Promotion of variant human mammary epithelial cell outgrowth by ionizing radiation: an agent-based model supported by in vitro studies

Introduction  

Most human mammary epithelial cells (HMEC) cultured from histologically normal breast tissues enter a senescent state termed stasis after 5 to 20 population doublings. These senescent cells display increased size, contain senescence associated β-galactosidase activity, and express cyclin-dependent kinase inhibitor, p16^INK4A (CDKN2A; p16). However, HMEC grown in a serum-free medium, spontaneously yield, at low frequency, variant (v) HMEC that are capable of long-term growth and are susceptible to genomic instability. We investigated whether ionizing radiation, which increases breast cancer risk in women, affects the rate of vHMEC outgrowth.     

Bronchial artery embolization: monitoring with somatosensory evoked potentials. Work in progress

Surgery remains the treatment of choice for massive and recurrent hemoptysis. In some instances, however, immediate surgical intervention is contraindicated. In these situations, bronchial artery embolization (BAE) has proved to be a successful definitive treatment for non-surgical candidates and a palliative therapy in patients requiring hemodynamic stabilization prior to surgery. The most serious complication of BAE is spinal cord ischemia. This relates directly to the potential anastomotic connections between the bronchial circulation and the anterior spinal artery. Somatosensory evoked potentials (SSEPs) have been used in the past to monitor spinal cord ischemia during procedures that threaten the vascularity of the spinal cord. The authors report two cases in which SSEPs were employed to monitor spinal cord ischemia during bronchial artery embolization.     

Chronotropic incompetence to exercise separates low body weight from established anorexia nervosa

Chronotropic incompetence (CI), characterized by an attenuated heart rate (HR) response to exercise could participate to the limitation of exercise capacity in anorexia nervosa (AN). Therefore, we evaluated the role of cardiac sympathetic responsiveness in AN patients. In addition, the ambulatory value of autonomic control using spectral analysis of heart rate variability (HRV) was determined and correlated to maximal exercise performance. Twenty-two patients hospitalized for weight loss and suspicion of AN were included in the study. All performed a symptom-limited exercise test with measurement of gas exchange for chronotropic response to exercise evaluation. Holter ECG recordings allowed daytime and night-time spectral domain HRV analysis in order to evaluate the alteration of sympathetic control of HR in free-living conditions. CI defined as a failure to achieve 80% of heart rate reserve (%HRR) was observed in 13 (59%) patients (CI+). This group presented a higher body mass deficit than the group without CI (CI-; -35.1 +/- 8.7% versus -26.1 +/- 10.7%; P<0.05). Obviously, patients with a lower body mass index (BMI < 16 kg m(-2), n = 14) revealed a more severe limitation to maximal exercise with a lower peak HR, a lower peak Vo(2), and a lower maximal O(2) pulse (P<0.05). BMI was significantly correlated to peak Vo(2), maximal HR, and %HRR achieved at peak exercise. Daytime HRV parameters reflecting the sympathetic autonomic equilibrium (LF nu, LF/HF ratio) were significantly lower in CI+ patients. Blunted sympathetic response to maximal exercise is frequent and correlated to weight deficit. The present data suggest a major autonomic derangement in AN characterized by a cardiac sympathetic withdrawal.     

The venous–arterial difference in CO<Subscript>2</Subscript> should be interpreted with caution in case of respiratory alkalosis in healthy volunteers

The venous–arterial difference in CO₂ (ΔCO₂) has been proposed as an index of the adequacy of tissue perfusion in shock states. We hypothesized that the variation in PaCO₂ (hyper- or hypocapnia) could impact ΔCO₂, partly through microcirculation adaptations. Fifteen healthy males volunteered to participate. For hypocapnia condition (hCO₂), the subjects were asked to hyperventilate, while they were asked to breathe a gas mixture containing 8 % CO₂ for hypercapnia condition (HCO₂). The 2 conditions were randomly assigned. Blood gases were measured at baseline before each condition, and after 5–7 min of either hCO₂ or HCO₂ condition. Microcirculation was assessed by the muscle reoxygenation slope measured with near infrared spectroscopy following a vascular occlusion test and by skin circulation with in vivo reflectance confocal microscopy. ΔCO₂ was significantly increased with hCO₂ while it tended to decrease with HCO₂ (non-significant). HCO₂ induced a moderate increase of the resaturation slope of NIRS oxygenation. Skin microcirculatory blood flow significantly dropped with hCO₂, while it remained unchanged with hypercapnia. Our results warrant cautious interpretation of ΔCO₂ as an indicator of tissue perfusion during respiratory alkalosis.     

Solitary fibrous tumor of the meninges: report of three cases

The authors expose the clinical, radiological and histological presentation of three cases of solitary fibrous tumors of the meninges, initially thought to be meningiomas. Actually, these three cases show typical anatomoclinical features. The authors also mention the differential diagnosis, and recall the essential contribution of immunohistochemistry.     

Simulation-based evaluation of OSEM iterative reconstruction methods in dynamic brain PET studies

The reconstruction of dynamic PET data is usually performed using filtered backprojection algorithms (FBP). This method is fast, robust, linear and yields reliable quantitative results. However, the use of FBP for low count data, such as dynamic PET data, generally results in poor visual image quality, exhibiting high noise, disturbing streak artifacts and low contrast. These signal-to-noise ratio and contrast in the reconstructed images may alter the quantification of physiological indexes, such as the regional Binding Potential (BP) obtained from kinetic modeling. Iterative reconstruction methods are often presented as viable alternatives to FBP reconstruction. In this study, we investigated the characteristics of the UW-OSEM and the ANW-OSEM iterative reconstruction methods in the context of ligand-receptor PET studies with low counts. The assessment was conducted using replicates of simulated [18F]MPPF acquisitions. The quantitative accuracy obtained with the iterative and analytical methods was compared. The results show that analytical methods are more robust to the low count data than iterative methods, and therefore enable a better estimate of the regional activity values and binding potential. The positivity constraint in MLEM-based algorithms leads to overestimations of the activity in regions with low activity concentration, typically the cerebellum. This overestimation results in significant bias in BP estimates with iterative reconstruction methods. The bias is confirmed from the reconstruction of real PET data.     

Motion correction of multi-frame PET data in neuroreceptor mapping: Simulation based validation

Patient motion during positron emission tomography scanning can affect the accuracy of the data analysis in two ways: 1) movement occurring during emission data acquisition alters the time activity curves (TACs), measured at a voxel or region of interest (ROI), and hence introduces errors in the parameter estimates derived from kinetic modeling; 2) emission–transmission mismatches introduce errors during attenuation and scatter correction, and hence in the radioactivity distribution estimates for each time frame of the scan. With the aim of designing an algorithm-based frame realignment method, we first conducted investigations that aimed at optimizing the parameters of a coregistration method, such as the choice of the target volume and the similarity criterion. Based on these results we designed a novel frame realignment strategy in a multi-step algorithm using uncorrected reconstructed images, cross-correlation similarity criteria for the determination of inter-frame motion parameters and emission-transmission mismatch for each frame. Features and validation results are reported here based on a multi-subject simulated [¹¹C]raclopride dynamic PET scan database incorporating intra-frame movements of various magnitudes and with various times of occurrence. Performances of the proposed algorithm were evaluated at regional and voxel-based level for binding potential parametric images.