Manganese toxicity with ephedrone abuse manifesting as parkinsonism: a case report

Introduction: Neurologic consequences of manganese toxicity have been recognized since 1837. A new form of presumed manganese poisoning has been reported in drug addicted persons from Eastern Europe and the Baltic states who have intravenously injected self-prepared methcathinone hydrochloride (ephedrone), which is synthesized from pseudoephedrine hydrochloride using potassium permanganate as a potent oxidant. This clinical syndrome is under-recognized in Western Europe and there are no reported cases in the literature from Ireland. Case presentation: We report a 30-year-old Eastern European man who presented with a two-year history of gait disturbance. A neurological assessment revealed features of parkinsonism which included hypophonia, hypomimia, mild bradykinesia and rigidity with no resting tremor. He held his arms slightly abducted from his sides when walking, with a reduction in arm swing. Magnetic resonance imaging of his brain showed a high signal on T1 in the globus pallidus and serum manganese levels were raised. He had no response to levodopa. Conclusion: Manganism secondary to ephedrone abuse causing parkinsonism has emerged in Western Europe in recent years due to mass immigration and often remains unrecognized. This paper highlights the various features of this rare cause of parkinsonism and aids in its recognition and subsequent diagnosis. Neurologists in Western Europe will increasingly encounter such patients

Prevalence of Helicobacter pylori infection among new outpatients with dyspepsia in Kuwait

<p>Abstract</p> <p>Background</p> <p>Testing and treatment for <it>Helicobacter pylori </it>has become widely accepted as the approach of choice for patients with chronic dyspepsia but no alarming features. We evaluated <it>H. pylori </it>status among outpatients with uninvestigated dyspepsia in Kuwait.</p> <p>Methods</p> <p>A prospectively collected database for 1035 patients who had undergone ¹³C-urea breath tests (UBT) for various indications was reviewed for the period from October 2007 to July 2009. The status of <it>H. pylori </it>in dyspeptic patients was determined by UBT.</p> <p>Results</p> <p>Among the 362 patients who had undergone UBT for uninvestigated dyspepsia, 49.7% were positive for <it>H. pylori </it>(95% CI = 44%-55%) and the percentage increased with age (35.8% at 20-29 years, 95% CI = 25.4% - 47.2%; 59.3% at 30-39 years, 95% CI = 48.5% - 69.5%) (P = 0.013). The prevalence of <it>H. pylori </it>was 42.6% among Kuwaitis (95% CI = 35%-50%) and 57.6% (95% CI = 49.8%-65%) among expatriates (p = 0.004). The prevalence among males was 51.3%, while in females it was 48.6%.</p> <p>Conclusions</p> <p>Almost half of the patients with dyspeptic symptoms in Kuwait were positive for <it>H. pylori</it>, though the prevalence varied with age and was higher among expatriates. The American Gastroenterology Association guidelines recommending testing and treatment for <it>H. pylori </it>for patients with uninvestigated dyspepsia should be endorsed in Kuwait.</p

Emergency percutaneous needle decompression for tension pneumoperitoneum

<p>Abstract</p> <p>Background</p> <p>Tension pneumoperitoneum as a complication of iatrogenic bowel perforation during endoscopy is a dramatic condition in which intraperitoneal air under pressure causes hemodynamic and ventilatory compromise. Like tension pneumothorax, urgent intervention is required. Immediate surgical decompression though is not always possible due to the limitations of the preclinical management and sometimes to capacity constraints of medical staff and equipment in the clinic.</p> <p>Methods</p> <p>This is a retrospective analysis of cases of pneumoperitoneum and tension pneumoperitoneum due to iatrogenic bowel perforation. All patients admitted to our surgical department between January 2005 and October 2010 were included. Tension pneumoperitoneum was diagnosed in those patients presenting signs of hemodynamic and ventilatory compromise in addition to abdominal distension.</p> <p>Results</p> <p>Between January 2005 and October 2010 eleven patients with iatrogenic bowel perforation were admitted to our surgical department. The mean time between perforation and admission was 36 ± 14 hrs (range 30 min - 130 hrs), between ER admission and begin of the operation 3 hrs and 15 min ± 47 min (range 60 min - 9 hrs). Three out of eleven patients had clinical signs of tension pneumoperitoneum. In those patients emergency percutaneous needle decompression was performed with a 16G venous catheter. This improved significantly the patients' condition (stabilization of vital signs, reducing jugular vein congestion), bridging the time to the start of the operation.</p> <p>Conclusions</p> <p>Hemodynamical and respiratory compromise in addition to abdominal distension shortly after endoscopy are strongly suggestive of tension pneumoperitoneum due to iatrogenic bowel perforation. This is a rare but life threatening condition and it can be managed in a preclinical and clinical setting with emergency percutaneous needle decompression like tension pneumothorax. Emergency percutaneous decompression is no definitive treatment, only a method to bridge the time gap to definitive surgical repair.</p

What are the risk factors of colonoscopic perforation?

