Voice Hearing in Borderline Personality Disorder Across Perceptual,Subjective, and Neural Dimensions

BackgroundAuditory verbal hallucinations (AVH) commonly occur in the context of borderline personality disorder (BPD) yet remain poorly understood. AVH are often perceived by patients with BPD as originating from inside the head and hence viewed clinically as “pseudohallucinations,” but they nevertheless have a detrimental impact on well-being.MethodsThe current study characterized perceptual, subjective, and neural expressions of AVH by using an auditory detection task, experience sampling and questionnaires, and functional neuroimaging, respectively.ResultsPerceptually, reported AVH correlated with a bias for reporting the presence of a voice in white noise. Subjectively, questionnaire measures indicated that AVH were significantly distressing and persecutory. In addition, AVH intensity, but not perceived origin (i.e., inside vs outside the head), was associated with greater concurrent anxiety. Neurally, fMRI of BPD participants demonstrated that, relative to imagining or listening to voices, periods of reported AVH induced greater blood oxygenation level–dependent activity in anterior cingulate and bilateral temporal cortices (regional substrates for language processing). AVH symptom severity was associated with weaker functional connectivity between anterior cingulate and bilateral insular cortices.ConclusionIn summary, our results indicate that AVH in participants with BPD are (1) underpinned by aberrant perceptual-cognitive mechanisms for signal detection, (2) experienced subjectively as persecutory and distressing, and (3) associated with distinct patterns of neural activity that inform proximal mechanistic understanding. Our findings are like analogous observations in patients with schizophrenia and validate the clinical significance of the AVH experience in BPD, often dismissed as “pseudohallucinations.” These highlight a need to reconsider this experience as a treatment priority.     

Factors affecting adequacy of Pipelle and Tao Brush endometrial sampling

Objective  To compare factors influencing adequacy of endometrial samples obtained using two outpatient sampling devices – Pipelle and Tao Brush.
Design  Pragmatic unblinded trial with investigation schedule randomised separately within two groups according to endometrial cancer risk.
Setting  Gynaecology outpatient clinic of a large city hospital in Edinburgh, Scotland.
Population  All women referred to a gynaecology outpatient clinic during a 28-month period complaining of abnormal vaginal bleeding.
Methods  Women were assigned to two 'risk groups' for endometrial cancer ('high risk' for postmenopausal women and 'moderate risk' for premenopausal women aged over 40 years or with other risk factors). Women in each risk group had both types of biopsy and were randomised to two outpatient visualisations: hysteroscopy and/or transvaginal ultrasound scan.
Main outcome measures  Completion of the investigation, adequacy of sample and acceptability of investigation to women.
Results  In 200 high-risk women, adequate samples were significantly more likely to be obtained by Tao Brush than Pipelle ( P < 0.001). Nulliparity was strongly associated with failed insertion for both devices ( P < 0.001). Inadequate samples were strongly associated with postmenopausal status only for Pipelle ( P < 0.001), and among premenopausal women, for both samplers, with nulliparity ( P < 0.001). A significantly greater proportion of women preferred the Tao Brush to the Pipelle endometrial sampler ( P < 0.001).
Conclusions  In postmenopausal women, Tao Brush sampling offers advantages over use of Pipelle, and the former should be considered as an alternative or additional sampling device in this group of women.     

The effect of uterine fibroids on embryo implantation

Uterine fibroids are common but their role in infertility and effect on embryo implantation is unclear. There is evidence that submucosal fibroids are associated with poor reproductive outcome and that treatment with myomectomy is associated with an improvement in pregnancy rates. Various theories have been proposed to explain this relationship. Fibroids cause a mechanical distortion of the endometrial cavity-their presence may alter gamete and embryo transport (due to blockage of the tubal ostia or by altering uterine contractility and peristalsis) and subsequent embryo implantation (due to compression of the endometrium). They may lead to disruption of the junctional zone within the myometrial layer, affecting general uterine function in the initial stages of embryo invasion and later placentation. Altered vasculature due to the abnormal expression of angiogenic factors by uterine fibroids (such as basic fibroblast growth factor and platelet-derived growth factor) could play a role in a reduced implantation rate in patients with fibroids. Similarly, changes in the endometrium mediated by inflammation and factors involved in the process of fibrosis (such as transforming growth factor) could also have a detrimental effect. In addition, fibroids may affect gene expression pattern in the endometrium (such as HOXA10), disrupting the window of implantation. The supporting evidence for these theories is discussed in this review.     

