The relationship between Chiari 1.5 malformation and sleep-related breathing disorders on polysomnography.

OBJECTIVE: Chiari 1.5 malformation is a subgroup of the Chiari malformation in which tonsillar descent into the foramen magnum is accompanied by brainstem descent. No data exist on whether operative decompression in patients with Chiari 1.5 improves sleep-related breathing disorders (SRBDs) and whether there are radiological parameters predicting improvement. METHODS: The authors performed a retrospective cohort study of consecutive pediatric patients with Chiari 1.5 malformation and SRBDs at the Alberta Children's Hospital. An SRBD was characterized using nocturnal polysomnography (PSG), specifically with the apnea-hypopnea index (AHI), the obstructive apnea index, and the central apnea index. Preoperative values for each of these indices were compared to those following surgical decompression. The authors also compared preoperative radiographic factors as predictors to both preoperative AHI and the change in AHI with surgery. Radiological factors included tonsillar and obex descent beneath the basion-opisthion line, the presence of syringomyelia, the frontooccipital horn ratio, the pB-C2 line, and the clivoaxial angle. RESULTS: Seven patients (5 males, 2 females) met inclusion criteria. One patient had two surgical decompressions, each with pre- and postoperative PSG studies (n = 8). The median age was 9 years. Before surgical decompression, 75% underwent tonsillectomy/adenoidectomy. The majority (87.5%) experienced snoring/witnessed apnea preoperatively. The median tonsillar and obex descent values were 21.3 mm and 11.2 mm, respectively. The median values for the pB-C2 line and clivoaxial angle were 5.4 mm (interquartile range [IQR] 4.5 mm, 6.8 mm) and 144° (IQR 139°, 167°), respectively. There was a statistically significant change from preoperative to postoperative AHI (19.7 vs 5.1, p = 0.015) and obstructive apnea index (4.5 vs 1.0, p = 0.01). There was no significant change in the central apnea index with surgery (0.9 vs 0.3, p = 0.12). No radiological factors were statistically significant in predicting preoperative AHI and change in AHI. CONCLUSIONS: This is the first series of pediatric patients with Chiari 1.5 with SRBDs who demonstrated a marked improvement in their PSG results postdecompression. Sleep apnea has a significant impact on learning and development in children, highlighting the urgency to recognize Chiari 1.5 as a more severe form of the Chiari I malformation.

Noninvasive monitoring of CO2 during polysomnography: a review of the recent literature.

PURPOSE OF REVIEW: Sleep-related breathing disorders are complex conditions that require the integration of clinical and sleep laboratory findings to support a diagnosis. Analysis of carbon dioxide (CO2) levels during sleep provides important additional information to the clinician that is not obtained from other polysomnographic indices, and that may have a direct impact on both diagnosis and patient mortality. Although arterial blood gas (ABG) is considered the gold standard for assessing PaCO2 levels, there are numerous drawbacks. Noninvasive methods for PaCO2 estimation include end-tidal and transcutaneous monitoring, which allow for continuous monitoring of trends. RECENT FINDINGS: Review of the recent literature suggests that transcutaneous methods correlate strongly with PaCO2 levels and can provide an accurate surrogate in replacement of ABGs. End-tidal methods provide breath to breath information that can be used to assess hypoventilation; however, they have more variability, especially in patients with increased dead space and small tidal volumes. To date, however, there are limited studies investigating noninvasive CO2 monitoring during sleep. SUMMARY: Given the benefits of CO2 monitoring and the importance of assessing for hypercapnia, noninvasive continuous CO2 monitoring should be considered for all patients undergoing polysomnography.

Noninvasive Positive Airway Pressure Treatment in Children Less Than 12 Months of Age.

