Biomedical subjects

Louise M O'Brien

Publications and source records attributed to Louise M O'Brien.

At least 19 recordsLinked to original sources

PubMed2007

Hypoxemia and obesity modulate plasma C-reactive protein and interleukin-6 levels in sleep-disordered breathing.

C-reactive protein (CRP) and interleukin-6 (IL-6) are pro-inflammatory proteins and important risk factors for atherosclerosis. Plasma CRP levels in snoring children may or may not be elevated. Since obesity is prevalent among snoring children and is associated with elevated CRP levels, we aimed to investigate the relative contributions of sleep-disordered breathing (SDB) and obesity to the inflammatory processes in snoring children in this prospective study. Two hundred forty-four children (mean age 8.9 +/- 3.4 years) underwent polysomnographic evaluation. CRP was measured the following morning, and plasma IL-6 levels from 111 randomly selected children were also examined. Plasma CRP and IL-6 levels were elevated in children with SDB. Log plasma CRP levels were higher in the moderate-severe SDB group (apnea/hypopnea index, AHI > or = 5) compared to the mild SDB group (AHI > or = 1 and <5; p < 0.0001) or the control group (AHI < 1; p = 0.0001). Log plasma CRP levels correlated with AHI, arousal index, relative BMI, and SpO(2) nadir (r = 0.30, p < 0.0001; r = 0.21, p = 0.002; r = 0.39, p < 0.0001, r = -0.36, p < 0.0001, respectively). Log plasma CRP levels were lower in children with SpO(2) nadir > or =90 (p < 0.0001). Sub-analysis of the 116 non-obese children in the cohort revealed similar findings. Log plasma IL-6 levels were increased in children with moderate-severe SDB compared to controls (p = 0.03) and correlated with AHI (r = 0.28, p = 0.003) and SpO(2) nadir (r = -0.24, p = 0.02). Children with SDB display significant severity-dependent increases in plasma CRP and IL-6 levels independent of obesity.

Adolescent↗

PubMed2006

Obesity increases the risk for persisting obstructive sleep apnea after treatment in children.

OBJECTIVE: To evaluate the impact of obesity at diagnosis on treatment outcomes in paediatric obstructive sleep apnea (OSA). METHODS: Children were included if they had both diagnostic and follow-up studies for OSA. Anthropological and polysomnographic data were collected at the time of both studies. Polysomnograms were scored using standard criteria and OSA was defined as a respiratory disturbance index (RDI) >or=5. Obesity was defined as a body mass index standard deviation (z-)score (BMIsds) greater than 2, adjusted for age and gender. RESULTS: For 69 children (49 males), mean age was 7.1+/-4.2 years and 29 (42%) children were obese. There was no significant difference in RDI between obese and non-obese children at diagnostic study. Following adenotonsillectomy the obese children had a significantly higher mean RDI (10.7+/-15.6 versus 3.7+/-4.3; p=0.01). Disease resolution occurred in 77.5% of non-obese compared to 45% of obese children (p=0.011). The odds ratio (OR) for persistent OSA in obese compared to non-obese children was 4.2 (95% CI: 1.5-11.9; p=0.005). Using initial RDI as a covariate, these data show that obesity in children has an adjusted OR for persistent OSA after adenotonsillectomy 3.7 (95% CI: 1.3-10.8, p=0.016). CONCLUSION: For children, obesity at the time of diagnosis is a major risk for persisting OSA after treatment, regardless of the severity of initial disease.

Adenoidectomy↗

PubMed2006

Multidimensional scaling of pediatric sleep breathing problems and bio-behavioral correlates.

