%0 Journal Article %~ PubMed %A Daniel, M %A Bailey, S %A Walker, K %A Hensley, R %A Kol-Castro, C %A Badawi, N %A Cheng, A %A Waters, K %T Airway, feeding and growth in infants with Robin sequence and sleep apnoea. %B International Journal of Pediatric Otorhinolaryngology %D 2013 %C Ireland %I Elsevier Ltd %V 77 %N 4 %P 499-503 %@ 1872-8464 %X %Z FOR Codes: 111403 110315 %0 Journal Article %~ PubMed %A Maclean, Joanna E %A Tan, Sara %A Fitzgerald, Dominic A %A Waters, Karen A %T Assessing ventilatory control in infants at high risk of sleep disordered breathing: A study of infants with cleft lip and/or palate. %B Pediatric Pulmonology %D 2013 %C United States %I John Wiley & Sons, Inc. %V 48 %N 3 %P 265-273 %@ 8755-6863 %X Neonatal exposure to intermittent hypoxia results in altered ventilatory response to subsequent hypoxia in animal models. The effect of similar exposure in human infants is unknown. Our objective was to determine the impact of sleep disordered breathing (SDB) in early infancy on ventilatory response in infants. We recruited consecutive infants with cleft lip and/or palate (CL/P) to undergo ventilatory response testing using exposure to a hypoxic (15% O(2) ) gas mixture during sleep. This population is at high risk of SDB because of smaller airway caliber and abnormal palatal muscle attachments predisposing them to airway obstruction of ranging severity from birth. Ventilatory responses were compared between infants with a low apnea-hypopnea index (AHI; AHI???3 were demonstrated on chromosome 19q13.4 (LOD = 3.04) for the trait pair RDI and HDL cholesterol. Candidate genes identified in this region include the killer cell immunoglobulin-like receptor genes. These genes are associated with modulating inflammatory responses in reaction to cellular stress and initiation of atherosclerotic plaque formation. We have identified a novel locus for genetic links between RDI and lipid factors associated with MeS in a chromosomal region containing genes associated with inflammatory responses. %Z FOR Codes: 60405 110203 %0 Journal Article %~ PubMed %A Tang, Samantha %A Machaalani, Rita %A Waters, Karen A %T Immunolocalisation of pro- and mature- brain derived neurotrophic factor (BDNF) and receptor TrkB in the human brainstem and hippocampus. %B Brain research %D 2010 %C Netherlands %I Elsevier BV %V 1354 %N %P 1-14 %@ 0006-8993 %X Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are essential in promoting normal development of the central nervous system. Specific functions that are affected in knockout models include respiratory control, coordination of movement and balance, and feeding activities. The expression of these markers has not yet been studied in the human infant brain. This study provides a detailed account of the distribution and localization of both pro- and mature-recombinant human (rh) forms of BDNF, and of TrkB in the human infant brainstem and hippocampus, and qualitatively compares this expression to that seen in the human adult. Using commercially available antibodies, we applied immunohistochemistry on formalin fixed and paraffin embedded human brain tissue [n=8 for infant, n=6 for adult], and qualitatively analyzed the expression of proBDNF, rhBDNF and TrkB. Amongst the brainstem regions studied, the greatest expression of the markers was in the mesencephalic trigeminal of the pons, and in the medulla, the inferior olive and arcuate nucleus. The lowest expression was in the substantia nigra of the midbrain and pontine locus coeruleus. Compared to adults, all the studied markers had a higher expression in the infant brainstem nuclei of the hypoglossal, vestibular, dorsal motor nucleus of the vagus, prepositus, cuneate, and dorsal raphe. In the hippocampus, only TrkB showed a higher expression in infants compared to adults. We conclude that BDNF and TrkB play important roles in controlling respiration, movement, balance and feeding in the brainstem and that the TrkB receptor is the most age-sensitive component of this system, especially in the hippocampus. %Z FOR Codes: 110903 %0 Journal Article %~ PubMed %A Waters, Karen %T Serotonin in the sudden infant death syndrome. %B Drug News & Perspectives %D 2010 %C Spain %I Prous Science %V 23 %N 9 %P 537-548 %@ 0214-0934 %X It seems likely that some infants who die from sudden infant death syndrome (SIDS) have a brainstem abnormality of the serotonergic system. Evidence suggests that infants who died from SIDS had defective respiratory and/or autonomic responses that led to death instead of recovery after an acute insult. The serotonergic neuromodulator system has roles in the control of cardiac autonomic and respiratory function, as well as now being identified as abnormal in infants with SIDS. This manuscript reviews the multiple roles of serotonin with reference to the functional aspects of the relevant brain regions. Correlations with pre- or postnatal exposure to stressors, or an underlying genetic process are also reviewed. Together, these studies indicate that perturbed function of the serotonin system will have significant physiological impact during early development. Understanding the functional importance of these systems assists understanding of the pathogenesis of SIDS. In conclusion, whether an infant inherits serotonergic defects and is therefore "inherently vulnerable", or whether postnatal stressors can induce the abnormalities, any functional abnormalities of the serotonergic system that result are likely to be subclinical in the majority of cases and not easily detected with current medical tools. %Z FOR Codes: 111403 111599 %0 Journal Article %~ PubMed %A Waters, Karen A %A Cheng, Alan T L %T Adenotonsillectomy in the context of obstructive sleep apnoea. %B Paediatric Respiratory Reviews %D 2009 %C United Kingdom %I Elsevier Ltd %V 10 %N 1 %P 25-31 %@ 1526-0542 %X Adenotonsillectomy (T&A) is a common surgical procedure. Its frequency is highest in the paediatric age range and its most common current indication is obstructive sleep apnoea (OSA). Sleep studies are used to document the presence and severity of OSA. This review will focus on indications for and complications of T&A in the context of the age range and setting where this surgery is undertaken for OSA in children. %Z FOR Codes: 111403 %0 Journal Article %~ PubMed %A Maclean, Joanna E %A Hayward, Peter %A Fitzgerald, Dominic A %A Waters, Karen %T Cleft lip and/or palate and breathing during sleep. %B Sleep medicine reviews %D 2009 %C France %I Elsevier Masson %V 13 %N 5 %P 345-54 %@ 1087-0792 %X Cleft of the lip and/or palate (CL/P) is a common defect which is associated with changes in facial structures and a smaller upper airway. As a result, infants and children with CL/P have an increased risk of sleep disordered breathing (SDB). This paper will review the anatomical and functional factors which place infants and children with CL/P at increased risk of SDB as well as review the literature which defines the magnitude of this risk. The information available on treatment of SDB in infants and children with CL/P will be presented. Finally, outstanding issues relevant to SDB in children with CL/P are discussed with direction for future research. %Z FOR Codes: 111403 %0 Journal Article %~ PubMed %A Tang, Samantha %A Machaalani, Rita %A Kashem, Mohammad %A Matsumoto, Izuru %A Waters, Karen %T Intermittent Hypercapnic Hypoxia Induced Protein Changes in the Piglet Hippocampus Identified by MALDI-TOF-MS. %B Neurochemical research %D 2009 %C United States %I Springer New York LLC %V 34 %N 12 %P 2215-25 %@ 1573-6903 %X Intermittent hypercapnic hypoxia (IHH) induces protein changes in the brainstem, but its effects on the hippocampus have not yet been studied. Using a proteomics-based approach, we tested the hypothesis that IHH up-regulates apoptotic promoters and down-regulates apoptotic inhibitors in the developing hippocampus. Male piglets aged 13-14 days were assigned to control (n = 6) or IHH (n = 5) groups. Using two-dimensional polyacrylamide gel electrophoresis, matrix-assisted laser desorption/ionisation-time of flight-mass spectrometry (MALDI-TOF-MS), a total of 26 protein spots were differentially expressed in IHH compared to control group. Thirteen of these (6 up-regulated, 7 down-regulated) were identified including 14-3-3??