Correlation between cephalometric variables and obstructive sleep apnoea severity in children.

AIM: Alterations in craniofacial growth have been associated with obstructive sleep apnoea in children. The main objectives of this study were to analyse the correlation between cephalometric variables and Obstructive Apnea/Hypopnea Index (OAHI) in order to investigate if craniofacial features may influence the severity of obstructive sleep apnoea and to study the correlation between upper nasopharyngeal width and maxillomandibular skeletal discrepancy in sagittal and vertical plane. MATERIALS AND METHODS: Study Design: Correlations between cephalometric variables and obstructive sleep apnoea/hypopnea index and between upper airways space and maxillomandibular skeletal discrepancy were investigated. Forty-seven children with obstructive sleep apnoea diagnosed by overnight sleep study (polysomnography) underwent a lateral radiograph, orthodontic and ear-nose-throat examinations. Cephalometric analysis according to Kirjavainen has been performed to define skeletal and upper airways variables. STATISTICS: Spearman's correlation analysis was performed between OAHI and all cephalometric variables. Pearson's correlation analysis was performed between cephalometric variables of upper airway space and cephalometric variables related to maxillomandibular discrepancy. Chi-square test was used to compare occlusal features with adenoidal and tonsillar hypertrophy. Kruskal-Wallis rank test was used to compare OAHI with occlusal variables and adenotonsillar hypertrophy. RESULTS: The results show a positive correlation between OAHI and maxillomandibular discrepancy measured by ANB angle (rho=0.32; p=0.023). A significant correlation was found between upper nasopharyngeal width and vertical maxillomandibular skeletal discrepancy: 1) ad1-PNS were correlated to Mandibular Plane/Sella- Nasion angle (r=-0.36; p=0.012), Palatal Plane/Mandibular Plane angle (r=-0.39; p=0.007), and Posterior-Anterior Facial Height % (r=0.29; p=0.045); 2) ad2-PNS was correlated to Palatal Plane/Mandibular Plane angle (r=-0.39; p=0.007). No statistically significant differences were found in non-parametric tests between OAHI and occlusal variables or adenoidal and tonsillar hypertrophy. CONCLUSIONS: The present study shows a significant correlation between maxillomandibular discrepancy and the severity of OSA. Moreover, the reduction of nasopharyngeal width was correlated to maxillomandibular hyperdivergent growth pattern. These results support the presence of a correlation between sleep-disordered breathing and craniofacial features even if the cause-effect relation is still unclear. Based on these evidences, we suggest the importance of orthodontic evaluation in the management of paediatric OSA.

Serum resistin levels in children with primary snoring.

Primary Snoring (PS) has been positioned at the milder end of the Sleep-Disordered Breathing severity continuum characterized by snoring and it is usually underestimated. PS is defined as snoring without apnea, frequent arousals, or gas exchange abnormalities and recent studies demonstrated that children with PS have increased blood pressure and reduced arterial distensibility. The association between adipokines and SDB has been recently investigated, though most of the studies were focused on OSAS where intermittent hypoxia characterizing the disease may lead to an inflammatory cascade and to the release of several adipokines, contributing to oxidative stress. Resistin, initially described s an adipokine increasing insulin resistance, has been recently identified as a novel important member of the cytokine family involved in the regulation of inflammation. The aim of our study was to investigate circulating resistin levels in normal weight children with PS. Sixty-five children of normal weight aged between 4 and 14 years of age were selected for habitual snoring. Children with positive polysomnography were excluded from the study. Serum resistin levels were detected in all children with PS. Thirty-three healthy non-snorer children with similar age, sex and BMI were selected as a control group. A significantly higher level of resistin was observed in patients with PS compared to the control group (4.67±1.91 ng/ml vs 3.98±1.58 ng/ml; p<0.01). Patients with inconclusive pulse oximetry showed significantly higher resistin levels than those with negative recordings recordings (5.29±1.91 ng/ml vs 4.20±1.93 ng/ml; p<0.008). Moreover, there was a significant increasing trend between sieric adipokine level and the frequency of snoring (p<0.006). Our results suggest that systemic inflammation and oxidative stress may also play a significant role in the pathophysiology of PS.

Recommendations for anesthesia and perioperative management of patients with neuromuscular disorders.

