What Are the Etiology and Epidemiology of Out‐of‐hospital Pediatric Cardiopulmonary Arrest in Ontario,Canada?

Background: Pediatric cardiopulmonary arrest (CPA) outside of the hospital has a very high mortality rate. Objectives: To evaluate the etiology and initial compromise of pediatric CPA cases in hopes of developing strategies to improve out‐of‐hospital resuscitation. Methods: The Ontario Prehospital Advanced Life Support (OPALS) study was a large multicenter initiative to evaluate the impact of emergency medical services (EMS) programs on 17 communities with 40,000 critically ill and injured patients who were older than 11 years. As part of this study, the authors conducted a retrospective observational cohort study that included all children younger than 18 years of age with out‐of‐hospital CPA, during an 11‐year period from 1991–2002. CPA was defined as patient being pulseless, apneic, and requiring chest compressions. Data were collected from ambulance call reports and centralized dispatch data and were reviewed by two independent investigators. Results: There were 503 children with CPA in the sample. Mean age was 5.6 years (range, 0–17 yr); 58.4% of patients were male, and 37.8% were younger than 1 year of age. Cardiopulmonary resuscitation (CPR) first was started by a bystander in 32.4% of cases, whereas 66.0% were unwitnessed arrests. Initial rhythms were asystole 77.2% of the time, pulseless electrical activity 16.4% of the time, and ventricular fibrillation or ventricular tachycardia 4% of the time. Annual incidence was 9.1/100,000 children. CPA was witnessed in 34.0% of cases; 80.7% of these were bystander‐witnessed, and 18.1% were EMS‐witnessed. Primary pathogenic cause of arrest was medical in 61.2% of cases, trauma in 37.2% of cases, and indeterminate in 1.6% of cases. Initial underlying physiologic compromise of witnessed arrests was judged to be respiratory in 39.8% of cases, sudden collapse (presumed electrical) in 16.4% of cases, progressive shock in 1.2% of cases, and indeterminate in 42.6% of cases. Presumed etiology was trauma, 37.6%; sudden infant death syndrome (SIDS), 20.3%; and respiratory disease, 11.6%, most commonly. Survival to hospital discharge was 2.0%. Conclusions: This is one of the largest population‐based, prospective cohorts of pediatric CPA reported to date, and it reveals that most pediatric arrests are unwitnessed and receive no bystander CPR. Those that are witnessed most often are caused by respiratory arrests or trauma. Trauma, SIDS, and respiratory disease are the most common etiologies overall. These data are vital to planning large resuscitation trials looking at specific interventions (i.e., increasing bystander CPR) and highlight the need for better strategies for prevention and early recognition.     

Resorption rate and biocompatibility characteristics of two polyester ventilation tubes in a guinea pig model

OBJECTIVES: Determine the resorption rate and biocompatibility characteristics of 2 polyester ventilation tubes, and to determine whether soap and water exposure accelerates polyester tube degradation. STUDY DESIGN AND SETTING: 50/50 poly (D, L-lactide-co-glycolide; PLGA-50) and poly (L-lactide; PLA) polymers were placed into the tympanic membranes of Hartley pigmented guinea pigs. Integrity of the tubes was determined by weekly otoscopic examination. Biocompatibility was assessed by comparing auditory brainstem response (ABR) thresholds and by examining tympanic membrane changes following tube resorption. Shah minigrommet ventilation tubes were used as controls. In the second portion of this study, implanted PLGA-50 and PLA tubes were exposed weekly to a mixture of soap and water (1:5) until complete resorption was observed. Biocompatibility was assessed by periodic ABR testing and tympanic membrane examination. RESULTS: The PLA tubes remained in the tympanic membrane for a longer period (63.2 +/- 19.3 days) than the PLGA-50 (18.8 +/- 8.1 days). The tympanic membrane and resorbable tube interface demonstrated equivalent findings for auditory thresholds and tissue histopathology at the implant site compared to nonresorbable controls. The resorption behavior was not altered by exposure to soap and water. Tympanic membranes of all animals following tube degradation and soap water exposure were intact with minimal scarring and no signs of persistent foreign body response. The histological analysis showed that implantation of resorbable tubes was not accompanied by secondary infection with otorrhea through the tube, did not result in a permanent perforation or dislocation of the tube into the middle ear cavity, and was not followed by excess tympanosclerosis or localized or diffuse membrane atrophy. CONCLUSIONS AND SIGNIFICANCE: Resorbable polyester pressure equalization tubes demonstrate predictable resorption behavior and similar biocompatibility characteristics when compared with nonresorbable Shah minigrommet ventilation tubes. Exposure to soap water does not accelerate polyester tube degradation nor change the host tissue response during the indwelling period or after complete resorption. The data suggests that resorbable ventilation tubes are substantially equivalent to other FDA-approved tympanostomy devices with regard to safety and biocompatibility in the guinea pig model examined and may provide improved clinical performance by combining this approach with sustained release technology. EBM RATING: B-2.     

