The effect of sleep deprivation and disruption on DNA damage and health of doctors.

Observational studies have highlighted the detrimental health effects of shift work. The mechanisms through which acute sleep deprivation may lead to chronic disease have not been elucidated, but it is thought that increased DNA damage or decreased repair can lead to disease. The objective of this study was to examine the effects of acute sleep deprivation on DNA damage. This was a cross-sectional observational study on 49 healthy, full-time doctors. Baseline blood was sampled from each participant after three consecutive days of adequate sleep. Participants (n = 24) who were required to work overnight on-site had additional blood sampled on a morning after acute sleep deprivation. DNA damage and expression of DNA repair genes were quantified. Information on health, working patterns and sleep diaries were collected. Independent t-tests were used to compare differences between groups and standardised mean differences expressed as Cohen's d. Overnight on-site call participants had lower baseline DNA repair gene expression and more DNA breaks than participants who did not work overnight (d = 1.47, p = 0.0001; and 1.48, p = 0.0001, respectively). In overnight on-site call participants, after acute sleep deprivation, DNA repair gene expression was decreased (d = 0.90, p = 0.0001) and DNA breaks were increased (d = 0.87, p = 0.0018). Sleep deprivation in shift workers is associated with adverse health consequences. Increased DNA damage has been linked to the development of chronic disease. This study demonstrates that disrupted sleep is associated with DNA damage. Furthermore, larger prospective studies looking at relationships between DNA damage and chronic disease development are warranted, and methods to relieve, or repair, DNA damage linked to sleep deprivation should be investigated.

The effect of remifentanil on propofol requirements to achieve loss of response to command vs. loss of response to pain.

When providing total intravenous anaesthesia, careful selection of end-points is required in titrating dose to effect during induction. Although propofol and remifentanil have predominantly different pharmacodynamic effects, they are seen to interact in achieving loss of consciousness and analgesia. To highlight these differences, we performed a double-blind, randomised controlled trial, comparing one group of patients receiving propofol alone (n = 42) with another group receiving remifentanil plus propofol (n = 46) as a target-controlled infusion of remifentanil (Minto; 3 ng.ml-1 ). Propofol was also titrated using a target-controlled infusion (Marsh effect model) to produce loss of response to tactile and vocal stimuli, and subsequently to loss of response to pain. The effect-site concentration of propofol at which 50% of patients lost tactile/verbal response was 2.9 µg.ml-1 in the propofol only group and 2.4 µg.ml-1 in the remifentanil with propofol group. In contrast, loss of pain response occurred at 4.4 µg.ml-1 in the propofol group, and 2.7 µg.ml-1 in the remifentanil with propofol group, with correspondingly lower bispectral index values. Judicious use of analgesia in total intravenous anaesthesia can have a propofol-sparing effect and potentially minimise the suppression of brain electrical activity. .

Bringing CLARITY to the human brain: visualization of Lewy pathology in three dimensions.

AIMS: CLARITY is a novel technique which enables three-dimensional visualization of immunostained tissue for the study of circuitry and spatial interactions between cells and molecules in the brain. In this study, we aimed to compare methodological differences in the application of CLARITY between rodent and large human post mortem brain samples. In addition, we aimed to investigate if this technique could be used to visualize Lewy pathology in a post mortem Parkinson's brain. METHODS: Rodent and human brain samples were clarified and immunostained using the passive version of the CLARITY technique. Samples were then immersed in different refractive index matching media before mounting and visualizing under a confocal microscope. RESULTS: We found that tissue clearing speed using passive CLARITY differs according to species (human vs. rodents), brain region and degree of fixation (fresh vs. formalin-fixed tissues). Furthermore, there were advantages to using specific refractive index matching media. We have applied this technique and have successfully visualized Lewy body inclusions in three dimensions within the nucleus basalis of Meynert, and the spatial relationship between monoaminergic fibres and Lewy pathologies among nigrostriatal fibres in the midbrain without the need for physical serial sectioning of brain tissue. CONCLUSIONS: The effective use of CLARITY on large samples of human tissue opens up many potential avenues for detailed pathological and morphological studies.

Contrast induced nephropathy in vascular surgery.

