Identification of Inflamed Atherosclerotic Lesions In Vivo Using PET-CT

Inflammation plays a major pathogenetic role in the development of atherosclerotic plaques and related thromboembolic events. The identification of vulnerable plaques is of the utmost importance, as this may allow the implementation of more effective preventive and therapeutic interventions. Fluorodeoxyglucose positron emission tomography (FDG-PET) has been shown to be useful for tracing inflammation within plaques. However, its relationship to immunohistochemical findings in different territories of the peripheral circulation was not completely elucidated. We aimed to determine whether plaque inflammation could be measured by PET in combination with computer tomography (CT) using FDG and what is the relationship between FDG uptake and immunohistochemical findings in the removed atherosclerotic lesions of the femoral and carotid arteries. The study included 31 patients, 21 patients with high-grade stenosis of the internal carotid artery (ICA) and 10 patients with occlusion of the common femoral artery (CFA), all of whom underwent endarterectomy. Before endarterectomy in all patients, FDG-PET/CT imaging was performed. FDG uptake was measured as the maximum blood—normalized standardized uptake value, known as the target to background ratio (TBR max). TBR max amounted to 1.72?±?0.8, and in patients with ICA, stenosis was not significantly different from patients with CFA occlusion. Immunohistochemical and morphometric analyses of the plaques obtained at endarterectomy showed that the density of T lymphocytes and macrophages (number of cells per square millimeter) was significantly higher in subjects with stenosis of the ICA than in subjects with occlusion of the femoral arteries: lymphocytes, 1.26?±?0.21 vs. 0.77?±?0.29; p?=?0.02 and macrophages, 1.01?±?0.18 vs. 0.69?±?0.23; p?=?0.003. In the whole group of patients, the density of inflammatory cells significantly correlated with FDG uptake represented by PET-TBR max: T lymphocytes, r?=?0.60; p?<?0.01 and macrophages, r?=?0.65; p?<?0.01. The results of our study show that FDG uptake is related to the accumulation of inflammatory cells in atherosclerotic lesions. This finding suggests that FDG uptake reflects the severity of atherosclerotic vessel wall inflammation, and in stenotic lesions, it could be an indicator of their vulnerability. However, data from large outcome studies is needed to estimate the usefulness of this technique in identifying the most dangerous atherosclerotic lesions and vulnerable patients.     

Time in bed,sleep quality and associations with cardiometabolic markers in children: the Prevention and Incidence of Asthma and Mite Allergy birth cohort study

We investigated associations of time in bed and multiple sleep quality characteristics with cardiometabolic markers in children. Data from the prevention and incidence of asthma and mite allergy study, a population‐based prospective birth‐cohort study started in 1996–1997 in the Netherlands, were analysed. In total 1481 children aged 11–12 years completed a questionnaire (including questions on sleep) and underwent a medical examination. We measured body mass index, waist circumference, total‐ and high‐density lipoprotein cholesterol, blood pressure and glycated haemoglobin. Results showed that in girls, some sleep characteristics were related to anthropometrics (body mass index, waist circumference) and cholesterol. Girls who had a long time in bed (11–12.5 h) had 0.16 lower body mass index z‐score (95% confidence interval ?0.31; ?0.01) and 0.99 cm smaller waist circumference (95% confidence interval ?2.01; ?0.13) compared with girls who spent 10–10.5 h in bed. Girls who went to bed late and rose early had 0.16 mm higher total cholesterol (95% confidence interval 0.01; 0.31) and 0.08 mm higher high‐density lipoprotein cholesterol (95% confidence interval 0.01; 0.14) than ‘early to bed/early rise’ girls. Girls with night‐time awakenings had 0.14 mm higher total cholesterol (95% confidence interval 0.03; 0.25) than girls without night‐time awakenings. Girls who felt sleepy/tired ≥1 day per week had 0.10 mm lower high‐density lipoprotein cholesterol (95% confidence interval ?0.16; ?0.04) and 0.17 mm higher total cholesterol/high‐density lipoprotein cholesterol ratio (95% confidence interval 0.02; 0.32) than girls who did not feel sleepy. No associations were found for boys. Sleep characteristics were not related to blood pressure and glycated haemoglobin, and effect sizes of the associations in girls were small. Therefore, we consider it premature to propose that improved sleep could reduce cardiovascular risk during childhood.     