Study Objectives. We identified the associated conditions of patients less than 12 months of age who were referred for polysomnogram (PSG) studies. We collated PSG findings and physician interpretation. We determined the correlation between the recommended treatment by the PSG interpreting physician and actual prescribed treatment by the referring or subjects' physician. We determined adherence with noninvasive positive airway pressure (PAP) treatment. Methods. This was a retrospective cohort study. Participants included children less than 12 months of age referred for PSG studies between 2007 and 2012. Results. 92 patients under the age of 12 months were included in the study analysis. Mean (standard deviation, SD) age in days at time of the PSG study was 208.5 (101.2). 35 (38%) patients had a diagnosis of Trisomy 21. Seven (8%) patients had no prior diagnosis. Median (Q1, Q3) apnea hypopnea index (AHI) was 22.5 (11.3-37.0). Agreement between the PSG interpreting physician's recommendation and actual prescribed treatment by the referring or subjects' physician was 85.9% [95% CI 77.1-91.6]. Mean (SD) percentage days with PAP therapy usage more than 4 hours was 25.2% (32). Conclusions. In our experience, despite consistent physician messaging to families, adherence with noninvasive PAP treatment is low.

Prevalence of Interictal Epileptiform Discharges in Children Less Than One Year of Age Referred for Polysomnography.

This study aimed to identify the prevalence of interictal epileptiform discharges (IEDs) in patients less than one year of age referred for polysomnogram (PSG), to quantify the number of IEDs and characterize sleep stage(s) during which IEDs occur, and to relate the reason for PSG referral and IED frequency. This was a retrospective cohort study of children less than 12 months of age referred for PSG studies. Fifty study participants had sufficient EEG data, and 49 were included in the study analysis. We identified an IED prevalence rate of 28% over the 2-year study period. The mean number (Standard Deviation; SD) of IEDs per hour of total sleep time was 0.4 (1.2). IEDs occurred most frequently in non-rapid eye movement (NREM) stages 2 and 3 of sleep. The most common reason for PSG referral in this patient cohort was for obstructive sleep apnea (OSA) (42/50). We concluded that patients less than 12 months of age referred for PSG may have abnormal brain activity. The relationship of that activity to PSG findings is unclear. This study offers a systematic process of identifying IEDs that should prompt referral to a neurologist for further evaluation.

Granulomatous lymphocytic interstitial lung disease in infancy.

The authors report a case involving a child with chronic respiratory symptoms, who did not respond to conventional treatment. Low serum immunoglobin levels and pathological findings on lung biopsy revealed an unusual diagnosis for his age group. A specific treatment led to clinical improvement.

Effect of inhaled hypertonic saline on hospital admission rate in children with viral bronchiolitis: a randomized trial.

OBJECTIVE: We sought to determine whether inhaled 3% hypertonic saline (HS) reduces admission to hospital in ambulatory children with moderately severe viral bronchiolitis. Secondary objectives compared changes in respiratory scores before and after treatment and assessed the need for unscheduled medical intervention within 7 days. METHODS: Children under the age of 2 years presenting with moderately severe viral bronchiolitis to the emergency department of 4 general hospitals from November 2008 to March 2009 were randomly assigned to receive 3 consecutive 4-mL doses of nebulized 3% HS (treatment group) or 0.9% normal saline (NS; control group) in a double blind fashion, each coadministered with 1 mg salbutamol. Outcome measures included the difference in hospital admission rate and changes in respiratory distress scores. RESULTS: A total of 81 children (mean age 8.9 mo, range 0.7-22 mo) were assessed over 88 visits on an intention-to-treat basis. No statistically significant differences were found between treatment groups. Children in the HS group had a nonsignificant trend toward greater improvement compared with NS controls with a same-day admission rate of 18% (95% confidence interval [CI] 9%-32%) versus 27% (95% CI 16%-42%), respectively. Respiratory Assessment Change Scores (RACS) favoured the HS group over NS controls (mean RACS 4.7 [95% CI 3.6-5.8] v. 3.7 [95% CI 2.5-4.9], respectively), although the CIs overlap and these differences were not statistically significant. CONCLUSION: The short-term use of nebulized 3% HS did not result in any statistically significant benefits, although a nonsignificant trend toward a decrease in admission rate and improvement in respiratory distress was found. A larger study would be required to determine whether these trends arise from a clinically relevant treatment effect.