<p>Abstract</p> <p>Background</p> <p>Knowledge of the factors influencing colonoscopic perforation (CP) is of decisive importance, especially with regard to the avoidance or minimization of the perforations. The aim of this study was to determine the incidence and risk factors of CP in one of the endoscopic training centers accredited by the World Gastroenterology Organization.</p> <p>Methods</p> <p>The prospectively collected data were reviewed of all patients undergoing either colonoscopy or flexible sigmoidoscopy at the Faculty of Medicine Siriraj Hospital, Bangkok, Thailand between January 2005 and July 2008. The incidence of CP was evaluated. Eight independent patient-, endoscopist- and endoscopy-related variables were analyzed by a multivariate model to determine their association with CP.</p> <p>Results</p> <p>Over a 3.5-year period, 10,124 endoscopic procedures of the colon (8,987 colonoscopies and 1,137 flexible sigmoidoscopies) were performed. There were 15 colonic perforations (0.15%). Colonoscopy had a slightly higher risk of CP than flexible sigmoidoscopy (OR 1.77, 95%CI 0.23-13.51; p = 1.0). Patient gender, emergency endoscopy, anesthetic method, and the specialty or experience of the endoscopist were not significantly predictive of CP rate. In multivariate analysis, patient age of over 75 years (OR = 6.24, 95%CI 2.26-17.26; p < 0.001) and therapeutic endoscopy (OR = 2.98, 95%CI 1.08-8.23; p = 0.036) were the only two independent risk factors for CP.</p> <p>Conclusion</p> <p>The incidence of CP in this study was 0.15%. Patient age of over 75 years and therapeutic colonoscopy were two important risk factors for CP.</p

Thermodynamics of Competitive Molecular Channel Transport: Application to Artificial Nuclear Pores

In an analytical model channel transport is analyzed as a function of key parameters, determining efficiency and selectivity of particle transport in a competitive molecular environment. These key parameters are the concentration of particles, solvent-channel exchange dynamics, as well as particle-in-channel- and interparticle interaction. These parameters are explicitly related to translocation dynamics and channel occupation probability. Slowing down the exchange dynamics at the channel ends, or elevating the particle concentration reduces the in-channel binding strength necessary to maintain maximum transport. Optimized in-channel interaction may even shift from binding to repulsion. A simple equation gives the interrelation of access dynamics and concentration at this transition point. The model is readily transferred to competitive transport of different species, each of them having their individual in-channel affinity. Combinations of channel affinities are determined which differentially favor selectivity of certain species on the cost of others. Selectivity for a species increases if its in-channel binding enhances the species' translocation probablity when compared to that of the other species. Selectivity increases particularly for a wide binding site, long channels, and fast access dynamics. Recent experiments on competitive transport of in-channel binding and inert molecules through artificial nuclear pores serve as a paradigm for our model. It explains qualitatively and quantitatively how binding molecules are favored for transport at the cost of the transport of inert molecules

Role of N-terminal tau domain integrity on the survival of cerebellar granule neurons

Although the role of the microtubule-binding domain of the tau protein in the modulation of microtubule assembly is widely established, other possible functions of this protein have been poorly investigated. We have analyzed the effect of adenovirally mediated expression of two fragments of the N-terminal portion - free of microtubule-binding domain - of the tau protein in cerebellar granule neurons (CGNs). We found that while the expression of the tau (1-230) fragment, as well as of full-length tau, inhibits the onset of apoptosis, the tau (1-44) fragment exerts a powerful toxic action on the same neurons. The antiapoptotic action of tau (1-230) is exerted at the level of Akt-mediated activation of the caspase cascade. On the other hand, the toxic action of the (1-44) fragment is not prevented by inhibitors of CGN apoptosis, but is fully inhibited by NMDA receptor antagonists. These findings point to a novel, physiological role of the N-terminal domain of tau, but also underlay that its possible proteolytic truncation mediated by apoptotic proteases may generate a highly toxic fragment that could contribute to neuronal death

Modelling the impact of atherosclerosis on drug release and distribution from coronary stents

Although drug-eluting stents (DES) are now widely used for the treatment of coronary heart disease, there remains considerable scope for the development of enhanced designs which address some of the limitations of existing devices. The drug release profile is a key element governing the overall performance of DES. The use of in vitro, in vivo, ex vivo, in silico and mathematical models has enhanced understanding of the factors which govern drug uptake and distribution from DES. Such work has identified the physical phenomena determining the transport of drug from the stent and through tissue, and has highlighted the importance of stent coatings and drug physical properties to this process. However, there is limited information regarding the precise role that the atherosclerotic lesion has in determining the uptake and distribution of drug. In this review, we start by discussing the various models that have been used in this research area, highlighting the different types of information they can provide. We then go on to describe more recent methods that incorporate the impact of atherosclerotic lesions

Sequence-Dependent Fluorescence of Cyanine Dyes on Microarrays

Cy3 and Cy5 are among the most commonly used oligonucleotide labeling molecules. Studies of nucleic acid structure and dynamics use these dyes, and they are ubiquitous in microarray experiments. They are sensitive to their environment and have higher quantum yield when bound to DNA. The fluorescent intensity of terminal cyanine dyes is also known to be significantly dependent on the base sequence of the oligonucleotide. We have developed a very precise and high-throughput method to evaluate the sequence dependence of oligonucleotide labeling dyes using microarrays and have applied the method to Cy3 and Cy5. We used light-directed in-situ synthesis of terminally-labeled microarrays to determine the fluorescence intensity of each dye on all 1024 possible 5′-labeled 5-mers. Their intensity is sensitive to all five bases. Their fluorescence is higher with 5′ guanines, and adenines in subsequent positions. Cytosine suppresses fluorescence. Intensity falls by half over the range of all 5-mers for Cy3, and two-thirds for Cy5. Labeling with 5′-biotin-streptavidin-Cy3/-Cy5 gives a completely different sequence dependence and greatly reduces fluorescence compared with direct terminal labeling