Low-dose inhaled nitric oxide improves the oxygenation and ventilation of infants and children with acute, hypoxemic respiratory failure.

OBJECTIVE: To describe the effects of inhaled nitric oxide on oxygenation and ventilation in patients with acute, hypoxic respiratory failure and to characterize those who respond to low doses with a significant improvement in PaO2. DESIGN: Prospective dose response trial of inhaled nitric oxide. Patients who demonstrated a > or =15% improvement in PaO2 were randomized to receive conventional mechanical ventilation with or without prolonged inhaled nitric oxide. SETTING: Pediatric intensive care unit of a tertiary care children's hospital serving as a regional referral center for respiratory failure. PATIENTS: Pediatric patients with an acute parenchymal lung disease requiring mechanical ventilation, an F(IO2) of > or =0.5, a positive end-expiratory pressure of > or =7 cm H2O, and whose PaO2/FIO2 ratio was < or =160. INTERVENTIONS: PaO2, PaCO2, pH, heart rate, blood pressure, and methemoglobin were recorded at baseline and after inhaling 1, 5, 10, and 20 ppm of nitric oxide. Peak expiratory flow rate and mean airway resistance were measured while subjects received 0 and 20 ppm of inhaled nitric oxide. Patients were followed up until extubation or death. MEASUREMENTS AND MAIN RESULTS: Twenty-six patients (median age, 2.6 yrs [range, 1 mo-18.2 yrs]) were enrolled in the study. PaO2 increased (p< .001) and Pa(CO2) fell (p< .0001) from baseline with the administration of inhaled nitric oxide. There was no statistical difference among 1, 5, 10, and 20 ppm with regard to effects on oxygenation. Sixteen patients (62%) responded to inhaled nitric oxide with a > or =15% improvement in PaO2; 14 of these responses occurred at a dose of 1 or 5 ppm. Response to inhaled nitric oxide was not associated with age, length of intubation, presence of primary lung disease, chest radiograph, or illness severity. Among patients weighing < or =20 kg, responders showed a greater fall in mean airway resistance (p < .05) than nonresponders. Mortality was not influenced by prolonged inhaled nitric oxide when analyzed by intention to treat. Patients receiving prolonged inhaled nitric oxide at doses of < or =20 ppm maintained methemoglobin levels of <3.0% and circuit concentrations of NO2 of <1 ppm. CONCLUSIONS: Inhaled nitric oxide at doses of < or =5 ppm improves the oxygenation and (to a lesser extent) ventilation of most children with acute, hypoxic respiratory failure. The unpredictable response of patients necessitates individualized dosing of inhaled nitric oxide, starting at concentrations of < or =1 ppm. Inhaled nitric oxide at < or =20 ppm may exert a small salutary effect on bronchial tone. The benefits of prolonged inhaled nitric oxide remain unknown.     

Sledding Injuries in Patients Presenting to the Emergency Department in a Northern City

OBJECTIVES: Sledding is a common recreational activity in northern communities. The objective of this study was to examine the frequency and nature of sledding injuries (SIs) in patients presenting to emergency departments (EDs). METHODS: The data were derived from a cohort of patients treated at all five EDs in an urban Canadian health region over a two-year period. Following chart review, consenting patients were interviewed by telephone about their sledding activities and the circumstances surrounding the injury. RESULTS: Three hundred twenty-eight patients were correctly coded as having SIs, with 212 patients (65%) reached during the follow-up survey. The median age of those with SIs was 12 years (IQR = 8, 21), and 206 (59%) were male. Injury rates peaked in the 10--14-year age group (87/100,000) for boys and in the 5--9-year age group (75/100,000) for girls. Most patients stated they were drivers (75%), fewer than half were thrown from the sled (42%), and fewer than half (44%) were sledding on community-designated sledding hills at the time of injury. Injuries to the lower extremity (32%), upper extremity (31%), and head (13%) were most common. Thirty-seven (11%) patients with SIs were admitted to hospital vs 4% of patients with other sports/recreation injuries (p < 0.05). CONCLUSIONS: Sledding injuries are common and potentially serious wintertime injuries in northern communities, involving primarily younger patients, with a large pre-adolescent group. However, older sledders (>20 years) have poorer outcomes (hospitalization, lost time from work/school) than their younger counterparts. The SIs treated in the ED appear to lead to hospitalization more frequently than other types of sport/recreation injury, and injury prevention strategies appear warranted.     