Contrast induced nephropathy (CIN) is traditionally associated with outpatient imaging studies. More recently, patients afflicted with vascular pathologies are increasingly undergoing endovascular treatments that require the use of iodinated contrast media (CM) agents, thus placing them as risk of developing CIN. As perioperative physicians, anaesthetists should be aware of the risk factors and measures that might minimize acute kidney injury caused by CM. This review evaluates recent data regarding preventive measures against CIN and where possible, places the evidence in the context of the patient receiving endovascular surgical treatment. Measures including the use of peri-procedural hydration, N-acetylcysteine, statins, remote ischaemic preconditioning, renal vasodilators and renal replacement therapy and the use of alternatives to iodinated contrast agents are discussed. It should be noted that most of the available data regarding CIN are from non-surgical patients.

Poisoning with illicit substances: toxicology for the anaesthetist.

The consumption of illicit substances represents a considerable threat to the health and wellbeing of particular sectors of our communities. Hospitalisation is sometimes required for the treatment of the direct toxic effects of the drugs as well as for injuries sustained while under their influence. Although poisoning with 'traditional' substances of abuse such as opioids, cocaine and cannabis still predominate in terms of numbers, the availability and use of new psychoactive substances are on the rise. These latter agents, some of which began life as failed pharmaceutical products, have enjoyed renewed status as recreational stimulants, entactogens or hallucinogens, properties that originally precluded them from legitimate use. These drugs may act by enhancing endogenous release of neurotransmitters, inhibiting their reuptake back into neurons or having direct effects on receptors, and may involve adrenergic, dopaminergic or serotonergic systems. The use of intravenous lipid emulsion for the symptomatic treatment of drug overdose has become a fertile ground for research and may hold promise as a non-specific treatment for poisoning with illicit substances. Dexmedetomidine, an α(2)-receptor agonist with a central sympatholytic effect, may be able to counteract the cardiovascular and central nervous system overstimulation that may accompany stimulant toxicity.

Pretreatment with intrathecal or intravenous morphine attenuates hepatic ischaemia-reperfusion injury in normal and cirrhotic rat liver.

BACKGROUND: Opioids have been shown to attenuate ischaemia-reperfusion injury (IRI) in a number of organs. We evaluated the effect of morphine pretreatment on IRI in both normal and cirrhotic rat liver. METHODS: Morphine was administered either i.v. or intrathecally (i.t.) 10 min before initiating 1 h of ischaemia followed by 6 h reperfusion in normal rat liver. Hepatic injury was assessed histologically using Suzuki's criteria. These manoeuvres were repeated using the optimal dose of morphine after administration of naloxone methiodide and wortmannin. Serum levels of transaminases were measured, and expression of phosphorylated Akt, Jak2, and STAT3 were assessed by immunoblotting. Similar procedures were repeated on rats with carbon tetrachloride-induced liver cirrhosis, and the levels of phosphorylated protein kinase C (PKC), haem oxygenase-1 (HO-1), and inducible nitric oxide synthase (iNOS) were also evaluated, as these proteins have beneficial effects during IRI. RESULTS: Morphine pretreatment at 100 µg kg(-1) (i.v.) or 10 µg (i.t.) reduced necrosis, apoptosis, and serum transaminase levels, and increased phosphorylated Akt and STAT3 but not JAK2 expression in normal liver. These changes were reversed by prior administration of naloxone methiodide and wortmannin. Although morphine preconditioning was also protective in cirrhotic liver, STAT3 and JAK2 phosphorylation status was unchanged. There was, however, increased expression of phosphorylated PKC and HO-1, and a reduction in iNOS. CONCLUSIONS: Morphine preconditioning protects against IRI in both normal and cirrhotic rat liver. This involves opioid receptors, phosphatidylinositol-3-kinase, and Akt. The downstream pathways involved are different for cirrhotic liver, with preliminary evidence suggesting involvement of HO-1.

Endovascular aneurysm repair: a perioperative perspective.

Endovascular aneurysm repair (EVAR), has surpassed open repair as the technique of choice in many centres in response to several large studies which showed significantly improved 30-day mortality. While several multicentre EVAR trials looked at surgical outcomes, very few have specifically investigated the effect of anaesthetic techniques or perioperative care of these patients. The purpose of this review to is to present some of the current evidence for the different aspects of perioperative management of patients undergoing EVAR. This includes surgical considerations, pre-operative assessment, and choice of anaesthetic technique as well as pharmacological protective strategies.