Systemic inflammation enhances stimulant-induced striatal dopamine elevation.

Changes in the mesolimbic dopamine (DA) system are implicated in a range of neuropsychiatric conditions including addiction, depression and schizophrenia. Dysfunction of the neuroimmune system is often comorbid with such conditions and affects similar areas of the brain. The goal of this study was to use positron emission tomography with the dopamine D2 antagonist tracer, 11C-raclopride, to explore the effect of acute immune activation on striatal DA levels. DA transmission was modulated by an oral methylphenidate (MP) challenge in order to reliably elicit DA elevation. Elevation in DA concentration due to MP was estimated via change in 11C-raclopride binding potential from the baseline scan. Prior to the post-MP scan, subjects were pre-treated with either the immune activator lipopolysaccharide (LPS) or placebo (PBO) in a cross-over design. Immune activation was confirmed by measuring tumor necrosis factor alpha (TNFα), interleukin (IL)-6 and IL-8 concentration in plasma. Eight healthy subjects were scanned four times each to determine the MP-induced DA elevation under both LPS and PBO pre-treatment conditions. MP-induced DA elevation in the striatum was significantly greater (P<0.01) after LPS pre-treatment compared to PBO pre-treatment. Seven of eight subjects responded similarly. This effect was observed in the caudate and putamen (P<0.02), but was not present in ventral striatum. DA elevation induced by MP was significantly greater when subjects were pre-treated with LPS compared to PBO. The amplification of stimulant-induced DA signaling in the presence of systemic inflammation may have important implications for our understanding of addiction and other diseases of DA dysfunction.

Systematic review and meta-analysis of steatosis as a risk factor in major hepatic resection.

BACKGROUND: The risk of major hepatic resection in patients with hepatic steatosis remains controversial. A meta-analysis was performed to establish the best estimate of the impact of steatosis on patient outcome following major hepatic surgery. METHODS: A systematic search was performed following Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Risk ratios (RRs) for complication and mortality rates were calculated for patients with no, less than 30 per cent and at least 30 per cent steatosis, and a meta-analysis was carried out. RESULTS: Of six observational studies identified, four including a total of 1000 patients were subjected to meta-analysis; two others were tabulated separately. Compared with patients without steatosis, those with less than 30 per cent and at least 30 per cent steatosis had a significantly increased risk of postoperative complications, with a RR of 1.53 (95 per cent confidence interval (c.i.) 1.27 to 1.85) and 2.01 (1.66 to 2.44) respectively. Patients with at least 30 per cent steatosis had an increased risk of postoperative death (RR 2.79, 95 per cent c.i. 1.19 to 6.51). CONCLUSION: Patients with steatosis had an up to twofold increased risk of postoperative complications, and those with excessive steatosis had an almost threefold increased risk of death.