BackgroundThe study determined the one year incidence of post operative cognitive decline (POCD) and evaluated the effectiveness of an intra-operative anaesthetic intervention in reducing post-operative cognitive impairment in older adults (over 60 years of age) undergoing elective orthopaedic or abdominal surgery.Methods and Trial DesignThe design was a prospective cohort study with a nested randomised, controlled intervention trial, using intra-operative BiSpectral index and cerebral oxygen saturation monitoring to enable optimisation of anaesthesia depth and cerebral oxygen saturation in older adults undergoing surgery.ResultsIn the 52 week prospective cohort study (192 surgical patients and 138 controls), mild (χ2 = 17.9 p<0.0001), moderate (χ2 = 7.8 p = 0.005) and severe (χ2 = 5.1 p = 0.02) POCD were all significantly higher after 52 weeks in the surgical patients than among the age matched controls. In the nested RCT, 81 patients were randomized, 73 contributing to the data analysis (34 intervention, 39 control). In the intervention group mild POCD was significantly reduced at 1, 12 and 52 weeks (Fisher’s Exact Test p = 0.018, χ2 = 5.1 p = 0.02 and χ2 = 5.9 p = 0.015), and moderate POCD was reduced at 1 and 52 weeks (χ2 = 4.4 p = 0·037 and χ2 = 5.4 p = 0.02). In addition there was significant improvement in reaction time at all time-points (Vigilance Reaction Time MWU Z =  −2.1 p = 0.03, MWU Z = −2.7 p = 0.004, MWU Z = −3.0 p = 0.005), in MMSE at one and 52 weeks (MWU Z = −2.9 p = 0.003, MWU Z = −3.3 p = 0.001), and in executive function at 12 and 52 weeks (Trail Making MWU Z = −2.4 p = .0.018, MWU Z = −2.4 p = 0.019).ConclusionPOCD is common and persistent in older adults following surgery. The results of the nested RCT indicate the potential benefits of intra-operative monitoring of anaesthetic depth and cerebral oxygenation as a pragmatic intervention to reduce post-operative cognitive impairment.Trial RegistrationControlled-Trials.com ISRCTN39503939

We expressed the cloned μ‐opioid receptor (μR) in high abundance (5.5 × 106 sites/cell) with an amino‐terminal epitope tag (EYMPME) in human embryonic kidney 293 cells. The epitope‐tagged receptor (EE‐μR) was similar to the untagged μR in ligand binding and agonist‐dependent inhibition of cyclic AMP accumulation. By confocal microscopy, the labeled receptor was shown to be largely confined to the plasma membrane. Pretreatment with morphine failed to affect the cellular distribution of the receptor as judged by immunofluorescence and tracer binding studies. In contrast, exposure to the μ‐specific peptide agonist [d‐Ala2,MePhe4,Glyol5]enkephalin (DAMGO) caused strong labeling of endocytic vesicles, indicating extensive agonist‐induced cellular redistribution of EE‐μR. Tracer binding studies suggested partial net internalization and a small degree of down‐regulation caused by DAMGO. EE‐μR‐containing membranes were solubilized in detergent [3‐[(3‐cholamidopropyl)dimethylammonio]‐1‐propanesulfonate] and immunoprecipitated by an anti‐epitope monoclonal antibody. Immunoblotting revealed a prominent band at ∼70 kDa with weaker bands at ∼65 kDa. EE‐μR was labeled with [γ‐32P]ATP in permeabilized cells, immunoprecipitated, and analyzed by polyacrylamide gel electrophoresis autoradiography. A prominent band at 65–70 kDa indicated the presence of basal receptor phosphorylation occurring in the absence of agonist, which was enhanced ∼1.8‐fold with the addition of morphine. In conclusion, intracellular trafficking of the μR appears to depend on the agonist, with morphine and DAMGO having markedly different effects. Unlike other G protein‐coupled receptors, basal phosphorylation is substantial, even in the absence of agonist.

No abstract

The p opioid receptor was shown to be phosphorylated at a basal rate in the absence of agonist, measured in permeablllzed HEK293 cells transfected with an epitope tagged p receptor (EE-p) [Arden, J., Segredo, V., Wang, Z., Lameh, J. and Sad&e, W. (1995) J. Neurochem. 65, 163616451. In the present study, basal phosphorylation was found to be Ca'+ dependent; however, several inhibitors of protein kinase C and Ca*+-cahnodulin dependent kinases failed to affect basal F receptor phosphorylation. Thus, the basal p receptor phosphorylating activity differed from the main kinases involved in receptor regulation. The general kinase inhibitor H7 (100 pM) suppressed basal p receptor phosphorylation. Pretreatment with the agonist morphine, followed by drug removal, resulted in a sustained increase of basal p receptor phosphorylation. The gradual agonist dependent modulation of basal p receptor phosphorylation suggests a novel regulatory mechanism which may play a role in narcotic tolerance and dependence.

No abstract

Background/Aims: Post-operative cognitive decline is frequent in older individuals following major surgery; however, biomarkers of this decline are less clearly defined. Methods: Sixty-eight participants over the age of 60 provided blood samples at baseline and 24 h post-surgery. Cognitive decline was measured at baseline and 52 weeks post-surgery using the Cambridge Assessment for Mental Disorder in the Elderly, section B (CAMCOG) score. Plasma levels of neuron-specific enolase (NSE) and S100B were measured by ELISA. Results: Baseline NSE and the change in NSE levels between baseline and 24 h were correlated with the change in CAMCOG score between baseline and 52 weeks. Conclusion: NSE concentrations may be a useful predictor of individuals at risk of more severe long-term cognitive decline.

No abstract

No abstract