Enhanced influenza A H1N1 T cell epitope recognition and cross-reactivity to protein-O-mannosyltransferase 1 in Pandemrix-associated narcolepsy type 1.

Narcolepsy type 1 (NT1) is a chronic neurological disorder having a strong association with HLA-DQB1*0602, thereby suggesting an immunological origin. Increased risk of NT1 has been reported among children or adolescents vaccinated with AS03 adjuvant-supplemented pandemic H1N1 influenza A vaccine, Pandemrix. Here we show that pediatric Pandemrix-associated NT1 patients have enhanced T-cell immunity against the viral epitopes, neuraminidase 175-189 (NA175-189) and nucleoprotein 214-228 (NP214-228), but also respond to a NA175-189-mimic, brain self-epitope, protein-O-mannosyltransferase 1 (POMT1675-689). A pathogenic role of influenza virus-specific T-cells and T-cell cross-reactivity in NT1 are supported by the up-regulation of IFN-γ, perforin 1 and granzyme B, and by the converging selection of T-cell receptor TRAV10/TRAJ17 and TRAV10/TRAJ24 clonotypes, in response to stimulation either with peptide NA175-189 or POMT1675-689. Moreover, anti-POMT1 serum autoantibodies are increased in Pandemrix-vaccinated children or adolescents. These results thus identify POMT1 as a potential autoantigen recognized by T- and B-cells in NT1.

Sleep disturbances in a community sample from preschool to school age.

OBJECTIVE: To study the prevalence of various sleep problems at school age in a Finnish community sample and to evaluate the persistence of the sleep problems from the preschool age to school age in a 4-year follow-up. METHODS: Parents completed the Sleep Disturbance Scale for Children questionnaire on their child's sleep during the preschool years (3-6 years) and again during the school years (7-11 years). At follow-up the parents also completed a questionnaire on family structure and socio-economic status. RESULTS: The parents of 481 children completed the questionnaires during both the first study and the follow-up (girls 49%, boys 51%; mean age 9, range 7-11). At the population level, sleep problems slightly declined from preschool to school age (P < 0.05). However, sleep problems at preschool age showed a strong persistence to school age. At the follow-up, 35% of the children who were considered to have a sleep disorder at preschool age still suffered from it at school age. At the community level, this equates to 9% of the children. The children with no sleep problems at preschool age rarely developed sleep problems at school age. CONCLUSIONS: This study showed that various types of sleep problems are common at school age. Sleep problems persisted from preschool to school age at the individual level. It is important to recognize all types of sleep problems, especially persistent ones. Persistent sleep problems in children may cause and exacerbate other somatic, cognitive and psychiatric problems. Therefore, more attention should be focused on sleep problems in paediatric health care with interventions aimed particularly at children with prolonged sleep problems.

Parental smoking, nasal resistance and rhinitis in children.

AIM: To determine whether parent-reported perennial rhinitis or objectively measured nasal resistance is more common in children from smoking families. To assess tonsillar size, nasopharyngeal airway and upper airway surgery frequency in children with smoking and non-smoking parents. METHODS: Ninety-five children (age 3-6 years, median 68 months) participated in this prospective cross-sectional clinical study. History of nasal symptoms was obtained, and all underwent an ear-nose-throat examination, anterior rhinomanometry and a lateral cephalogram. Regular smoking by either parent and their child's snoring was inquired about with a parental questionnaire. We compared children with a parental smoker and children without a parental smoker in the family. RESULTS: Smoking in the family led to increased risk for perennial rhinitis in the children up to 2.76-fold (aOR, 95%CI 1.00-7.67), but with no difference in nasal resistance between children from smoking and non-smoking households. Neither tonsillar size, nasopharyngeal airway nor upper airway surgery was associated with parental smoking. CONCLUSIONS: Parental smoking is associated with symptoms of perennial rhinitis in children. The possible role of environmental tobacco smoke should be taken into account in parent counselling and in evaluation of children being treated for symptoms of rhinitis and nasal obstruction.

Sleep problems and daytime tiredness in Finnish preschool-aged children-a community survey.