Patients with neuromuscular disorders are at high risk of intraoperative and postoperative complications. General anesthesia in these patients may exacerbate respiratory and cardiovascular failure due to a marked sensitivity to several anesthetic drugs. Moreover, succinylcholine and halogenated agents can trigger life-threatening reactions, such as malignant hyperthermia, rhabdomyolysis and severe hyperkalemia. Therefore, regional anesthesia should be used whenever possible. If general anesthesia is unavoidable, special precautions must be taken. In particular, for patients at increased risk of respiratory complications (i.e., postoperative atelectasis, acute respiratory failure, nosocomial infections), noninvasive ventilation associated with aggressive airway clearance techniques can successfully treat upper airway obstruction, hypoventilation and airway secretion retention, avoiding prolonged intubation and tracheotomy. Anesthesia and perioperative management of patients with neuromuscular disorders are described in this article. To grade the strength of recommendations and the quality of evidence we adopted the GRADE approach. In case of low-quality evidence, these recommendations represent the collective opinion of the expert panel.

Estrogen blocks the protective action of melatonin in a behavioral model of ethanol-induced hangover in mice.

Melatonin has antioxidant and neuroprotective properties in human beings and experimental models, as well as 'anti-estrogenic' effects. Ethanol (EtOH) affects various behavioral parameters during a period known as ethanol-induced hangover. Our study evaluated the neuroprotective effect of melatonin on motor performance during ethanol hangover in male and female Swiss mice. The females were subjected to specific hormonal states: ovariectomized (OVX) and OVX estrogenized (OVX-E(2)). Mice received melatonin (25 µg/ml) or vehicle in their drinking water for seven days and were given intraperitoneal (i.p.) injections of EtOH (3.8 g/kg) or saline on the morning of the eighth day. Motor performance was evaluated by the tightrope test 6h after EtOH exposure (hangover onset). During ethanol hangover, males exhibited lower motor performance than controls (p<0.01) but pretreatment with melatonin significantly improved performance during hangover (p<0.05). In females, melatonin treatment before ethanol-induced hangover led to a better motor performance in OVX compared with intact females (p<0.01) and a lower performance in OVX-E(2) compared with not-estrogenized OVX (p<0.05). Consequently, estrogen reversed the motor performance enhancement afforded by melatonin. We conclude that estrogen interferes with the protective action of melatonin on motor performance during ethanol hangover.

Dumping syndrome: an unusual cause of severe hyperinsulinemic hypoglycemia in neurologically impaired children with gastrostomy.

This paper describes severe hyperinsulinemic hypoglycemia during bolus enteral feeding in two neurologically impaired children. Both children were affected by dysphagia with swallowing difficulties; caloric intake was inadequate. For these reasons, percutaneous endoscopic gastrostomy had been positioned during the first months of life. In one patient due to persisting vomiting, after a few months, a gastrojejunal tube (PEG-J) was inserted. Hypoglycemia was revealed by routine blood tests, without evidence of specific symptoms. Continuous subcutaneous glucose monitoring showed wide glucose excursions, ranging from hypoglycemia to hyperglycemia. Extremely high levels of insulin were detected at the time of hypoglycemia. A diagnosis of dumping syndrome (DS) was suspected in both children. In the child with PEG, the tip of the gastrostomy catheter was found to be lying in the bulbus duodeni. Once this had been pulled back, hypoglycemic episodes disappeared. The child with PEG-J needed continuous enteral feeding to reach a normal glucose balance. DS is a relatively common complication in children with gastrostomy, but extremely irregular glucose levels, ranging from hypoglycemia to hyperglycemia, and increased insulin secretion had not been previously demonstrated. The incidence of DS is probably underestimated in children receiving enteral feeding for neurological impairment. In these patients intensive monitoring of blood glucose levels should be performed to calibrate meals. Repeated underestimated hypoglycemic episodes could worsen neurological damage and cause a deterioration in clinical conditions.

Fos immunoreactivity in the suprachiasmatic nuclei of golden hamsters bearing an ectopic pituitary graft.

Young male golden hamsters, made hyperprolactinemic by a pituitary graft under the kidney capsule, were exposed to a light pulse (1,000 lx/30 min) at Zeitgeber time (ZT) 18. Controls included hamsters receiving a sham graft (muscle). Fos immunoreactive cells were counted in both suprachiasmatic nuclei (SCN) of each animal, using an image analyzer system. The Fos immunoreactivity (Fos-ir) of the ventrolateral and dorsomedial SCN regions was greater in the pituitary-grafted hamsters. Indeed, light induced the greatest response in grafted animals in both SCN regions. However, the SCN of pituitary-grafted hamsters in the absence of light showed the lowest Fos-ir in both regions. The results support the occurrence of a dual effect of hyperprolactinemia on Fos-ir in the SCN of hamsters at ZT 18, with inhibition of Fos expression in the absence of light and potentiation of early gene expression when animals were exposed to a light pulse.

