[Dental treatment under general anaesthesia in young children]. / Algehele anesthesie bij jonge kinderen in de tandheelkunde.

General anaesthesia in children younger than 4 years of age can cause brain damage with cognitive and behavioral problems as a result. The chance of these side effects is small, but increases with prolonged duration of the anaesthesia or when the general anaesthesia is provided more frequently. It goes without saying that the indication for anaesthesia should be very strictly set. In order to reduce the chance of damage, the anaesthesia itself should be performed in consultation between the anaesthesiologist and care provider, according to a set protocol. The parents need to be informed of the potential risks of general anaesthesia. Delayed treatment (and thereby provision of the anaesthesia) should be considered.

[Neurotoxicity of sedatives and anaesthetics in young children]. / Neurotoxiciteit van sedativa en anesthetica bij jonge kinderen.

Many histological studies, animal experiments and also human studies during the past 30 years have proven that the use of general anaesthesia in young children under the age of four can have a permanent effect on the brain, which is still developing, and can therefore cause learning and/or behaviour problems later in life. This knowledge has to be taken seriously into account in the discussion with parents whether general anaesthesia is really necessary for the treatment of Early Childhood Caries in very young children.

[The risk of general anaesthesia and sedation in the older people]. / Gevaar van algehele anesthesie en sedatie bij ouderen.

Temporary memory problems and aggravation of pre-existing memory disorders may occur after treatment under general anaesthesia. A frequency of postoperative cognition disorders between 10 and 50% has been identified in the literature. Risk factors for the occurrence of postoperative memory disorders are advanced age, low level of education, intellectual comorbidity, the onset of dementia and other neurodegenerative disorders, existing sleep disorders and the experience of postoperative pain. The morphological changes seen in the brain after general anaesthesia are similar to the changes occurring in Alzheimer's disease. In addition to metabolic changes, general anaesthetics directly enhance the apoptosis of brain cells. Older people are already familiar with a decrease in the number of neurons, which provides them with a limited spare capacity. Moreover, older people are often known to have the risk factors for the occurrence of postoperative memory disorders as mentioned before. Caution and restraint in the indication for dental -treatment under general anaesthesia or sedation is therefore required.

A systematic review and meta-regression analysis of mivacurium for tracheal intubation.

We systematically reviewed factors associated with intubation conditions in randomised controlled trials of mivacurium, using random-effects meta-regression analysis. We included 29 studies of 1050 healthy participants. Four factors explained 72.9% of the variation in the probability of excellent intubation conditions: mivacurium dose, 24.4%; opioid use, 29.9%; time to intubation and age together, 18.6%. The odds ratio (95% CI) for excellent intubation was 3.14 (1.65-5.73) for doubling the mivacurium dose, 5.99 (2.14-15.18) for adding opioids to the intubation sequence, and 6.55 (6.01-7.74) for increasing the delay between mivacurium injection and airway insertion from 1 to 2 min in subjects aged 25 years and 2.17 (2.01-2.69) for subjects aged 70 years, p < 0.001 for all. We conclude that good conditions for tracheal intubation are more likely by delaying laryngoscopy after injecting a higher dose of mivacurium with an opioid, particularly in older people.

Tryptophan hydroxylase(2) gene polymorphisms predict brain serotonin synthesis in the orbitofrontal cortex in humans.

Brain regional serotonin synthesis can be estimated in vivo using positron emission tomography (PET) and α-[((11))C]methyl-L-tryptophan ((11)C-AMT) trapping (K*) as a proxy. Recently, we reported evidence of lower normalized (11)C-AMT trapping in the orbitofrontal cortex (OBFC) of subjects meeting the criteria for an impulsive and/or aggressive behavioral phenotype. In this study, we examined whether part of the variance in OBFC serotonin synthesis is related to polymorphisms of the gene that encodes for the indoleamine's rate-limiting enzyme in the brain, tryptophan hydroxylase-2 (TPH(2)). In all, 46 healthy controls had PET (11)C-AMT scans and were genotyped for 11 single-nucleotide polymorphisms (SNPs) distributed across the TPH(2) gene and its 5' upstream region. Several TPH(2) SNPs were associated with lower normalized blood-to-brain clearance of (11)C-AMT in the OBFC. Dose-effect relationships were found for two variants (rs6582071 and rs4641527, respectively, located in the 5' upstream region and intron 1) that have previously been associated with suicide. Associations in the OBFC remained statistically significant in a mixed larger sample of patients and controls. These results suggest that in humans, genetic factors might partly account for variations in serotonin synthesis in the OBFC.