BACKGROUND: Sleep is important to the well-being and development of children. Specially, small children are vulnerable to the effects of inadequate sleep. However, not much is known about the frequency of all types of sleep problems and daytime tiredness in preschool-aged children. OBJECTIVE: To evaluate the prevalence of a wide spectrum of sleep problems, daytime tiredness and associations between these in 3- to 6-year-old Finnish children. METHODS: A population-based study where parents of 3- to 6-year-old children (n= 904) living in Helsinki filled in the Sleep Disturbance Scale for Children (SDSC). RESULTS: Of the children, 45% had at least one sleep-related problem occurring at least three times a week: 14.1% were unwilling to go to bed, 10.2% had difficulties in falling asleep, 10.2% had bruxism, 6.4% sleep talking, 2.1% sleep terrors, 8.2% had sleep-related breathing problem, 11.2% had excessive sweating while falling asleep and 12.9% excessive sweating during sleep. Age and gender were related to phenotype of the sleeping problems. In multiple regression analysis, the difficulties in initiating and maintaining sleep were most strongly associated with tiredness in the morning and during the day. CONCLUSIONS: Different types of sleep problems are frequent in preschool-aged children. Poor sleep quality is associated with morning and daytime tiredness. In screening for sleep problems in children, attention should be paid not only to sleep amount but also to sleep quality.

Heart rate and blood pressure control in infants exposed to maternal cigarette smoking.

AIM: Exposure to maternal cigarette smoking is a major risk factor for sudden infant death syndrome (SIDS). Foetal and postnatal smoke-exposure may alter cardiovascular control in infants. We studied heart rate (HR) and blood pressure (BP) responses in smoke-exposed infants. METHODS: Eleven infants exposed to maternal cigarette smoking were studied at the age of 12 +/- 2.1 (range 10-16) weeks. Twenty healthy, age-matched infants from non-smoking families served as controls. During confirmed slow-wave sleep (NREM3), 3-5 sec side motion and 45 sec 45 degrees head-up tilt tests were performed. RESULTS: Control infants showed consistent biphasic HR and BP responses to side motion, with an initial 2-5% increase followed by a 2% decrease (p < 0.0001). In smoke-exposed infants, the initial HR (p = 0.009) and BP responses (p < 0.0001) were markedly reduced, and the subsequent decrease in BP was more prominent (systolic blood pressure, SBP, p = 0.005; diastolic blood pressure, DBP, p = 0.03). No differences were observed between the groups in tilt test results, HR variability or HR responses to spontaneous arousals. CONCLUSION: Maternal cigarette smoking may alter vestibulo-mediated cardiovascular control in early infancy. This may contribute to increased SIDS risk.

nCPAP improves abnormal autonomic function in at-risk-for-SIDS infants with OSA.

We evaluated cardiovascular autonomic control and arousability during sleep in infants with obstructive sleep apnea (OSA) before and after 10 +/- 4 (mean +/- SD) days of treatment with nasal continuous positive airway pressure (nCPAP). Six OSA infants and 12 age-matched control infants were studied with polygraphic sleep studies at the age of 13 +/- 4 wk. During the study, 45 degrees head-up tilt tests were performed in slow-wave and rapid eye movement sleep. Blood pressure (BP) and heart rate (HR) were continuously monitored. All OSA infants had decreased initial BP and HR responses, followed by hypotension in two and hypertension in two. OSA infants displayed higher arousal thresholds in response to the tilt in rapid eye movement sleep (P < 0.005) and higher baseline HR (P < 0.05) than controls. nCPAP treatment normalized BP and HR responses as well as arousal thresholds to tilting and stabilized HR levels. OSA in infants may be linked with cardiovascular autonomic control disturbances and decreased arousability during sleep. These defects are improved by control of OSA with nCPAP.

Postnatal adaptation after Caesarean section or vaginal delivery, studied with the static-charge-sensitive bed.