Effect of unilateral superior cervical ganglionectomy on mandibular incisor eruption rate in rats.

To assess the effect of sympathectomy on rat tooth eruption, the effect of a unilateral superior cervical ganglionectomy (SCGx) on eruption rate of ipsi- and contralateral lower incisors was examined. Two experiments were performed. In a first experiment, the eruption rate of ipsilaterally denervated incisors was similar to that of contralaterally innervated incisors, when assessed for up to 28 days after surgery. In a second experiment, under conditions of unilateral unimpeded eruption of incisors performed ipsilaterally or contralaterally to a unilateral SCGx, a significantly lower eruption rate of denervated incisors at the impeded eruption side, and a significantly higher eruption rate of denervated incisors at the unimpeded side were observed, when computed every 2 days. Significant differences in individual Student's t tests at every time interval occurred mainly during the first and the last week of examination. When average daily eruption rate was computed in weekly intervals, a significant interaction between SCGx and the side of impeded or unimpeded eruption was found in a factorial ANOVA, that is, for each of the 4 weeks of examination, sympathetically denervated incisors showed lower eruption rates at the impeded eruption side, and higher eruption rates at the unimpeded side. These results indicate that incisor eruption is not modified by a local sympathetic denervation unless the contralateral lower rat incisor is cut out of occlusion.

Effect of parasympathetic decentralization on interferon-gamma release from rat submandibular lymph nodes in vitro.

The aim of this study was to examine the regulation of interferon (IFN)-gamma release by cells from submandibular lymph nodes of rats subjected to a unilateral parasympathetic decentralization by severing the ipsilateral chorda tympani 7 days earlier. Cells obtained from contralateral sham-operated submandibular lymph nodes were employed as control. Parasympathetic decentralization of lymph nodes resulted in significantly less IFN-gamma release as compared to that found in innervated lymph nodes. Mitogens (lipopolysaccharide, concanavalin A) stimulated IFN-gamma release in cells derived from the innervated lymph nodes only. The muscarinic agonist metacholine decreased IFN-gamma release in cells derived from innervated lymph nodes. At the highest concentration employed (10(-4) M), metacholine suppressed the stimulatory effect of mitogens on IFN-gamma release in cells of innervated lymph nodes while the muscarinic antagonist atropine (10(-8) - 10(-4) M) lacked to affect IFN-gamma release. Addition of nicotine (10(-5) - 10(-3) M) failed to modify IFN-gamma release. The results support the occurrence of significant effects of local parasympathetics in modulating IFN-gamma release by submandibular lymph nodes.

Effect of superior cervical ganglionectomy on 24-h variations in hormone secretion from the anterior hypophysis and in hypothalamic monoamine turnover during the preclinical phase of Freund's adjuvant arthritis in rats.

The effect of superior cervical ganglionectomy (SCGx) on 24-h rhythms of circulating adrenocorticotropic hormone (ACTH), growth hormone (GH), prolactin and luteinizing hormone (LH) and of hypothalamic noradrenaline content and dopamine and serotonin turnover, was assessed in rats 3 days after administering Freund's complete adjuvant. In sham-operated rats, Freund's adjuvant injection increased serum ACTH without affecting its diurnal rhythmicity. SCGx, performed 10 days earlier, suppressed 24-h rhythmicity and augmented mean values of circulating ACTH. A depressive effect of immunization on GH release was found in both sham-operated and SCGx rats. GH concentrations did not exhibit diurnal rhythmicity and decreased after immunization. Time-of-day-related changes in serum prolactin were significant for all examined groups, except for SCGx-immunized rats. Freund's adjuvant administration augmented prolactin secretion. Daily changes in serum LH concentration and a decrease after immunization were found in both sham-operated and SCGx rats. SCGx: (i) counteracted inhibition of daily variations of noradrenaline content in medial hypothalamus of Freund's adjuvant-injected rats; (ii) decreased anterior hypothalamic dopamine turnover and augmented it in the medial hypothalamus; (iii) lowered amplitude of serotonin turnover rhythm in medial hypothalamus. The data indicate that several early changes in levels and 24-h rhythms of circulating ACTH and prolactin, and in hypothalamic noradrenaline content and dopamine and serotonin turnover, were modified by a previous SCGx in Freund's adjuvant-injected rats.

Effect of melatonin on bone metabolism in ovariectomized rats.

