New investigations into the genotoxicity of cobalt compounds and their impact on overall assessment of genotoxic risk.

The genotoxicity of cobalt metal and cobalt compounds has been widely studied. Several publications show induction of chromosomal aberrations, micronuclei or DNA damage in mammalian cells in vitro in the absence of S9. Mixed results were seen in gene mutation studies in bacteria and mammalian cells in vitro, and in chromosomal aberration or micronucleus assays in vivo. To resolve these inconsistencies, new studies were performed with soluble and poorly soluble cobalt compounds according to OECD-recommended protocols. Induction of chromosomal damage was confirmed in vitro, but data suggest this may be due to oxidative stress. No biologically significant mutagenic responses were obtained in bacteria, Tk(+/-) or Hprt mutation tests. Negative results were also obtained for chromosomal aberrations (in bone marrow and spermatogonia) and micronuclei at maximum tolerated doses in vivo. Poorly soluble cobalt compounds do not appear to be genotoxic. Soluble compounds do induce some DNA and chromosomal damage in vitro, probably due to reactive oxygen. The absence of chromosome damage in robust GLP studies in vivo suggests that effective protective processes are sufficient to prevent oxidative DNA damage in whole mammals. Overall, there is no evidence of genetic toxicity with relevance for humans of cobalt substances and cobalt metal.

Improving the efficiency of advanced life support training: a randomized, controlled trial.

BACKGROUND: Each year, more than 1.5 million health care professionals receive advanced life support (ALS) training. OBJECTIVE: To determine whether a blended approach to ALS training that includes electronic learning (e-learning) produces outcomes similar to those of conventional, instructor-led ALS training. DESIGN: Open-label, noninferiority, randomized trial. Randomization, stratified by site, was generated by Sealed Envelope (Sealed Envelope, London, United Kingdom). (International Standardized Randomized Controlled Trial Number Register: ISCRTN86380392) SETTING: 31 ALS centers in the United Kingdom and Australia. PARTICIPANTS: 3732 health care professionals recruited between December 2008 and October 2010. INTERVENTION: A 1-day course supplemented with e-learning versus a conventional 2-day course. MEASUREMENTS: The primary outcome was performance in a cardiac arrest simulation test at the end of the course. Secondary outcomes comprised knowledge- and skill-based assessments, repeated assessment after remediation training, and resource use. RESULTS: 440 of the 1843 participants randomly assigned to the blended course and 444 of the 1889 participants randomly assigned to conventional training did not attend the courses. Performance in the cardiac arrest simulation test after course attendance was lower in the electronic advanced life support (e-ALS) group compared with the conventional advanced life support (c-ALS) group; 1033 persons (74.5%) in the e-ALS group and 1146 persons (80.2%) in the c-ALS group passed (mean difference, -5.7% [95% CI, -8.8% to -2.7%]). Knowledge- and skill-based assessments were similar between groups, as was the final pass rate after remedial teaching, which was 94.2% in the e-ALS group and 96.7% in the c-ALS group (mean difference, -2.6% [CI, -4.1% to 1.2%]). Faculty, catering, and facility costs were $438 per participant for electronic ALS training and $935 for conventional ALS training. LIMITATIONS: Many professionals (24%) did not attend the courses. The effect on patient outcomes was not evaluated. CONCLUSION: Compared with conventional ALS training, an approach that included e-learning led to a slightly lower pass rate for cardiac arrest simulation tests, similar scores on a knowledge test, and reduced costs. PRIMARY FUNDING SOURCE: National Institute of Health Research and Resuscitation Council (UK).

Temperature monitoring during cardiopulmonary bypass--do we undercool or overheat the brain?

OBJECTIVE: Brain cooling is an essential component of aortic surgery requiring circulatory arrest and inadequate cooling may lead to brain injury. Similarly, brain hyperthermia during the rewarming phase of cardiopulmonary bypass may also lead to neurological injury. Conventional temperature monitoring sites may not reflect the core brain temperature (Tdegrees). We compared jugular bulb venous temperatures (JB) during deep hypothermic circulatory arrest and normothermic bypass with Nasopharyngeal (NP), Arterial inflow (AI), Oesophageal (O), Venous return (VR), Bladder (B) and Orbital skin (OS) temperatures. METHODS: 18 patients undergoing deep hypothermia (DH) and 8 patients undergoing normothermic bypass (mean bladder Tdegrees-36.29 degreesC) were studied. For DH, cooling was continued to 15 degreesC NP (mean cooling time-66 min). At pre-determined arterial inflow Tdegrees, NP, JB and O Tdegree's were measured. A 6-channel recorder continuously recorded all Tdegree's using calibrated thermocouples. RESULTS: During the cooling phase of DH, NP lagged behind AI and JB Tdegree's. All these equilibrated at 15 degreesC. During rewarming, JB and NP lagged behind AI and JB was higher than NP at any time point. During normothermic bypass, although NP was reflective of the AI and JB Tdegrees trends, it underestimated peak JB Tdegrees (P=0.001). Towards the end of bypass, peak JB was greater than the arterial inflow Tdegrees (P=0.023). CONCLUSIONS: If brain venous outflow Tdegrees (JB) accurately reflects brain Tdegrees, NP Tdegrees is a safe surrogate indicator of cooling. During rewarming, all peripheral sites underestimate brain temperature and caution is required to avoid hyperthermic arterial inflow, which may inadvertently, result in brain hyperthermia.

Bioaccessibility testing of cobalt compounds.

Testing of metal compounds for solubility in artificial fluids has been used for many years to assist determining human health risk from exposure to specific compounds of concern. In lieu of obtaining bioavailability data from samples of urine, blood, or other tissues, these studies measured solubility of compounds in various artificial fluids as a surrogate for bioavailability. In this context, the measurement of metal "bioaccessibility" can be used as an in vitro substitute for measuring metal bioavailability. Bioaccessibility can be defined as a value representing the availability of metal for absorption when dissolved in in vitro surrogates of body fluids or juices. The aim of this study was to measure and compare the bioaccessibility of selected cobalt compounds in artificial human tissue fluids and human serum. A second aim was to initiate studies to experimentally validate an in vitro methodology that would provide a conservative estimate of cobalt bioavailability in the assessment of dose from human exposure to various species of cobalt compounds. This study evaluated the bioaccessibility of cobalt(II) from 11 selected cobalt compounds and an alloy in 2 physical forms in 5 surrogate human tissue fluids and human serum. Four (4) separate extraction times were used up to 72 hours. The effect of variables such as pH, dissolution time, and mass-ion effect on cobalt bioaccessibility were assessed as well. We found that the species of cobalt compound as well as the physico-chemical properties of the surrogate fluids, especially pH, had a major impact on cobalt solubility. Cobalt salts such as cobalt(II) sulfate heptahydrate were highly soluble, whereas cobalt alloys used in medical implants and cobalt aluminate spinels used as pigments, showed minimal dissolution over the period of the assay.