Paediatric procedural sedation using ketamine in a UK emergency department: a 7 year review of practice.

BACKGROUND: Ketamine is growing in popularity for procedural sedation in the paediatric population, yet safety concerns remain. We performed a retrospective review of practice and outcomes of paediatric ketamine sedation using the World SIVA International Sedation Task Force reporting tool. METHODS: A retrospective inspection of the dedicated emergency department electronic sedation database and subsequent note and sedation chart review was performed for all paediatric sedations throughout a 7 yr period from September 2006. All adverse events were stratified. RESULTS: During the study period, procedural sedation was provided for a total of 243 children, of whom 215 were sedated with ketamine, most commonly for wound management (n=131). The median patient age was 4 yr (14 months to 15 yr), and 63.7% were male. Of the total, 76.7% were discharged home either directly (n=101) or after brief observation (n=64). One patient required subsequent general anaesthesia after a failed sedation with paradoxical agitation. Of the total, 9.8% of patients had an adverse event, the most severe risk stratification being 'minor risk'. All interventions were 'minimal risk'. There were no 'sentinel risk' outcomes. CONCLUSIONS: These data support the ongoing use of ketamine for paediatric procedural sedation in the emergency department by emergency physicians. Relatively high resource requirements mean that ensuring adequate numbers of procedures may prove challenging.

Consistent individual differences in the social phenotypes of wild great tits, Parus major.

Despite growing interest in animal social networks, surprisingly little is known about whether individuals are consistent in their social network characteristics. Networks are rarely repeatedly sampled; yet an assumption of individual consistency in social behaviour is often made when drawing conclusions about the consequences of social processes and structure. A characterization of such social phenotypes is therefore vital to understanding the significance of social network structure for individual fitness outcomes, and for understanding the evolution and ecology of individual variation in social behaviour more broadly. Here, we measured foraging associations over three winters in a large PIT-tagged population of great tits, and used a range of social network metrics to quantify individual variation in social behaviour. We then examined repeatability in social behaviour over both short (week to week) and long (year to year) timescales, and investigated variation in repeatability across age and sex classes. Social behaviours were significantly repeatable across all timescales, with the highest repeatability observed in group size choice and unweighted degree, a measure of gregariousness. By conducting randomizations to control for the spatial and temporal distribution of individuals, we further show that differences in social phenotypes were not solely explained by within-population variation in local densities, but also reflected fine-scale variation in social decision making. Our results provide rare evidence of stable social phenotypes in a wild population of animals. Such stable social phenotypes can be targets of selection and may have important fitness consequences, both for individuals and for their social-foraging associates.

Toll-like receptor-associated sequence variants and prostate cancer risk among men of African descent.

Recent advances demonstrate a relationship between chronic/recurrent inflammation and prostate cancer (PCA). Among inflammatory regulators, toll-like receptors (TLRs) have a critical role in innate immune responses. However, it remains unclear whether variant TLR genes influence PCA risk among men of African descent. Therefore, we evaluated the impact of 32 TLR-associated single-nucleotide polymorphisms (SNPs) on PCA risk among African Americans and Jamaicans. SNP profiles of 814 subjects were evaluated using Illumina's Veracode genotyping platform. Single and combined effects of SNPs in relation to PCA risk were assessed using age-adjusted logistic regression and entropy-based multifactor dimensionality reduction (MDR) models. Seven sequence variants detected in TLR6, TOLLIP (Toll-interacting protein), IRAK4 (interleukin-1 receptor-associated kinase 4) and IRF3 (interferon regulatory factor 3) were marginally related to PCA. However, none of these effects remained significant after adjusting for multiple hypothesis testing. Nevertheless, MDR modeling revealed a complex interaction between IRAK4 rs4251545 and TLR2 rs1898830 as a significant predictor of PCA risk among US men (permutation testing P-value=0.001). However, these findings require further assessment and validation.

Following up the follow up--long-term complications in paediatric burns.

Paediatric burn follow-up optimally follows a balance between complication detection and avoiding unnecessary hospital visits. In a long-term review, we assessed complication patterns in children with burns requiring surgery. Using the Welsh Burns Centre database, a retrospective note review of paediatric burns over 3 years from 1995 was performed, identifying all children undergoing surgery for their burns. 94 patients were identified with a median follow-up since injury of 13.6 years. Mean age was 5.27 (SD=4.9) years. TBSA ranged from <1 to 70%. 94% underwent split-skin grafting. 18% (n=17) developed contractures and 33% (n=31) developed hypertrophic scarring. Those developing contractures were younger, and suffered significantly greater TBSA burns (p<0.05) than those developing hypertrophic scarring or those without complications. All contractures developed within 1-13 months, and hypertrophic scarring within 1-17 months. All patients sustaining axillary burns developed contractures, whilst 75% of contractures developed around the upper limb. In conclusion, younger patients with larger TBSA burns in the upper limb were at higher risk for contractures and hypertrophic scarring, which all presented within 18 months. Therefore any patients that are complication-free 18 months after-injury can be safely discharged, allowing streamlining of follow-up for the benefit of patients, parents and hospital resources.