A influência da goma de Cissus nas propriedades mecânicas e de liberação de comprimidos de paracetamol - uma análise fatorial / The influence of cissus gum on the mechanical and release properties of paracetamol tablets ? a factorial analysis

The quantitative effects of a new gum, used as a binder, on the mechanical and release properties of paracetamol tablet formulations were analyzed in a 23 full factorial experiment. Cissus gum extracted from Cissus populnea Guill. & Perr. (Vitaceae) was compared with official gelatin. The individual and interaction effects of type of binder, concentration of binder and packing fraction on the friability, tensile strength, brittle fracture index, disintegration time and drug release profile of tablets were determined. Changing the binder from gelatin to cissus gum led to an increase in friability and a decrease in tensile strength, brittle fracture index (BFI) and drug release variables. Increasing binder concentration from 2.0w/w to 4.0%w/w, and increasing relative density from 0.80 to 0.90, led to increases in lamination tendency and release rate of the formulations. Tablets containing gelatin had higher tensile strength, lower friability, longer disintegration time and a greater tendency to laminate than those with cissus gum. Hence, care must be taken in choosing a suitable binder for tablet formulations, with respect to their mechanical and release characteristics. The study suggests that cissus gum should be preferred to gelatin in tablet formulations that tend to cap or laminate or in formulations meant for rapid drug release

Os efeitos quantitativos de uma nova goma como agente agregante nas propriedades mecânicas e de liberação de formulações de comprimidos de paracetamol foram avaliados utilizando um modelo fatorial 23 experimental. A goma foi obtida de Cissus populnea Guill. & Perr. (Vitaceae) e comparada com a gelatina oficial. Os efeitos individuais e de interação do tipo de agregante, concentração de agregante, porcentagem de friabilidade, resistência à tração, índice de fratura e tempo de desintegração e liberação do fármaco dos comprimidos foram determinados. A mudança do agente agregante de gelatina para goma de cissus levou a um aumento da friabilidade e a uma diminuição na resistência à tração, no índice de fratura e nos parâmetros de liberação do fármaco. O aumento da concentração do agregante de 2,0% p/p para 4,0% p/p e da densidade relativa de 0,80 a 0,90 levou a um aumento na tendência de laminação e na taxa de liberação das formulações. Comprimidos contendo gelatina apresentaram maior resistência à tração com menor friabilidade e maior tempo de desintegração e dissolução com maior tendência para laminado, quando comparados com a goma de cissus. Por isso, cuidados devem ser tomados na escolha de um agente agregante para formulações de comprimidos no que diz respeito às características mecânicas e de liberação. O estudo sugere que a goma de cissus pode ser empregada ao invés de gelatina em formulações de comprimidos que apresentam tendência de formar laminado ou decapeamento ou em formulações para liberação controlada de fármacos.

The cell migration molecule UNC-53/NAV2 is linked to the ARP2/3 complex by ABI-1.

The shape changes that are required to position a cell to migrate or grow out in a particular direction involve a coordinated reorganization of the actin cytoskeleton. Although it is known that the ARP2/3 complex nucleates actin filament assembly, exactly how the information from guidance cues is integrated to elicit ARP2/3-mediated remodeling during outgrowth remains vague. Previous studies have shown that C. elegans UNC-53 and its vertebrate homolog NAV (Neuronal Navigators) are required for the migration of cells and neuronal processes. We have identified ABI-1 as a novel molecular partner of UNC-53/NAV2 and have found that a restricted calponin homology (CH) domain of UNC-53 is sufficient to bind ABI-1. ABI-1 and UNC-53 have an overlapping expression pattern, and display similar cell migration phenotypes in the excretory cell, and in mechanosensory and motoneurons. Migration defects were also observed after RNAi of proteins known to function with abi-1 in actin dynamics, including nck-1, wve-1 and arx-2. We propose that UNC-53/NAV2, through its CH domain, acts as a scaffold that links ABI-1 to the ARP2/3 complex to regulate actin cytoskeleton remodeling.