Prevalence and Risk Factors for Obstructive Sleep Apnea Syndrome Among Children and Adolescents with Cleft lip and Palate: A Survey Study in Hong Kong.

OBJECTIVE: To investigate the prevalence of obstructive sleep apnea syndrome (OSAS) risk and related risk factors among children and adolescents of Hong Kong with cleft lip and/or palate (CL/P). DESIGN: Retrospective survey study adopting three questionnaires, obstructive sleep apnea-18 (OSA-18), pediatric sleep questionnaire-22 (PSQ-22), and modified Epworth Sleepiness Scale (ESS). SETTINGS: Multicenter study in two public hospitals. PATIENTS: A total of 351 Chinese children and adolescents with non-syndromic CL/P (6-18-year-old, 57% males) visited between September 2017 and November 2019, with primary palatal repair surgery done before 3-year-old. MAIN OUTCOME MEASURE: Positive OSAS risk was determined based on cut-off ≥60 for OSA-18, ≥8 for PSQ-22, and >8 for ESS. Age, sex, overweight presence, cleft type, embryonic secondary palate involvement, palatal repair surgery, palatal revision surgery, and orthodontic treatment were analyzed as possible risk factors. RESULTS: A total of 9.5% of patients had positive OSAS risk based on OSA-18, 13.6% based on PSQ-22, and 13.2% according to ESS. A higher prevalence of patients with positive OSAS risk was of younger age (OSA-18, p = .034), had cleft involving embryonic secondary palate (PSQ-22, p = .009), and history of fixed orthodontic treatment (ESS, p = .002). The regression model identified only involvement of embryonic secondary palate as a risk factor (PSQ-22, odds ratio = 3.7, p = .015). CONCLUSIONS: OSAS risk among children and adolescents of Hong Kong with CL/P was 9.5% to 13.6%. Patients at higher risk were those with cleft involving embryonic secondary palate. OSAS risk assessment may be influenced by different aspects of the disease spectrum, and a multimodal approach should be considered for such assessment.

In vitro evaluation of the influence of velocity on sliding resistance of stainless steel arch wires in a self-ligating orthodontic bracket.

INTRODUCTION: Of the variables used by in vitro studies of resistance to sliding (RS) in orthodontics, sliding velocity (SV) of the wire is often the one farthest from its clinical counterpart. We investigated whether velocity influences the RS at values approximating the orthodontic movement. METHODS: A SS self-ligating bracket with a NiTi clip was fixed onto a custom-made model. Different shaped orthodontic SS wires of four sizes and two types (round, 0.020″ and 0.022″; rectangular, 0.016″×0.022″ and 0.017″×0.025″) were tested using an Instron® testing machine. Wires were pulled at four velocities (1×10-2  mm/s, 1×10-3  mm/s, 1×10-4  mm/s, 1×10-5  mm/s). Shapiro-Wilk test was used to evaluate the normal distribution of the data; two-way ANOVA was performed to compare means in the RS with wire characteristics and SV. Significance level was set at P<.05. RESULTS: RS was higher for rectangular wires, and for those with larger diameters. Lower SV was associated with lower RS, with wire type and size having an interaction effect. The RS relatively to SV can be represented as: RS ∝ α[ln(SV)]+ß, where α and ß are constants. CONCLUSIONS: At very low SV and low normal forces, SV influences the RS of SS archwires in orthodontic brackets, and the proportionality is logarithmic. Although respecting these parameters in vitro is challenging, quantitative evaluations of RS should be carried out at clinically relevant velocities if aiming at translational application in the clinical scenario.

Central deficiency of beta-endorphin in alcohol addicts.

Alcohol addiction may induce its dependence through a mechanism involving opiate receptors and opioid peptides. For these reasons, we measured ACTH, beta-lipotropin, and beta-endorphin in the plasma and cerebrospinal fluid (CSF) of 29 alcohol addicts and compared these values with those found in 8 normal volunteers. Although no significant differences existed in peripheral concentrations of the 3 peptides, alcohol addicts had beta-endorphin levels in CSF (mean +/- SE, 29.4 +/- 4.5 fmol/ml) that were 3-fold lower than those of the controls (98.4 +/- 10.5 fmol/ml; P less than 0.001) and ACTH levels 4 times higher than control values (30.0 +/- 1.8 vs. 7.4 +/- 1.1 fmol/ml in controls; P less than 0.001), while no difference was found in beta-lipotropin levels. These results suggest that alcohol addiction is associated with a marked alteration in the CSF content of proopiocortin-related peptides which may play a role in the alcohol-seeking behavior typical of the syndrome.

