Background and Objectives: Advances in endoscopic techniques have transformed the management of urolithiasis. We sought to evaluate the role of such urological interventions for the treatment of complex biliary calculi. Methods: We conducted a retrospective review of all patients (n=9) undergoing percutaneous holmium laser lithotripsy for complicated biliary calculi over a 4-year period (12/2003 to 12/2007). All previously failed standard techniques include ERCP with sphincterotomy (n=6), PTHC (n=7), or both of these. Access to the biliary system was obtained via an existing percutaneous transhepatic catheter or T-tube tracts. Endoscopic holmium laser lithotripsy was performed via a flexible cystoscope or ureteroscope. Stone clearance was confirmed intra-and postoperatively. A percutaneous transhepatic drain was left indwelling for follow-up imaging. Results: Mean patient age was 65.6 years (range, 38 to 92). Total stone burden ranged from 1.7 cm to 5 cm. All 9 patients had stones located in the CBD, with 2 patients also having additional stones within the hepatic ducts. All 9 patients (100%) were visually stone-free after one endoscopic procedure. No major perioperative complications occurred. Mean length of stay was 2.4 days. At a mean radiological follow-up of 5.4 months (range, 0.5 to 21), no stone recurrence was noted. Conclusions: Percutaneous endoscopic holmium laser lithotripsy is a minimally invasive alternative to open salvage surgery for complex biliary calculi refractory to standard approaches. This treatment is both safe and efficacious. Success depends on a multidisciplinary approach.

Context Inflammatory cytokines or cytokine inducers can alter basal ganglia activity, including reducing responsiveness to rewarding stimuli that may be mediated by cytokine effects on dopamine function. Objectives To determine whether long-term administration of the inflammatory cytokine interferon alfa reduces the basal ganglia response to reward and whether such changes are associated with decreased presynaptic striatal dopamine function and altered behavior. Design Cross-sectional and longitudinal studies. Setting Outpatient research unit and neuroimaging facilities at Emory University, Atlanta, Georgia. Patients Medically stable adults with chronic hepatitis C virus (HCV) infection eligible for interferon alfa treatment. Main Outcome Measures Neural activity in the ventral striatum during a hedonic reward task as measured by functional magnetic resonance imaging, uptake and turnover of radiolabeled fluorodopa F 18 (18F-dopa) in caudate and putamen using positron emission tomography, and interferon alfa–induced depression, anhedonia, fatigue, and neurotoxicity. Results Patients with HCV receiving interferon alfa for 4 to 6 weeks (n=14) exhibited significantly reduced bilateral activation of the ventral striatum in the win vs lose condition of a gambling task compared with patients with HCV awaiting interferon alfa treatment (n=14). Reduced activation of the ventral striatum was, in turn, significantly correlated with anhedonia, depression, and fatigue. In a separate longitudinal study, patients with HCV treated with interferon alfa for 4 to 6 weeks (n=12) exhibited significantly increased 18F-dopa uptake and decreased 18F-dopa turnover in caudate and putamen and in the same ventral striatal regions identified in the functional magnetic resonance imaging study. Baseline and percentage change in 18F-dopa uptake and turnover were correlated with behavioral alterations, including depression, fatigue, and neurotoxicity, during interferon alfa administration. Conclusions These data replicate and extend findings that inflammatory stimuli, including inflammatory cytokines, such as interferon alfa, alter basal ganglia activity and behavior in association with significant changes in presynaptic striatal dopamine function consistent with decreased dopamine synthesis or release.

Background Consequences of chronic exposure to cytokines of the innate immune system on sleep in humans and the association of cytokine-induced sleep alterations with behavior, motor performance and cortisol secretion are unknown. Methods Thirty-one patients with hepatitis C without pre-existing sleep disorders underwent nighttime polysomnography, daytime multiple sleep latency testing, behavioral assessments, neuropsychological testing and serial blood sampling at baseline and after ~12 weeks of either treatment with the innate immune cytokine, interferon (IFN)-alpha (n=19) or no treatment (n=12). Fatigue and sleepiness were assessed using the Multidimensional Fatigue Inventory and Epworth Sleepiness Scale. Results IFN-alpha administration led to significant increases in wake after sleep onset and significant decreases in Stage 3/4 sleep and sleep efficiency. REM latency and Stage 2 sleep were significantly increased during IFN-alpha treatment. Decreases in Stage 3/4 sleep and increases in REM latency were associated with increases in fatigue, whereas decreases in sleep efficiency were associated with reduced motor speed. Increased wake after sleep onset was associated with increased evening plasma cortisol. Despite IFN-alpha-induced increases in fatigue, daytime sleepiness did not increase. In fact, IFN-alpha-treated patients exhibited decreased propensity to fall asleep during daytime nap opportunities. Conclusions Chronic exposure to an innate immune cytokine reduced sleep continuity and depth, and induced a sleep pattern consistent with insomnia and hyperarousal. These data suggest that innate immune cytokines may provide a mechanistic link between disorders associated with chronic inflammation including medical and/or psychiatric illnesses and insomnia, which in turn is associated with fatigue, motor slowing and altered cortisol.