/?? (increased), glial fibrillary acidic protein (increased) and a-internexin (decreased). Further analysis with western blot validated these proteins and immunohistochemistry showed specific regional changes in the subiculum, stratum radiatum and CA1 of the hippocampus. Most proteins identified were involved in promoting cell survival under apoptotic conditions. These findings improve our understanding of the cellular processes that occur in the hippocampus during IHH exposure, and have important implications in clinical settings where IHH is experienced, for example, during prone sleeping or with obstructive sleep apnea in an infant. %Z FOR Codes: 110903 %0 Journal Article %~ PubMed %A Maclean, J E %A Waters, K %A Fitzsimons, D %A Hayward, P %A Fitzgerald, D A %T Screening for obstructive sleep apnea in preschool children with cleft palate. %B The Cleft palate-craniofacial journal %D 2009 %C United States %I Allen Press Inc. %V 46 %N 2 %P 117-123 %@ 1055-6656 %X Objective: The objective of this study was to explore the prevalence, range of reported symptoms, and clinical risk factors of obstructive sleep apnea in preschool children with cleft lip and/or palate. Design: Questionnaires were distributed to parents/guardians of all children from birth to 5 years of age who were followed by the cleft clinic. Results: Questionnaire data and cleft classification were available for 248 children, with a mean age of 33.4 months. Obstructive sleep apnea was identified in 31.4% of the children. Only 29.5% of children with obstructive sleep apnea had undergone an investigation of these symptoms. The three most common symptoms reported in children with a questionnaire diagnosis of obstructive sleep apnea were (1) "heavy or loud breathing," (2) "easily distracted," and (3) "on the go" or "driven by a motor." The only clinical risk factor associated with a questionnaire diagnosis of obstructive sleep apnea was the presence of a syndrome (chi(2) = 3.5, p = .05). There were no significant differences in risk of obstructive sleep apnea by age, cleft classification, and surgical status. Conclusion: Preschool children with cleft lip and/or palate have a risk of obstructive sleep apnea that is as much as five times that of children without cleft. Obstructive sleep apnea appears to be underrecognized in this group of children. Further research is needed to investigate important risk factors for obstructive sleep apnea in children with cleft lip and/or palate. %Z FOR Codes: 1114 %0 Journal Article %~ PubMed %A Machaalani, Rita %A Say, Meichien %A Waters, Karen %T Serotoninergic receptor 1A in the sudden infant death syndrome brainstem medulla and associations with clinical risk factors. %B Acta neuropathologica %D 2009 %C Germany %I Springer %V 117 %N 3 %P 257-65 %@ 1432-0533 %X The immunoreactivity of the serotoninergic receptor subtype 1A (5HT(1A)R) was quantitatively analyzed in the human infant brainstem medulla (caudal and rostral levels). We hypothesized that immunoreactivity of 5HT(1A)R would be reduced in infants diagnosed with sudden infant death syndrome (SIDS). In particular that those infants with known clinical risk factors (including cigarette smoke exposure, bed sharing and sleep position) would have greater changes than those without clinical risks. Comparing SIDS (n = 67) to infants who died suddenly with another diagnosis (non-SIDS, n = 25), we found decreased 5HT(1A)R immunoreactivity in the majority of the nuclei studied at the rostral medulla level including dorsal motor nucleus of the vagus (DMNV), nucleus of the solitary tract, vestibular, and inferior olivary nucleus (ION). There was a significant relationship with all risk factors for 5HT(1A)R, especially for DMNV, suggesting that 5HT(1A)Rs are highly vulnerable to various insults within the SIDS DMNV. This study not only provides further evidence of abnormalities within the brainstem serotoninergic system of SIDS infants, but also shows that these changes may be associated with exposure to clinical risk factors. %Z FOR Codes: 110903 %0 Journal Article %~ PubMed %A Browne, Cherylea J %A Sharma, Nidhi %A Waters, Karen A %A Machaalani, Rita %T The effects of nicotine on the alpha-7 and beta-2 nicotinic acetycholine receptor subunits in the developing piglet brainstem. %B