Meningeal leukemia diagnosed by cytocentrifuge study of cerebrospinal fluid. A study of 631 cerebrospinal fluid samples from 87 patients.

Owing to improved therapy and lengthened life span, the incidence of neuromeningeal involvement in leukemia is increasing. Careful examination of the cerebrospinal fluid (CSF) is important for an early diagnosis. Among the available techniques, the use of cytocentrifugation enables us to demonstrate central nervous system leukemia even if the white blood cell count in the CSF is under 10/cu mm. We describe the results obtained by examining 631 CSF samples from 87 patients affected by acute leukemia; central nervous system luekemia was found in 22.7% of the patients suffering from acute lymphocytic leukemia and in 6.4% of those with acute nonlymphocytic leukemia (ANLL), but this ratio is higher in ANLL compared with the survival as measured in months (a ratio of 2.0 in ANLL compared with 0.50 in acute lymphocytic leukemia). A "leukemic" CSF was found in 51.5% of prophylactically treated patients and in 73.1% of the untreated ones.

Familial hemiplegic migraine versus migraine with prolonged aura: an uncertain diagnosis in a family report.

Four of five members of a family complained of repeated attacks of hemiplegic migraine, migraine with aura of different types, or migraine without aura. The hemiplegia always outlasted the headache and was often accompanied by altered consciousness, aphasia, and, in one patient, coma; in this latter patient, the ictal EEG, recorded during two attacks, showed delta activity in the hemisphere contralateral to the hemiplegia. At least 2 months after their latest attacks, three patients showed dyscalculia, attentional disturbances, and impaired long-term verbal memory on neuropsychologic assessment. There were no cognitive disturbances in the unaffected relative. The severity of cognitive impairment appears to be correlated with migraine history. We attempt to classify these cases according to the criteria of the International Headache Society.

Synchronization of the EEG and sedation induced by neuroleptics depend upon blockade of both D1 and D2 dopamine receptors.

Blockade of dopamine (DA) receptors by neuroleptics tends to produce sedation, as shown by increased sleeping time, reduction of the arousal response to sensory stimuli and slowing of the electrical (EEG) activity of the brain. The EEG and behavioural effects of the selective compounds, SCH 23390 and raclopride, which block either D1 or D2 receptor subtypes, respectively were evaluated. Groups of rabbits were prepared for the measurement of EEG activity (neocortex and hippocampus). The EEG was analyzed visually and by spectral power analysis. Gross behaviour was also observed. The D1 antagonist, SCH 23390, by itself (0.03-0.3 mg/kg i.v.) produced small changes in the EEG and no evidence of sedation. Periods of slow waves occurred sporadically. Computerized EEG analysis showed moderate increases of total power density. The D2 receptor blocker, raclopride, alone (1-3 mg/kg i.v.) produced changes of the activity of the EEG, mostly, short periods of slow waves and slight increases of total power. No sedation was noted. Although both selective antagonists were studied at larger doses than those minimally effective, they produced slight EEG and behavioural changes which were not comparable with the marked actions produced by classical neuroleptics, such as haloperidol. However, when raclopride (1 mg/kg) was given after treatment with SCH 23390 (0.03 mg/kg) there was a marked synchronized activity in the EEG, associated with a state of sedation and diminished responsiveness to sensory stimuli. The data indicate that EEG synchronization and sedation, classically associated with treatment with neuroleptics, do not depend upon the selective blockade of either D1 or D2 receptors but, instead, require concurrent blockade of both subtypes of receptor.

Effects of remoxipride, a dopamine D-2 antagonist antipsychotic, on sleep-waking patterns and EEG activity in rats and rabbits.

