Reproductibilité en scintigraphie osseuse planaire,TEMP et TEMP/TDM du pied douloureux : importance d’une sémiologie standardisée

AimThe diagnostic benefit of bone single photon emission computed tomography/computed tomography (SPECT/CT) is currently being demonstrated. However, until now, reproducibility has been poorly investigated. Therefore, a study was undertaken to assess intra- and inter-reader reliability comparing bone planar views, SPECT and SPECT/CT.MethodsThe study was carried out on a cohort of 50 adults consecutively referred to two distinct Nuclear Medicine departments for clinical and radiological suspicion of a reflex sympathetic dystrophy (RSD) of the foot. Each set of planar views and SPECT/CT was independently re-read by two Nuclear Medicine physicians (one junior and one senior expert) in a blinded fashion. An array of bone scan and CT semiological criteria depicting RSD and main differential diagnoses was initially elaborated. Reliability was measured by percentage of agreement and computation of unweighted kappa.ResultsAmong the 50 patients, only four actually suffered from RSD. Among the 46 patients who did not suffer from RSD, 28 were affected by miscellaneous skeletal lesions. This is the reason why the study shifted from focusing on RSD to the etiologic diagnosis of a painful foot. Percentage of inter-reader agreement rose from 74% for planar scintigraphy and SPECT to 96% for SPECT/CT. This study showed reliability indices higher than in literature mainly due to the use of predefined detailed semiological criteria and to the learning effect of the junior physician at senior physician school.ConclusionBone SPECT/CT provides significantly stronger intra-reader and inter-reader agreement in comparison to planar images and stand-alone SPECT.     

Problème diagnostique posé par une lésion hépatique hypermétabolique en TEP à la fluorocholine (18F) : à propos d’un cas

IntroductionWe report a case of atypical fluorocholine (18F) PET/CT hypermetabolic hepatic lesion discovered during the staging of a prostate carcinoma.Case reportBecause of elevated PSA serum level, the patient had prostate biopsies which elicited an adenocarcinoma with a Gleason score of 8 (4 + 4). Pelvic MRI did not display any extracapsular disease extension. The PET/CT scan demonstrated a prostatic focal uptake and a liver increased uptake area matching with a segment VII hepatic nodule measuring 25 mm within a fatty liver, which was hypometabolic on the PET scan and hypodense on the CT scan. The liver ultrasound study reported the lesion as a focal spared area of healthy liver tissue within steatosis, whereas MRI diagnostic conclusion was inflammatory hepatocellular adenoma. When asking the patient, it appeared that the hepatic nodule had been known for 7 years, its size was unchanged, and, from previous radiologic imaging, it had been considered as an adenoma. However, there was no histological proof.DiscussionIn the interpretation of the PET/CT scan findings, we excluded a hepatocellular carcinoma and a prostate metastasis due to the long period of time during which the nodule had been followed up without significant change. We thought that focal nodular hyperplasia, which is fluorocholine avid, was the most likely diagnosis, knowing that hepatocellular adenomas, including the inflammatory type, have not been reported to display increased fluorocholine uptake. We noticed that the patient's fatty liver uptake was low, which could have accounted for a falsely increased uptake by the nodule. But, similarly to other authors, we could not find any relationship between CT density and fluorocholine uptake.ConclusionThis case shows a discrepancy between the radiologic and nuclear medicine findings. However, this hepatic nodule is likely to be benign because of the lesion characteristics and the patient medical history.     

Nebulisation of receptor-targeted nanocomplexes for gene delivery to the airway epithelium

Background

Gene therapy mediated by synthetic vectors may provide opportunities for new treatments for cystic fibrosis (CF) via aerosolisation. Vectors for CF must transfect the airway epithelium efficiently and not cause inflammation so they are suitable for repeated dosing. The inhaled aerosol should be deposited in the airways since the cystic fibrosis transmembrane conductance regulator gene (CFTR) is expressed predominantly in the epithelium of the submucosal glands and in the surface airway epithelium. The aim of this project was to develop an optimised aerosol delivery approach applicable to treatment of CF lung disease by gene therapy.

Methodology

The vector suspension investigated in this study comprises receptor-targeting peptides, cationic liposomes and plasmid DNA that self-assemble by electrostatic interactions to form a receptor-targeted nanocomplex (RTN) of approximately 150 nm with a cationic surface charge of +50 mV. The aerodynamic properties of aerosolised nanocomplexes produced with three different nebulisers were compared by determining aerosol deposition in the different stages of a Next Generation Pharmaceutical Impactor (NGI). We also investigated the yield of intact plasmid DNA by agarose gel electrophoresis and densitometry, and transfection efficacies in vitro and in vivo.

Results

RTNs nebulised with the AeroEclipse II BAN were the most effective, compared to other nebulisers tested, for gene delivery both in vitro and in vivo. The biophysical properties of the nanocomplexes were unchanged after nebulisation while the deposition of RTNs suggested a range of aerosol aerodynamic sizes between 5.5 µm–1.4 µm cut off (NGI stages 3–6) compatible with deposition in the central and lower airways.