International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience %D 2009 %C United Kingdom, Cana %I Pergamon %V 28 %N 0 %P 1-7 %@ 1873-474X %X Exposure to cigarette smoke is a major risk factor for sudden infant death syndrome (SIDS). We tested the hypothesis that nicotine increases expression of the nicotinic acetylcholine receptor (nAChR) subunits alpha7 and beta2 in a piglet model. Piglets exposed to 2mg/kg/day nicotine for 14 days postnatally (n=14) were compared to non-exposed controls (n=14), (equal gender proportions). Immunohistochemistry was performed to identify and quantify changes in, alpha7 and beta2 nAChR subunits in 8 nuclei of the medulla at both the rostral and caudal levels. Compared to controls, nicotine exposed piglets had decreased alpha7 in the rostral dorsal motor nucleus of the vagus (rDMNV) (p=0.01), and increased beta2 in the caudal DMNV (cDMNV) (p=0.05), caudal nucleus of the spinal trigeminal tract (cNSTT) (p=0.03) and caudal nucleus of the solitary tract (cNTS) (p=0.04). Analysis by gender showed that in the control group, compared to males, females had higher beta2 in the caudal hypoglossal (cXII) (p<0.01) and caudal inferior olivary (p=0.04) nuclei, while in the nicotine group females had higher beta2 in the cDMNV (p=0.02). Compared to control males, nicotine exposed males had lower beta2 in the cXII (p<0.01). Overall, changes in alpha7 were specific to nicotine exposure with no gender differentiation. Changes in beta2 were more widespread but showed gender-specific effects. These findings provide evidence that early postnatal exposure to nicotine significantly affects nAChR subunit expressions in the developing brainstem. %Z FOR Codes: 110903 60603 %0 Journal Article %~ PubMed %A Robinson, P D %A Waters, K %T Are children just small adults? The differences between paediatric and adult sleep medicine. %B Internal medicine journal %D 2008 %C Australia %I Blackwell Publishing Asia %V 38 %N 0 %P 719-31 %@ 1444-0903 %X Several important physiological and maturational changes occur in sleep development during the paediatric age range, particularly during infancy and in early childhood. As the pathology of sleep apnoea is superimposed onto a developing and often plastic physiological system, children often show a different pathophysiology to their adult counterparts. These factors need to be incorporated into the evaluation of a child''s sleep problems. Particular attention should be paid to the developmental stage of the child. Investigation, interpretation and subsequent management provide further unique challenges and during successive reviews predicted normal changes must also be taken into account. This review article discusses the important physiological and maturational changes that occur in sleep during childhood, some common paediatric sleep conditions and their presentation and the appropriate evaluation and management of these conditions. In the course of the discussion, we have stressed important differences between paediatric and adult sleep medicine. %Z FOR Codes: 1114 %0 Journal Article %~ PubMed %A Tang, Samantha %A Machaalani, Rita %A Waters, Karen A %T Brain-derived neurotrophic factor (BDNF) and TrkB in the piglet brainstem after post-natal nicotine and intermittent hypercapnic hypoxia. %B Brain research %D 2008 %C Netherlands %I Elsevier BV %V 1232 %N 1232 %P 195-205 %@ 0006-8993 %X Brain-derived neurotrophic factor (BDNF) and its receptor TrkB play a significant role in the regulation of cell growth, survival and death during central nervous system development. The expression of BDNF and TrkB is affected by noxious insults. Two insults during the early post-natal period that are of interest to our laboratory are exposure to nicotine and to intermittent hypercapnic hypoxia (IHH). Piglet models were used to mimic the conditions associated with the risk factors for the sudden infant death syndrome (SIDS) including post-natal cigarette smoke exposure (nicotine model) and prone sleeping where the infant is subjected to re-breathing of expired gases (IHH model). We aimed to determine the effects of nicotine and IHH, alone or in combination, on pro- and rhBDNF and TrkB expression in the developing piglet brainstem. Four piglet