Age of uptake of early cancer detection facilities by low-risk and high-risk patients with familial breast and ovarian cancer.

INTRODUCTION: Some 5-10% of all cases of breast cancer and ovarian cancer have a hereditary genesis. In the setting of an interdisciplinary cancer genetics clinic, a study of the age at which patients first take advantage of early cancer detection (ECD) facilities was conducted in order to assess the influence of familial risk on health issues. METHODS: The study included 556 women who fulfilled the inclusion criteria (IC) for genetic analysis of the BRCA1 and BRCA2 genes, as well as 205 who did not meet these criteria but attended the primary consultation. RESULTS: Consulters who met the inclusion criteria took advantage of nearly all methods of ECD at an earlier time than women who did not. A comparison of consulters with or without breast cancer showed that those without breast cancer participated in all methods of ECD at an earlier time. CONCLUSION: Methods of improving and increasing participation in ECD facilities, and of encouraging women who are at risk to start on such programs at a younger age, need to be discussed. In this study, familial risk already resulted in a younger age of uptake of ECD facilities.     

Integrity testing of a smooth surface resin sealant around orthodontic brackets using a new Fluorescence-aided Identification Technique (FIT)

Objective:To investigate the integrity of a fluorescing resin-based sealant placed around orthodontic brackets using the Fluorescence-aided Identification Technique (FIT).Materials and Methods:Standard brackets were bonded to the buccal surfaces of 17 extracted sound permanent premolar crowns sealed with ProSeal^®. Specimens were thermocycled (20,000 cycles, 5–55°C), and toothbrushing was simulated using an electric toothbrush and artificial aqueous toothpaste slurry. Changes in the sealed area were measured after one, two, three, and four alternating thermocycling-brushing cycles simulating 2 years of wear. Digital images were captured applying FIT (405 nm) using a digital camera–equipped stereomicroscope. ImageJ was used to measure sealant integrity and loss.Results:There was a time-dependent decrease in sealed areas by between 21% and 100% (mean 54%). The sealant lost its integrity immediately after the first cycle, and unfilled areas were observed in all samples.Conclusions:The analyzed sealant lost its integrity over time. Using the proposed FIT, sealed surfaces were easily verified and quantified.     

Virological and immunological determinants of intrahepatic virus-specific CD8+ T-cell failure in chronic hepatitis C virus infection

Virus-specific CD8+ T-cells play an important role in the outcome of acute hepatitis C virus (HCV) infection. In the chronic phase, however, HCV can persist despite the presence of virus-specific T-cell responses. Therefore, we set out to perform a full-breadth analysis of the intrahepatic virus-specific CD8+ T-cell response, its relation to the peripheral T-cell response, and the overall influence of viral escape and the genetic restriction on intrahepatic CD8+ T-cell failure. Intrahepatic and peripheral CD8+ T-cells from 20 chronically HCV infected patients (genotype 1) were comprehensively analyzed using overlapping peptides spanning the entire HCV polyprotein in concert with autologous viral sequences that were obtained for all targeted regions. HCV-specific CD8+ T-cell responses were detectable in most (90%) chronically HCV-infected patients, and two thirds of these responses targeted novel previously undescribed epitopes. Most of the responses were detectable only in the liver but not in the peripheral blood, indicating accumulation and enrichment at the site of disease. Of note, only approximately half of the responses were associated with viral sequence variations supported by functional analysis as viral escape mutations. Escape mutations were more often associated with HLA-B alleles. CONCLUSION: Our results show an unexpected high frequency of intrahepatic virus-specific CD8+ T-cells, a large part of which continue to target the present viral antigens. Thus, our results suggest that factors other than mutational escape contribute to the failure of intrahepatic virus-specific CD8+ T-cells.     

Stereotactic Magnetic Resonance Guidance for Anatomically Targeted Ablations of the Fossa Ovalis and the Left Atrium

INTRODUCTION: Targets for radiofrequency ablation (RFA) of atrial fibrillation are increasingly being selected based on anatomic considerations. Because fluoroscopy provides only limited information about the relationship between catheter positions and cardiac structures, we evaluated whether stereotactic catheter guidance might facilitate anatomical catheter navigation and RFA to the great vessels, the fossa ovalis and the left atrium (LA). METHODS AND RESULTS: An electromagnetic catheter's position system was superimposed on three-dimensional (3D) MR images using fiducial markers. This allowed the dynamic display of the catheter position on the true anatomy of previously acquired MRI in real-time. To assess the reproducibility of RFA, repeat ablations were created at the identical anatomic site in the inferior vena cava (IVC) in 5 swine. Average distance of the repeated ablations was 4.4 +/- 2.4 mm.In five swine the catheter was anatomically guided with the MRI to the fossa ovalis and a single RFA was performed. On the pathological specimen all ablation sites were located within the fossa ovalis with an average distance of 3.9 +/- 2.1 mm from its center. In two of the experiments the ablation catheter was passed into the left atrium and anatomically targeted ablation performed in the lateral wall of the left atrial appendage. Catheter location and ablation site were confirmed by autopsy and histology. CONCLUSION: Real-time display of the catheter position on 3D-MRI allows anatomically targeted catheter navigation and RFA in the IVC, the fossa ovalis, and the left atrium. This may facilitate anatomically based interventions like septal puncture or pulmonary vein ablation and decrease fluoroscopy times.     

Left atrial thrombus two years after placement of a left atrial appendage closure device: Unexplored area of the Watchman

A 72‐year‐old man who underwent a left atrial appendage (LAA) closure device 2 years ago presented with atrial flutter with rapid ventricular rate and was referred for cardioversion. Precardioversion transesophageal echocardiogram showed left atrial thrombus and therefore the procedure was aborted. Currently, there is no guideline on imaging surveillance or anticoagulation in patients with LAA closure device who develop intracardiac thrombus after the initial 6‐month surveillance period.