Drug-induced myocarditis precipitated by amlodipine overdose:a case report

Background: Amlodipine is the most commonly prescribed calcium channel blocker (CCB), used in the treatment of a variety of cardiovascular conditions. Calcium channel blockers remain a well-established cause of cardiovascular drug overdose. We present the case of an intentional overdose with 250 mg of amlodipine resulting in acute left ventricular dysfunction and myocarditis. Case summary: A 46-year-old man with no significant past medical history presented to the emergency department 8 h after intentionally ingesting 250 mg of amlodipine. Although initially asymptomatic with unremarkable physical examination, the patient developed progressively worsening dyspnoea over the next 2 days. Subsequent findings from chest X-ray, electrocardiogram, echocardiogram, and cardiac magnetic resonance imaging (MRI) were consistent with a diffuse myocarditis process with severe left ventricular systolic dysfunction. The patient was managed with diuretics and discharged once stable. Discussion: Our case highlights myocarditis as a potential complication of CCB overdose. Amlodipine is the most commonly prescribed CCB and is associated with cardiac toxicity at high doses. The long duration of action and high volume of distribution of amlodipine further increase the risk of morbidity and mortality from overdose. Known cardiac complications of amlodipine overdose include bradycardia, myocardial depression, and pulmonary oedema secondary to heart failure; however, diffuse myocarditis is a complication that has not previously been described in the literature. The mechanism of development of this complication remains unclear

Interaction of UVA (320-380 nm) radiation with human skin cells

The generation of reactive oxygen species (ROS) by UVA radiation (320-380 nm) is responsible for damage to intracellular biological macromolecules, cytotoxicity and many other effects. Both the endogenous chromophore protoporphyrin IX (PPIX) and 'free' iron are potentially important sources of ROS after UVA irradiation in human cells. The aim of this study was to determine the importance of PPIX in the inactivation of human cells after UVA irradiation, and to determine what effect UVA irradiation had on intracellular 'free' iron levels. By modulating levels of the intracellular chromophore PPIX in human cells by exogenous administration of the haem precursor #delta#-aminolevulinic acid (ALA) and irradiating these cells with graded doses of UVA, it was determined that the basal content of PPIX in TK6 human lymphoblastoid cells is insufficient to make a significant contribution to the UVA-mediated inactivation of these cells. The basal content of PPIX was however found to make a significant contribution to LTVA-mediated inactivation of the primary human fibroblast cell line, FEK4, which implicates PPIX as a critical UVA chromophore in this cell line. We document in this study the development of a flow cytometry-based fluorescence assay system that is capable of determining membrane damage and changes in intracellular 'free' iron levels. By using this assay and the cytoplasmic aconitase assay, we have confirmed that UVA irradiation of human skin cells results in an increase in intracellular 'free' iron levels. We also demonstrate that while administration of ALA to FEK4 cells does lower the intracellular 'free' iron levels, this type of treatment strongly exacerbates the increase in 'free' iron levels observed after UVA irradiation. The effects of ALA treatment and UVA irradiation on ferritin levels in FEK4 cells was also determined in this study using a polyclonal (anti-ferritin) antibody enzyme-linked immunosorbent assay. We demonstrate in this study that UVA irradiation of cells, and to a much greater extent, UVA irradiation of cells treated with ALA, results in the degradation of ferritin. This provides strong evidence for ferritin being a major source of the increase in intracellular 'free' iron levels observed after such treatments. It is hoped that data obtained from this study will contribute to an advancement in the understanding of the intracellular effects of UVA irradiation and that this may help in the protection against, and prevention of, processes such as UVA-induced photocarcinogenesis and photoageing. (author)Available from British Library Document Supply Centre-DSC:DXN032872 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Arthur John Arberry(1905-1969): A Critical Evaluation of an Orientalist

