality assessed by polysomnography also improved. Hospitalization rates (p = 0.002) and health care costs (p = 0.003) decreased. QOL remained stable after NIV, despite disease progression. Conclusion: Treatment of respiratory failure, in children with neuromuscular disease, with noninvasive ventilation results in a reduction in symptoms, hospitalizations, and health care costs without adverse effects on quality of life.
Journal of Paediatrics and Child Health | 2006
Charmaine S. Tam; Melanie Wong; Rachel McBain; Sherryn Bailey; Karen A. Waters
Aim: To evaluate a range of inflammatory measures in children with obstructive sleep apnoea (OSA).
Journal of Sleep Research | 2007
Karen A. Waters; Benjamin T. Mast; Silvano Vella; Roland de la Eva; Louise O'Brien; Sherryn Bailey; Charmaine S. Tam; Melanie Wong; Louise A. Baur
Obstructive sleep apnea (OSA), often concomitant with obesity, increases the risk for the metabolic syndrome. One mechanism that may participate in this association is upregulation of inflammatory pathways. We used structural equation modeling to assess the interrelations between childhood obesity, OSA, inflammation, and metabolic dysfunction. One hundred and eighty‐four children (127 boys, mean age: 8.5 ± 4.1years) had height and weight measured, underwent overnight polysomnography and had fasting blood taken. The blood was analyzed for insulin, glucose, lipids, leptin, and cytokines [interferon (IFN)‐γ, granulocyte macrophage–colony stimulating factor, interleukin (IL)‐1β, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10, IL‐12, tumor necrosis factor‐α]. Structural equation modeling (SEM) was used to evaluate associations between the outcomes of interest including hypoxia, arousal (related to respiratory and spontaneous), obesity, metabolic dysfunction, and inflammatory markers. Two cytokine factors and one metabolic factor were derived for the SEM. These factors provided good fit in the structural equation model (χ2/df = 2.855; comparative fit index = 0.90, root mean squared error of approximation = 0.10) and all factor loadings were significantly different from zero (P ≤ 0.01). Overall, our results indicate that while obesity (as measured by body mass index z‐score) has a major influence on the metabolic dysfunction associated with OSA, arousal indices, and cytokine markers may also influence this association. Our results support the hypothesis that OSA is a contributor to the mechanisms that link sleep, systemic inflammation and insulin resistance, and show that the interrelations may begin in childhood.
Pediatric Pulmonology | 2000
Valerie G. Kirk; Angela Morielli; David Gozal; Carole L. Marcus; Karen A. Waters; Lynn A. D'Andrea; Carol L. Rosen; Marcel J. Deray; Robert T. Brouillette
The prevalence of moderate to severe sleep‐disordered breathing (SDB) in patients with myelomeningocele may be as high as 20%, but little information is available regarding treatment of these patients. To assess the efficacy and complications of treatments for these children, we collected data on 73 patients from seven pediatric sleep laboratories.
Archives of Disease in Childhood | 1993
Karen A. Waters; F Everett; D Sillence; E Fagan; C E Sullivan
Overnight sleep studies were performed in 20 subjects with achondroplasia to document further the respiratory abnormalities present in this group. Somatosensory evoked potentials (SEPs) were recorded in 19 of the subjects to screen for the presence of brainstem abnormalities, which are one of the potential aetiological mechanisms. Fifteen children aged 1 to 14 years, and five young adults, aged 20 to 31 years were included. All had upper airway obstruction and 15 (75%) had a pathological apnoea index (greater than five per hour). Other sleep associated respiratory abnormalities, including partial obstruction, central apnoea, and abnormal electromyographic activity of accessory muscles of respiration, also showed a high prevalence. SEPs were abnormal in eight (42%), but there was no correlation between abnormal SEPs and apnoea during sleep, either qualitatively or quantitatively. A high prevalence of both sleep related respiratory abnormalities and abnormal SEPs in young subjects with achondroplasia was demonstrated. However, the sleep related respiratory abnormalities do not always result in significant blood gas disturbances or correlate with abnormal SEPs in this group.