Clinical implications of trials investigating drug-drug interactions between cannabidiol and enzyme inducers or inhibitors or common antiseizure drugs

Highly purified cannabidiol (CBD) has demonstrated efficacy with an acceptable safety profile in patients with Lennox-Gastaut syndrome or Dravet syndrome in randomized, double-blind, add-on, controlled phase 3 trials. It is important to consider the possibility of drug-drug interactions (DDIs). Here, we review six trials of CBD (Epidiolex/Epidyolex; 100 mg/mL oral solution) in healthy volunteers or patients with epilepsy, which investigated potential interactions between CBD and enzymes involved in drug metabolism of common antiseizure drugs (ASDs). CBD did not affect CYP3A4 activity. Induction of CYP3A4 and CYP2C19 led to small reductions in exposure to CBD and its major metabolites. Inhibition of CYP3A4 activity did not affect CBD exposure and caused small increases in exposure to CBD metabolites. Inhibition of CYP2C19 activity led to a small increase in exposure to CBD and small decreases in exposure to CBD metabolites. One potentially clinically important DDI was identified: combination of CBD and clobazam (CLB) did not affect CBD or CLB exposure, but increased exposure to major metabolites of both compounds. Reduction of CLB dose may be considered if adverse reactions known to occur with CLB are experienced when it is coadministered with CBD. There was a small increase of exposure to stiripentol (STP) when coadministered with CBD. STP had no effect on CBD exposure but led to minor decreases in exposure to CBD metabolites. Combination of CBD and valproate (VPA) did not cause clinically important changes in the pharmacokinetics of either drug, or 2-propyl-4-pentenoic acid. Concomitant VPA caused small increases in exposure to CBD metabolites. Dose adjustments are not likely to be necessary when CBD is combined with STP or VPA. The safety results from these trials were consistent with the known safety profile of CBD. These trials indicate an overall low potential for DDIs between CBD and other ASDs, except for CLB.     

Mitochondrial DNA A3243G mutation in patients with early- or late-onset type 2 diabetes mellitus in Hong Kong Chinese

BACKGROUND: AND OBJECTIVES: The mitochondrial DNA A to G mutation at nucleotide 3243 (mt3243) is associated with a subtype of diabetes characterized by maternal transmission and deafness. We have previously reported a 2.7% prevalence of this mutation in a cohort of young patients with either type 1 or type 2 diabetes. In this study, we aimed to confirm this finding by examining for the prevalence of this mutation in a large-scale study. SUBJECTS AND METHODS: Nine hundred and six unrelated Chinese patients with type 2 diabetes and 213 nondiabetic controls were studied. The presence of mt3243 mutation was determined by polymerase chain reaction amplification and ApaI digestion. RESULTS: This mutation was found in four of 133 (3.0%) patients with early onset ( 40 years) diabetes and no family history. Basal pancreatic beta-cell function, as assessed by fasting plasma C-peptide, was variable amongst mutation carriers, and did not correlate with the level of heteroplasmy of mutation. CONCLUSIONS: In agreement with most studies, our results suggest that despite the high prevalence of positive maternal family history of diabetes amongst our type 2 diabetic patients, mt3243 mutation was not a major cause of diabetes in either early- or late-onset diabetic patients in Hong Kong. The role of other genetic, environmental and intrauterine factors needs further investigation.     