STUDY OBJECTIVES: Complex relationships exist between pediatric sleep disorders and daytime behavior. Using a multidimensional scaling model, we investigated these relationships in 126 children with sleep breathing disorders (SBD). METHOD: Validated questionnaires on nighttime behavior, daytime behavior, and respiratory health were administered to a large number of school children in Belgium. Children who met the criterion of having at least one sleep-related breathing problem (three or more times per week during the past six months) were selected for further analyses. A total of 26 indicators were defined and modeled, including sleep problems, sleep efficiency, sleep environment, sleep enuresis, internalised and externalised behavioral problems, respiratory health of the child and relatives, smoking exposure, and caffeine consumption. RESULTS: From 3,045 questionnaire responses 4.1% of the children were reported to have a SBD symptom. SBD children differed on sleep and health domains from non-SBD children. Furthermore, through scaling of the (dis)similarities among the 26 indicators the SBD child was able to be modeled. By way of an internal analysis of the data-matrix the following indicators were eliminated: sleep correlates, health of the family, and behavior rated by teachers, followed by caffeine intake, drugs, and behavior rated by the parents. This revealed a two-dimensional model, consisting of primary SBD and secondary SBD. CONCLUSION: Children with SBD differ on many domains from children without such disorders and an underlying two-fold SBD concept was found. Firstly, the SBD-indicator positioned in between investigated correlates with disorders of initiating and maintaining sleep and sleep hyperhydrosis on one hand and with respiratory-related illnesses on the other; this was labeled primary SBD. Secondly, the SDB-indicator not closely associated with any of the investigated correlates can be interpreted as secondary SBD.

Child↗

PubMed2006

Reciprocal interactions between spontaneous and respiratory arousals in adults with suspected sleep-disordered breathing.

BACKGROUND AND PURPOSE: Excessive daytime sleepiness (EDS) is a major consequence of sleep-disordered breathing (SDB) in adults. In snoring children, spontaneous and respiratory arousals display reciprocal interactions, allowing for development of a new quantitative measure, the sleep pressure score (SPS), which provides intra-polysomnographic estimates of sleep pressure/disruption. The aim of the present study was to assess the interactions between respiratory and spontaneous arousals in adults with suspected SDB, and to examine whether the SPS and the Epworth sleepiness scale (ESS) are correlated. PATIENTS AND METHODS: Retrospective chart review of 530 adult patients who underwent polysomnographic evaluation for suspected SDB in two medical centers was performed. Polysomnographic studies reports, patients' demographics and ESS scores were reviewed. RESULTS: Spontaneous and respiratory arousal indices and the apnea-hypopnea index (AHI) displayed negative and positive correlations respectively (r=-0.25, r=0.97, P<0.0001) indicating reciprocal interactions between respiratory and spontaneous arousals during sleep. The AHI corresponding to the SPS at which the respiratory arousal/total arousal fraction exceeded the spontaneous arousal/total arousal fraction occurred at approximately 14/h of total sleep time (TST) (compared to 7/h TST in children) (P<0.001). No correlation was found between SPS values and ESS scores. CONCLUSIONS: As in children, snoring adults exhibit reciprocal interactions between respiratory and spontaneous arousals that can also be expressed as a single quantitative measure, the SPS, which is highly dependent on the severity of SDB and could possibly serve as a more reliable index of sleep disruption, considering that the ESS is unrelated to either SPS or AHI.

Adult↗

PubMed2006

Persistence of obstructive sleep apnea syndrome in children after adenotonsillectomy.

OBJECTIVE: To investigate the relative contribution of various risk factors to the surgical outcome of adenotonsillectomy for obstructive sleep apnea syndrome in children. STUDY DESIGN: Children (n = 110; mean age, 6.4 +/- 3.9 years) underwent two polysomnographic evaluations before and after adenotonsillectomy. In addition, 22 control children were studied. History for allergy and family history of sleep-disordered breathing was taken before each polysomnographic evaluation. RESULTS: Significant changes in sleep stage percentages and sleep fragmentation were found in the postsurgery study compared with the presurgery study; 25% of the children had apnea/hypopnea index (AHI) </=1, 46% had AHI >1 and <5, and 29% had AHI >/=5 in the postsurgery study. The frequency of subjects with AHI </=1 after surgery was significantly lower among obese subjects (P < .05). Comparison between the children who had AHI </=1 after surgery and 22 control children showed complete normalization of sleep architecture after surgery. CONCLUSIONS: Adenotonsillectomy yields improvements in respiratory abnormalities in children with obstructive sleep apnea syndrome. Complete normalization occurs in only 25% of the patients. Obesity and AHI at diagnosis are the major determinant for surgical outcome. When normalization of respiratory measures occurs after surgery, normalization of sleep architecture will also ensue.