AIM: To compare postnatal adaptation between Caesarean and vaginal deliveries, by studying sleep states, oxygenation, heart rate and body movements. Another aim was to follow the adaptation of healthy, term, vaginally born babies. METHODS: Ten vaginally born and 12 neonates born by elective Caesarean section were recorded with a movement sensor (SCSB, static-charge-sensitive bed), electrocardiogram and oximeter. The recordings started 1.5 h after birth and lasted for 12 h. For the vaginal group, another 12 h recording was performed during the third night postpartum. RESULTS: Delivery mode did not affect sleep state distribution. The vaginal group had more oxyhaemoglobin desaturation episodes <95% than the Caesarean section group (mean +/- SD: 59 +/- 10% vs 42 +/- 22% of epochs, p = 0.03), especially in active sleep, but baseline saturation was similar (96 +/- 1% vs 95 +/- 3%, p = 0.93). The vaginal group had fewer movements during sleep than the Caesarean section group (movements of 5-10 s: 5 +/- 1 h(-1) vs 10 +/- 3 h(-1), p = 0.0001). During the first 3 d, the amount of sleeping and active sleep increased, whereas wakefulness and quiet sleep decreased. Baseline oxyhaemoglobin saturation and the number of movements of over 5 s increased. CONCLUSION: Delivery mode did not affect sleep state distribution but, unexpectedly, the vaginal group had more oxyhaemoglobin desaturation events and fewer body movements than the Caesarean section group. These differences during the first postnatal day remain unexplained, but they may reflect stress and pain during labour. After a few days, changes in sleep organization, and increases in oxyhaemoglobin saturation and frequency of body movements were noted in the vaginal group, which may represent recovery and adaptation to extrauterine life.

Hemodynamic responses to obstructive respiratory events during sleep are augmented in women with preeclampsia.

Preeclampsia is the most common disease of pregnancy, occurring in up to 10% of the pregnant population. The cause of the disease is as yet undetermined; however, most of the clinical effects are commonly attributed to damage to the endothelial layer, leading to increased pressor activity of all the maternal blood vessels. Therefore, we suspected that if obstructive sleep apnea (OSA) coexisted with preeclampsia in pregnancy, the hemodynamic effects of the OSA would be markedly potentiated. To test this hypothesis, we performed full sleep studies and overnight beat-to-beat blood pressure (BP) monitoring. The control patient group included 10 pregnant women with OSA and no evidence of hypertensive disease either before or during their current pregnancy. The test group included 10 women with preeclampsia and coexisting OSA. The pressor responses to obstructive respiratory events during sleep were enhanced in preeclamptic patients compared with control OSA patients (21+/-2/12+/-1 mm Hg and 38+/-5/25+/-4 mm Hg above baseline in control OSA and preeclamptic OSA patients, respectively, P = .005/.005). In contrast, there was no difference in heart rate responses between the two groups of subjects (34+/-5 beats/min and 49+/-13 beats/min above baseline in control and preeclamptic patient groups, respectively, P = .326). We suggest that the augmented pressor responses in preeclamptic women occur as a result of maternal endothelial damage induced by the preeclampsia disease process. These findings may have important implications in the management of preeclamptic patients.

Cardiovascular responses to three simple, provocative tests of autonomic activity in sleeping infants.

Whereas defective cardiovascular autonomic control has been implicated in the sudden infant death syndrome, relatively little is known about the normal development of autonomic control, due to the inability to measure blood pressure in infants noninvasively. We studied 12 normal infants [age: 13 +/- 2 (SD) wk] using a noninvasive method of continuous blood pressure recording and examined the cardiovascular responses to 45 degrees head-up tilting, a modified cold face test, and a loud noise. In head-up tilting, in both slow-wave sleep and rapid eye movement sleep, all infants displayed a rapid biphasic heart rate response (mean increase of 16% and mean decrease of 21%) and blood pressure response (mean increase of 16% and mean decrease of 16%), with a return to pretest values within 20 s. Both ice and noise caused a less pronounced biphasic response. In conclusion, at 3 mo, infants show the adult pattern of response to postural challenge. The short latency of the response suggests that neural inputs, apart from baroreceptors, are involved in the initial phase of the response.

The balance of the autonomic nervous system is normal in colicky infants.

UNLABELLED: Excessively crying, hard-to-soothe infants are described as colicky. The self-limiting course of infantile colic during early infancy suggests an etiology of transient developmental dysmaturation. It has been proposed that emotional characteristics such as temperament and self-soothing ability are correlated with the balance of the autonomic nervous system. Heart rate variability (HRV) analysis was used for evaluating the balance of the autonomic nervous system in colicky and control infants during and after the colicky period. HRV analysis was carried out on 12 colicky infants and 14 control infants at the age of 2 mo, and repeated on 10 colicky and 11 normal infants at the age of 7 mo. Measurements were performed during polygraphically confirmed slow-wave sleep (sleep stages 3 and 4). Three HRV frequency bands were defined, including a high (0.2-1.0 Hz), middle (0.12-0.2 Hz) and low (0.025-0.12 Hz) frequency variability. There were no differences between the study groups in any of the three HRV frequency bands analyzed. The high frequency variability increased significantly with age in both study groups (p = 0.009). CONCLUSION: The findings suggest that imbalance between the parasympathetic and the sympathetic nervous system is not associated with infantile colic and that, in accordance with previous findings, control of HRV shifts in a parasympathetic direction with increasing age during the first year of life.