Synchronous diagnosis of colorectal malignancy and lymphoma.

AIM: To perform case series from one centre over 9 years, and review of the literature. The synchronous diagnosis of colorectal malignancy and lymphoma is rare. METHOD: Case note review of patients identified from clinical databases. RESULTS: Five patients were identified and findings discussed. In two patients colorectal malignancy staging CT scans identified pathological lymphadenopathy consistent with lymphoma. A further two patients had an incidental lymphoma on histological examination of the colorectal malignancy specimen. The fifth patient was found to have suspicious superior mesenteric lymph nodes at laparotomy. Histology confirmed two nodular lymphocyte-predominant Hodgkin's lymphomas, a lymphocytic-rich classical Hodgkin's lymphoma, a diffuse large B-cell lymphoma and a B-cell follicular lymphoma. CONCLUSION: There is a need for vigilance for the possibility of dual pathologies in all specialties.

Germline BCL-2 sequence variants and inherited predisposition to prostate cancer.

Apoptosis is an essential physiological process that regulates cellular proliferation. Here, we explored the effect of DNA sequence variation within the BCL-2 gene on prostate cancer susceptibility in three clinical populations, consisting of 428 African Americans, 214 Jamaicans and 218 European Americans. We observed a 70% reduced risk for prostate cancer among the European Americans who had possessed two copies of a promoter variant -938C/A. Additionally, common BCL-2 haplotypes appeared to influence prostate cancer risk; however, studies in larger data sets are needed to confirm our findings. Our data suggest that inherited BCL-2 variants may be associated with a decrease in prostate cancer susceptibility.

Mouse embryonic stem cells carrying one or two defective Msh2 alleles respond abnormally to oxidative stress inflicted by low-level radiation.

Chronic oxidative stress may play a critical role in the pathogenesis of many human cancers. Here, we report that mouse embryonic stem (ES) cells deficient in DNA mismatch repair responded abnormally when exposed to low levels of ionizing radiation, a stress known to generate oxidative DNA damage. ES cells derived from mice carrying either one or two disrupted Msh2 alleles displayed an increased survival following protracted exposures to low-level ionizing radiation as compared with wild-type ES cells. The increases in survival exhibited by ES cells deficient in DNA mismatch repair appeared to have resulted from a failure to efficiently execute cell death (apoptosis) in response to radiation exposure. For each of the ES cell types, prolonged low-level radiation treatment generated oxidative genome damage that manifested as an accumulation of oxidized bases in genomic DNA. However, ES cells from Msh2(+/-) and Msh2(-/-) mice accumulated more oxidized bases as a consequence of low-level radiation exposure than ES cells from Msh2(+/+) mice. The propensity for normal cells with mismatch repair enzyme deficiencies, including cells heterozygous for inactivating mismatch repair enzyme gene mutations, to survive promutagenic genome insults accompanying oxidative stresses may contribute to the increased cancer risk characteristic of the hereditary nonpolyposis colorectal cancer syndrome.

Metabolism of benz[a]anthracene by human liver microsomes.

The metabolism of benz[a]anthracene (BA) by human hepatic microsomes was investigated. Only dihydrodiols were observed when BA was the substrate. No tetrahydrotetrols were detected, indicating lack of diol epoxide formation. The BA-dihydrodiols identified by GCMS analysis and comparison to authentic standards were BA-8,9-dihydrodiol (42.4% of total metabolites), BA-5,6-dihydrodiol (25%), BA-10,11-dihydrodiol (24.8%), BA-3,4-dihydrodiol (5.3%), and BA-1,2-dihydrodiol (< 1.5%). BA-dihydrodiols were also used individually as substrates. Only BA-1,2-dihydrodiol, the least abundant isomer produced from BA, was converted efficiently to a tetrahydrotetrol (> 72% conversion). BA-10,11-dihydrodiol was converted to BA-8,9,10,11-tetrahydrotetrols in < 12% yield. BA-10,11- and BA-3,4-dihydrodiols were not converted to tetrahydrotetrols.