APOE ε4 and late-life cognition: mediation by structural brain imaging markers

European Journal of Epidemiology - The apolipoprotein E allele 4 (APOE-ε4) is established as a major genetic risk factor for cognitive decline and late-onset Alzheimer’s disease....     

Modified positioning of a smartphone based single-lead electrocardiogram device improves detection of atrial flutter

Introduction

The AliveCor Kardia Mobile (AKM) is a handheld, smartphone based cardiac rhythm monitor that records a lead-I electrocardiogram (ECG). Despite being efficacious for detection of atrial fibrillation (AF), it is unclear whether atrial flutter (AFL) may be misdiagnosed as sinus rhythm due to regular R-R intervals. We hypothesised that generating lead-II tracings through repositioning of the AKM may improve visualisation of flutter waves and clinician diagnosis of AFL compared to traditional lead-I tracings.

Hammock mitral valve: A rare cause of congenital mitral regurgitation – A case report

Hammock valve, also known as anomalous mitral arcade is a rare mechanism for congenital mitral insufficiency. We report a case of a two-week-old neonate who presented with features of heart failure and an apical systolic murmur. Echocardiogram showed severe mitral regurgitation and abnormal mitral valve with direct attachment of mitral leaflets to papillary muscle without intervening chordae tendinae, typical of hammock valve. Heart failure was controlled with ionotrpes and diuretics. The literature on the hammock mitral valve is reviewed.     

An unusual cause of acute cor pulmonale – Significance of the ‘continuous diaphragm sign’

A patient presented with chest pain and clinical features of acute right heart failure. Initial work up revealed the presence of severe PAH. Acute pulmonary embolism is the commonest and most life-threatening cause for acute cor pulmonale. Even though the clinical picture suggested pulmonary embolism, a subtle sign was missed from the first chest X-ray taken in the emergency department. However on reanalysis the ‘continuous diaphragm sign’ later guided us towards the diagnosis. Our case represents one of the first reports of a rare etiology for acute cor pulmonale – hypersensitivity pneumonitis. Right ventricular dysfunction was caused by an acute rise in pulmonary artery pressures as well as by the compressive effects of pneumomediastinum. We emphasize the role played by a good quality chest X-ray early in the management of acute chest pain syndromes. However pulmonary embolism should be ruled out conclusively before redirecting attention to less malignant conditions.     

Oral controlled release formulation of diclofenac sodium by microencapsulation with ethyl cellulose

The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of diclofenac sodium (DFS) using different proportions of ethyl cellulose (EC) as the retardant material to extend the release. The formulated microcapsules were then compressed into tablets to obtain controlled release oral formulations. Phase separation-coacervation technique was employed to prepare microcapsules of DFS using different proportions of EC in cyclohexane. Physical characteristics of microcapsules and their tablets, in vitro release pattern of the designed microcapsules and their tablets prepared from them were studied using USP dissolution apparatus (USP 2000) type 2 (paddle method) in triple distilled water. The prepared microcapsules were white, free flowing and spherical in shape, with the particle size varying from 49.94-52.72 microm. The duration of DFS release from microcapsules was found to be directly proportional to the proportion of EC and, thus, coat thickness. All tablets were of good quality with respect to appearance, drug content uniformity, hardness, weight variation, friability and thickness uniformity. In vitro release study of the tabletted microcapsules in triple distilled water showed a zero order release kinetics and extended release beyond 24 h. A good correlation was obtained between drug release (t(60)) and proportion of EC in the microcapsules. In the case of tabletted microcapsules, very good correlation could be established between t(60), proportion of EC, weight of the tablets and between release rate constant (K) and proportion of EC. All the formulations were highly stable and possessed reproducible release kinetics across the batches.     

Aberrant promoter hypermethylation of multiple genes in head and neck squamous cell carcinoma

PURPOSE: Epigenetic alteration, via promoter hypermethylation, inactivates genes important for the development of head and neck squamous cell carcinoma (SCCHN). The aim of this study is to characterize and correlate, with clinical parameters, the promoter methylation profile of DNA repair genes, hMLH1 and O6-methylguanine-DNA methyltransferase (MGMT), and tumor-suppressor gene p16. MATERIALS AND METHODS: Fifty-one cases of SCCHN, collected from the paraffin block archives (1997-1999) in the Department of Pathology at the University of Arkansas for medical sciences, provided DNA for methylation-specific PCR using primers specific for hMLH1, MGMT, and p16. RESULTS: Sixty-two percent displayed promoter hypermethylation in at least one gene, with 23% seen for hMLH1, 30% for MGMT, and 36% for p16. Promoter hypermethylation of these genes separately or in combination was not associated with history of smoking and alcohol use, tumor size, nodal status, clinical stage, and overall survival. Promoter hypermethylation of more than 1 gene was significantly associated with increased 2-year disease-free survival. The probability of surviving 2 years without tumor recurrence was 100% with promoter hypermethylation in 2 or 3 genes and 46% with promoter hypermethylation in none or just 1 gene (P=.013). Promoter hypermethylation of 2 or 3 genes was independently related to increased 2-year cumulative disease-free survival (P=.028). CONCLUSIONS: Promoter hypermethylation of hMLH1, MGMT, and p16 genes was commonly detected in 47 SCCHN cases with up to 65% showing aberrant promoter hypermethylation in at least 1 gene. Promoter hypermethylation of 2 or 3 genes was significantly associated with increased 2-year disease-free survival, suggesting that promoter hypermethylation of multiple genes might improve survival. Significant correlation was also noted between a positive alcohol use history and promoter hypermethylation of the MGMT gene with no promoter hypermethylation of the p16 gene.     

Jaw-winking ptosis in a patient with Kabuki syndrome

We present a case of a child with Kabuki syndrome and jaw-winking ptosis. Kabuki syndrome is rare and consists of a constellation of findings including mental retardation, characteristic oculofacial features, and skeletal abnormalities. The association of Kabuki syndrome and jaw-winking ptosis has not been previously reported.     

Diabetes mellitus is an independent predictor of obstructive coronary artery disease in patients presenting with atrial fibrillation and elevated troponin

Atrial fibrillation can present with symptoms of myocardial infarction and elevated troponin, even in the absence of obstructive coronary artery disease (CAD). We sought to determine the characteristics that predict underlying obstructive CAD. Obstructive CAD was far more likely in those with troponin elevation. In those with elevated troponin, diabetes mellitus was an independent predictor of obstructive CAD.