To assess the effect of pharmacological dose of melatonin on bone metabolism in ovariectomized rats, urinary deoxypyridinoline (a marker of bone resorption) and calcium excretion, circulating levels of calcium, phosphorus and bone alkaline phosphatase activity (a marker of bone formation), and bone mineral density (BMD), mineral content (BMC) and bone area (BA) of total body, were measured in adult rats for up to 60 days after surgery. Rats received melatonin in the drinking water (25 microg/ml water) or drinking water alone. Urinary deoxypyridinoline increased significantly after ovariectomy by 51% (30 days after surgery) and by 47% (60 days after surgery). The increase in urinary deoxypyridinoline found 30 days after ovariectomy was not observed in melatonin-treated rats. Urinary calcium concentration was similar in the 4 experimental groups studied, as was the circulating calcium concentration at every time interval examined. Fifteen days after surgery, a significant increase in serum phosphorus and bone alkaline phosphatase levels occurred in ovariectomized rats receiving melatonin as compared to their controls. Sixty days after surgery BMD, BMC and BA decreased significantly in ovariectomized rats, an effect not modified by melatonin. Serum estradiol decreased significantly by 30 days after ovariectomy to attain values close to the limit of detection of the assay by 60 days after ovariectomy. The results support the conclusion that a pharmacological amount of melatonin modifies bone remodeling after ovariectomy and that the effect may need adequate concentrations of estradiol.

Effect of unilateral superior cervical ganglionectomy on bone mineral content and density of rat's mandible.

To assess the effect of a local sympathectomy on bone metabolism, the effect of a unilateral superior cervical ganglionectomy (Gx) on growth and bone mineral content and density of the ipsi- and contralateral mandibles was examined in female rats. A significant increase in the hemi-mandibular bone ipsilateral to Gx was found as compared to the contralateral, sham-operated side 30 days, but not 15 days, after surgery. Bone mineral content of the hemi-mandibular bones was significantly lower in the side ipsilateral to Gx in the group of rats killed on the 30th day after surgery. Since no difference in areas between innervated and denervated hemi-mandibles was found, bone mineral density was also significantly lower in the hemi-mandible ipsilateral to Gx. The results further support that a regional sympathectomy causes qualitative alterations in bone modeling and remodeling, leading to bone resorption.

Seasonally dependent effect of ectopic pituitary grafts on 24-hour rhythms in serum prolactin and gonadotropins in rats.

To assess to what extent the presence of an ectopic pituitary differentially affected circulating prolactin (PRL) and gonadotropin levels at different times of the year, rats kept under 12 h light, 12 h dark (12:12 LD) photoperiods and receiving a pituitary graft or a sham operation in summer or winter were examined 3 months later. In both male and female sham-operated rats, a circadian variation in serum PRL levels was found, with an acrophase varying from 21:53 h to 00:54 h and the mesor and amplitude higher in spring than autumn in males and higher in autumn than in spring in females. After grafting a pituitary, changes in serum PRL related to time of day were no longer observed. In pituitary-grafted male rats killed during spring, serum PRL levels were higher than controls at only a few time points throughout the 24 h cycle, whereas in rats killed during autumn, there were no significant differences in PRL levels between grafted and control rats. Pituitary-grafted female rats killed during spring showed serum PRL levels significantly higher than those of sham-operated rats, while in female rats killed in autumn, PRL levels of pituitary-grafted and sham-operated rats did not differ. Significant variations of luteinizing hormone (LH) related to time of day were found in sham-operated male rats only, with acrophases at 23:52 h and 00:24 h for spring and autumn, respectively, and the mesor and amplitude of the rhythm significantly higher in autumn. Pituitary transplants suppressed 24th variations in circulating LH and depressed its levels during the two seasons examined. As far as follicle-stimulating hormone (FSH), pituitary grafts decreased circulating levels, with the extent of decrease higher during autumn than in spring. The results indicate that some endocrine consequences of the grafting of an ectopic pituitary are dependent on time of year.

Evidence that a novel type of progestational phase control occurs in the corn mouse, a South American murid rodent.

Most Muridae display a short luteal phase that becomes functional as a consequence of the prolactin release induced by the stimulation of copulation and/or lactation. The corn mouse also shows a short luteal phase, and we wanted to know whether copulation and/or lactation would release prolactin and maintain progesterone secretion in this species. Females in postpartum estrus were either allowed to copulate with an intact male or not, and either to lactate their young or not. Afterward, plasma progesterone was elevated over the baseline level only in females that had copulated and were bearing growing embryos (whether or not they were lactating), while prolactin was elevated only in lactating females. In another experiment, endometrial scratching induced decidualization both in females that had copulated with a vasectomized male and in those that had not copulated; sham operations had no effect in either case. Progesterone levels were elevated in decidualized animals as compared with their sham-operated controls. Results indicate that the initiation of the progestational phase in the corn mouse is not dependent on prolactin release. A short luteal phase during which nidation may occur has not yet been described in any other mammal.