Adenoidectomy↗

PubMed2006

Correlates of sleep and pediatric bipolar disorder.

STUDY OBJECTIVE: To determine, based on a large community sample, the prevalence and associated sleep characteristics of children with a bipolar mood disturbance behavioral profile. METHODS: Participants who fit the pediatric bipolar disorder profile as derived from the Child Behavior Checklist were matched to control participants for age, sex, ethnicity, parentally reported attention-deficit/hyperactivity disorder, psychotropic medication usage, and apnea-hypopnea indexes. Paired comparisons were made between the groups to examine differences on polysomnographic data and parentally reported sleep characteristics. RESULTS: Thirteen (approximately 3%) of 438 participants fit the pediatric bipolar disorder profile. These children demonstrated significant sleep-continuity disturbances with poorer sleep efficiency and more awakenings after sleep onset, less rapid eye movement sleep, and longer periods of slow-wave sleep than their matched counterparts during overnight polysomnography. In addition, responses to a parental-report questionnaire about child sleep behavior suggest these children have significant sleep problems, including more difficulty initiating sleep, restless sleep, nightmares, and morning headaches relative to the control group. CONCLUSIONS: Children with a pediatric bipolar disorder profile display consistent quantitative differences in sleep relative to matched controls. Prevalence rates of pediatric bipolar disorder, as assessed by the Child Behavior Checklist, are consistent with those found in the adult bipolar population.

Aggression↗

PubMed2006

Plasma adhesion molecules in children with sleep-disordered breathing.

STUDY OBJECTIVES: To determine whether childhood sleep-disordered breathing (SDB) is associated with elevated levels of plasma adhesion molecules. DESIGN: Prospective, observational study. SETTING: Sleep Medicine Center of Kosair Children's Hospital. PARTICIPANTS: Thirty-nine children with SDB (apnea-hypopnea index [AHI] > 5/h), 47 children with mild SDB (AHI 1 to 5/h), and 42 healthy control subjects (AHI < 1/h). MEASUREMENTS AND RESULTS: One hundred twenty-eight children underwent a standard polysomnographic assessment with a blood draw the following morning. Plasma levels of CRP and the adhesion molecules intercellular adhesion molecule (ICAM)-1 and P-selectin were measured. No differences were observed in ICAM-1 levels among the groups; however, obese children had higher ICAM-1 levels than nonobese children (425.0 +/- 123.0 ng/mL vs 375.6 +/- 107.1 ng/mL, p = 0.04) [mean +/- SD]. P-selectin levels were significantly higher in the SDB group (84.0 +/- 52.2 ng/mL) and the mild SDB group (89.3 +/- 49.9 ng/mL) when compared to control subjects (49.5 +/- 22.3 ng/mL; p < 0.001 for both groups). Furthermore, P-selectin correlated with AHI (r = 0.32, p < 0.001), respiratory arousal index (r = 0.27, p = 0.002), and nadir of oxygen saturation as measured by pulse oximetry (r = - 0.19, p = 0.038). Plasma CRP levels were found to correlate with P-selectin even after controlling for BMI (r = 0.20, p = 0.05). No correlations were found between CRP and ICAM-1. CONCLUSIONS: Children with SDB have plasma elevations of P-selectin, a marker of platelet activation, lending support to the premise that inflammatory processes are elicited by SDB in children, and may contribute to accelerated risk for cardiovascular morbidity. In contrast, elevations in ICAM-1 are primarily associated with obesity rather than SDB.

Biomarkers↗

PubMed2006

Polysomnographic characteristics in normal preschool and early school-aged children.