Infants with colic have a normal sleep structure at 2 and 7 months of age.

OBJECTIVE: To compare nighttime sleep structure between infants with colic and a control group. STUDY DESIGN: Sleep and cry times of 15 infants with colic and 16 infants in a control group were recorded with the use of a daily diary at the ages of 5 weeks and 6 months. The diary was kept at home for a 1-week period. Overnight polygraphic sleep recordings in a sleep laboratory were performed when the infants were 2 months of age and were repeated for 11 infants with colic and 14 infants in a control group at 7 months of age. RESULTS: Daily sleep time was shorter in infants with colic compared with the control group at 5 weeks of age (P =.001). Polygraphic data showed a similar sleep structure between the study groups at 2 and 7 months of age. Infants with colic had somewhat more obstructive apneas during rapid eye movement sleep at the age of 2 months (P =.04), and they had fewer awakenings at the age of 7 months than the control group (P =.003). CONCLUSION: Infants with colic had normal sleep polygraphic finding at 2 and 7 months of age including sleep structure, movements, and breathing. Despite the shorter reported daily sleep times, the polygraphic data did not suggest infantile colic to be associated with a sleep disorder.

Site and mechanics of spontaneous, sleep-associated obstructive apnea in infants.

To examine the mechanics of infantile obstructive sleep apnea (OSA), airway pressures were measured using a triple-lumen catheter in 19 infants (age 1-36 wk), with concurrent overnight polysomnography. Catheter placement was guided by correlations between measurements of magnetic resonance images and body weight of 70 infants. The level of spontaneous obstruction was palatal in 52% and retroglossal in 48% of all events. Palatal obstruction predominated in infants treated for OSA (80% of events), compared with 38.6% from infants with infrequent events (P = 0.02). During obstructive events, successive respiratory efforts increased in amplitude (mean intrathoracic pressures -11.4, -15.0, and -20.4 cmH(2)O; ANOVA, P < 0.05), with arousal after only 29% of the obstructive and mixed apneas. The soft palate is commonly involved in the upper airway obstruction of infants suffering OSA. Postterm, infant responses to upper airway obstruction are intermediate between those of preterm infants and older children, with infrequent termination by arousal but no persisting "upper airway resistance" and respiratory efforts exceeding baseline during the event.

Orthopedic cervical headgear with an expanded inner bow in class II correction.

Forty consecutively referred children, 20 boys and 20 girls, with a Class II division I malocclusion and protrusive maxilla were treated with orthopedic cervical headgear with a 10 mm expanded inner bow and a long outer bow bent 15 degrees upwards. The mean age of the children at the beginning of treatment was 9.3 years (SD 1.3, range 6.6 to 12.4 years), and the average treatment time was 1.8 years (SD 0.6, range 0.8 to 3.1 years). In all patients Class II molar relationships were successfully corrected to Class I molar relationships. This was accompanied by a marked widening of both maxillary and mandibular dental arches. The cephalometric analysis suggested that the observed improvement of the occlusion was due to an inhibition of forward growth of the maxilla and anterior downward rotation of the palate.

Nasal continuous positive airway pressure reduces sleep-induced blood pressure increments in preeclampsia.

