Cognitive Impairment In Stable Wilson Disease Across Phenotype.

Background: In Wilson disease (WD), mutations in the gene encoding the ATP7B copper transport protein causes accumulation of copper especially in liver and brain. WD typically presents with hepatic and/or neuropsychiatric symptoms. Impaired cognition is a well-described feature in patients neurological WD, while the reports on cognition in hepatic WD patients are fewer and less conclusive. We examined cognition in a cohort of WD patients with both phenotypes. Methods: In this cross-sectional pilot study, we investigated cognition in 28 stable Danish WD patients by portosystemic encephalopathy (PSE) and continuous reaction time (CRT) tests. Half of the patients were female and median age was 35.5 years (IQR 24.5). The phenotype was hepatic in 14 (50%), neurologic in 10 (36%) and mixed in 4 4 (14%). The duration of treatment was >2 year in all patients, and the condition stable as judged by urinary copper excretion, liver enzymes, and clinical assessment.Results: In total, 16 (57%) patients performed worse than normal in the PSE and/or CRT tests. The two tests correlated (rho=0.60, p=0.0007) with each other, but neither correlated with phenotype, MELD-, Child-Pugh score, 24h-U-Cu, or treatment type.Conclusion: Measurable cognitive impairment was present in more than half of the stable WD patients independent of phenotype. Thus, our data questions the existence of a purely hepatic phenotype.

Patient reported outcomes and neuropsychological testing in patients with chronic non-cancer pain in long-term opioid therapy: a pilot study

Background and aims Opioid consumption has increased dramatically in patients with chronic non-cancer pain (CNCP), but long-term consequences are still unclear. The aim of this study is to investigate the effects of long-term opioid treatment on pain, cognition, mood, sleep and quality of life in CNCP patients. Methods In this cross-sectional pilot study, two groups of patients with CNCP treated in a multidisciplinary pain center were selected: (1) opioid group: ≥30 mg morphine equivalent/day for >4 weeks, and (2) control group: no opioid consumption for >4 weeks. Socio-demographic data, alcohol consumption, smoking habits and body mass index (BMI) were registered and pain (brief pain inventory), mood (Hospital Anxiety and Depression Scale), sleep (Pittsburgh Sleep Quality Index) and quality of life (RAND 36-Item Health Survey) were assessed. Continuous Reaction Time and the Digit Span Test were used to evaluate cognitive function. Data was analyzed with a Fisher’s exact test and Wilcoxon two-sample test. Results Forty-two patients with CNCP were included (21 in each group). No differences regarding socio-demographics, smoking/alcohol habits and duration, type, or intensity of pain were found. More patients in the opioid group had significantly higher BMI (62% above BMI 25 vs. 33.3%, p = 0.042). Consequently, the subsequent data analyses were controlled for BMI. The two groups did not differ in pain, cognition, anxiety, depression, sleep or quality of life but both showed lower values than the normal standards. Further, the opioid group presented a tendency to lower ratings regarding pain and social function and performed below the normal cut off in the continuous reaction time. Conclusions No significant differences between the two groups were found regarding any of the above-mentioned variables. Interestingly, the patients assessed, regardless of taking opioids or not, could be classified with moderate pain intensity, anxiety and low quality of sleep and life compared to norm standards. Implications The findings of this pilot study suggested that long-term opioid treatment may influence pain and quality of life among CNCP patients. A larger cohort is needed to verify these findings.

Disruption of Cortical Connectivity during Remifentanil Administration Is Associated with Cognitive Impairment but Not with Analgesia

Background: The authors investigated the effect of remifentanil administration on resting electroencephalography functional connectivity and its relationship to cognitive function and analgesia in healthy volunteers. Methods: Twenty-one healthy male adult subjects were enrolled in this placebo-controlled double-blind cross-over study. For each subject, 2.5 min of multichannel electroencephalography recording, a cognitive test of sustained attention (continuous reaction time), and experimental pain scores to bone-pressure and heat stimuli were collected before and after infusion of remifentanil or placebo. A coherence matrix was calculated from the electroencephalogram, and three graph-theoretical measures (characteristic path-length, mean clustering coefficient, and relative small-worldness) were extracted to characterize the overall cortical network properties. Results: Compared to placebo, most graph-theoretical measures were significantly altered by remifentanil at the alpha and low beta range (8 to 18 Hz; all P < 0.001). Taken together, these alterations were characterized by an increase in the characteristic path-length (alpha 17% and low beta range 24%) and corresponding decrements in mean clustering coefficient (low beta range −25%) and relative small-worldness (alpha −17% and low beta range −42%). Changes in characteristic path-lengths after remifentanil infusion were correlated to the continuous reaction time index (r = −0.57; P = 0.009), while no significant correlations between graph-theoretical measures and experimental pain tests were seen. Conclusions: Remifentanil disrupts the functional connectivity network properties of the electroencephalogram. The findings give new insight into how opioids interfere with the normal brain functions and have the potential to be biomarkers for the sedative effects of opioids in different clinical settings.

Continuous Esterification of n-Butyl Acetate Catalyzed by Ionic Liquid

An ionic liquid, 2-Pyrrolidonium hydrogen sulfate (IL, [Hnhp]HSO4) together with a rectification column, was applied in continuous preparation of n-butyl acetate (n-BuAc) from n-butanol (n-BuOH) and acetic acid (HAc). [Hnhp]HSO4 was used as a catalyst which showed good activity for the esterification. Optimum conditions were as follows: base fluid n(HAc):n(n-BuOH): n(IL) =6:1:0.3 in reactor at 120 °C, feedstock n(n-BuOH):n(HAc) =1.05:1 by feeding to the reactorat 20 mL·h-1, aqueous reflux 18 mL·h-1 by feeding to the upper segment of the column and reflux ratio 1. During 48 hours of continuous reaction time, n-BuAc content ranged from 97 % to 85 % in the ester phase from overhead liquid-liquid separator and the reactive distillation system could maintain a good balance.