Characterization of mitral valve prolapse with cardiac computed tomography: comparison to echocardiographic and intraoperative findings

A single imaging modality that can accurately assess both coronary anatomy and mitral valve (MV) anatomy prior to surgery may be desirable. We sought to determine the diagnostic accuracy of cardiac computed tomography (CT) to detect and characterize mitral valve prolapse (MVP) compared to echocardiography. Consecutive patients referred for ‘single-source’ cardiac CT for investigation prior to non-coronary cardiac sugery were identified. MV anatomy was assessed for MVP and results were compared to echocardiography and to intra-operative visual assessment of the MV. Comparison between the three modalities was performed at the per-patient, per-leaflet and per-scallop levels. A total of 67 consecutive patients that were referred for Cardiac CT prior to non-coronary cardiac surgery and were prospectively recruited into a Cardiac CT registry. Of these, 65 patients underwent cardiac surgery. 63 patients had echocardiography and 32 patients had intra-operative visual assessment of the mitral valve. Compared to echocardiography, cardiac CT had excellent sensitivity (92.6%) and specificity (97.1%) for the detection of any MVP, but had poor sensitivity (68.5%) for the detection of individual prolapsing scallop. Compared to intra-operative visual assessment of the prolapsing scallop, both cardiac CT and echocardiography had low sensitivity (58.1 and 78.1%, respectively). Cardiac CT was able to identify patients with MVP but had difficulty identifying the prolapsed scallops compared to echocardiography. Single-source CT may not be ready for characterization of individual mitral valve scallops.     

Enhanced Antitumor Efficacy of Vasculostatin (Vstat120) Expressing Oncolytic HSV-1

Oncolytic viral (OV) therapy is a promising therapeutic modality for brain tumors. Vasculostatin (Vstat120) is the cleaved and secreted extracellular fragment of brain-specific angiogenesis inhibitor 1 (BAI1), a brain-specific receptor. To date, the therapeutic efficacy of Vstat120 delivery into established tumors has not been investigated. Here we tested the therapeutic efficacy of combining Vstat120 gene delivery in conjunction with OV therapy. We constructed RAMBO (Rapid Antiangiogenesis Mediated By Oncolytic virus), which expresses Vstat120 under the control of the herpes simplex virus (HSV) IE4/5 promoter. Secreted Vstat120 was detected as soon as 4 hours postinfection in vitro and was retained for up to 13 days after OV therapy in subcutaneous tumors. RAMBO-produced Vstat120 efficiently inhibited endothelial cell migration and tube formation in vitro (P = 0.0005 and P = 0.0184, respectively) and inhibited angiogenesis (P = 0.007) in vivo. There was a significant suppression of intracranial and subcutaneous glioma growth in mice treated with RAMBO compared to the control virus, HSVQ (P = 0.0021 and P < 0.05, respectively). Statistically significant reduction in tumor vascular volume fraction (VVF) and microvessel density (MVD) was observed in tumors treated with RAMBO. This is the first study to report the antitumor effects of Vstat120 delivery into established tumors and supports the further development of RAMBO as a possible cancer therapy.     

Importance of lactobacilli in food and feed biotechnology

The genus Lactobacillus is a heterogeneous group of lactic acid bacteria (LAB) with important implications in food fermentation. The ability to colonize a variety of habitats is a direct consequence of the wide metabolic versatility of this group of LAB. Consequently, lactobacilli have been used for decades in food preservation, as starters for dairy products, fermented vegetables, fish and sausages as well as silage inoculants. Lactobacilli have also been proposed as probiotics and microbial cell factories for the production of nutraceuticals. However, a wide range of applications of lactobacilli in food biotechnology remains potential, whereas a number of important strains still need to be discovered and characterized. This article provides an overview of the taxonomy of lactobacilli and describes four of the most significant case studies on the application of this group of LAB in food and feed biotechnology, including their use as probiotics, dairy starters, silage inoculants, and microbial cell factories. The importance of access to and exchange of biological material within and between different strain collections as a crucial step in expanding the range of different biotechnological applications of lactobacilli is also emphasized.