OBJECTIVE: The objective of this study was to describe overnight polysomnographic measures in normal children aged 3 to 7 years. We conducted a retrospective analysis of normal polysomnographic evaluations from participants in 2 large community-based studies of sleep-disordered breathing among preschoolers and early school-aged children at Kosair Children's Hospital Sleep Medicine Research Center at the University of Louisville. Participants included 542 healthy children with ages ranging from 3.2 to 8.6 years. RESULTS: Subjects were excluded from analysis if they had documented snoring during polysomnography, an obstructive apnea-hypopnea index of > or =1.0, or a periodic leg-movement index of > or =5.0. Because the greatest differences in polysomnography occurred between ages 5 and 6 years, analyses were performed for children 3 to 5 years and for ages > or =6. Sleep cyclicity was distinct between age groups, with both showing an initial brief rapid-eye-movement period, which lengthened across the night, but only the older group showing a decrease in cycle length across the night. Average obstructive apnea indices were 0.03 per hour of total sleep time (TST) for 3- to 5-year-old children and 0.05 per hour of TST for > or =6-year-old children, whereas central apnea indices were 0.82 and 0.45 per hour of TST, respectively. Older children spent a greater percentage of sleep time supine, and the apnea-hypopnea index differed according to body position. Twenty percent of all subjects had end tidal carbon dioxide values of >45 mm Hg, and 2.2% had recorded values >50 mm Hg during > or =50% TST. High variance was present on all measures. CONCLUSIONS: Developmental changes occur in several polysomnographic measures among normal children from 3 to 7 years of age, particularly during transition from preschool to early school age. Our findings in a large number of healthy community children comprise the most extensive compilation of normative reference values for laboratory-based pediatric polysomnography to date.

Arousal↗

PubMed2005

Cultural influences on the bedtime behaviors of young children.

BACKGROUND AND PURPOSE: This study was designed to assess potential relationships of race and socioeconomic status (SES) to bedtime behavior from a community sample of 2- to 7-year-old children. PATIENTS AND METHODS: A previously validated sleep questionnaire was administered to parents of children enrolled in the Jefferson County, Kentucky school system. The sleep behavior of African-American (n=973) and Caucasian (n=2398) children was analyzed. Median annual income of residential zip codes was used as a proxy for SES. RESULTS: Mean age was 4.8+/-1.1 years. Two composite 'sleep behavior scores' were generated related to excessive daytime sleepiness and sleep-related behavior. Children in the lower SES group had significantly more impaired 'sleep behavior scores' than those in the higher SES group, regardless of race or age. African-American children had later bedtimes than Caucasian children with similar rise times, resulting in significantly shorter sleep duration and more excessive daytime sleepiness, independent of SES and age. CONCLUSIONS: Cultural variables impact sleep-related behavior in children. Race and SES have independent relationships with sleep behavior. Independent of SES, African-American children sleep less due to later bedtimes. SES does play a role, however, in parentally reported sleep-related behavior problems. Thus, cultural variables such as race and SES are important modifiers of sleep behaviors in children and should be addressed in sleep education programs.

Child↗

PubMed2005

PHOX2B genotype allows for prediction of tumor risk in congenital central hypoventilation syndrome.

The Phox2b gene is necessary for autonomic nervous-system development. Phox2b-/- mice die in utero with absent autonomic nervous system circuits, since autonomic nervous system neurons either fail to form or degenerate. We first identified the Phox2b human ortholog, PHOX2B, as the gene underlying congenital central hypoventilation syndrome (CCHS, or Ondine curse), with an autosomal dominant mode of inheritance and de novo mutation at the first generation. We have subsequently shown that heterozygous mutations of PHOX2B may account for several combined or isolated disorders of autonomic nervous-system development--namely, tumors of the sympathetic nervous system (TSNS), such as neuroblastoma and late-onset central hypoventilation syndrome. Here, we report the clinical and molecular assessments of a cohort of 188 probands with CCHS, either isolated or associated with Hirschsprung disease and/or TSNS. The mutation-detection rate was 92.6% (174/188) in our series, and the most prevalent mutation was an in-frame duplication leading to an expansion of +5 to +13 alanines in the 20-alanine stretch at the carboxy terminal of the protein. Such findings suggest PHOX2B mutation screening as a simple and reliable tool for the diagnosis of CCHS, independent of the clinically variable phenotype. In addition, somatic mosaicism was detected in 4.5% of parents. Most interestingly, analysis of genotype-phenotype interactions strongly supports the contention that patients with CCHS who develop malignant TSNS will harbor either a missense or a frameshift heterozygous mutation of the PHOX2B gene. These data further highlight the link between congenital malformations and tumor predisposition when a master gene in development is mutated.

