A comparison of the effect of high- and low-dose fentanyl on the incidence of postoperative cognitive dysfunction after coronary artery bypass surgery in the elderly

Background. Postoperative cognitive dysfunction (POCD) after coronary artery bypass graft surgery is a common complication for which, despite many clinical investigations, no definitive etiology has been found. The current use of both high and low-dose fentanyl as anesthetic techniques allowed us to investigate the effect of fentanyl on the incidence of POCD. Methods. Three hundred fifty patients scheduled to undergo elective coronary artery bypass graft surgery were randomized to receive either high-dose fentanyl (50 mu g/kg) or low-dose fentanyl (10 mu g/kg) as the basis of the anesthetic. All patients underwent neuropsychological testing before surgery and at 1 week, 3 months, and 12 months after surgery. Results. One hundred sixty-eight patients in the low-dose group and 158 patients in the high-dose group were included in the final analysis. Neuropsychological testing was performed on 88%, 93%, and 92% of patients at 1 week, 3 months, and 12 months, respectively. There was no difference between group mean scores at any of the three testing times. Analysis of individual patients by the 20% rule did not detect any differences between groups. The one SD rule, which has fewer false-positive results, detected significantly more patients with POCD in the low-dose group than in the high-dose group at 1 week (23.6% vs. 13.7%; P = 0.03) but not at the other testing times. Patients with POCD spent an average of 1.2 days longer in the hospital than those without POCD (P = 0.021). Conclusions: High-dose fentanyl is not associated with a difference in the incidence of POCD at 3 or 12 months after surgery. Low-dose fentanyl leads to shorter postoperative ventilation times and may be associated with a greater incidence of POCD 1 week after surgery. Early POCD is associated with an increased duration of stay in the hospital.

Association between apolipoprotein E epsilon 4 and neuropsychiatric symptoms during interferon alpha treatment for chronic hepatitis C

Neuropsychiatric complications are common in patients with chronic hepatitis C undergoing treatment with interferon alpha. These side effects include alterations of mood, cognition, and neuroendocrine function and are unpredictable. In a number of neurological disorders characterized by neuropsychiatric symptoms and cognitive dysfunction, inheritance of an apolipoprotein E (APOE) epsilon4 allele is associated with adverse neuropsychiatric outcomes. The authors present evidence that the APOE genotype may influence a patient's neuropsychiatric response to interferon alpha treatment. The inheritance of APOE genotypes was examined in 110 patients with chronic hepatitis C treated with interferon alpha. A retrospective investigation was conducted by assessing the rates of psychiatric referral and neuropsychiatric symptoms experienced during treatment along with other complaints indicating psychological distress. A highly statistically significant association was seen between APOE genotypes and interferon-induced neuropsychiatric symptoms. Patients with an epsilon4 allele were more likely to be referred to a psychiatrist and had more neuropsychiatric symptoms during antiviral treatment than those without an epsilon4 allele. Additionally, patients with an epsilon4 allele were more likely to experience irritability or anger and anxiety or other mood symptoms. These data demonstrate that an individual's APOE genotype may influence the neuropsychiatric response to antiviral therapy with interferon alpha. Prospective studies evaluating the importance of APOE in susceptibility to interferon alpha-induced neuropsychiatric complications are needed. Moreover, pathways involving APOE should be considered in understanding the pathophysiology of interferon alpha-induced neuropsychiatric complications.