groups were studied, with equal gender ratios in each: control (n=14), nicotine (n=14), IHH (n=10) and nic+IHH (n=14). Applying immunohistochemistry, and studying six nuclei of the caudal medulla, we found that compared to controls, TrkB was the only protein significantly decreased after nicotine and nic+IHH exposure regardless of gender. For pro-BDNF and rhBDNF however, observed changes were more evident in males than females exposed to nicotine and nic+IHH. The implications of these findings are that a prior nicotine exposure makes the developing brainstem susceptible to greater changes in the neurotrophic effects of BDNF and its receptor TrkB in the face of a hypoxic insult, and that the effects are greater in males than females. %Z FOR Codes: 110903 %0 Journal Article %~ PubMed %A Aouad, Leyla J %A Tam, Kim %A Waters, Karen A %T Effects of acute intermittent hypercapnic hypoxia on insulin sensitivity in piglets using euglycemic clamp. %B Metabolism: clinical and experimental %D 2008 %C United States %I WB Saunders Co. %V 57 %N 8 %P 1056-1063 %@ 0026-0495 %X Continuous hypoxia is associated with insulin resistance, altered glucose metabolism, and increased sympathetic nervous activity. This study examined the effect of 2 successive exposures to intermittent hypercapnic hypoxia (IHH) on glucose metabolism and insulin sensitivity in neonatal piglets. Piglets were assigned to 2 groups. One group was exposed to 2 x 90 minutes of hypercapnic hypoxia (8% O(2), 7% CO(2)), intermittently in 6-minute cycles alternating with 6-minute air. The second group was given 2 x 90 minutes of air. Blood pressure, blood gases, glucose, insulin, and lactate were measured during exposures. Insulin sensitivity was assessed using the euglycemic clamp before and after the exposures. Piglets in the IHH group exhibited reduced PO(2) (from 111.4 +/- 14.2 to 43.3 +/- 21.7), increased PCO(2) (from 33.6 +/- 1.9 to 49.4 +/- 5.4), and lactic acidosis. Compared with air, IHH decreased blood glucose (control [CON] 4.44 +/- 0.72 mmol/L vs IHH 2.67 +/- 1.2 mmol/L, P = .007), insulin (CON 12.5 +/- 7.4 muU/mL vs IHH 3.6 +/- 3.1 muU/mL, P = .03), and mean arterial pressure (CON 143.0 +/- 7.9 mm Hg vs IHH 112.5 +/- 9.5 mm Hg, P < .001) over 90 minutes. Maximal insulin-stimulated glucose disposal was not different between the groups on either day, nor was endogenous glucose production. Overall, exposure to hypoxia in an intermittent pattern reduced sympathetic drive as indicated by blood pressure and did not alter insulin sensitivity, resulting in decreases in blood glucose and insulin. We speculate that an intermittent hypoxic stimulus results in failure of initiation of compensatory responses to increased energy requirements that would usually be observed during sustained exposure to hypoxia. %Z FOR Codes: 110306 %0 Journal Article %~ PubMed %A Waters, Karen %T Interventions in the paediatric sleep laboratory: the use and titration of respiratory support therapies. %B Paediatric respiratory reviews %D 2008 %C United Kingdom %I WB Saunders Co. Ltd. %V 9 %N 3 %P 181-191 %@ 1526-0542 %X 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 airway pressure and non-invasive ventilation. Ventilation may be with either pressure or volume cycle devices. Overnight PSG is used for the titration and monitoring of these treatments since all these forms of respiratory support require regular adjustment to match patient requirements. The methods for titration and goals of optimal therapy in the paediatric sleep laboratory are discussed. %Z FOR Codes: 111403 110203 %0 Journal Article %~ PubMed %A Machaalani, Rita %A Waters, Karen A %T Neuronal cell death in the Sudden Infant Death Syndrome brainstem and associations with risk factors. %B Brain %D 2008 %C United Kingdom %I Oxford University Press %V 131 %N Pt 1 %P 218-228 %@ 1460-2156 %X Immunoreactive expression of three cell death markers was quantitatively analysed in the human infant brainstem medulla. We assessed active caspase-3, TUNEL and single-stranded DNA (ssDNA) in a cohort of 92 infants, and analysed for: (i) variations in the immunoreactive expression with development; (ii) comparison of infants diagnosed with the Sudden Infant Death