A Cluster Analysis of Oral and Cognitive Health Indicators: An Exploratory Study on Cholinergic Activity as the Link.

INTRODUCTION: Poor oral health has been suggested as a risk factor for cognitive decline. Yet, biologically plausible mechanisms explaining this relationship remain unknown. OBJECTIVES: We aimed (1) to identify oral and cognitive health clustering patterns among middle-aged to elderly Canadians and (2) to investigate the extent to which these patterns could be explained by bone mineral density (BMD), a proxy measure of the cholinergic neurons' activity. METHODS: This cross-sectional study used baseline data from the Comprehensive cohort of the Canadian Longitudinal Study of Aging (CLSA). Oral health was assessed by a self-report questionnaire, and 7 task-based instruments measured cognitive health. We identified oral and cognitive health clusters, our outcome variables, using latent class analysis. Two sets of multivariate logistic regression and 95% confidence intervals were used to investigate whether BMD explains the odds of membership in a certain oral and cognitive health group. The final models were adjusted for socioeconomic, health, and lifestyle factors. RESULTS: Our study sample (N = 25,444: 13,035 males, 12,409 females) was grouped into 5 and 4 clusters based on the oral health status and performance on the cognitive tasks, respectively. After adjusting for all potential covariates, increase in BMD was not associated with higher odds of membership in classes with better oral health (odds ratio [OR] = 1.58 [95% confidence interval {CI}: 0.85-2.92]) and cognitive health (OR = 1.61 [95% CI: 1-2.6]) compared with the groups with the least favorable oral and cognitive health status, respectively. CONCLUSION: Middle-aged and elderly Canadians show different oral and cognitive health profiles, based on their denture-wearing status and performance on cognitive tests. No evidence could be found to support BMD in place of cholinergic neurons' activity as the common explanatory factor behind the association between oral health and cognitive health. KNOWLEDGE TRANSFER STATEMENT: This study is probably the first of its kind to shed light on the cholinergic system as a potential pathway influencing oral and cognitive health. Our findings may support the notion that any potential association between poor oral health and cognitive health might be explained by common contributors, helping clinicians to find the common risk factors for both conditions.

A descriptive analysis of first trimester urinary concentrations of 14 bisphenol analogues in the MIREC Canadian pregnancy cohort.

BACKGROUND: Concern over the health effects of BPA, particularly for the developing fetus, has led to an increasing use of bisphenol analogues in industrial and consumer products, which may be as hormonally active as BPA. Biomonitoring data for many bisphenol analogues, especially in pregnant populations, are limited. METHODS: We measured concentrations of 14 bisphenol analogues in 1st trimester urine samples (n = 1851) from the Maternal-Infant Research on Environmental Chemicals (MIREC) Canadian pregnancy cohort (2008-2011). We examined patterns of exposure according to sociodemographic and sampling characteristics as well as occupation and frequency of consumption of canned fish within the previous 3 months. RESULTS: BPA was detected in 89% of participants with a specific gravity standardized geometric mean concentration of 0.990 µg/L. Biphenol 4,4' (BP 4,4'), 4,4'-dihydroxydiphenyl ether (DHDPE), and bisphenol E (BPE) were detected in >97% of participants. Bisphenol F (BPF) and bisphenol S (BPS) were detected in >60% of participants. Specific gravity standardized geometric mean concentrations of these 5 compounds ranged from 0.024 to 0.564 µg/L. Nine bisphenol analogues were detected in <9% of participants. Concentrations of BP 4,4', DHDPE, and BPE were higher in younger women and those with higher pre-pregnancy BMI, lower household income, lower education, and among smokers. We found a similar pattern of differences in BPF for age, education, and smoking status while BPS similarly differed across categories of pre-pregnancy BMI. Participants who were unemployed or working in the service industry had higher molar sum of 7 bisphenol analogues than those working in healthcare, education, or an office setting. Canned fish consumption was not related to bisphenol analogue concentrations. CONCLUSION: BP 4,4', DHDPE, BPE, BPF, and BPS were highly detected in 1st trimester urine samples in this large pan-Canadian pregnancy cohort. This suggests widespread exposure to these analogues around 2008-2011 and warrants further investigation into associations with health outcomes.

Immunoinflammatory processes: Overlapping mechanisms between obesity and eating disorders?