No triazolam-induced expression of Fos protein in raphe nuclei of the male Syrian hamster.

While the visual projections to the suprachiasmatic nuclei (SCN) play a role in mediating the effects of light on circadian rhythms, the functional significance of the serotonergic projection from the raphe nuclei (RN) to the SCN is uncertain. Because previous results indicated that RN would appear to be a likely site for triazolam (Tz)-induced phase shifts, we used the expression of Fos-protein as a marker of Tz-induced neuronal activation. Immunocytochemistry was used to visualize the presence of Fos-like protein. Tz-induced Fos-labeled nuclei were found in superior colliculi, Edinger-Westphal nuclei (EW) and dorsal tegmental nuclei (DTg), but not in the RN. The SCN showed only occasionally labeled nuclei in all experimental groups, whereas there was no Tz-induced Fos-immunoreactivity in the intergeniculate leaflet (IGL). The present data not necessarily exclude the implication of the RN in the phase shifting effect of Tz. The phase shift could still be accomplished using a different set of immediate early genes (IEG), or without an IEG response. Alternatively, as will be discussed, other pathways could mediate the phase shifting effect of Tz.

Enhanced allergic sensitisation related to parental smoking.

The objective of this study was to assess the role of parental smoking in changes, after a four year interval (1983-7), in the prevalence and severity of the atopic state in 166 pre-adolescent children. Allergy skin prick tests were related to parental smoking habits and their changes during this same interval. The total number of cigarettes smoked by parents decreased in 56 families while it increased in only 16. Boys had significantly more persistently positive skin tests and changed more frequently from negative to positive. The skin test index did not show significant changes in girls. This index did not change in children of persistent non-smokers or those starting to smoke during this period, while it increased among sons of those that quit smoking and of persistent smokers. This was not only due to those boys who became skin test positive during follow up. When analysis was restricted to 14 boys who had been skin test positive in 1983 and whose parents were persistent smokers, the index increased in eight, remained unchanged in four, and decreased in only two. This report supports the hypothesis that parental smoking is a factor that, together with specific allergenic exposure, may enhance allergic sensitisation in children.

T-cell subpopulations in pediatric healthy children: age-normal values.

Assessment of the percentage and absolute number of T cells as well as of their main subpopulations is presently a routine procedure for the diagnosis and follow-up of a wide array of pediatric immunologic disorders. For several clinical applications (severe immunodeficiencies or leukaemias) the diagnostic usefulness of their enumeration does not require close comparison with age normal values, while in other circumstances such as follow-up of immunomodulating or immunosuppressive treatments or detection of minor immune defects, the expected changes of T cell subsets are more subtile and they are likely to be detected only by comparison with well-defined age normal values. In the present study CD3, CD4 and CD8 positive cells were enumerated in a group of 410 healthy children of age ranging from 30 days to 9 years. No significant changes in percentage or absolute number were observed during infancy and childhood. Furthermore the sum of CD4 and CD8 positive cells was close to the percentage of CD3 positive cells, suggesting a phenotype maturity of T cells from infancy.

Increased serum IgE and increased prevalence of eosinophilia in 9-year-old children of smoking parents.

We studied the relationship of serum IgE levels and eosinophil counts with passive smoking in 9-year-old, nonselected children from three Italian towns near Rome. Male children of smoking parents had a significantly higher total count and percentage of eosinophils (p = 0.008) and higher IgE levels (p = 0.01) than male children of nonsmoking parents. Prevalence of eosinophilia (defined as greater than or equal to 4% of total white blood cell count) was significantly correlated with the number of cigarettes smoked by parents among boys (p = 0.003) but not among girls (p = 0.20). There was a significant trend (p = 0.008) for prevalence of eosinophilia to increase with increasing levels of serum IgE. For any given level of serum IgE, the frequency of eosinophilia was higher among children of smoking parents than among children of nonsmoking parents. When parental smoking was studied in a multivariable analysis and after controlling for the other variable, it was still significantly associated with eosinophilia in the children of these smoking parents but not with serum IgE levels. We conclude that parental smoking is associated with a significant enhancement of the expression of the most important markers of allergic sensitization in the children of smoking parents. This is particularly evident for boys and may explain, at least in part, the increased frequency of respiratory symptoms in children of smoking parents.