Animals↗

PubMed2005

Autonomic dysfunction in children with sleep-disordered breathing.

STUDY OBJECTIVES: To measure sympathetic responses in children with and without sleep-disordered breathing. DESIGN: Prospective, observational study. SETTING: Kosair Children's Hospital Sleep Medicine and Apnea Center. PARTICIPANTS: Subjects were prospectively recruited from children undergoing overnight polysomnographic assessments and were retrospectively grouped according to the results of the polysomnogram. Sleep-disordered breathing was defined as an apnea-hypopnea index >5 and children were assigned to the control group if their apnea-hypopnea index was < 1. INTERVENTION: N/A. MEASUREMENTS AND RESULTS: During quiet wakefulness, pulse arterial tonometry was used to assess changes in sympathetic activity following vital capacity sighs in 28 children with sleep-disordered breathing and 29 controls. Each child underwent a series of 3 sighs, and the average maximal pulse arterial tonometry signal attenuation was calculated. Further, a cold pressor test was conducted in a subset of 14 children with sleep-disordered breathing and 14 controls. The left hand was immersed in ice cold water for 30 seconds while right-hand pulse arterial tonometry signal was continuously monitored during immersion and 20-minute recovery periods. Signal amplitude changes were expressed as percentage change from corresponding baseline. RESULTS: The magnitude of sympathetic discharge-induced attenuation of pulse arterial tonometry signal was significantly increased in children with sleep-disordered breathing during sigh maneuvers (74.1% +/- 10.7% change compared with 59.2% +/- 13.2% change in controls; P<.0001) and the cold pressor test (83.5% +/- 7.3% change compared with 74.1% +/- 11.4% change in controls; P=.039). Further, recovery kinetics in control children were faster than those of children with sleep-disordered breathing. CONCLUSION: Children with sleep-disordered breathing have altered autonomic nervous system regulation as evidenced by increased sympathetic vascular reactivity during wakefulness.

Adolescent↗

PubMed2005

Odds, prevalence and predictors of sleep problems in school-age normal children.

The objectives of the study were to describe the prevalence, odds, and predictors of 36 paediatric sleep behaviours and describe their coexistence in a school-age normal population. The design was community-based questionnaire survey of sleep-wake patterns, sleep environment, and 36 sleep behaviours indicative of six sleep disorder-subscales using the Health-Behaviour Questionnaire. A caregivers' report of 3045 children aged 6-13 years in Belgium constituted the participants. Prevalence of each sleep behaviour was calculated. Log-linear modelling within and between the sleep disorder-subscales was used to screen for coexistence. The effect size of selected night-time parameters to the likelihood of sleep behaviours and disorder-subscale was expressed as odds ratios via logit regression analysis. Significant differences in sleep-wake patterns were found between weekday and weekend. Ranking by odds showed that: (1) sleep problems such as 'tired when waking up', 'repetitive limb movements', 'going to bed reluctantly', and 'sleep paralysis' and; (2) the disorder-subscale 'excessive somnolence' are common in children. Coexistences within and between disorder-subscales of sleep problems are evident in a school-age, normal population. These results suggest that disorders of excessive somnolence (DES) are highly prevalent in a non-clinical sample of school-age children. Furthermore, sleep-onset latency and a noisy, not well-darkened room are predictive towards the odds for exhibiting sleep problems and disorders. It is advocated that more information on the importance of good sleep-wake hygiene should reach parents and children.