Syndrome (SIDS, n = 67) to infants who died suddenly with another diagnosis (non-SIDS, n = 25); and (iii) correlations with known clinical risk factors for SIDS. Five nuclei from the brainstem medulla (caudal and rostral levels) were studied, including the hypoglossal (XII), dorsal motor nucleus of the vagus (DMNV), the dorsal column nuclei (gracile and cuneate) and the arcuate nucleus. Our main hypothesis was that neuronal cell death would be increased in SIDS compared to non-SIDS infants, and the increase would correlate with risk factors such as prone sleeping and cigarette smoke exposure. Comparing SIDS to non-SIDS, there was an increase in caspase-3 in the rostral DMNV (P = 0.01), and a trend to increased TUNEL in the arcuate nucleus (P = 0.1), which was statistically significant when comparing the male SIDS to male non-SIDS cohort (P = 0.04). No major changes for ssDNA immunoreactivity were found. Moreover, TUNEL expression was affected by post-conceptional age, by sleep-related risk factors (predominantly affecting the dorsal column nuclei), and by cigarette smoke exposure in the rostral DMNV and arcuate nucleus. Active caspase-3 was affected by post-conceptional age but only in the XII, while gender-related differences were seen in the arcuate nucleus. This study provides further evidence of increased apoptosis in the brainstem of SIDS infants, but shows for the first time that these changes are also affected by age and gender, and by clinical risk factors such as the sleep position and cigarette smoke exposure. %Z FOR Codes: 110903 111403 %0 Journal Article %~ PubMed %A MacLean, J E %A Fitzsimons, D %A Hayward, P %A Waters, K A %A Fitzgerald, D A %T The identification of children with cleft palate and sleep disordered breathing using a referral system. %B Pediatric pulmonology %D 2008 %C United States %I John Wiley & Sons Inc %V 43 %N 3 %P 245-250 %@ 8755-6863 %X BACKGROUND: Cleft palate is associated with an increased risk of sleep disordered breathing (SDB) but the magnitude of this risk and specific risk factors are unclear. A better understanding of these components of risk will aid the early identification of SDB in this group of children. OBJECTIVE: To describe the clinical characteristics and results of sleep studies undertaken in a cohort of children with cleft palate. Clinical features will be examined to determine potential associations with SDB in this group. METHOD: A retrospective chart review was undertaken to ascertain sleep study results and clinical data for all children with cleft palate. Clinical features of interest included age, gender, syndrome diagnosis, cleft classification, and surgical status. RESULTS: A total of 99 sleep studies were available from 62 children. The sample included a select group of children with cleft palate with features predictive of a high risk of SDB. Baseline sleep study results were consistent with SDB for 87% of children and 28% (15 of 54) of these children demonstrated severe SDB. Uni-variate analysis showed that age, syndrome, and surgical status had significant association with the severity of SDB. On multi-variate analysis only surgical status maintained this association, such that pre-palatoplasty/pharyngoplasty was associated with more severe SDB. Follow-up studies were completed in one-third of the cohort. CONCLUSION: Children with cleft palate appear to have a significant risk of SDB. A prospective study of a population of children with cleft palate is needed to further define the characteristics of this risk and important risk factors. %Z FOR Codes: 1114 %0 Journal Article %~ PubMed %A Machaalani, Rita %A Arlotto, Marie %A Waters, Karen A %A Gozal, Evelyne %A Berger, François %A Dematteis, Maurice %T A Novel Method of Tissue Collection and Storage: Validation Using SELDI-TOF MS Analysis. %B Clinical chemistry %D 2007 %C United States %I American Association of Clinical Chemistry %V 53 %N 7 %P 1387-1389 %@ 0009-9147 %X %Z FOR Codes: 110106 %0 Journal Article %~ PubMed %A Machaalani, R %A Rodriguez, M %A Waters, K A %T Active caspase-3 in the sudden infant death syndrome (SIDS) brainstem. %B Acta neuropathologica %D 2007 %C Germany %I Springer %V 113 %N 5 %P 577-584 %@ 0001-6322 %X In a retrospective postmortem study, we examined the neuronal expression of active caspase-3, a specific apoptotic marker, in the brainstem of 67 infants dying from sudden infant death syndrome (SIDS), and 25 age-matched control infants (non-SIDS). Neuronal immunostaining for active caspase-3 was semi-quantitatively scored in nuclei from five brainstem levels: rostral, mid and caudal pons, and rostral and caudal medulla. Regardless of the cause of death (SIDS vs. non-SIDS), age-related differences in active caspase-3 expression were identified, predominantly in the medulla. No gender-related differences were identified. Comparing SIDS to non-SIDS cases, increased active caspase-3 expression was restricted to four nuclei in the caudal pons (abducens, facial, superior olivary, and pontine nuclei) and two nuclei in the rostral medulla (hypoglossal and dorsal motor nucleus of the vagus). We conclude that neuronal apoptosis is increased in the brainstem of SIDS compared to non-SIDS infants. %Z FOR Codes: 110903 %0 Journal Article %~ PubMed %A Say, Meichien %A Machaalani, Rita %A Waters, Karen A %T Changes in serotoninergic receptors 1A and 2A in the piglet brainstem after intermittent hypercapnic hypoxia (IHH) and nicotine. %B Brain research %D 2007 %C Osney Mead, Oxford, %I Elsevier Science %V 1152 %N %P 17-26 %@ 0006-8993 %X We studied the effects of intermittent hypercapnic hypoxia (IHH) and/or nicotine on the immunoreactivity of serotoninergic (5-HT) receptors 1A and 2A in the piglet brainstem. These exposures were developed to mimic two common risk factors for Sudden Infant Death Syndrome (SIDS); prone sleeping (IHH) and cigarette smoke exposure (nicotine). Immunoreactivity for 5-HT(1A)R and 5-HT(2A)R were studied in four nuclei of the caudal medulla. Three exposure groups were compared to controls (n=14): IHH (n=10), nicotine (n=14), and nicotine+IHH (n=14). In control piglets, the immunoreactivity of 5-HT(1A)R was highest in the hypoglossal nucleus (XII), followed by inferior olivary nucleus (ION), nucleus of the solitary tract (NTS) and dorsal motor nucleus of the vagus (DMNV), whereas for 5-HT(2A)R, the immunoreactivity was highest in DMNV/NTS and then ION. Compared to controls, IHH reduced 5-HT(1A)R immunoreactivity in all studied nuclei (p<0.05) but had no effect on 5-HT(2A)R immunoreactivity. Nicotine reduced 5-HT(1A)R immunoreactivity in the DMNV, ION and NTS (p<0.001), and reduced 5-HT(2A)R immunoreactivity in DMNV/NTS (p<0.05). Nicotine+IHH reduced 5-HT(1A)R in DMNV, ION and NTS (p<0.001) but had no effect on 5-HT(2A)R immunoreactivity. Effects of nicotine on the DMNV were more significant in males compared to the females. These results show for the first time that IHH and/or nicotine can reduce 5-HT receptor immunoreactivity within functionally important nuclei of the piglet medulla. The findings support our hypothesis that 5-HT receptor abnormalities may be caused by postnatal exposures to clinically-relevant stimuli such as cigarette smoke exposure and/or prone sleeping. %Z FOR Codes: 110903 %0 Journal Article %~ PubMed %A Young, H K %A Lowe, A %A Fitzgerald, D A %A Seton, C %A Waters, K A %A Kenny, E %A Hynan, L S %A Iannaccone, S T %A North, K N %A Ryan, M M %T Outcome of noninvasive ventilation in children with neuromuscular disease. %B Neurology %D 2007 %C US %I Lippincott Williams & Wilkins %V 68 %N 3 %P 198-201 %@ 0028-3878 %X 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. %Z FOR Codes: 110904 110203 %0 Journal Article %~ PubMed %A Waters, Karen A %A Mast, Benjamin T %A Vella, Silvano %A De La Eva, Roland %A O'Brien, Louise M %A Bailey, Sherryn %A Tam, Charmaine S %A Wong, Melanie %A Baur, Louise A %T Structural equation modeling of sleep apnea, inflammation, and metabolic dysfunction in children. %B Journal of sleep research %D 2007 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 16 %N 4 %P 388-395 %@ 0962-1105 %X 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)-gamma, granulocyte macrophage-colony stimulating factor, interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor-alpha]. 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 (chi(2)/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