The antipsychotic remoxipride, a selective dopamine D-2 receptor antagonist, was studied for its effects on sleep-waking patterns in the rat and electroencephalographic (EEG) activity in the rabbit. Haloperidol, which has lesser selectivity for D-2 receptors, was used for comparison. In the rat, remoxipride (1-10 mg/kg SC) did not affect either total sleep or non-rapid eye movement (non-REM) sleep. Only REM was slightly reduced by the high dose of 10 mg/kg. Haloperidol (0.1-1 mg/kg PO) enhanced duration of both total sleep and non-REM sleep. In the rabbit, remoxipride (3 and 10 mg/kg IV) induced no significant changes of the EEG power spectrum over 0.1-38.5 Hz or individual frequency bands. In both cortex and hippocampus the drug did not alter the arousal response to acoustic sensory stimuli. Plasma concentration of remoxipride 10 mg/kg IV in rabbits declined biexponentially and was 4 and 2 mumol/l at 30 min and 1 h, respectively. Haloperidol (0.3 and 1 mg/kg) slowed down the EEG activity, enhanced the power spectrum of the cortical and hippocampal activity, and significantly reduced the duration of arousal induced by sensory stimuli. The results indicate that, unlike haloperidol, remoxipride has weak or no sedative effects. The data also provide support to the notion that D-2 receptors are not involved in the regulation of states of sleep and sedation.

Blood noradrenaline and 5-HT levels in depressed women during amitriptyline or lithium treatment.

Noradrenaline levels and platelet and free serotonin concentrations were studied in depressed women in-patients (n=78) before and during amitriptyline (n=41) or lithium treatment (n=37). Pronounced monthly differences in platelet serotonin level have been shown in these subjects before treatment. In all clinical subgroups (neurotic, involutional, manic-depressive patients) a significant fall in platelet serotonin level was observed with amitriptyline medication while an increase was noted with lithium. No significant correlations between serotonin concentrations and clinical outcome were found. Amitriptyline treatment also produced a decrease in peripheral noradrenaline concentration in all subgroups, while an increase was observed with lithium. Some correlations between noradrenaline level and degree of depression were noted in patients treated with amitriptyline or lithium. A more extended analysis of blood amine levels could supply meaningful information on the peripheral action of antidepressive drugs on noradrenaline and serotonin concentrations in depression.

Aspects of amitriptyline and nortriptyline plasma levels monitoring in depression.

Fifty-nine depressed female inpatients were treated with 100 mg amitriptyline (AMT) IM for 4 weeks. Depression ratings and determinations of the parent drug and nortriptyline (NT) were performed weekly. No direct relationship between plasma AMT + NT concentrations and therapeutic response was apparent, but beneficial therapeutic responses and significantly lower side-effect scores were more frequently noted in subjects with concentrations in the 100-200 ng/ml range. AMT + NT concentrations were significantly correlated with age. No significant difference was found in the number of responders between younger and older subjects with two clinical improvement criteria; however, a significant difference emerged when a third more restrictive clinical outcome criterion was adopted. The implications of the present findings for patient treatment and for the interpretation of previous studies are discussed. The data collected point to a possible usefulness of monitoring AMT and NT plasma levels, even if further investigations are needed.

Neuropeptides and cerebral electric activity in rabbits.

The effects of some neuropeptides infused into the cerebral ventricles on the spontaneous cerebral electric activity were studied in unanasthetized rabbits. The following peptides were investigated: physalaemin, caerulein, bombesin, litorin (supplied by Farmitalia). The rabbits were prepared according to Monnier and Gangloff's [10] method in order to record the spontaneous cortical activity. Each of these substances affects the electroencephalographic (EEG) records in a specific and dose-related way. Bombesin induces a biphasic pattern (synchronization followed by a partial activation), litorin is partially activating and physalaemin brings about a marked desynchronization. In spite of the marked structural analogy between bombesin and litorin, their EEG effects differ.

Centrally administered N-terminal fragments of ACTH (1-10, 4-10, 4-9) display convulsant properties in rabbits.

