Pharmacological validation of individual animal locomotion, temperature and behavioural analysis in group-housed rats using a novel automated home cage analysis system: A comparison with the modified Irwin test.

BACKGROUND: The ActualHCA™ system continuously monitors the activity, temperature and behavior of group-housed rats without invasive surgery. The system was validated to detect the contrasting effects of sedative and stimulant test agents (chlorpromazine, clonidine and amphetamine), and compared with the modified Irwin test (mIT) with rectal temperature measurements. METHODS: Six male Han Wistar rats per group were used to assess each test agent and vehicle controls in separate ActualHCA™ recordings and mIT. The mIT was undertaken at 15, 30 mins, 1, 2, 4 and 24 h post-dose. ActualHCA™ recorded continuously for 24 h post-dose under 3 experimental conditions: dosed during light phase, dark phase, and light phase with a scheduled cage change at the time of peak effects determined by mIT. RESULTS: ActualHCA™ detected an increase stimulated activity from the cage change at 1-2 h post-dose which was obliterated by chlorpromazine and clonidine. Amphetamine increased activity up to 4 h post-dose in all conditions. Temperature from ActualHCA™ was affected by all test agents in all conditions. The mIT showed effects on all 3 test agents up to 4 h post-dose, with maximal effects at 1-2 h post-dose. The maximal effects on temperature from ActualHCA™ differed from mIT. Delayed effects on activity were detected by ActualHCA™, but not on mIT. CONCLUSIONS: Continuous monitoring has the advantage of capturing effects over time that may be missed with manual tests using pre-determined time points. This automated behavioural system does not replace the need for conventional methods but could be implemented simultaneously to improve our understanding of behavioural pharmacology.

Population-based analysis of sudden death in children: The Oregon Sudden Unexpected Death Study.

BACKGROUND: There is a lack of prospective population-based data regarding sudden death in children. OBJECTIVE: The purpose of this study was to assess the burden of sudden cardiac arrest (SCA) in the pediatric population in a 3-year community-wide study. METHODS: During 2002-2005, all residents of Multnomah County, Oregon (population 660,486) who underwent SCA were ascertained from emergency medical services, the medical examiner, and emergency rooms of 16 area hospitals. A comprehensive evaluation was performed, including analysis of circumstances of death, medical records, and available autopsy data. Annual incidence rates were calculated for all residents age <18 years using the 2000 U.S. Census data. RESULTS: A total of 33 children met the criteria for SCA (58% female, median age 0.37 years, range 0.03-12.3 years). The majority of SCAs (76%) occurred in children age <1 year. At least 90% of this subgroup also met the criteria for the sudden infant death syndrome (SIDS). Pediatric SCAs constituted 2.8% of all SCAs. The pediatric annual incidence rate per 100,000 population was 1.7 (95% confidence interval [CI] 1.1-2.3), compared with 60/100,000 for all ages. The pediatric annual incidence rate per 100,000 children was 7.5 (95% CI 5.1-10.5). The annual incidence rate of SIDS was 0.8/1000 live births. In contrast to an adult survival rate of 8%, none of the children survived to be discharged from the hospital. CONCLUSIONS: The burden of pediatric sudden death was low (3% of all sudden deaths), but 90% occurred before the age of 1 year, and the majority were diagnosed as SIDS (70% of overall sudden deaths in children). Population education to prevent SIDS and enhanced postnatal diagnosis of occult heart disease are likely to have the greatest impact on the prevention of pediatric sudden death.