Arthur John Arberry (1905–1969): A Critical Evaluation of an Orientalist Arthur J. Arberry is widely recognised as one of the leading British scholars of Oriental Studies in the mid-twentieth century. This thesis aims to re-evaluate Arberry’s contribution to the field by examining his works and translations from a post-colonial perspective. After having provided a background to A. J. Arberry, this PhD thesis focuses on discussing and defining the concept of Orientalism as understood by its critics, especially Edward Said. We analyse the influence of empire and imperialism on Said’s experiences and academic works, concluding that post-colonialism informed Said’s views. The post-colonial critique is the foundation to analyse the opus of Arberry and examine concepts of empire and colonialism in his works and his attitudes to the Middle East. A selection of Arberry’s works reveals that his interpretation of Islamic culture is that of a Western scholar. His wartime work for the Ministry of Information and the BBC showed that he was a strong supporter of British values but also that his contributions were evidence of his inability to adjust his scholarly practices to the need to communicate effectively with audiences abroad. Theories of translation provide additional analytical tools to assess his Orientalist views as revealed by his translations of Arabic and Persian texts, including those of Iqbal. His frequently acclaimed versions of the Qur’an will be scrutinised in detail with the result that their accuracy of interpretation and style of translation are open to question. The thesis finds that Arberry was a text-based Oriental scholar who did not consider contemporary life in the countries from which the texts originated. His outlook was conservative, declining to venture into fields of study outside his discipline, being unsuited to fully engage with challenges emanating from a changing world. The thesis agrees with the critique that his works show essentialism, absence and otherness. Examination of Arberry’s works has demonstrated the nature of scholarly Orientalism of the mid-twentieth century. The phrase ‘post‐colonial perspective’ is used to describe a new methodological revisionism which enables a wholesale critique of western structures of knowledge and power; the term indicates the theoretical and methodological approach used in the analysis and critique. For post‐colonialism in general, see E. Said, Orientalism (London: Routledge & Keegan Paul, 1978

The application of inelastic neutron scattering to investigate the interaction of methyl propanoate with silica

A modern industrial route for the manufacture of methyl methacrylate involves the reaction of methyl propanoate and formaldehyde over a silica-supported Cs catalyst. Although the process has been successfully commercialised, little is known about the surface interactions responsible for the forward chemistry. This work concentrates upon the interaction of methyl propanoate over a representative silica. A combination of infrared spectroscopy, inelastic neutron scattering, DFT calculations, X-ray diffraction and temperature-programmed desorption is used to deduce how the ester interacts with the silica surface

Multi-Choice Minority Game

The generalization of the problem of adaptive competition, known as the minority game, to the case of $K$ possible choices for each player is addressed, and applied to a system of interacting perceptrons with input and output units of the type of $K$-states Potts-spins. An optimal solution of this minority game as well as the dynamic evolution of the adaptive strategies of the players are solved analytically for a general $K$ and compared with numerical simulations.Comment: 5 pages, 2 figures, reorganized and clarifie

(2R,5S)-2-Tri­chloro­methyl-3-oxa-1-aza­bi­cyclo­[3.3.0]­octane-4,8-dione

The crystal structure of the title bicyclic oxazolidindione, C7H6Cl3NO3, confirmed the absolute stereochemistry as 2R,5S

Steviamine, a new class of indolizidine alkaloid [(1R,2S,3R,5R,8aR)-3-hydroxy­meth­yl-5-methyl­octa­hydro­indolizine-1,2-diol hydro­bromide]

X-ray crystallographic analysis of the title hydro­bromide salt, C10H20N+·Br−, of (1R,2S,3R,5R,8aR)-3-hydroxy­meth­yl-5-methyl­octa­hydro­indolizine-1,2-diol defines the absolute and relative stereochemistry at the five chiral centres in steviamine, a new class of polyhydroxy­lated indolizidine alkaloid isolated from Stevia rebaudiana (Asteraceae) leaves. In the crystal structure, mol­ecules are linked by inter­molecular O—H⋯Br and N—H⋯Br hydrogen bonds, forming double chains around the twofold screw axes along the b-axis direction. Intra­molecular O—H⋯O inter­actions occur

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care