New imaging techniques in prostate cancer

Correct staging of prostate cancer at initial diagnosis, as well as accurate staging and tumor localization with biochemical recurrence, remains generally inaccurate with current imaging techniques. Newer modalities are being investigated to accurately identify patients with prostate cancer at different stages of disease. Identification of locally recurrent disease or distant metastasis at the time of biochemical failure after local therapy will help guide treatment options and avoid potentially toxic salvage therapies in patients who will not benefit. A review of prostate cancer imaging literature over the past 12 months was performed to identify emerging imaging modalities that may be beneficial in the management of prostate cancer. Enhanced transrectal ultrasonography modalities, including ultrasound contrast agents, color and power Doppler, and elastrography, have demonstrated incremental benefit when combined with standard grayscale ultrasonography to accurately target and diagnose prostate cancer. Endorectal MRI, with contrast enhancement and spectroscopic imaging, shows promise in the initial staging of prostate cancer prior to local therapy. The use of positron-emission tomography scan for prostate cancer remains to be defined, but may help delineate the site of recurrence with biochemical failure after local therapy. Several new imaging modalities show promise for the evaluation of the patient with prostate cancer. Enhanced ultrasonography techniques may prove to be more accurate in diagnosing prostate cancer over standard gray-scale ultrasonography. Accumulating evidence supports the use of endorectal MRI and spectroscopy to help treatment planning with either surgical or radiotherapeutic approaches. Although intriguing, the available data for positron-emission tomography in prostate cancer remains too shallow to advocate routine use.     

Proteasome inhibitor model of Parkinson's disease in mice is confounded by neurotoxicity of the ethanol vehicle.

Defects in the ubiquitin-proteasome system have been implicated in Parkinson's Disease (PD). Recently, a rat model of PD was developed using a synthetic proteasome inhibitor (PSI), (Z-lle-Glu(OtBu)-Ala-Leu-al). We attempted to transfer this model to mouse studies, where genetics can be more readily investigated due to the availability of genetically modified mice. We treated C57BL/6 (B6) mice with six intraperitoneal injections of 6 mg/kg PSI in 50 mul of 70% ethanol over a 2-week-period. We found significant decreases in nigrostriatal dopamine in PSI-treated mice compared with saline-treated mice. However, we observed similar decreases in the ethanol-treated vehicle control group. Administration of ethanol alone led to significant long-term alterations in dopamine levels. Ethanol significantly eclipses the effects of PSI in the dopamine system, and therefore is a confounding vehicle for this model.     

Automated three-dimensional analysis of histological and autoradiographic rat brain sections: application to an activation study.

Besides the newly developed positron emission tomography scanners (microPET) dedicated to the in vivo functional study of small animals, autoradiography remains the reference technique widely used for functional brain imaging and the gold standard for the validation of in vivo results. The analysis of autoradiographic data is classically achieved in two dimensions (2D) using a section-by-section approach, is often limited to few sections and the delineation of the regions of interest to be analysed is directly performed on autoradiographic sections. In addition, such approach of analysis does not accommodate the possible anatomical shifts linked to dissymmetry associated with the sectioning process. This classic analysis is time-consuming, operator-dependent and can therefore lead to non-objective and non-reproducible results. In this paper, we have developed an automated and generic toolbox for processing of autoradiographic and corresponding histological rat brain sections based on a three-step approach, which involves: (1) an optimized digitization dealing with hundreds of autoradiographic and histological sections; (2) a robust reconstruction of the volumes based on a reliable registration method; and (3) an original 3D-geometry-based approach to analysis of anatomical and functional post-mortem data. The integration of the toolbox under a unified environment (in-house software BrainVISA, http://brainvisa.info) with a graphic interface enabled a robust and operator-independent exploitation of the overall anatomical and functional information. We illustrated the substantial qualitative and quantitative benefits obtained by applying our methodology to an activation study (rats, n=5, under unilateral visual stimulation).     

