Preliminary investigation of the feasibility of magnetic propulsion for future microdevices in blood vessels

The Magnetic Resonance Submarine (MR-Sub) project is a first attempt to validate a new propulsion method for future small magnetically controlled microdevices suited for minimally invasive applications in blood vessels. A Magnetic Resonance Imaging (MRI) system provides the driving force in three dimensions to a ferromagnetic core that could be embedded onto a specialised microdevice. The paper describes preliminary tests made to match the magnetic force induced by an MRI system on a ferromagnetic sphere with the drag force it encompasses in a cylindrical tube. These tests provide a proof of concept demonstrating that this new method of propulsion is very promising within the constraints of such types of operations. This conclusion is based on specific measurements showing that 1010/1020 carbon steel spheres (3.175 mm and 2.381 mm in diameter) can withstand a maximum flow of 0.370 +/- 0.0064 l/min (19.5 cm/s) and 0.311 +/- 0.01209 l/min (16.4 cm/s) respectively when placed inside a 6.35 mm diameter PMMA tube and subjected to a 18 mT/m magnetic field gradient.     

Neural network involved in time perception: an fMRI study comparing long and short interval estimation

In this study, long ( approximately 1,300 ms) and short duration ( approximately 450 ms) estimation trials in an event-related functional MRI (fMRI) study were contrasted in order to reveal the regions within a time estimation network yielding increased activation with the increase of the duration to be estimated. In accordance with numerous imaging studies, our results showed that the presupplementary motor area (preSMA), the anterior cingulate, the prefrontal and parietal cortices, and the basal ganglia were involved in the estimation trials whatever the duration to be estimated. Moreover, only a subset of the regions within this distributed cortical and subcortical network yielded increased activation with increasing time, namely, the preSMA, the anterior cingulate cortex, the right inferior frontal gyrus (homolog to Broca's area), the bilateral premotor cortex, and the right caudate nucleus. This suggests that these regions are directly involved in duration estimation. We propose that the caudate-preSMA circuit, the anterior cingulate, and the premotor-inferior frontal regions may support a clock mechanism, decision and response-related processes, and active maintenance of temporal information, respectively.     

Conformity of carotid stents with vascular anatomy: evaluation in carotid models

BACKGROUND AND PURPOSE: Conformity between self-expanding Wallstents and vascular anatomy is limited. Because of a lack of longitudinal flexibility, straightening effects on vascular curves occur and may result in stent-induced kinking. Our purpose was to evaluate the conformity of self-expanding stents with the course and endoluminal surface of silicone models of the normal human carotid artery. METHODS: Five different types of self-expanding carotid stents were implanted into simplified pulsatile perfused silicone models of the carotid bifurcation. The models embody elastic properties of the vessel wall similar to those of normal human arteries. All stents had the same nominal diameter and length and bridged the external carotid artery origin as well as a consecutive curve at the initial segment of the internal carotid artery. Conventional radiographs of the model were compared before and after stent placement to record changes of shape and course of the silicone artery. Dehiscences between stent filaments and arterial wall were measured on digital subtraction angiograms of the model. RESULTS: Implantation of braided Wallstents or the Expander with continuous filaments induced considerable straightening effects on the bifurcation angle, as well as on the curves of the internal carotid artery. Segmented designs of modular nitinol stents complied better with vascular tortuosity and showed improved adaption between stent and the endoluminal surface of the model. CONCLUSION: Model experiments show that segmented nitinol stents improve the conformity between the prosthesis and vascular anatomy, and confirm new carotid stent concepts as an alternative to the Wallstent.     

Motor execution and imagination networks in post-stroke dystonia

Reorganization of motor execution and imagination networks was studied in six patients with unilateral dystonia secondary to a subcortical stroke and compared with seven control subjects using fMRI. Patients performed imagined and real auditory-cued hand movements. Movements of the dystonic hand resulted in overactivity in bilateral motor, premotor, and prefrontal cortex, insula, precuneus, and cerebellum, in parietal areas and the striatum contralateral to the lesion. Movements of the unaffected hand resulted in overactivity in bilateral preSMA, prefrontal, and parietal areas, insula and cerebellum, the ipsilateral premotor cortex and the contralateral striatum to the lesion. Mental representation of movements with each hand resulted in overactivity in bilateral parietal, premotor and prefrontal areas. These results suggest that execution and mental representation of movement are altered in these patients.     

CTLA-4 blockade in combination with xenogeneic DNA vaccines enhances T-cell responses, tumor immunity and autoimmunity to self antigens in animal and cellular model systems

Xenogeneic DNA vaccination can elicit tumor immunity through T cell and antibody-dependent effector mechanisms. Blockade of CTLA-4 engagement with B7 expressed on APCs has been shown to enhance T cell-dependent immunity. We investigated whether CTLA-4 blockade could increase T-cell responses and tumor immunity elicited by DNA vaccines. CTLA-4 blockade enhanced B16 tumor rejection in mice immunized against the melanoma differentiation antigens tyrosinase-related protein 2 and gp100, and this effect was stronger when anti-CTLA-4 was administered with booster vaccinations. CTLA-4 blockade also increased the T-cell responses to prostate-specific membrane antigen (PSMA) when given with the second or third vaccination. Based on these pre-clinical studies, we suggest that anti-CTLA-4 should be tested with xenogeneic DNA vaccines against cancer and that special attention should be given to sequence and schedule of administration.     

Abnormal cytogenetics and significant bone marrow plasmacytosis are predictive of early progression and short survival in patients with low tumor mass asymptomatic multiple myeloma

In order to evaluate the prognostic factors for progression and survival in patients with a low tumor mass asymptomatic multiple myeloma (MM), we studied 59 patients who had a long term follow-up. Cytogenetic abnormalities (using conventional cytogenetics) were observed in 14 out of 45 analyzable patients (31%). An abnormal karyotype and a bone marrow (BM) plasmacytosis > 15% were found to be adverse prognostic factors for progression in univariate and multivariate analysis.