MDMA produces stimulant-like conditioned locomotor activity

Daily administration of a drug in a distinctive environment establishes contingencies that support Pavlovian conditioning. Environmental cues that are paired with the drug injection and that predict the onset of drug action can become conditioned stimuli. Ultimately, the conditioned stimuli come to predict the availability of drug and develop the potential to engender conditioned drug responses. Various psychostimulant drugs can produce conditioned locotnotion when tested in the presence of environmental cues that were repeatedly associated with the drug experience. The ability of amphetamine and cocaine to produce conditioned locomotion was demonstrated in the present study. Stimulant-like properties of methylenedioxymethamphetamine (MDMA) have been reported in locomotor paradigms, drug discrimination procedures, and human subjective questionnaires. MDMA (5 mg/kg), paired for 5 days to a distinct environment signalled by the presence of a distinct odor, produced enhanced locomotion during a test probe with the odor alone indicating that MDMA can also produce conditioned locomotion. The observation that the stimulus properties of MDMA can also become associated with environmental cues supports the hypothesis that some of the behavioral effects of MDMA resemble those of other classical psychostimulants such as amphetamine and cocaine.This is publication number 5732BCR from the Research Institute of Scripps Clinic     

The effects of X monosomy on brain development: Monozygotic twins discorcant for Turner's syndrome

Monosomy for the X chromosome is the most frequent cause of Turner's syndrome, a common clinical syndrome associated with particular physical and neurobehavioral features. The results from comprehensive assessment of prepubertal monozygotic female twins discordant for X monosomy are presented. Zygosity was established with DNA Fingerprinting and no evidence of chromosomal mosaicism was seen in either child. Physical features in the affected twin were relatively mild with respect to the full spectrum of physical malformations and disabilities associated with Turner's syndrome. The neurobehavioral phenotypes of the twins were compared. Although both sisters scored in the superior range of intelligence, the affected twin's Performance IQ was 18 points less than her sister, whereas Verbal IQ showed only a 3-point difference between the sisters. Other relative differences were noted within the executive, visuospatial, and visuomotor domains of function. Behavioral evaluation indicated greater problems with attention, hyperactivity, and anxiety in the affected twin. Quantitative analysis of brain anatomy revealed evidence of both general and regional effects of X monosomy on neurodevelopment. Cerebrospinal fluid volume was increased by 25% in the affected twin compared with her sister with a corresponding decrease in gray matter volume. The right frontal, right parietal–occipital, and left parietal-perisylvian regions showed the greatest discrepancy between the sisters with respect to increased cerebrospinal fluid and decreased gray matter volumes in the twin with X monosomy. Differences in the posterior fossa were also noted with a 50% relative increase in the volumes of the fourth ventricle and cisterna magna and a 10 to 15% relative reduction in size of the cerebellar vermis, pons, and medulla in the affected twin. The association between the neurobehavioral and neuroanatomical findings in the affected twin is discussed. The unique nature of the naturally occurring genetic phenomenon seen in this twin pair provides an opportunity to more fully elucidate the neurobehavioral phenotype associated with X monosomy and Turner's syndrome.     

Rabbit Liver Class III Alcohol Dehydrogenase: A Cathodic Isoform with Formaldehyde Dehydrogenase Activity

Electrophoresis of rabbit liver homogenate on starch gel followed by activity staining revealed multiple forms of alcohol dehydrogenase (ADH) which, based on their electrophoretic mobilities, had been tentatively labeled as class "I," class "II," and dass "III" ADHs. The class II enzyme has now been purified to homogeneity by ion exchange and affinity chromatography and, except for an isoelectric point of 7.7, close: resembles human class III ADH. It is a homodimer of molecular weight near 80,000 with a similar amino acid composition and comparable kinetic parameter for the oxidation of primary alcohols. Like the rat, human, and Escherichia coli class III ADHs, the rabbit enzyme is a glutathione-dependent formaldehyde dehydrogenase, and catalyzes the oxidation of S-hydroxymethylglutathione and the hemithiolacetal of 8-thiooctenolc acid. Ethanol up to 3 M does not saturate the enzyme, whereas longer chain primary alcohols exhibit Michaelis-Menten kinetics. Key Words: XX-ADH, FDH.     

