Array CGH analysis identifies two distinct subgroups of primary angiosarcoma of bone

Molecular genetic studies on vascular tumors are rare. Recently, possible involvement of MYC and KDR has been documented in a subset of angiosarcomas of soft tissue. We performed a cytogenetic analysis of primary angiosarcomas of bone (n = 13) and soft tissue (n = 5) using high density array‐comparative genomic hybridization (array‐CGH). Regions of interest were validated by fluorescence in situ hybridization (FISH). Antibodies for candidate genes (SKI, MYC, KDR, and MAPK9) were selected and immunohistochemistry was performed. Six angiosarcomas of bone and four angiosarcomas of soft tissue showed chromosomal losses, gains, and high level amplifications. Cluster analysis identified two groups: a group with a complex genetic profile and a group with only few genetic aberrations. Five regions of interest were selected, which were located at chromosome bands 1p36.23, 2q32‐34, 5q35, 8q24, and 17q21.32‐24.2. Interphase FISH confirmed the high‐level amplifications. Immunohistochemical analysis showed high expression of MYC (16/60), MAPK9 (63/69), and SKI (52/62). There were no differences between the two groups with regards to location, immunohistochemical expression nor survival. In summary, we identified two subgroups of angiosarcoma: those with few or no gross aberrations and those which show numerous genetic aberrations consisting of chromosomal losses, gains and high level amplifications or complex aberrations. The most common finding was amplification of 2q and 17q in both angiosarcoma of bone and soft tissue, suggesting overlap in tumorigenesis irrespective of their location. We show MYC amplification in primary angiosarcoma indicating this is not entirely specific for radiation‐induced angiosarcoma. © 2014 Wiley Periodicals, Inc.     

Cell cycle analysis can differentiate thin melanomas from dysplastic nevi and reveals accelerated replication in thick melanomas

Cell replication integrates aberrations of cell cycle regulation and diverse upstream pathways which all can contribute to melanoma development and progression. In this study, cell cycle regulatory proteins were detected in situ in benign and malignant melanocytic tumors to allow correlation of major cell cycle fractions (G1, S-G2, and G2-M) with melanoma evolution. Dysplastic nevi expressed early cell cycle markers (cyclin D1 and cyclin-dependent kinase 2; Cdk2) significantly more (p?<?0.05) than common nevi. Post-G1 phase markers such as cyclin A, geminin, topoisomerase IIα (peaking at S-G2) and aurora kinase B (peaking at G2-M) were expressed in thin (≤1 mm) melanomas but not in dysplastic nevi, suggesting that dysplastic melanocytes engaged in the cell cycle do not complete replication and remain arrested in G1 phase. In malignant melanomas, the expression of general and post-G1 phase markers correlated well with each other implying negligible cell cycle arrest. Post-G1 phase markers and Ki67 but none of the early markers cyclin D1, Cdk2 or minichromosome maintenance protein 6 (Mcm6) were expressed significantly more often in thick (>1 mm) than in thin melanomas. Marker expression did not differ between metastatic melanomas and thick melanomas, with the exception of aurora kinase A of which the expression was higher in metastatic melanomas. Combined detection of cyclin A (post-G1 phase) with Mcm6 (replication licensing) and Ki67 correctly classified thin melanomas and dysplastic nevi in 95.9 % of the original samples and in 93.2 % of cross-validated grouped cases at 89.5 % sensitivity and 92.6 % specificity. Therefore, cell cycle phase marker detection can indicate malignancy in early melanocytic lesions and accelerated cell cycle progression during vertical melanoma growth.     

Chest Pain Associated with Moderator Band Pacing

A 65-year-old man was evaluated for chronic chest pain that had been present for 8 years after placement of a dual-chamber implantable cardioverter-defibrillator to treat inducible ventricular tachycardia. Previous coronary angiography had revealed nonobstructive coronary artery disease and a left ventricular ejection fraction of 0.45 to 0.50, consistent with mild idiopathic nonischemic cardiomyopathy. Evaluation with chest radiography and transthoracic echocardiography showed the implantable cardioverter-defibrillator lead to be embedded within the right ventricle at the moderator band, which had mild calcification. Treatment included extraction of the dual-coil lead and placement of a new single-coil right ventricular lead at the mid septum. The patient had complete relief of symptoms after the procedure. This case shows that chest pain can be associated with the placement of a right ventricular implantable cardioverter-defibrillator lead in the moderator band and that symptomatic relief can occur after percutaneous lead extraction and the implantation of a new right ventricular lead to the mid septal region.     