Adolescent↗

PubMed2005

Autonomic function in children with congenital central hypoventilation syndrome and their families.

STUDY OBJECTIVES: Congenital central hypoventilation syndrome (CCHS) is a genetic disorder characterized by failure of automatic control of breathing in the absence of obvious anatomic lesions. There have been several reports suggesting that CCHS patients display autonomic dysregulation. Pulse arterial tonometry (PAT) is a novel technique that provides noninvasive moment-to-moment measurements of sympathetic tone changes to the cutaneous vascular bed. We hypothesized that autonomic function as measured by PAT would be altered in children with CCHS. DESIGN: Prospective study. SETTING: CCHS Family Conference, Orlando, FL, and the local community in Louisville, KY. PARTICIPANTS: Nineteen CCHS patients and 31 parents as well as 24 control children and 15 adult control subjects. INTERVENTIONS: Children with CCHS and their parents underwent sympathetic challenges (vital capacity sigh and cold hand pressor test) and a test of reactive hyperemia (brachial artery occlusion) while PAT was continuously monitored from the right hand. Control children and control adults underwent the same procedure. MEASUREMENTS AND RESULTS: The maximal change of the PAT signal compared to the preceding baseline was averaged and expressed as percentage change for each of the challenges. The magnitude of sympathetic discharge-induced attenuation of PAT signal following a sigh was reduced in CCHS children compared to control subjects for both the vital capacity sighs and the cold hand pressor test. There were no differences observed in the magnitude of PAT attenuation between parents of children with CCHS and control adults. No differences were observed between either CCHS and control subjects or CCHS parents and adult control subjects for the brachial artery occlusion test. CONCLUSION: CCHS patients show an attenuated response to endogenous sympathetic stimulation, supporting the presence of autonomic nervous system dysfunction as a consistent feature of this condition. No differences were found in parents of children with CCHS compared to control adults, consistent with the finding that CCHS is primarily the result of a de novo gene mutation.

Autonomic Nervous System↗

PubMed2005

Obesity rather than severity of sleep-disordered breathing as the major determinant of insulin resistance and altered lipidemia in snoring children.

OBJECTIVE: Sleep-disordered breathing (SDB) is associated with insulin resistance and dyslipidemia in adults and in obese children. However, the prevalence of such metabolic abnormalities among snoring children is unknown. This study was done to prospectively assess the relative contribution of SDB and obesity to metabolic disturbances in a large cohort of snoring children. METHODS: Measurements of fasting serum glucose, insulin, and lipids were obtained after polysomnographic evaluation in 116 snoring children and in 19 control subjects. Insulin resistance was assessed using the insulin/glucose ratio (I/G ratio) and homeostasis model assessment (HOMA). RESULTS: A total of 135 children (79 boys; mean age: 8.9 +/- 3.5 years) were studied. Sixty-four children had moderate to severe SDB (AHI = 5 per hour of total sleep time [TST]), 52 had mild SDB (AHI = 1 but <5 per hour of TST), and 19 were control subjects (AHI <1 per hour of TST). Seventy of these children were obese. No significant correlations were found between AHI, lowest arterial oxygen saturation, or arousal index and serum insulin, serum glucose, I/G ratio, HOMA, or serum lipids for either the whole group or the obese children only. However, significant positive correlations were found between I/G ratio and relative BMI (relBMI; r = 0.58), HOMA and relBMI (r = 0.52), triglycerides and relBMI (r = 0.30), and high-density lipoprotein and relBMI (r = 0.50). No significant differences were found in relBMI, I/G ratio, and lipid levels between boys and girls. CONCLUSIONS: Among children with suspected SDB, insulin resistance and dyslipidemia seem to be determined primarily by the degree of body adiposity rather than by the severity of SDB.

Adolescent↗

PubMed2004

Clumping factor B, a fibrinogen-binding MSCRAMM (microbial surface components recognizing adhesive matrix molecules) adhesin of Staphylococcus aureus, also binds to the tail region of type I cytokeratin 10.