Electroencephalographic and behavioral effects of the following ACTH fragments: 1-4, 4-9, 4-11, 1-10, 4-10, 1-13, 1-17 and 1-24 were studied in rabbits. Sequences 4-9, 1-10 and 4-10 displayed some epileptic properties, i.e., they induced epileptic seizures (only electrographic or also behavioral) or increased hippocampal spiking. The 4-9 sequence seemed to be the common sequence responsible for these proconvulsant effects. The possible involvement of the enkephalinergic system is discussed.

Synchronizing, sedative and anticonvulsive effects of centrally administered somatostatin in the conscious rabbit.

The effects of intracerebroventricular injection of somatostatin-14 on the cortical and deep structure electrical activity, somatic behavior and rectal temperature, were studied in 45 unanesthetized rabbits. In addition the antiepileptic action of the peptide was tested in these models: pentamethylenetetrazole-induced cortical spikes and waves, epileptic focus by topical application of strychnine and voltage-threshold for amygdala after-discharge. The results indicate that somatostatin exerts synchronizing, sedative and weak antiepileptic effects when centrally administered to rabbits.

Identification of N-carboxyethyl gamma-aminobutyric acid in bovine brain and human cerebrospinal fluid.

The di-carboxylated derivative of spermidine, N-carboxyethyl gamma-aminobutyric acid (CEGABA) has been identified in bovine brain and human cerebrospinal fluid by HPLC. This discovery strongly suggests the existence of a metabolic pathway connecting polyamines and GABA via putreanine and CEGABA through progressive oxidative deamination of the amino terminal groups in spermidine.

The spectrum of actions of thyrotropin-releasing hormone on the CNS: a polygraphic study on rabbits.

The effects of i.c.v. administered thyrotropin-releasing hormone (TRH) on EEG, rectal temperature and behaviour were studied on rabbits in basal conditions and after different pretreatments. The effects of TRH on the EEG and behaviour do not seem to involve serotoninergic, catecholaminergic and cholinergic systems. A possible involvement of the GABAergic system is hypothesized.

Aminoacid recovery via microdialysis and photoinduced focal cerebral ischemia in brain cortex of rats.

A photochemical method using the Rose Bengal dye as thrombogenic agent was employed to induce focal cerebral ischemia in frontoparietal cortex of rats. A transcerebral microdialysis probe was used to collect samples from ischemic cortical area. An increase in glutamate (6-fold) and in taurine (4-fold) within the first hour occurred. Neuropathological investigations demonstrate a reproducible damaged area surrounded by a thin peripheral area showing neuronal apoptotic phenomena. The method represents a reproducible model of focal cerebral ischemia with neuropathological aspects superimposable to those characteristic of thrombogenic stroke in man. This method could also be relevant in the study of neurotransmitters during the evolution of ischemia. Furthermore, the presence of apoptotic phenomena in the perilesional halo confirms an ischemic penumbra suggesting the significance of preclinical pharmacological trials.

Antagonism of EEGraphic and behavioural effects of methamphetamine by selective receptor blockers (SCH 23390 and raclopride) in the rabbit.

1. The interactions between selective D1 and D2 antagonists (SCH 23390 and raclopride) and methamphetamine on EEG arousal and behaviour was studied in rabbits. Haloperidol, a "classic neuroleptic" was used as reference drug. 2. Both 23390 and raclopride, which were used at low dosage (0.03-0.09 mg/kg i.v. for the former and 1-3 mg/kg for the latter), were able to block completely the behaviour induced but do not inhibit completely the EEG arousal pattern induced by methamphetamine. 3. The blockade of both behaviour and EEG arousal took only when the two drugs were administered concomitantly at the lower dosage. 4. The antagonistic effects obtained with the concomitantly administration of the two drugs were of higher degree in confront of those obtained with the pretreatment with haloperidol 0.3 mg/kg i.v. 5. Our data indicate that both D1 and D2 antagonists are able to block, at the dosage used, motor hyperactivity and stereotyped behaviour typically induced by methamphetamine and that SCH 23390 and raclopride are potentiated also in this experimental model.

Eegraphic and behavioural effects of ondansetron, a 5HT3 antagonist, in rabbits.