Movement and motor development in ELBW infants at 1 year is related to cognitive and motor abilities at 4 years

A relationship between motor ability and cognitive performance has been previously reported. This study aimed to investigate the association between movement and cognitive performance at 1 and 4 years corrected age of children born less than 1000 g, and whether developmental testing of movement at 1 year is predictive of cognitive performance at 4 years. Motor development was assessed at both ages using the neurosensory motor developmental assessment (NSMDA) and motor development was classified as normal, or minimal, mild, moderate-severe dysfunction. Cognitive performance was assessed on the Griffith Mental Developmental Scale at 1 year and McCarthy Scales of Children's Abilities at 4 years. Subjects included 198 children of birthweight less than 1000 g. Of these 132 children returned for follow-up at the corrected ages of both 1 and 4 years. The 66 children not included had a slight increase in gestational age, while the mothers were younger and had a lower level of education. A significant association was found between NSMDA group classification at 1 year and cognitive performance at both 1 and 4 years (p

Improvement in measures of psychological distress amongst amphetamine misusers treated with brief cognitive-behavioural therapy (CBT)

This trial of cognitive-behavioural therapy (CBT) based amphetamine abstinence program (n = 507) focused on refusal self-efficacy, improved coping, improved problem solving and planning for relapse prevention. Measures included the Severity of Dependence Scale (SDS), the General Health Questionnaire-28 (GHQ-28) and Amphetamine Refusal Self-Efficacy. Psychiatric case identification (caseness) across the four GHQ-28 sub-scales was compared with Australian normative data. Almost 90% were amphetamine-dependent (SDS 8.15 +/- 3.17). Pretreatment, all GHQ-28 sub-scale measures were below reported Australian population values. Caseness was substantially higher than Australian normative values {Somatic Symptoms (52.3%), Anxiety (68%), Social Dysfunction (46.5%) and Depression (33.7%). One hundred and sixty-eight subjects (33%) completed and reported program abstinence. Program completers reported improvement across all GHQ-28 sub-scales Somatic Symptoms (p < 0.001), Anxiety (p < 0.001), Social Dysfunction (p < 0.001) and Depression (p < 0.001)}. They also reported improvement in amphetamine refusal self-efficacy (p < 0.001). Improvement remained significant following intention-to-treat analyses, imputing baseline data for subjects that withdrew from the program. The GHQ-28 sub-scales, Amphetamine Refusal Self-Efficacy Questionnaire and the SDS successfully predicted treatment compliance through a discriminant analysis function (p

NMDA receptor dysfunction in Alzheimer's disease

The inherent neurotoxic potential ofthe endogenous excitatory amino acid glutamate, may be causally related to the pathogenesis ofAD neurodegeneration disorders. Neuronal excitotoxicity is conceivably mediated by the N-methyl-D-aspartate-(NMDA)-Ca2+- ionotropic receptor. NMDA receptors exist as multimeric complexes comprising proteins from two families – NR1 and NR2(A-D). The polyamines, spermine and spermidine bind to, and modulate NMDA receptor efficacy via interaction with exon 5, an alternatively-spliced, 21 amino acid, N-terminal cassette. AD associated cognitive impairment may therefore occur via subunitspecific NMDA receptor dysfunction effecting regional selectivity of neuronal degradation.

NMDA receptor dysfunction in Alzheimer's disease

The inherent neurotoxic potential ofthe endogenous excitatory amino acid glutamate, may be causally related to the pathogenesis ofAD neurodegeneration disorders. Neuronal excitotoxicity is conceivably mediated by the N-methyl-D-aspartate-(NMDA)-Ca2+- ionotropic receptor. NMDA receptors exist as multimeric complexes comprising proteins from two families – NR1 and NR2(A-D). The polyamines, spermine and spermidine bind to, and modulate NMDA receptor efficacy via interaction with exon 5, an alternatively-spliced, 21 amino acid, N-terminal cassette. ADassociated cognitive impairment may therefore occur via subunitspecific NMDA receptor dysfunction effecting regional selectivity ofneuronal degradation. Total RNA was prepared from pathologically spared and susceptible regions from AD cases and matched controls. Quantitation was performed using standard curve methodology in which a known amount ofa synthetic ribonucleic acid competitor deletion construct was co-amplified against total RNA. Expression profile analysis oftwo NR1 mRNA subsets has revealed significant differences in NR11XX mRNA levels in cingulate gyrus, P.