Preeclampsia is the predominant cause of admissions to neonatal intensive care. The diurnal blood pressure pattern is flattened or reversed in preeclampsia. We hypothesized that snoring and partial upper airway obstruction contribute to nocturnal rises in blood pressure. We tested this hypothesis by controlling sleep- induced upper airway flow limitation and snoring with nasal positive pressure. Eleven women with preeclampsia underwent two consecutive polygraphic sleep studies with simultaneous beat-to-beat blood pressure monitoring. Average blood pressure for the night overall and in each sleep stage was calculated. Sleep architecture was similar on the two study nights. Sleep-induced partial upper airway flow limitation occurred in all patients in the initial study. Autosetting nasal continuous positive airway pressure (CPAP) applied at a mean maximal pressure of 6 +/- 1 cm H(2)O eliminated flow limitation throughout sleep on the treatment night. Blood pressure was markedly reduced on the treatment night [(128 +/- 3)/(73 +/- 3)] when compared with the initial nontreatment study night [(146 +/- 6)/(92 +/- 4)], p = (0.007)/(0.002). We conclude that partial upper airway obstruction during sleep in women with preeclampsia is associated with increments in blood pressure, which can be eliminated with the use of nasal CPAP.

Altered control of submaximal bite force during bruxism in humans.

The control of bite force during varying submaximal loads was examined in patients suffering from bruxism compared to healthy humans not showing these symptoms. The subjects raised a bar (preload) with their incisor teeth and held it between their upper and lower incisors using the minimal bite force required to keep the bar in a horizontal position. Further loading was added during the preload phase. A sham load was also used. Depending on the session, the teeth were loaded by the experimenter or the subject and in one session the subject did not see the load (no visual feedback). The bite force was measured continuously using a calibrated force transducer. In all the subjects, the bite force increased with increasing load. Following the addition of the load, the level of the tonic bite force was reached rapidly with no marked overshoot. The patients with bruxism used significantly higher bite forces to hold the submaximal loads compared to the control subjects. In the control subjects, the holding forces for each submaximal load were identical in the men and the women and were independent of subject maximal bite force. Sham loading evoked no marked responses in biting force. Whether the subject or the experimenter added the load or whether the subject had visual feedback or not were not significant factors in determining the level of bite force. The results indicated that the patients with bruxism used excessively large biting forces for each given submaximal load. This study showed no evidence that the inappropriate control of bite force by patients with bruxism was due to an abnormality in the higher cortical circuits that regulates the function of trigeminal motoneurons in the brainstem. This was shown by a lack of abnormality in coordination of voluntary hand movement with biting force, a lack of abnormal anticipation response to a sham load and a lack of any effect of visual feedback. The results were in line with the hypothesis that afferent input from oral (periodontal or masticatory muscle) tissues does not provide an appropriate control of motor command in bruxism.

Recombinant forms of rat and human luteinizing hormone and follicle-stimulating hormone; comparison of functions in vitro and in vivo.

We have previously described the preparation, purification and partial characterization of recombinant (rec) forms of rat luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In the present study, the special functional features of these hormones were studied further, in vitro and in vivo, and compared with human recLH and recFSH, as well as with human urinary choriongonadotropin (hCG) and rat pituitary LH (NIDDK-RP3). In radioreceptor assay, the affinity of hCG binding to rat testis membranes was 5-fold higher than that of human recLH and 100-fold higher than that of rat recLH. In in vitro bioassay, using dispersed adult mouse interstitial cells or a mouse Leydig tumor cell line (BLT-1), hCG and human recLH were 10- to 20-fold more potent than rat recLH. Correspondingly, rat pituitary LH was about 10-fold less potent than rat recLH, and evoked a maximum testosterone response that was about half of that elicited by the other LH/CG preparations. Rat recFSH was about 10-fold less potent than human recFSH in stimulating cAMP production of a mouse Sertoli cell line (MSC-1) expressing the recombinant rat FSH receptor. The circulating half-times (T1/2) of rat and human rec hormones were assessed after i.v. injections into adult male rats rendered gonadotropin-deficient by treatment with a gonadotropin-releasing hormone antagonist. A novel immunometric assay was used for the rat FSH measurements. In the one-component model the T1/2 values of rat and human recLH were 18.2 +/- 1.9 min (n = 7) and 44.6 +/- 3.1 min (n = 7) respectively and those of rat and human recFSH were 88.4 +/- 10.7 min (n = 6) and 55.0 +/- 4.2 min (n = 6) respectively; the two-component models revealed similar differences between the rec hormone preparations. Collectively, rat recLH was eliminated significantly faster from the circulation than human recLH (P < 0.0001). In contrast, the elimination of rat recFSH was significantly slower than that of human recFSH (P = 0.02). In conclusion, rat recFSH and rat recLH display lower biopotencies per unit mass than the respective human hormones in vitro, and also in vivo for LH. This is paralleled by shorter T1/2 of rat recLH than the respective human hormone in the circulation, whereas human recFSH has a shorter T1/2 than human FSH. The special functional features of the rat rec gonadotropins emphasize the use of these preparations on studies of gonadotropin function in the rat, an important animal model for reproductive physiology.

