Withdrawal-induced delirium associated with a benzodiazepine switch: a case report

<p>Abstract</p> <p>Introduction</p> <p>Introduced in the early 1960s, diazepam remains among the most frequently prescribed benzodiazepine-type sedatives and hypnotics. Patients with chronic use of short-acting benzodiazepines are frequently switched to diazepam because the accumulating, long-acting metabolite, N-desmethyl-diazepam, prevents benzodiazepine-associated withdrawal symptoms, which can occur during trough plasma levels of short-acting benzodiazepines. Although mild to moderate withdrawal symptoms are frequently observed during benzodiazepine switching to diazepam, severe medical complications associated with this treatment approach have thus far not been reported.</p> <p>Case presentation</p> <p>A 64-year-old female Caucasian with major depression, alcohol dependence and benzodiazepine dependence was successfully treated for depression and, after lorazepam-assisted alcohol detoxification, was switched from lorazepam to diazepam to facilitate benzodiazepine discontinuation. Subsequent to the benzodiazepine switch, our patient unexpectedly developed an acute delirious state, which quickly remitted after re-administration of lorazepam. A newly diagnosed early form of mixed dementia, combining both vascular and Alzheimer-type lesions, was found as a likely contributing factor for the observed vulnerability to benzodiazepine-induced withdrawal symptoms.</p> <p>Conclusion</p> <p>Chronic use of benzodiazepines is common in the elderly and a switch to diazepam often precedes benzodiazepine discontinuation trials. However, contrary to common clinical practice, benzodiazepine switching to diazepam may require cross-titration with slow tapering of the first benzodiazepine to allow for the build-up of N-desmethyl-diazepam, in order to safely prevent severe withdrawal symptoms. Alternatively, long-term treatment with low doses of benzodiazepines may be considered, especially in elderly patients with chronic use of benzodiazepines and proven vulnerability to benzodiazepine-associated withdrawal symptoms.</p

Tumors and tumor-like lesions of the heart valves

Valvular tumors and tumor-like lesions may have similar morphological and clinical characteristics, and may place the patients at a high risk of stroke in different ways. From January 2004 to June 2008, 11 patients underwent surgery for a suspected valvular tumor. Valvular tumor and tumor-like lesions accounted for 0.32% of adult cardiac operations. Five (45.5%) valvular lesions were papillary fibroelastomas, one (9.1%) was myxoma, 2 (18.2%) were organized thrombi, and 3 (27.3%) were calcification lesions. There was a total of 5 (45.5%) atrioventricular valve lesions, 4 arising from the atrial side of the leaflets, and one from the ventricular side. All 5 (45.5%) semilunar valvular lesions were from the aortic valve. One (9.1%) lesion originated from the chorda tendinea of the mitral valve. All leaflet lesions were resected by a simple shave technique, and all the patients recovered favorably. Valvular tumor and tumor-like lesions are rare. Pre-operative differential diagnoses among these valvular lesions pose important clinical implications for appropriate treatment for the underlying diseases. Prompt therapeutic measures in view of the underlying diseases of the valvular lesions are essential to prevent potential embolic events

The Emergence of Consensus: a primer

The origin of population-scale coordination has puzzled philosophers and scientists for centuries. Recently, game theory, evolutionary approaches and complex systems science have provided quantitative insights on the mechanisms of social consensus. This paper overviews the main dimensions over which the debate has unfolded and discusses some representative results, with a focus on those situations in which consensus emerges `spontaneously' in absence of centralised institutions. Covered topics include the macroscopic consequences of the different microscopic rules of behavioural contagion, the role of social networks, and the mechanisms that prevent the formation of a consensus or alter it after it has emerged. Special attention is devoted to the recent wave of experiments on the emergence of consensus in social systems

Baryonic Popcorn

In the large N limit cold dense nuclear matter must be in a lattice phase. This applies also to holographic models of hadron physics. In a class of such models, like the generalized Sakai-Sugimoto model, baryons take the form of instantons of the effective flavor gauge theory that resides on probe flavor branes. In this paper we study the phase structure of baryonic crystals by analyzing discrete periodic configurations of such instantons. We find that instanton configurations exhibit a series of "popcorn" transitions upon increasing the density. Through these transitions normal (3D) lattices expand into the transverse dimension, eventually becoming a higher dimensional (4D) multi-layer lattice at large densities. We consider 3D lattices of zero size instantons as well as 1D periodic chains of finite size instantons, which serve as toy models of the full holographic systems. In particular, for the finite-size case we determine solutions of the corresponding ADHM equations for both a straight chain and for a 2D zigzag configuration where instantons pop up into the holographic dimension. At low density the system takes the form of an "abelian anti-ferromagnetic" straight periodic chain. Above a critical density there is a second order phase transition into a zigzag structure. An even higher density yields a rich phase space characterized by the formation of multi-layer zigzag structures. The finite size of the lattices in the transverse dimension is a signal of an emerging Fermi sea of quarks. We thus propose that the popcorn transitions indicate the onset of the "quarkyonic" phase of the cold dense nuclear matter.Comment: v3, 80 pages, 18 figures, footnotes 5 and 7 added, version to appear in the JHE