Obesity and eating disorders are conditions that involve eating behaviors and are sometimes comorbid. Current evidence supports alterations in immunoinflammatory processes in both obesity and eating disorders. A plausible hypothesis is that immunoinflammatory processes may be involved in the pathophysiology of obesity and eating disorders. The aim of this review is to highlight the link between obesity and eating disorders, with a particular focus on immunoinflammatory processes. First, the relation between obesity and eating disorders will be presented, followed by a brief review of the literature on their association with immunoinflammatory processes. Second, developmental factors will be discussed to clarify the link between obesity, eating disorders, and immunoinflammatory processes. Genetic and epigenetic risk factors as well as the potential roles of stress pathways and early life development will be presented. Finally, implications of these findings for future research are discussed. This review highlighted biological and developmental aspects that overlap between obesity and EDs, emphasizing the need for biopsychosocial research approaches to advance current knowledge and practice in these fields.

The relation between skin temperature increase and sensory block height in spinal anaesthesia using infrared thermography.

BACKGROUND AND OBJECTIVES: To evaluate the feasibility of determining the extent of sympathetic blockade by skin temperature measurement with infrared thermography and relate the cranial extent of the temperature increase to that of the sensory block after spinal anaesthesia. METHODS: Before and 5, 10 and 20 min after the administration of spinal anaesthesia, skin temperatures were measured with infrared thermography at the dermatomes T2-L3, in 12 male patients scheduled for lower limb surgery. The most cephalad dermatome at which sensory blockade occurred was related to the dermatome at which the largest temperature jump (corrected for baseline temperature) occurred. RESULTS: The baseline temperatures showed considerable variation across the dermatomes, being lower below T12 than at the thoracic dermatomes. The mean difference between the level of the cephalad skin temperature elevation front (mean 1.03 °C, SD 0.8 °C) and cranial sensory block height was 0.10 dermatomes (SD 1.16), correlation coefficient (0.88, P<0.001). CONCLUSION: The varying baseline temperatures across the trunk, the limited sympathetic block-induced increase in skin temperature at the trunk and the difficult control of influences from the surroundings partly obscured the extent of the skin temperature increase and its correlation to sensory block height. These factors have to be controlled to improve the use of infrared cameras as an easy bedside tool for predicting the cranial extent of (sympathetic blockade during) spinal anaesthesia.

Comparison of mechanomyography and acceleromyography for the assessment of rocuronium induced neuromuscular block in myotonic dystrophy type 1.

We measured acceleromyography and mechanomyography simultaneously with monitoring of rocuronium-induced neuromuscular block in four patients with myotonic dystrophy type 1. Furthermore, we compared neuromuscular block measures from these patients with those from normal controls from previous studies. In myotonic dystrophy type 1 patients, the dose-response curve obtained with acceleromyography was steeper and right-shifted compared with that obtained using mechanomyography. However, the effective doses to produce 95% neuromuscular block determined with both acceleromyography and mechanomyography were similar to each other and to values found in normal patients. In the three myotonic dystrophy type 1 patients with mild to moderate disease, times to recovery from block were similar to those observed in normal controls. In both patients and normal controls, neuromuscular block recovered faster with acceleromyography. However, in one patient with severe muscle wasting, recovery of neuromuscular block was prolonged. We conclude that mechanomyography and acceleromyography cannot be used interchangeably to monitor neuromuscular block in myotonic dystrophy type 1 patients.

A new approach to anesthesia management in myasthenia gravis: reversal of neuromuscular blockade by sugammadex.

A neuromuscular blocking drug (NMBD) induced neuromuscular blockade (NMB) in patients with myasthenia gravis usually dissipates either spontaneously or by administration of neostigmine. We administered sugammadex to a patient with myasthenia gravis to reverse a rocuronium-induced profound NMB. NMBDs predispose such patients to severe postoperative residual paralysis and respiratory complications. Sugammadex binds steroidal NMBDs and, therefore reverses a rocuronium or vecuronium-induced NMB, without interfering with cholinergic transmission. A rapid and complete recovery from profound NMB was achieved and no adverse events were observed. This case suggests that sugammadex is a safe and effective antagonist of a rocuronium induced NMB blockade in patients with myasthenia gravis.

Interpersonal capitalization moderates the associations of chronic caregiving stress and depression with inflammation.