Changes in dental arch dimensions by use of an orthopedic cervical headgear in Class II correction.

Orthopedic cervical headgears are commonly used in Finland for early treatment of the Class II malocclusion, but there is a lack of follow-up studies on the effect of this treatment. We have evaluated the effects of the cervical headgear therapy with an expanded inner bow to treat Class II malocclusion and dental arches. Forty children, 20 boys and 20 girls, with Class II, Division 1 malocclusion, were treated with the orthopedic cervical headgear. No other appliances were used. The mean age of the subjects in the beginning of the treatment was 9.3 +/- 1.3 years (range 6.6 to 12.4 years). The mean treatment time was 1.8 +/- 0.6 years (range 0.8 to 3.1 years). The cervical headgear was used with a 10 mm expanded inner bow and a 15 degrees upward bend of the long outer bow, 12 to 14 hours a day with a force of 500 gm per side. Class I relationships were achieved in all subjects. At the same time, the maxillary and mandibular dental arches were widened. The annual increment in the intercanine and intermolar distances was significantly greater than in healthy control subjects (literature data), except for the mandibular intercanine distance in boys. The maxillary arch lengths were also significantly increased; there were no consistent changes of the mandibular arch lengths. Class II malocclusion may be treated with the orthopedic cervical headgear. The treatment results in increased growth of the dental arch widths by expansion of the inner bow of the headgear. The widening of the maxilla is followed by spontaneous widening of the mandible.

The static-charge-sensitive bed in the monitoring of respiration during sleep in infants and young children.

The performance of the static-charge-sensitive bed (SCSB) in the monitoring of nocturnal breathing was studied in 22 infants and young children at the mean age of 24 weeks (SD 24, range 1-79 weeks). The conventional polysomnogram (PSG) was used as a reference method. Episodes of central apnoea were detected with high sensitivity by the SCSB. Episodes of obstructive apnoea and obstructive parts of mixed apnoea were not identified. When the SCSB recordings were scored with the airflow signal some mixed events were identified, but the detection of obstructive apnoea episodes remained poor. Partial upper airway obstruction increased the amount of SCSB spiking (high-frequency components of breathing), which may have diagnostic value. In conclusion, the SCSB enables simple, non-invasive detection of central apnoea episodes, periodic breathing and the behavioural state of the child.

Respiratory and body movements as indicators of sleep stage and wakefulness in infants and young children.

Conventional polysomnographic (PSG) sleep staging to sleep staging based on a static-charge-sensitive bed (SCSB) recording in infants and young children was compared. The study consisted of whole-night clinical sleep studies in 22 children at 24 weeks (SD 24, range 1-79 weeks) of age. Most of the children presented with respiratory disturbances during sleep. From the SCSB record, sleep stages were differentiated according to regularity of breathing, presence of body movements, and most important, presence of high-frequency components of breathing (SCSB spikes). With both methods, three sleep/wake stages were distinguished: rapid eye movement (REM) sleep, non-rapid eye movement (NREM) sleep and wakefulness. The average interscorer reliability of the PSG sleep staging controlled in nine subjects was 88%. The average concordance between the two methods ranged from 82 to 85%, depending on the criteria used for scoring the SCSB. The mean sensitivity of the SCSB to detect NREM sleep ranged from 77 to 90% and the mean sensitivity to detect REM sleep ranged from 61 to 86%. The mean positive predictive value was 89-96% for NREM sleep and 54-67% for REM sleep. In conclusion, REM sleep is characterized by irregular breathing with superimposed fast respiratory movements. These changes are specific enough to allow distinction between episodes of NREM sleep, REM sleep and wakefulness with the non-invasive SCSB method in infants and young children. Incomplete concordance between PSG and SCSB score was most frequently observed during sleep stage transition periods, where the behavioural state and electrophysiological criteria disagreed. When combined with the PSG, the SCSB provides complementary information about the behavioural state of child.