Cannabinoids and the Microbiota–Gut–Brain Axis: Emerging Effects of Cannabidiol and Potential Applications to Alcohol Use Disorders

The endocannabinoid system (ECS) has emerged in recent years as a potential treatment target for alcohol use disorders (AUD). In particular, the nonpsychoactive cannabinoid cannabidiol (CBD) has shown preclinical promise in ameliorating numerous clinical symptoms of AUD. There are several proposed mechanism(s) through which cannabinoids (and CBD in particular) may confer beneficial effects in the context of AUD. First, CBD may directly impact specific brain mechanisms underlying AUD to influence alcohol consumption and the clinical features of AUD. Second, CBD may influence AUD symptoms through its actions across the digestive, immune, and central nervous systems, collectively known as the microbiota–gut–brain axis (MGBA). Notably, emerging work suggests that alcohol and cannabinoids exert opposing effects on the MGBA. Alcohol is linked to immune dysfunction (e.g., chronic systemic inflammation in the brain and periphery) as well as disturbances in gut microbial species (microbiota) and increased intestinal permeability. These MGBA disruptions have been associated with AUD symptoms such as craving and impaired cognitive control. Conversely, existing preclinical data suggest that cannabinoids may confer beneficial effects on the gastrointestinal and immune system, such as reducing intestinal permeability, regulating gut bacteria, and reducing inflammation. Thus, cannabinoids may exert AUD harm-reduction effects, at least in part, through their beneficial actions across the MGBA. This review will provide a brief introduction to the ECS and the MGBA, discuss the effects of cannabinoids (particularly CBD) and alcohol in the brain, gut, and immune system (i.e., across the MGBA), and put forth a theoretical framework to inform future research questions.     

A rare cause of upper gastrointestinal haemorrhage: Ruptured cystic artery pseudoaneurysm with concurrent cholecystojejunal fistula

INTRODUCTION Cystic artery pseudoaneurysms and cholecystoenteric fistulae represent two rare complications of gallstone disease.PRESENTATION OF CASE An 86 year old male presented to the emergency department with obstructive jaundice, RUQ pain and subsequent upper gastrointestinal bleeding. Upper GI endoscopy revealed bleeding from the medial wall of the second part of the duodenum and a contrast-enhanced computed tomography scan revealed a cystic artery pseudoaneurysm, concurrent cholecystojejunal fistula and gallstone ileus. This patient was successfully managed surgically with open subtotal cholecystectomy, pseudoaneurysm resection and fistula repair.DISCUSSION To date there are very few cases describing haemobilia resulting from a bleeding cystic artery pseudoaneurysm. This report is the first to describe upper gastrointestinal bleeding as a consequence of two synchronous rare pathologies: a ruptured cystic artery pseudoaneurysm causing haemobilia and bleeding through a concurrent cholecystojejunal fistula.CONCLUSION Through this case, we stress the importance of accurate and early diagnosis through ultra- sonography, endoscopy, and contrast-enhanced CT imaging and emphasise that haemobilia should be included in the differential diagnosis of anyone presenting with upper gastrointestinal bleeding. We have demonstrated the success of surgical management alone in the treatment of such a case, but accept that consideration of combined therapeutic approach with angiography be given in the first instance, when available and clinically indicated.     

The effect of selegiline on total scavenger capacity and liver fat content: a preliminary study in an animal model

Selegiline is a selective irreversible inhibitor of the B-type of monoamine oxidase (MAO-B). The spectrum of its pharmacological activity is wide, possesses antioxidant, antiapoptotic and neuroprotective properties and, additionally, we found it is effective on the total scavenger capacity (TSC), and the regulation of fat content in rat liver kept on lipid-rich diet. Our aim was to clarify whether the oral treatment with selegiline is protective on oxidative damage of Sprague?CDawley adult rats in vivo. Four groups of rats (five animals in a group) were examined: (1) lipid-rich diet, (2) normal rat food, (3) lipid-rich diet?+?selegiline and (4) normal rat food?+?selegiline. Selegiline solution (2.5???g/ml) was supplied with the drinking water, which was freely available for the animals. Regarding the drinking habit of the rats (20?C30?ml/day), the daily dose was roughly equal with that used in the human therapy (5?C10?mg/day). TSC was determined both at the beginning (0?day) and at the end of the study (28?days), when the blood samples were taken for chemiluminometric assay. Fat content of the liver was determined in the freshly frozen tissue by Sudan staining. TSC was increased in both the selegiline-treated groups. Selegiline treatment prevented the increase of liver fat in the group fed with lipid-rich diet. Our results led us to the conclusion that prolonged selegiline administration can raise the antioxidant capacity of the animals and prevents the accumulation of fat in their livers.