1. EEGraphic and behavioural effects of ondansetron, a 5HT3 antagonist, have been studied in the rabbit. Subsequently we tested the neurophysiological and behavioural interactions between ondansetron and L-5-HTP induced serotonergic syndrome. 2. The drug produced a dose-dependent (0.001, 0.01, 0.1 mg/kg i.v.) increase in the cortical power density spectrum, particularly in the range of the lowest frequencies bands. This effect is expression of cortical synchronization. 3. The lowest and mild dose, but not the highest, failed to produce behavioural sedation and to inhibit the arousal induced by vibroacustical stimulation. 4. L-5-HTP (10 mg/kg i.v.) administration generated a typical EEGraphic-behavioural pattern characterized by a decrease of cortical power spectrum density and stereotyped movements. The EEGraphic effects were significantly suppressed by administration of mild and higher doses of ondansetron, while the behavioural effects were inhibited by all doses tested. 5. It is concluded that ondansetron acts with considerably efficacy on central nervous system. The administration of low and mild doses shows a singular dissociation between EEGraphic and behavioural actions. The inhibition of the L-5-HTP behavioural syndrome by ondansetron suggests that this drug acts on behaviour only when there is an altered physiological pattern.

Role of dopamine D-1 and D-2 antagonists in a model of focal epilepsy induced by electrical stimulation of hippocampus and amygdala in the rabbit.

1. The differential role played by blockade of D-1 or D-2 dopamine receptors in mechanisms underlying seizures was studied in a model of EEG after-discharge induced by electrical stimulation of selective brain regions (dorsal hippocampus and amygdala) in the rabbit. 2. The D-2 antagonist haloperidol (1 mg/Kg) increased significantly after-discharge duration after stimulation of either hippocampus or amygdala and lowered after-discharge threshold in few animals. 3. The D-1 antagonist SCH 23390 (0.3 mg/Kg) caused no changes following stimulation of amygdala and reduced after-discharge duration when hippocampus was stimulated. 4. Haloperidol exerted a proconvulsant action in this experimental model, having a clearer influence on D-2 receptors. SCH 23390 had no effect on amygdala whereas it exerted protection on the hippocampus. 5. The present data suggest that D-1 and D-2 receptors have different roles in generating and spreading the epileptic activity.

Cognitive impairment and cerebral atrophy in "heavy drinkers".

1. Aim of the work was to verify the following three hypotheses in alcoholics: a) right hemisphere; b) diffuse brain deficit; c) anterior brain deficit, by means of a neuropsychological and a neuroradiological assessment. 2. 15 alcoholic right-hand male subjects and 15 matched controls were enrolled in the study. 3. Specifically designed neuropsychological testing was performed to investigate logical abilities, selective attention and memory. 4. Neurological investigation was performed by a standard CT scan to assess the degree and localization of brain damage. 5. Alcoholics performed worse than controls on some neuropsychological tests, i.e. Attention Matrices Test, Verbal Judgement Test, Forward Digit Span, Story Recall and Remote Memory Test. The analysis of variance adjusted by the attentional score showed no significant differences between alcoholics and controls. 6. Neuroradiological data showed a preeminent and a more frequent atrophy of the frontal region. 7. No correlations emerged between neuropsychological and neuroradiological data. 8. In conclusion, the hypothesis of anterior brain deficit seems to be confirmed by our study.

The effects of flumazenil on focal, electroinduced after-discharge in rabbits.

1. The anticonvulsive efficacy of flumazenil 10 mg/kg i.v., a BDZ antagonist, was studied in two models of experimental epilepsy electrically induced. 2. The EEG after-discharge, which was induced by the electrical stimulation of selected brain regions [(notably the dorsal hippocampus (Hip) and the amygdala (CAm)] was evaluated in rabbits pre- and post-drug administration. 3. In the animals submitted to electrical stimulation of the amygdala, flumazenil exerted a protective action, thereby inducing an increase in the after-discharge threshold and/or a decrease in after-discharge duration. 4. In the animals submitted to electrical stimulation of the hippocampus, flumazenil did not induced changes statistically significant. 5. Finally, the paper discusses the two possible mechanisms of action of flumazenil (a "per se" partial BDZ activity and/or a BDZ agonistic activity, which displaces the inverse agonist-like ligand) and the differencies in GABA distribution in the hippocampus and the amygdala.