Previous microvascular decompression decreases the chances of pain free in patients treated with Gamma Knife radiosurgery for TIC

Object: The authors sought to establish whether the safety-efficacy of Gamma Knife radiosurgery (GKRS) as a second treatment for intractable trigeminal neuralgia (ITN) are influenced by prior microvascular decompression (MVD) which remains, for some of the authors, the reference technique. Methods: Between July 1992 and November 2010, 737 patients have been operated with GKRS for ITN and prospectively evaluated in Timone University Hospital in Marseille, France. Among these, 54 patients had a previous MVD history. Radiosurgery using a Gamma Knife (model B or C or Perfexion) was performed relying on both MR and CT targeting. A single 4 mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 7.6 mm (range 3.9- 11.9) anteriorly to the emergence of the nerve (retrogasserian target). A median maximum dose of 85 Gy (range 70-90) was delivered. Are further analyzed only 45 patients with previous MVD and a follow-up longer than one year (the patients with megadolichobasilar artery compression and multiple sclerosis were excluded). Results: The median age in this series was 56.75 years (range 28.09-82.39). The median follow-up period was 39.48 months (range 14.10-144.65). All the patients had a past history of surgery, with at least one previous failed MVD, but also a radiofrequency lesion (RFL) in 16 (35.6%) patients, balloon microcompression in 7 (15.6%) patients and glycerol rhizotomy in 1 case (2.2%). Thirty-five patients (77.8%) were initially pain free in a median time of 14 days (range 0, 180). Patients from this group had less probability of being pain free compared to our global population of essential trigeminal neuralgia without previous MVD history (p=0.010, hazard ratio of 0.64). Their probability of remaining pain free at 3, 5, 7 and 10 years was 66.5%, 59.1%, 59.1% and 44.3%, respectively. Twelve patients (34.3%) initially pain free experienced a recurrence with a median delay of 31.21 months (range 3.40-89.93). The hypoesthesia actuarial rate at 1 year was 9.1% and remained stable till 12 years with a median delay of onset of 8 months (range 8-8). Conclusions: Retrogasserian GKRS proofed to be safe and effective on the long-term basis even after failed previous MVD. Even if the initial result of pain free was of only 77.8%, the toxicity was low with only 9.1% hypoesthesia. No patient reported a bothersome hypoesthesia. The probability of maintaining pain relief in long-term was of 44.3% at 10 years.

A neuronal gamma oscillatory signature during morphological unification in the left occipitotemporal junction.

Morphology is the aspect of language concerned with the internal structure of words. In the past decades, a large body of masked priming (behavioral and neuroimaging) data has suggested that the visual word recognition system automatically decomposes any morphologically complex word into a stem and its constituent morphemes. Yet the reliance of morphology on other reading processes (e.g., orthography and semantics), as well as its underlying neuronal mechanisms are yet to be determined. In the current magnetoencephalography study, we addressed morphology from the perspective of the unification framework, that is, by applying the Hold/Release paradigm, morphological unification was simulated via the assembly of internal morphemic units into a whole word. Trials representing real words were divided into words with a transparent (true) or a nontransparent (pseudo) morphological relationship. Morphological unification of truly suffixed words was faster and more accurate and additionally enhanced induced oscillations in the narrow gamma band (60-85 Hz, 260-440 ms) in the left posterior occipitotemporal junction. This neural signature could not be explained by a mere automatic lexical processing (i.e., stem perception), but more likely it related to a semantic access step during the morphological unification process. By demonstrating the validity of unification at the morphological level, this study contributes to the vast empirical evidence on unification across other language processes. Furthermore, we point out that morphological unification relies on the retrieval of lexical semantic associations via induced gamma band oscillations in a cerebral hub region for visual word form processing.

Evaluation of uptake and transport of cationic and anionic ultrasmall iron oxide nanoparticles by human colon cells

Nanoparticles (NPs) are in clinical use or under development for therapeutic imaging and drug delivery. However, relatively little information exists concerning the uptake and transport of NPs across human colon cell layers, or their potential to invade three-dimensional models of human colon cells that better mimic the tissue structures of normal and tumoral colon. In order to gain such information, the interactions of biocompatible ultrasmall superparamagnetic iron oxide nanoparticles (USPIO NPs) (iron oxide core 9-10 nm) coated with either cationic polyvinylamine (aminoPVA) or anionic oleic acid with human HT-29 and Caco-2 colon cells was determined. The uptake of the cationic USPIO NPs was much higher than the uptake of the anionic USPIO NPs. The intracellular localization of aminoPVA USPIO NPs was confirmed in HT-29 cells by transmission electron microscopy that detected the iron oxide core. AminoPVA USPIO NPs invaded three-dimensional spheroids of both HT-29 and Caco-2 cells, whereas oleic acid-coated USPIO NPs could only invade Caco-2 spheroids. Neither cationic aminoPVA USPIO NPs nor anionic oleic acid-coated USPIO NPs were transported at detectable levels across the tight CacoReady? intestinal barrier model or the more permeable mucus-secreting CacoGoblet? model.