Chronic stress and depression can enhance chronic low-grade inflammation. Interpersonal factors may buffer the impact of stress and depression on inflammation. Interpersonal capitalization is a social support process in which one discloses positive personal events and experiences to close others. Greater capitalization may attenuate the deleterious impact of chronic stress and depression. The goal of the current study was to assess whether interpersonal capitalization is associated with inflammation and whether it moderates the association of chronic stress and depression with inflammation. In this cross-sectional study of chronic caregiving stress, 222 caregiving mothers of adolescents with developmental disabilities or comparison mothers of typically developing adolescents completed a self-reported daily diary assessment of capitalization, the Center for Epidemiological Study-Depression scale, and provided blood samples to assess interleukin-6, tumor necrosis factor-α, and C-reactive protein, three circulating inflammatory markers. Regression analysis indicated that there was no main effect of capitalization on inflammation, p = .24, R2 = .006. However, there was a significant three-way interaction among capitalization, chronic caregiving stress, and depressive symptoms, p = .01, R2 = .02. Among participants with lower capitalization, greater depressive symptoms were associated with higher inflammation in the caregiving group, but not in the comparison group. Among participants with higher capitalization, greater depressive symptoms were no longer significantly associated with higher inflammation among caregivers, but were marginally related to inflammation in the comparison group. Capitalization may thus be an interpersonal process mitigating the effects of chronic stress and depression on inflammation.

Cyclodextrins and the emergence of sugammadex.

Residual paralysis, with its subsequent postoperative pulmonary sequelae, is one of the major complications of anaesthesia, and was recognised shortly after the introduction of neuromuscular blocking drugs into routine clinical practice. Although its incidence decreased with the introduction of intermediate duration drugs, and further diminished with routine neuromuscular monitoring and reversal with cholinesterase inhibitors, residual paralysis still remained a problem. In the search for alternatives to stop the effect of neuromuscular blocking drugs and to match their duration of action to clinical need, chelation of the non-depolarising neuromuscular blocking drugs was considered. It was recognised that cyclodextrins could encapsulate steroidal molecules and thereby inactivate the aminosteroidal neuromuscular blocking drugs. In order to improve the binding of rocuronium to the cyclodextrin and to increase the compound's water solubility, the molecule was modified. This led to the development of sugammadex (Org 25969), a modified gamma-cyclodextrin. The modification of the molecule and the initial in vitro studies that led to in vivo and later human studies of this conceptually new drug for anaesthesia are described.

In vivo animal studies with sugammadex.

A review is presented of animal studies of the selective steroidal neuromuscular blocking drug binding agent sugammadex. These studies demonstrate that sugammadex is faster in onset than the currently used acetylcholinesterase inhibitors, has no muscarinic effects, and is characterised by lack of adverse effects on other organs. These results offer support for the further development of sugammadex for clinical use in humans.

[Sugammadex. New pharmacological concept for antagonizing rocuronium and vecuronium]. / Sugammadex. Neues pharmakologisches Konzept zur Antagonisierung von Rocuronium und Vecuronium.

Up to now only acetylcholine esterase inhibitors, such as neostigmine, were available as antagonists of residual neuromuscular blocks. Sugammadex is a modified gamma-cyclodextrin that binds rocuronium and chemically similar aminosteroidal muscle relaxants, such as vecuronium. The underlying mechanism of action is new and differs completely from that of acetylcholine esterase inhibitors. This review summarizes data published so far within the framework of the licensing procedure about the efficacy, safety and side-effects of sugammadex and presents potential new anesthesiological concepts using this compound.

The effects of experimentally lowered serotonin function on emotional information processing and memory in remitted depressed patients.

It has been well documented that acute tryptophan depletion (ATD) induces symptoms in remitted depressed patients treated with an SSRI. ATD also has effects on cognition, both in patients and in healthy samples. The exact nature of ATD-induced cognitive changes in depression remains unclear. It is also unclear whether cognitive effects can be induced through partial ('low-dose') depletion. The aim of this study is to investigate the differential effects of low-dose and high-dose ATD on emotional information processing and mood in remitted depressed patients. Eighteen remitted depressed patients received high-dose and low-dose ATD in a randomized, double-blind, within-subjects crossover design. Mood was assessed before and after administration of the depletion drink. Five hours after administration, patients conducted tests measuring neutral and emotional information processing. High-dose ATD increased depressive symptoms and induced a temporary depressive 'relapse' in half of the patients. High-dose ATD also decreased the recognition of fear and impaired learning and memory retrieval. The impaired learning occurred only in mood-responders. Low-dose ATD had no effects on mood but speeded the recognition of facial expressions of disgust. Accurate recognition of sad faces at baseline was associated with mood response to ATD. High-dose ATD leads to changes in memory and in the recognition of negative facial expressions in SSRI-treated remitted depressed patients. The effect of low-dose ATD on mood and cognition seems to be quite limited. Emotional information processing at baseline predicts mood-response to ATD.