The primary habitat of Staphylococcus aureus in humans is the moist squamous epithelium of the anterior nares. We showed previously that S. aureus adheres to desquamated epithelial cells and that clumping factor B (ClfB), a surface-located MSCRAMM (microbial surface components recognizing adhesive matrix molecules) known for its ability to bind to the alpha-chain of fibrinogen, is partly responsible (O'Brien, L. M., Walsh, E. J., Massey, R. C., Peacock, S. J., and Foster, T. J. (2002) Cell. Microbiol. 4, 759-770). We identified cytokeratin 10 (K10) as the ligand recognized by ClfB. Here we have shown that purified recombinant human and murine K10 immobilized on a plastic surface supports adherence of S. aureus in a ClfB-dependent manner. Furthermore, the recombinant A domain of ClfB (rClfB 45-542) bound to immobilized K10 dose-dependently and saturably. Subdomains of human and murine K10 were expressed and purified. The N-terminal head domain (residues 1-145) did not support the binding of rClfB or adherence of S. aureus ClfB+. In contrast, the C-terminal tail domains (human rHK10 452-593, mouse rMK10 454-570) promoted avid binding and adherence. Isothermal titration microcalorimetry and intrinsic tryptophan fluorescence experiments gave dissociation constants for rClfB 45-542 binding to rMK10 454-570 of 1.4 and 1.7 microM, respectively. The tail region of K10 is composed largely of quasi-repeats of Tyr-(Gly/Ser)n. A synthetic peptide corresponding to a typical glycine loop (YGGGSSGGGSSGGY; Y-Y loop peptide) inhibited the adherence of S. aureus ClfB+ to immobilized MK10 to a level of 80%, whereas control peptides had no effect. The KD of rClfB 45-542 for the Y-Y loop peptide was 5.3 microm by intrinsic tryptophan fluorescence. Thus ClfB binds to the glycine loop region of the tail domain of keratin 10 where there are probably multiple binding sites. Binding is discussed in the context of the dock-lock-latch model for MSCRAMM-ligand interactions. We provide an explanation for the molecular basis for S. aureus adherence to the squamous epithelium and suggest that nasal colonization might be prevented by reagents that inhibit this interaction.

Adhesins, Bacterial↗

PubMed2004

Detection of obstructive sleep apnea in pediatric subjects using surface lead electrocardiogram features.

STUDY OBJECTIVES: To investigate the feasibility of detecting obstructive sleep apnea (OSA) in children using an automated classification system based on analysis of overnight electrocardiogram (ECG) recordings. DESIGN: Retrospective observational study. SETTING: A pediatric sleep clinic. PARTICIPANTS: Fifty children underwent full overnight polysomnography. INTERVENTION: N/A. MEASUREMENTS AND RESULTS: Expert polysomnography scoring was performed. The datasets were divided into a training set of 25 subjects (11 normal, 14 with OSA) and a withheld test set of 25 subjects (11 normal, 14 with OSA). Features, calculated from the ECG of the 25 training datasets, were empirically chosen to train a modified quadratic discriminant analysis classification system. The selected configuration used a segment length of 60 seconds and processed mean, SD, power spectral density, and serial correlation measures to classify segments as apneic or normal. By combining per-segment classifications and using receiver-operator characteristic analysis, a per-subject classifier was obtained that had a sensitivity of 85.7%, specificity of 90.9%, and accuracy of 88% on the training datasets. The same decision threshold was applied to the withheld datasets and yielded a sensitivity of 85.7%, specificity of 81.8%, and accuracy of 84%. The positive and negative predictive values were 85.7% and 81.8%, respectively, on the test dataset. CONCLUSIONS: The ability to correctly identify 12 out of 14 cases of OSA (with the 2 false negatives arising from subjects with an apnea-hypopnea index less than 10) indicates that the automated apnea classification system outlined may have clinical utility in pediatric patients.