Effect of Parasympathetic Stimulation on Brain Activity During Appraisal of Fearful Expressions

Autonomic nervous system activity is an important component of human emotion. Mental processes influence bodily physiology, which in turn feeds back to influence thoughts and feelings. Afferent cardiovascular signals from arterial baroreceptors in the carotid sinuses are processed within the brain and contribute to this two-way communication with the body. These carotid baroreceptors can be stimulated non-invasively by externally applying focal negative pressure bilaterally to the neck. In an experiment combining functional neuroimaging (fMRI) with carotid stimulation in healthy participants, we tested the hypothesis that manipulating afferent cardiovascular signals alters the central processing of emotional information (fearful and neutral facial expressions). Carotid stimulation, compared with sham stimulation, broadly attenuated activity across cortical and brainstem regions. Modulation of emotional processing was apparent as a significant expression-by-stimulation interaction within left amygdala, where responses during appraisal of fearful faces were selectively reduced by carotid stimulation. Moreover, activity reductions within insula, amygdala, and hippocampus correlated with the degree of stimulation-evoked change in the explicit emotional ratings of fearful faces. Across participants, individual differences in autonomic state (heart rate variability, a proxy measure of autonomic balance toward parasympathetic activity) predicted the extent to which carotid stimulation influenced neural (amygdala) responses during appraisal and subjective rating of fearful faces. Together our results provide mechanistic insight into the visceral component of emotion by identifying the neural substrates mediating cardiovascular influences on the processing of fear signals, potentially implicating central baroreflex mechanisms for anxiolytic treatment targets.     

What the heart forgets: Cardiac timing influences memory for words and is modulated by metacognition and interoceptive sensitivity

Mental functions are influenced by states of physiological arousal. Afferent neural activity from arterial baroreceptors at systole conveys the strength and timing of individual heartbeats to the brain. We presented words under limited attentional resources time‐locked to different phases of the cardiac cycle, to test a hypothesis that natural baroreceptor stimulation influences detection and subsequent memory of words. We show memory for words presented around systole was decreased relative to words at diastole. The deleterious memory effect of systole was greater for words detected with low confidence and amplified in individuals with low interoceptive sensitivity, as indexed using a heartbeat counting task. Our observations highlight an important cardiovascular channel through which autonomic arousal impacts a cognitive function, an effect mitigated by metacognition (perceptual confidence) and interoceptive sensitivity.     

Systematic review of enhanced recovery after gastro-oesophageal cancer surgery

Introduction

Fast track methodology or enhanced recovery schemes have gained increasing popularity in perioperative care. While evidence is strong for colorectal surgery, its importance in gastric and oesophageal surgery has yet to be established. This article reviews the evidence of enhanced recovery schemes on outcome for this type of surgery.

Methods

A systematic literature search was conducted up to March 2014. Studies were retrieved and analysed using predetermined criteria.

Results

From 34 articles reviewed, 18 eligible studies were identified: 7 on gastric and 11 on oesophageal resection. Three randomised controlled trials, five case-controlled studies and ten case series were identified. The reported protocols included changes to each stage of the patient journey from pre to postoperative care. The specific focus following oesophageal resections was on early mobilisation, a reduction in intensive care unit stay, early drain removal and early (or no) contrast swallow studies. Following gastric resections, the emphasis was on reducing epidural anaesthesia along with re-establishing oral intake in the first three postoperative days and early removal of nasogastric tubes.In the papers reviewed, mortality rates following fast track surgery were 0.8% (9/1,075) for oesophageal resection and 0% (0/329) for gastric resection. The reported morbidity rate was 16.5% (54/329) following gastric resection and 38.6% (396/1,075) following oesophageal resection. Length of stay was reduced in both groups compared with conventional recovery groups in comparative studies.

Conclusions

The evidence for enhanced recovery schemes following gastric and oesophageal resection is weak, with only three (low volume) published randomised controlled trials. However, the enhanced recovery approach appears safe and may be associated with a reduction in length of stay.