Conclusions

RTNs showed their ability at delivering genes via nebulisation, thus suggesting their potential applications for therapeutic interventions of cystic fibrosis and other respiratory disorders.     

Genome-wide association analysis of oxidative stress resistance in Drosophila melanogaster

Background

Aerobic organisms are susceptible to damage by reactive oxygen species. Oxidative stress resistance is a quantitative trait with population variation attributable to the interplay between genetic and environmental factors. Drosophila melanogaster provides an ideal system to study the genetics of variation for resistance to oxidative stress.

Methods and Findings

We used 167 wild-derived inbred lines of the Drosophila Genetic Reference Panel for a genome-wide association study of acute oxidative stress resistance to two oxidizing agents, paraquat and menadione sodium bisulfite. We found significant genetic variation for both stressors. Single nucleotide polymorphisms (SNPs) associated with variation in oxidative stress resistance were often sex-specific and agent-dependent, with a small subset common for both sexes or treatments. Associated SNPs had moderately large effects, with an inverse relationship between effect size and allele frequency. Linear models with up to 12 SNPs explained 67–79% and 56–66% of the phenotypic variance for resistance to paraquat and menadione sodium bisulfite, respectively. Many genes implicated were novel with no known role in oxidative stress resistance. Bioinformatics analyses revealed a cellular network comprising DNA metabolism and neuronal development, consistent with targets of oxidative stress-inducing agents. We confirmed associations of seven candidate genes associated with natural variation in oxidative stress resistance through mutational analysis.

Conclusions

We identified novel candidate genes associated with variation in resistance to oxidative stress that have context-dependent effects. These results form the basis for future translational studies to identify oxidative stress susceptibility/resistance genes that are evolutionary conserved and might play a role in human disease.     

Selective inactivation of the exonuclease activity of bacteriophage T7 DNA polymerase by in vitro mutagenesis

The 3' to 5' exonuclease activity of bacteriophage T7 DNA polymerase (gene 5 protein) can be inactivated selectively by reactive oxygen species. Differences in the enzymatic properties between the two forms are exploited to show by a chemical screen that modification of a histidine residue reduces selectively the exonuclease activity. In vitro mutagenesis of the histidine at residue 123, and of the neighboring residues, results in varying reduction of the exonuclease activity, including mutant enzymes that have no detectable exonuclease activity; as a consequence their polymerase activity is increased up to 9-fold. T7 phage containing the mutant genes have a greatly reduced burst size and demonstrate up to a 14-fold increase in the spontaneous mutation rate.     

The effect of fermentation on the growth and survival ofSalmonella typhimurium,Staphylococcus aureus,Bacillus cereus andPseudomonas aeruginosa in fermenting tef (Eragrostis tef)

Summary Growth ofSalmonella typhimurium, Staphylococcus aureus, Bacillus cereus andPseudomonas aeruginosa was inhibited when the pH of fermenting tef approached 5.0, 5.0, 5.5 and 5.0, respectively. However the test organisms grew in far more acidic conditions in broth than in fermenting tef and this is due to antimicrobial substance(s) being produced by some of the lactic acid bacteria. Except forBacillus cereus spores, all the test organisms were heat-inactivated during the baking process of the final tef injera.

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Effet de la fermentation sur la croissance et la survie de Salmonella typhimurium, Staphylococcus aureus, Bacillus cereus et Pseudomonas aeruginosa dans le tef (Eragrostis tef) en fermentation

Résumé La croissance deSalmonella typhimurium, deStaphylococcus aureus, deBacillus cereus et dePseudomonas aeruginosa est inhibée lorsque les pH du tef en fermentation approchent respectivement 5:0, 5.0, 5.5 et 5.0. Toutefois, les organismes tests croissent dans des conditiones bien plus acides que dans le tef en fermentation. Ceci est dû à des substances antimicrobiennes produites par certaines bactéries lactiques. A l'exception des spores deBacillus cereus, tous les organismes tests sont inactivés par la chaleur durant le processus de cuisson.

     

Modeling flow in collecting lymphatic vessels: one-dimensional flow through a series of contractile elements

The lymphatic system comprises a series of elements, lymphangions, separated by valves and possessed of active, contractile walls to pump interstitial fluid from its collection in the terminal lymphatics back to the main circulation. Despite its importance, there is a dearth of information on the fluid dynamics of the lymphatic system. In this article, we describe linked experimental and computational work aimed at elucidating the biomechanical properties of the individual lymphangions. We measure the static and dynamic mechanical properties of excised bovine collecting lymphatics and develop a one-dimensional computational model of the coupled fluid flow/wall motion. The computational model is able to reproduce the pumping behavior of the real vessel using a simple contraction function producing fast contraction pulses traveling in the retrograde direction to the flow.