Nuclear well logging in soils. Calibration of slim hole nuclear tools gamma-gamma and neutron-thermal neutron.

The calculation of elasticity parameters by sonic and ultra sonic wave propagation in saturated soils using Biot's theory needs the following variables : forpiation density and porosity (p, ø), compressional and shear wave velocities (Vp, Vs), fluid density, viscosity and compressibility (Pfi Ilfi Ki), matrix density and compressibility (p" K), The first four parameters can be determined in situ using logging probes. Because fluid and matrix characteristics are not modified during core extraction, they can be obtained through laboratory measurements. All parameters necessitate precise calibrations in various environments and for specific range of values encountered in soils. The slim diameter of boreholes in shallow geophysics and the high cost of petroleum equipment demand the use of specific probes, which usually only give qualitative results. The measurement 'of density is done with a gamma-gamma probe and the measurement of hydrogen index, in relation to porosity, by a neutron probe. The first step of this work has been carried out in synthetic formations in the laboratory using homogeneous media of known density and porosity. To establish borehole corrections different casings have been used. Finally a comparison between laboratory and in situ data in cored holes of known geometry and casing has been performed.

Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles.

PURPOSE: To study the kinetics of polylactide (PLA) nanoparticle (NP) localization within the intraocular tissues and to evaluate their potential to release encapsulated material. METHODS: A single intravitreous injection (5 micro L) of an NP suspension (2.2 mg/mL) encapsulating either Rh-6G (Rh) or Nile red (Nr) was performed. Animals were killed at various times, and the NPs localization within the intraocular tissues was studied by environmental scanning electron microscopy (ESEM), confocal microscopy, light microscopy histology, fluorescence microscopy, and immunohistochemistry. Eyes injected with blank NPs, free Rh, or PBS solution were used as the control. RESULTS: ESEM showed the flow of the NPs from the site of injection into the vitreous cavity and their rapid settling on the internal limiting membrane. Histology demonstrated the anatomic integrity of the injected eyes and showed no toxic effects. A mild inflammatory cell infiltrate was observed in the ciliary body 6 hours after the injection and in the posterior vitreous and retina at 18 to 24 hours. The intensity of inflammation decreased markedly by 48 hours. Confocal and fluorescence microscopy and immunohistochemistry showed that a transretinal movement of the NPs was gradually taking place with a later localization in the RPE cells. Rh encapsulated within the injected NPs diffused and stained the retina and RPE cells. PLA NPs were still present within the RPE cells 4 months after a single intravitreous injection. CONCLUSIONS: Intravitreous injection of PLA NPs appears to result in transretinal movement, with a preferential localization in the RPE cells. Encapsulated Rh diffuses from the NPs and stains the neuroretina and the RPE cells. The findings support the idea that specific targeting of these tissues is feasible. Furthermore, the presence of the NPs within the RPE cells 4 months after a single injection shows that a steady and continuous delivery of drugs can be achieved.

Fat poetry: a kingdom for PPAR gamma.

Adipose tissue is not an inert cell mass contributing only to the storage of fat, but a sophisticated ensemble of cellular components with highly specialized and complex functions. In addition to managing the most important energy reserve of the body, it secretes a multitude of soluble proteins called adipokines, which have beneficial or, alternatively, deleterious effects on the homeostasis of the whole body. The expression of these adipokines is an integrated response to various signals received from many organs, which depends heavily on the integrity and physiological status of the adipose tissue. One of the main regulators of gene expression in fat is the transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma), which is a fatty acid- and eicosanoid-dependent nuclear receptor that plays key roles in the development and maintenance of the adipose tissue. Furthermore, synthetic PPARgamma agonists are therapeutic agents used in the treatment of type 2 diabetes.This review discusses recent knowledge on the link between fat physiology and metabolic diseases, and the roles of PPARgamma in this interplay via the regulation of lipid and glucose metabolism. Finally, we assess the putative benefits of targeting this nuclear receptor with still-to-be-identified highly selective PPARgamma modulators.

The murine interleukin-2 receptor gamma chain gene: organization, chromosomal localization and expression in the adult thymus.