Neuroscience | 2005
Rita Machaalani; Karen A. Waters; Kellie D. Tinworth
Exposure to cigarette smoke is a risk factor for the sudden infant death syndrome (SIDS), but the ability to distinguish between the neuropathological effects of pre- versus postnatal exposure is limited in the clinical setting. To test whether postnatal nicotine exposure could contribute to the increased neuronal expression of apoptotic markers that we have previously observed in SIDS infants, as well as including study of gender influences, we developed a piglet model to mimic passive smoking in the early postnatal period. Piglets were exposed to nicotine (2 mg/kg/day infused via an implanted osmotic minipump) within 48 h of birth until the age of 13-14 days, when the brain was collected for study. Four piglet groups included: control females (n=7), control males (n=7), nicotine females (n=7), and nicotine males (n=7). Apoptotic markers included immunohistochemistry for activated caspase-3, and for DNA fragmentation or terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) in seven nuclei of the brainstem caudal medulla and two subregions of the hippocampus (CA4 and dentate gyrus). Among control females compared with males, there was less active caspase-3 and less TUNEL in the dorsal motor nucleus of vagus (DMNV), and there was less TUNEL in the nucleus of the spinal trigeminal tract (NSTT). Compared with controls, nicotine-exposed male piglets had increased TUNEL staining in the cuneate nucleus (P=0.05), and increased active caspase-3 in the hypoglossal, gracile and dentate gyrus (P<0.05 for each). Nicotine-exposed females showed no change in TUNEL staining in any of the nuclei studied, but increased active caspase-3 in the hypoglossal, DMNV and NSTT (P<0.05 for each). These results show for the first time that postnatal nicotine exposure can lead to an increase in apoptotic markers in the brain. In piglets, these effects showed regional and gender-specific differences, suggesting that passive, postnatal nicotine exposure may be responsible for some neuropathological changes observed in infants dying from SIDS.
International Journal of Pediatric Otorhinolaryngology | 2013
Matija Daniel; S. Bailey; Karen Walker; R. Hensley; C. Kol-Castro; Nadia Badawi; Alan Cheng; Karen A. Waters
OBJECTIVE Robin sequence (RS) is associated with airway abnormalities that result in functional problems of obstructive sleep apnoea (OSA), feeding difficulties, and consequent poor growth. We evaluated the relationships between OSA severity, airway and feeding interventions, and weight at 12 months in infants with RS and OSA. METHODS Retrospective notes review of children with RS managed at our neonatal unit (1998-2010, inclusive). RESULTS Of 39 infants studied, 10 (25.6%) had mild/moderate OSA, and 29 (74.4%) severe. Infants with severe OSA required more airway interventions in hospital (82.8 vs 30.0%, p = 0.004) and at discharge (72.4 vs 20.0%, p = 0.007) than those with mild/moderate OSA; 30.0% of infants with mild/moderate OSA required continuous positive airway pressure (CPAP) during admission and 20.0% on discharge, but amongst those with severe OSA 82.8% required airway interventions as an inpatient, 17.2% underwent mandibular distraction osteogenesis, and 55.2% required CPAP on discharge. Those with severe OSA were also more likely to require tube feeding on discharge (89.7 vs 50.0%, p = 0.02). Overall, children were on a lower weight centiles at discharge compared to birth (-10.2 centiles) and at 12 months of age compared to birth (-14.8 centiles), but this occurred irrespective of OSA severity or need for airway interventions or tube feeding. CONCLUSIONS Infants with RS commonly have OSA, feeding and airway difficulties. Weight at 12 months appeared not to be influenced by OSA severity, feeding or airway problems, suggesting that current intervention/management strategy results in the severely affected infants growing as well as those affected less severely.
Archives of Disease in Childhood | 2012
Joanna E. MacLean; David A. Fitzsimons; Dominic A. Fitzgerald; Karen A. Waters
Objective To determine the prevalence of sleep-disordered breathing (SDB) symptoms and respiratory events during sleep in infants with cleft lip and/or palate (CL/P). Design Prospective observational study. Setting Cleft palate clinic, tertiary care paediatric hospital, before palate surgery. Patients Consecutive newborn infants with CL/P. Main outcome measures Demographics, clinical history, sleep symptoms, facial measurement and polysomnography (PSG; sleep study) data. Results Fifty infants completed PSG at 2.7±2.3 months; 56% were male, and 30% had a clinical diagnosis of Pierre Robin sequence (PRS) or a syndrome. The majority of infants (75%) were reported to snore frequently or constantly, while 74% were reported to have heavy or loud breathing during sleep. The frequency of parent-reported difficulty with breathing during sleep was 10% for infants with isolated CL/P, 33% for those with syndrome, and 43% for PRS (χ2 16.1, p<0.05). All infants had an Obstructive–Mixed Apnoea–Hypopnoea Index (OMAHI) >1 event/h, and 75% had an OMAHI >3 events/h. Infants with PRS had higher OMAHI (34.3±5.1) than infants with isolated CL/P (7.6±1.2) or infants with syndromes (15.6±5.7, F stat, p<0.001). Multivariate analysis showed that PRS was associated with higher OMAHI (B 0.53±0.22, p=0.022), but the majority of the variance for SDB was unexplained (constant B 1.31±0.55, p=0.024). Conclusions The results highlight that infants across the spectrum of CL/P have a high risk of SDB symptoms and obstructive respiratory events before palate surgery. Clinicians should enquire about symptoms of SDB and consider investigation with polysomnography in all infants with CL/P.