Clinical,hematologic, and immunologic effects of interleukin-10 in humans

We conducted a double-blind, placebo-controlled study to investigate the safety, pharmacokinetics, and immunological properties of interleukin-10 (IL-10) administration in healthy humans. Volunteers received a single intravenous bolus injection of recombinant human IL-10 (1, 10, or 25g/kg) or placebo. Cytokine production in whole blood and peripheral blood mononuclear cells (PBMC) was assessed before and 3, 6, 24, and 48 hr after the injection. Peak serum concentrations of IL-10 (15±1.1, 208±20.1, and 505±22.3 ng/ml) occurred after 2–5 min for 1, 10, and 25g/kg IL-10, respectively. The terminal-phase half-life was 3.18 hr. A transient leukocytosis (24–63% above baseline) was observed 6 hr after injection, which coincided with a dose-dependent decrease (12–24%) in neutrophil superoxide generation. There was a marked inhibition (60–95%) of endotoxin-induced IL-6 production from whole blood in each group receiving IL-10. Production of IL-8 in endotoxin-stimulated blood was reduced in the 10g/kg group. In PBMC stimulated with phytohemagglutinin and phorbol ester, there was a decrease (72–87%) in interferon- (IFN) production 6 hr after IL-10 with a return to pre-IL-10 levels after 24 hr. This reduction was only partially associated with a decrease in the number of CD2-bearing cells. We conclude that IL-10 administration into humans is without significant side effects, and a single injection reducesex vivo production of IL-6, IL-8, and IFN.     

DNA restriction fragment length polymorphism differentiates crossed from independent infections in nosocomial Xanthomonas maltophilia bacteremia.

Restriction fragment length polymorphisms of total DNA and rDNA were used to study the relationship between 11 isolates of Xanthomonas maltophilia, obtained from seven patients with nosocomial bacteremia in four distinct wards of a single hospital, and the type strain of the species, ATCC 13637. Our results indicated that there were episodes of cross-infection among the patients of two wards, but there were also independent infectious episodes in the two other wards.     

Evidence for the genetic unrelatedness of nosocomial vancomycin-resistant Enterococcus faecium strains in a pediatric hospital.

Vancomycin-resistant enterococci are now found with increasing frequency. Up to now, epidemiological studies of enterococci have been limited by the lack of convenient and accessible methods for comparing strains. In this study, we report an epidemiological investigation on 16 nosocomial vancomycin-resistant Enterococcus faecium strains isolated from 15 patients in four different wards of a children's hospital over a period of 17 months. Analysis of restriction fragment length polymorphism (RFLP) of total DNA and of ribosomal DNA regions (ribotyping) was used as a typing approach. Each strain produced a different total DNA RFLP pattern after HindIII and PvuII digestion, except for two strains that were isolated from a single patient and that gave indistinguishable patterns. In our system, ribotyping was less discriminative than RFLP of total DNA. This approach, therefore, shows the genetic unrelatedness of the nosocomial strains studied and excludes patient-to-patient strain transmission either in the same ward or between wards.     

Molecular Epidemiology of Ampicillin-Resistant Non-β-Lactamase-Producing Haemophilus influenzae

Resistance to ampicillin without β-lactamase production is not a frequent occurrence among Haemophilus influenzae strains. This kind of resistance is encountered in unencapsulated strains isolated from bronchial secretions and ear, nose, and throat specimens and is exceptional in H. influenzae type b. We studied 29 of these strains from various areas in France and 2 reference strains. Strains were compared by using ribotyping, arbitarily primed PCR with two primers, and pulsed-field gel electrophoresis. Each technique enabled the identification of 20 to 23 different patterns among the 31 strains. The combination of the different patterns for the strains obtained by the different techniques provided 27 distinct profiles. According to these results, it seems that the clonal propagation of these resistant strains does not occur.     

Factors affecting the size of the detour effect in the kinaesthetic perception of Euclidean distance

Three experiments investigated the mechanisms by which we estimate Euclidean distances on the basis of kinaesthetic cues. In all experiments, blindfolded participants followed straight and curvilinear paths with a stylus. Then, with a straight response movement, they estimated the distance between the end-points of the previously explored path. Experiment 1 was designed to validate the hypothesis—made on the basis of results from a previous study—that errors in the kinaesthetic estimations of distances (detour effect) originate from the difficulty to decompose the displacement vector into relevant and irrelevant components, which would become more severe at points of inflection. Using elliptic paths (no inflections), we demonstrated that errors are indeed reduced considerably. The role of the orientation of the work plane was investigated in Experiment 2 in which the same paths used in our previous study were oriented in the frontal rather than the horizontal plane. The results indicate that the detour effect is independent of the orientation. Moreover, despite the asymmetry that gravity introduces between upward and downward movements, errors in the two directions are almost identical. Experiment 3 addressed two issues. First, we demonstrated that introducing a delay between the exploration of the path and the response did not alter significantly the pattern of errors. By contrast, we demonstrated that errors are severely reduced when the number of paths to be explored is reduced by half. The results of the three experiments are discussed within the context of current theories of sensori-motor coding.