Synaptic modifications accompanying epileptogenesis in vitro: long-term depression of GABA-mediated inhibition

We used an in vitro model similar to kindling to examine the processes underlying epileptogenesis. A 60 Hz train was applied every 5–10 min to the Schaffer collateral pathways in guinea pig hippocampal slices until epileptiform bursting was elicited in the CA3 region. The resultant alterations in both spontaneous and evoked activities were studied using intracellular recordings from CA3 pyramidal cells. An attempt was made to elucidate the synaptic modifications responsible for the conversion to this state of enhanced excitability. Analyses revealed that the emergence of epileptiform discharge was accompanied by a long-term depression of evoked inhibitory conductances. This tetanus-induced reduction of inhibition involved both the early and late phases of the evoked hyperpolarization, suggesting modification of both the GABA_A and GABA_B receptor-mediated events. Previous studies have suggested that NMDA receptor activation plays an important role in the induction of epileptiform activity in this model. Our data, showing that depression of inhibition can be induced in the presence of CNQX, is consistent with this hypothesis. The parallel development of long-term depression of inhibition and epileptiform bursting following tetanic stimulation suggests that plasticity of the inhibitory transmission process is a potential source of vulnerability contributing to epileptogenesis.     

dazed gene is necessary for late cell type development and retinal cell maintenance in the zebrafish retina.

Several molecules, such as growth factors and neurotrophic factors, are required both for the differentiation of specific retinal cell types and the long-term cell survival of all retinal neurons. As diffusible factors, these molecules act non-cell-autonomously. Here, we describe the loss of function phenotype for dazed (dzd), a gene that acts cell-autonomously for retinal cell survival and affects the differentiation of rod photoreceptors and the Muller glia. By 3 days after fertilization, dazed mutant embryos have small eyes and slight heart edema. Acridine orange staining indicated a significant degree of retinal cell death occurring by 48 hr after fertilization, and histological analysis revealed that dying cells were found in the inner and outer nuclear layers and near the marginal zones. Although molecular and morphological differentiation of the inner retina and cone photoreceptors occurred, rod photoreceptors failed to differentiate beyond a small patch in the ventral retina and rod precursors failed to respond to exogenously added retinoic acid, which normally potentiated rod differentiation. Mosaic analysis indicated that the dazed gene acts cell-autonomously for rod production and cell survival, as dazed clones failed to produce rods outside the ventral patch and dazed cells were not maintained in wild-type hosts. Raising mutants under constant light resulted in severe retinal degeneration, whereas raising embryos under constant darkness did not provide any additional protection from cell death. Behavioral analysis showed that a subpopulation of adult fish that were heterozygous for the dazed mutation had elevated visual thresholds and were night blind, suggesting that dazed may also be required for long-term dim-light vision. Taken together, our studies suggest a role for the dazed gene in rod and Muller cell development and overall retinal cell survival and maintenance.     

Changes in gut bacterial communities in canaries infected by Macrorhabdus ornithogaster

Macrorhabdus ornithogaster is an opportunistic yeast that colonizes the gastric mucosa of many avian species. Until now, no studies have focused on the influence of a gastric infection on the balance of the intestinal microbiota of birds. In this study, 44 faecal samples from individual canaries, with and without M. ornithogaster infection, were analysed. The detection of the yeast was evaluated by 18S rRNA PCR. In order to evaluate the impact of the Macrorhabdus infection on the bacterial communities, culture-independent methods, by the use of amplicon-based sequencing as well as 16S rRNA-DGGE, were adopted. The different health status of animals affected the relative abundance of the main OTUs, with a greater diversification of the gut microbiota in healthy animals compared to the infected. In particular, Lactococcus, Pseudomonas, Acinetobacter, Lachnospiraceae, Propionibacterium and Weissella were found to be characteristic of uninfected animals (FDR?<?0.05), while Lactobacillus and Candidatus Arthromitus were characteristic of infected animals (FDR?<?0.05). Both these taxa have been reported as immunostimulatory, involved in immunological disorders. In infected animals the inferred metagenome assessed by PICRUST clearly showed a positive correlation between the presence of M. ornithogaster and KEGG genes related to ether lipid metabolism, already reported to be immunostimulatory by activation of macrophages and to play a pathophysiological role in several immunological disorders. Finally, our results show an interaction between infection of the digestive tract and intestinal microbiota of pet birds and provide insight into the changing of the complex enteric bacterial community.

• HIGHLIGHTS

• Macrorabdus ornithogaster is a gastric yeast that colonizes a wide range of birds.

• Differences were found between infected and healthy animals in gut microbiota.

• Candidatus Arthromitus was closely associated with infected birds.

• M. ornithogaster can affect intestinal microbiota composition of canaries.