Synapse Pathology in Psychiatric and Neurologic Disease

Inhibitory and excitatory synapses play a fundamental role in information processing in the brain. Excitatory synapses usually are situated on dendritic spines, small membrane protrusions that harbor glutamate receptors and postsynaptic density components and help transmit electrical signals. In recent years, it has become evident that spine morphology is intimately linked to synapse function—smaller spines have smaller synapses and support reduced synaptic transmission. The relationship between synaptic signaling, spine shape, and brain function is never more apparent than when the brain becomes dysfunctional. Many psychiatric and neurologic disorders, ranging from mental retardation and autism to Alzheimer’s disease and addiction, are accompanied by alterations in spine morphology and synapse number. In this review, we highlight the structure and molecular organization of synapses and discuss functional effects of synapse pathology in brain disease

The ruptured Achilles tendon: operative and non-operative treatment options

The Achilles tendon is the strongest and thickest tendon in the human body. Like any other tendon in the body, however, it is susceptible to rupture. Many surgeons advocate early operative repair of the ruptured Achilles tendon, citing decreased re-rupture rates and improved functional outcome. Waiting for surgical repair for longer than one month may lead to inferior functional results postoperatively. Non-operative treatment has higher re-rupture rates as compared to surgically repaired tendons, but may be the treatment of choice in some patients. While for many years, patients were rigidly immobilized in a non-weightbearing cast for 6–8 weeks postoperatively, newer studies have shown excellent results with early weightbearing, and this is quickly becoming the standard of care amongst many physicians

Pin1-dependent signaling negatively affects GABAergic transmission by modulating neuroligin2/gephyrin interaction

The cell adhesion molecule Neuroligin2 (NL2) is localized selectively at GABAergic synapses, where it interacts with the scaffolding protein gephyrin in the post-synaptic density. However, the role of this interaction for formation and plasticity of GABAergic synapses is unclear. Here, we demonstrate that endogenous NL2 undergoes proline-directed phosphorylation at its unique S714-P consensus site, leading to the recruitment of the peptidyl-prolyl cis-trans isomerase Pin1. This signalling cascade negatively regulates NL2' s ability to interact with gephyrin at GABAergic post-synaptic sites. As a consequence, enhanced accumulation of NL2, gephyrin and GABA A receptors was detected at GABAergic synapses in the hippocampus of Pin1-knockout mice (Pin1\ufffd/\ufffd) associated with an increase in amplitude of spontaneous GABA A -mediated post-synaptic currents. Our results suggest that Pin1-dependent signalling represents a mechanism to modulate GABAergic transmission by regulating NL2/gephyrin interaction. \ufffd 2014 Macmillan Publishers Limited. All rights reserved

RIC-7 Promotes Neuropeptide Secretion

Secretion of neurotransmitters and neuropeptides is mediated by exocytosis of distinct secretory organelles, synaptic vesicles (SVs) and dense core vesicles (DCVs) respectively. Relatively little is known about factors that differentially regulate SV and DCV secretion. Here we identify a novel protein RIC-7 that is required for neuropeptide secretion in Caenorhabditis elegans. The RIC-7 protein is expressed in all neurons and is localized to presynaptic terminals. Imaging, electrophysiology, and behavioral analysis of ric-7 mutants indicates that acetylcholine release occurs normally, while neuropeptide release is significantly decreased. These results suggest that RIC-7 promotes DCV–mediated secretion

Olfactory Sex Recognition Investigated in Antarctic Prions

Chemical signals can yield information about an animal such as its identity, social status or sex. Such signals have rarely been considered in birds, but recent results have shown that chemical signals are actually used by different bird species to find food and to recognize their home and nest. This is particularly true in petrels whose olfactory anatomy is among the most developed in birds. Recently, we have demonstrated that Antarctic prions, Pachyptila desolata, are also able to recognize and follow the odour of their partner in a Y-maze

Knowledge of risk factors, beliefs and practices of female healthcare professionals towards breast cancer in a tertiary institution in Lagos, Nigeria

<p>Abstract</p> <p>Background</p> <p>Breast cancer is the leading female malignancy in Nigeria. Screening for early detection has led to reduction in mortality from the disease. It is known that attitudes of physicians and motivation by community nurses influence uptake of screening methods by women. This study aims to investigate knowledge of breast cancer risk factors, beliefs about treatment and practice of screening methods among a cohort of female healthcare professionals in Lagos, Nigeria.</p> <p>Methods</p> <p>A cross-sectional study was conducted using a self-administered questionnaire to assess the knowledge of breast cancer risk factors, beliefs about treatment and practice of screening methods among 207 female doctors, nurses and other healthcare professionals working in a university teaching hospital in Lagos, Nigeria. Stratified random sampling method was employed. Chi square test, analysis of variance and Mantel-Haenszel test were performed in data analysis using SPSS v10.0 and Epi Info version 6 statistical packages.</p> <p>Results</p> <p>Female doctors obtained a mean knowledge score of 74% and were the only professional group that had satisfactory knowledge of risk factors. Majority (86%) believed that early breast cancer is curable while half of participants believed that prayer can make breast cancer disappear from the affected breast. Eighty three percent practice breast self-examination (BSE) once a month and only 8% have ever had a mammogram. Age, knowledge of risk factors, profession and beliefs were not significantly associated with rate of BSE in this study.</p> <p>Conclusion</p> <p>Results from this study suggest the need for continuing medical education programmes aimed at improving knowledge of breast cancer among female healthcare providers other than doctors.</p