Defects in the interleukin-2 receptor gamma (IL-2R gamma) chain in the man result in an X-linked severe combined immunodeficiency, SCIDX1, characterized by an absence of T-cell differentiation. This phenotype may result from pertubations in IL-2, IL-4-, IL-7- or IL-15-mediated signaling, as the IL-2R gamma chain forms an integral component of these receptor systems. We have isolated and characterized cDNA and genomic clones for the murine IL-2R gamma. The gene (Il2rg) is well conserved between mouse and man with respect to overall structure and size, and contains regions of high conservation in the promoter region as well. Il2rg maps to mouse X chromosome region 40, in a region of synteny with human Xq12-13.1. We have also explored the expression of the IL-2R gamma during thymocyte development. IL-2R gamma transcripts are detected in the earliest thymocyte precursor cells and persist throughout intrathymic development into the mature peripheral compartment. Genomic clones for the murine IL-2R gamma will allow for further studies on the regulation and function of this gene in vivo.

Steady-state equilibrium phase inversion recovery ON-resonant water suppression (IRON) MR angiography in conjunction with superparamagnetic nanoparticles. A robust technique for imaging within a wide range of contrast agent dosages.

PURPOSE: To investigate the ability of inversion recovery ON-resonant water suppression (IRON) in conjunction with P904 (superparamagnetic nanoparticles which consisting of a maghemite core coated with a low-molecular-weight amino-alcohol derivative of glucose) to perform steady-state equilibrium phase MR angiography (MRA) over a wide dose range. MATERIALS AND METHODS: Experiments were approved by the institutional animal care committee. Rabbits (n = 12) were imaged at baseline and serially after the administration of 10 incremental dosages of 0.57-5.7 mgFe/Kg P904. Conventional T1-weighted and IRON MRA were obtained on a clinical 1.5 Tesla (T) scanner to image the thoracic and abdominal aorta, and peripheral vessels. Contrast-to-noise ratios (CNR) and vessel sharpness were quantified. RESULTS: Using IRON MRA, CNR and vessel sharpness progressively increased with incremental dosages of the contrast agent P904, exhibiting constantly higher contrast values than T1 -weighted MRA over a very wide range of contrast agent doses (CNR of 18.8 ± 5.6 for IRON versus 11.1 ± 2.8 for T1 -weighted MRA at 1.71 mgFe/kg, P = 0.02 and 19.8 ± 5.9 for IRON versus -0.8 ± 1.4 for T1-weighted MRA at 3.99 mgFe/kg, P = 0.0002). Similar results were obtained for vessel sharpness in peripheral vessels, (Vessel sharpness of 46.76 ± 6.48% for IRON versus 33.20 ± 3.53% for T1-weighted MRA at 1.71 mgFe/Kg, P = 0.002, and of 48.66 ± 5.50% for IRON versus 19.00 ± 7.41% for T1-weighted MRA at 3.99 mgFe/Kg, P = 0.003). CONCLUSION: Our study suggests that quantitative CNR and vessel sharpness after the injection of P904 are consistently higher for IRON MRA when compared with conventional T1-weighted MRA. These findings apply for a wide range of contrast agent dosages.

Role of high normal gamma-glutamyltransferase level in identifying heavy alcohol use in young men.

The objective of the current study was to determine the predictive value of high normal gamma-glutamyltransferase (GGT) level as an indication of heavy drinking in young men. In a sample of 577 men attending a one-day army recruitment process mandatory for all Swiss men at age 19 years, GGT level was evaluated as the dependent variable for each of eight dichotomous classifications of individuals on the basis of meeting cut-off criteria for five indexes of alcohol use, two indexes of alcohol-related problems, and one index of body mass. The sensitivity, specificity, and predictive values of GGT level in identifying subjects as either heavy drinkers or being overweight were determined. Compared with findings for their counterparts, GGT level was higher in subjects reporting consumption of more than 14 drinks per week (20.5 +/- 7.81 vs. 18.9 +/- 7.60, P <.05), in those reporting being drunk at least once during the past 30 days (20.3 +/- 7.80 vs. 18.3 +/- 7.43, P <.001), and in individuals with body mass indexes >or=25 kg/m(2) (25.8 +/- 10.84 vs. 18.3 +/- 6.59, P <.001). At a GGT level cut-off of 20 U/l, the sensitivity, specificity, and positive and negative predictive values of either being a heavy drinker or overweight were 48.2%, 70.2%, 67.7%, and 51.2%, respectively. Exclusion of subjects with body mass indexes of >or=25 kg/m(2) revealed similar results. High normal GGT level in young men is indicative of heavy alcohol use or being overweight; when present, subjects should be screened further for potential concomitant drinking problems.