Adult↗

PubMed2004

Peripheral arterial tonometry events and electroencephalographic arousals in children.

STUDY OBJECTIVES: Peripheral arterial tonometry (PAT) is a sensitive measure of moment-to-moment changes in sympathetic activity and reliably identifies arousals in adult subjects. We investigated whether PAT events during sleep are associated with visually recognizable electroencephalographic arousals in healthy children and in children with sleep-disordered breathing. DESIGN: Prospective cohort. SETTING: Pediatric Sleep Research Laboratory. PARTICIPANTS: Twenty children with obstructive sleep apnea syndrome, 20 children with mild sleep-disordered breathing, and 20 control children with a mean age of 7.6 +/- 2.6 years (range: 5.7-16.5 years); 53% of children were boys. INTERVENTIONS AND MEASUREMENTS: Polysomnographic evaluation in the sleep laboratory with concomitant recording of PAT. PAT events were defined as attenuations from immediately preceding baseline of 20% to 50% (PAT20) and > 50% (PAT50) for at least 5 seconds and the indexes calculated per hour of sleep time that included good-quality PAT signals. Total PAT index (the sum of PAT20 index and PAT50 index) was also calculated. RESULTS: Total PAT index correlated with total arousal index and spontaneous arousal index (r = 0.55, P < .0001, r = 0.64, P < .001, respectively), especially in the group with obstructive sleep apnea syndrome (r = 0.71, P < .0001). The sensitivity and specificity of PAT for identifying electroencephalographic arousals were 95% and 35%, respectively. The PAT device identified pathologic arousals indexes (> or = 16 per hour) (area under the curve 0.79, P = .002). Thirty-five percent of respiratory events (eg, obstructive apnea or hypopnea) were associated with a visual electroencephalographic arousal, compared to 92% being associated with PAT attenuation events. CONCLUSIONS: Arousals in sleeping children are associated with increased sympathetic discharge, as evidenced by attenuations in PAT signal. However, a significant proportion of PAT attenuations were not accompanied by visual electroencephalographic arousals. Thus, the importance of these autonomic arousals has yet to be explored in association with morbidities related to sleep-disordered breathing and, therefore, PAT technology cannot be recommended as an alternative tool for measuring arousals in children. Nevertheless, these data further support the contention that adult criteria for the measurement for arousals may not be adequate in children.

Arousal↗

PubMed2004

Sleep pressure score: a new index of sleep disruption in snoring children.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS), as measured by objective criteria, is infrequent in snoring children despite a high prevalence of EDS-related behavioral manifestations. We hypothesized that sleep architecture and arousal indexes may be altered relative to the severity of sleep-disordered breathing (SDB). DESIGN: Retrospective and prospective study. SETTING: Questionnaires were distributed through sleep clinic or school program; polysomnograms were performed at Kosair Children's Hospital in Louisville, Kentucky. PARTICIPANTS: To examine this issue, 182 children with SDB, 163 children with primary snoring, and 214 control children with a mean age of 6.9 +/- 2.6 years underwent polysomnographic evaluation in the laboratory. MEASUREMENTS AND RESULTS: Significant increases in slow-wave sleep (percentage of total sleep time) and decreases in rapid eye movement sleep (percentage of total sleep time) occurred in the SDB group (P < .0001). Spontaneous and respiratory arousal indexes and the apnea-hypopnea index (AHI) displayed negative and positive correlations, respectively, suggesting reciprocal interactions. Based on these observations, a sleep pressure score (SPS) was derived as a surrogate numeric measure for disrupted sleep homeostasis. The SPS exhibited linear increases relative to AHI, reaching a plateau at an AHI of 30 to 40 per hour of total sleep time. Furthermore, SPS values were significantly higher among African American and obese children (P < .0001). CONCLUSIONS: Sleep architecture is not preserved in children with SDB. An algorithm allowing for calculation of sleep propensity and disturbed sleep homeostasis in children who snore is proposed and may be of practical value in the assessment of sleepiness.

Body Mass Index↗