Associations among oxytocin receptor gene (OXTR) DNA methylation in adulthood, exposure to early life adversity, and childhood trajectories of anxiousness.

Recent models propose deoxyribonucleic acid methylation of key neuro-regulatory genes as a molecular mechanism underlying the increased risk of mental disorder associated with early life adversity (ELA). The goal of this study was to examine the association of ELA with oxytocin receptor gene (OXTR) methylation among young adults. Drawing from a 21-year longitudinal cohort, we compared adulthood OXTR methylation frequency of 46 adults (23 males and 23 females) selected for high or low ELA exposure based on childhood socioeconomic status and exposure to physical and sexual abuse during childhood and adolescence. Associations between OXTR methylation and teacher-rated childhood trajectories of anxiousness were also assessed. ELA exposure was associated with one significant CpG site in the first intron among females, but not among males. Similarly, childhood trajectories of anxiousness were related to one significant CpG site within the promoter region among females, but not among males. This study suggests that females might be more sensitive to the impact of ELA on OXTR methylation than males.

Tooth Loss Increases the Risk of Diminished Cognitive Function: A Systematic Review and Meta-analysis.

Emerging evidence suggests that oral health is associated with cognitive function. This review aims to systematically assess this association in adult populations via prospective cohort study designs. Eligible study reports were identified by searching the MEDLINE (via Ovoid), EMBASE, PsycoINFO, and Cochrane Library databases. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated with a random effects model. From 1,251 identified articles, 10 were included in the systematic review and 8 in the meta-analysis. Random effects analysis showed, with statistically low heterogeneity, that individuals with suboptimal dentition (<20 teeth) were at a 20% higher risk for developing cognitive decline (HR = 1.26, 95% CI = 1.14 to 1.40) and dementia (HR = 1.22, 95% CI = 1.04 to 1.43) than those with optimal dentition (≥20 teeth). Studies on the association between periodontal disease and cognitive status showed conflicting results. Within the limits of the quality of published evidence, this meta-analysis lends further support to the hypothesis that tooth loss is associated with an increased risk of cognitive impairment and dementia. Knowledge Transfer Statement: Based on the published literature, the results of this study show that the risk for cognitive impairment and dementia increases with loss of teeth. This information adds to the evidence showing links between oral and general health and suggests that oral health strategies aimed to preserve teeth may be important in reducing risk of systemic disease.

Dopamine cross-sensitization between psychostimulant drugs and stress in healthy male volunteers.

Dysregulation of the stress response system is a potential etiological factor in the development of and relapse to multiple neuropsychiatric disorders. Previously we reported that repeated intermittent d-amphetamine administration can lead to progressively greater dopamine release, thereby providing evidence of drug-induced neurochemical sensitization. Here, we test the hypothesis that repeated exposure to d-amphetamine increases dopaminergic responses to stress; that is, produces cross-sensitization. Using positron emission tomography, we measured in 17 healthy male volunteers (mean ± s.d. = 22.1 ± 3.4 years) [(11)C]raclopride binding responses to a validated psychosocial stress task before and 2 weeks after a regimen of repeated d-amphetamine (3 × 0.3 mg kg(-1), by mouth; n = 8) or placebo (3 × lactose, by mouth; n = 9). Mood and physiological measurements were recorded throughout each session. Before the d-amphetamine regimen, exposure to the stress task increased behavioral and physiological indices of stress (anxiety, heart rate, cortisol, all P ⩽ 0.05). Following the d-amphetamine regimen, the stress-induced cortisol responses were augmented (P < 0.04), and voxel-based analyses showed larger stress-induced decreases in [(11)C]raclopride non-displaceable binding potential across the striatum. In the placebo group, re-exposure to stress led to smaller clusters of decreased [(11)C]raclopride binding, primarily in the sensorimotor striatum (P < 0.05). Together, this study provides evidence for drug × stress cross-sensitization; moreover, random exposure to stimulants and/or stress cumulatively, while enhancing dopamine release in striatal areas, may contribute to a lowered set point for psychopathologies in which altered dopamine neurotransmission is invoked.