CA19-9, a biomarker that is clinically used to differentiate benign from malignant gastrointestinal disorders, is elevated in 45% of PCLD patients without proof of malignancy. CA19-9 is produced by cyst epithelium, and as a consequence high CA19-9 levels are present in cyst fluid.27 Other tumor markers such as CA-125, CEA, and alpha-fetoprotein may be elevated, although not in the range of CA19-9.28-30 The principle aim of treatment of PLD is to reduce symptoms by decreasing liver volume. Options buy 3-Methyladenine for the management include conservative management, invasive, or medical measures. Aspiration-sclerotherapy involves aspiration of a cyst followed by injection

of a sclerosing agent that causes destruction of the epithelial lining inhibiting fluid production.31, 32 The main indication for aspiration-sclerotherapy is a large symptomatic liver cyst. In PLD it is best to select a dominant

cyst that is likely to be responsible for the symptoms, usually the largest cyst (Figs. 1, 2). Most commonly, cysts with a diameter of >5 cm are good candidates for therapy. The technique involves puncture of the cyst with a 5 or 7 French catheter with an aspiration needle.33 After aspiration of the total content of the cyst, a sclerosing agent is injected and left in the cyst for a predetermined time (Supporting Information Table 1). In general, hepatic AZD5363 mw cysts do not communicate with the biliary tree. The value of routine use of contrast media remains to be determined. The most commonly used sclerosing agent is ethanol, but minocycline and tetracycline are also used. These latter agents destroy the cyst wall by the low pH that is created in the cyst.34, 35

The volume of ethanol used varies learn more from 10% to 25% of the volume of aspirated cyst fluid (Fig. 3). A literature review revealed 34 articles on 292 patients who had either solitary (50%) or multiple (50%) cysts. The main indications were pain or discomfort of the abdomen, abdominal mass, fullness, and early satiety. The diameter of the treated cysts was between 5 and 20 cm. The procedure was mostly performed in a single session, but some protocols used repeated procedures on consecutive days.36 The most common complication was pain during ethanol instillation, which was probably due to peritoneal irritation. The needle or catheter used did not influence outcome, nor did the duration of alcohol exposure. Cysts totally regressed in 22%, whereas partial regression occurred in 19%. Some 21% had recurrence of the treated cysts during follow-up, although most of these patients were free of symptoms. In the majority of patients, symptoms totally disappeared or a reduction of symptoms occurred (Supporting Table 1). Fenestration is a technique that combines aspiration and surgical deroofing of the cyst in a single procedure (Fig. 3).

Prospective studies demonstrated that viral clearance in acute HCV infection did not correlate with the development of neutralizing antibodies in chimpanzees.15, 22 In our study, CH10274 seroconverted and developed neutralizing antibodies against the homologous rechallenge

strain (JFH-1, genotype 2a) and a heterologous strain (genotype 1a), indicating the production of genotype crossreactive antibodies. However, LY2157299 mouse such antibodies were not able to prevent reinfection with the H77 strain. Thus, neutralizing antibodies may be capable of preventing low-level subclinical infection, such as the JFH-1cc infection,16 but they are not sufficient to control a robust high-viremic infection like the H77 infection.18 Following challenge with H77 virus in CH10274 and CH10273, we observed two distinct clinical courses. CH10273 had what appeared to be protective immunity because no viremia was detected. By contrast, CH10274 was infected with a fluctuating course of

viremia and viral clearance almost a year later. In humans, chronic HCV infection is characterized by selleckchem a 1-2 log decrease in viral load followed by a viral load stabilization in most cases of persistent infection within several months. However, fluctuating viremia in both patients with resolution of learn more infection and those with chronic infection

including intermittent negative HCV RNA test results after initial viremia have been observed. Furthermore, although most patients with an acute and self-limited course of HCV infection clear infection within 6 months, viral clearance has been also reported 1 and 2 years after diagnosis of acute infection.23 As discussed above, although CH10274 possessed antibodies with neutralizing activity against the rechallenging viral strain, the antibodies appeared insufficient to prevent reinfection. We did not observe any significant level of neutralizing antibodies in CH10273 following heterologous challenge, suggesting that the observed sterilizing immunity was not associated with the development of neutralizing antibodies. Although both animals demonstrated HCV-specific T-cell responses in the blood, the magnitude of the HCV-specific T-cell response was higher in CH10274, who became reinfected. Because there is an ongoing redistribution and migration of T cells between blood, lymph nodes, and liver, we examined the intrahepatic immune response in both animals. Compared to other organs, the liver is particularly enriched with cells of the innate immune system, including natural killer (NK), natural killer T (NKT) cells, Kupffer cells (KC), DCs, and T cells, which participate in adaptive immune responses.

However, the evidence for a unique fructose effect is sufficiently weak in both studies that the authors appear left with two solutions in search of a problem. The evidence of

AZD8055 in vivo Abdelmalek et al.1 for a fructose-specific role in NAFLD is not convincing for several reasons. First, in the categorization of subjects by sweetened beverage intake, the designation “no fructose consumers” is misleading; fructose intake from nonbeverage sources was neither calculated nor reported and could have significantly altered clinical and histological conclusions. Second, the raw data in Table 1 of their article (before statistical manipulation) demonstrate inconsistent fructose dose–dependent trends for all but two of the seven metabolic parameters and for all of the histological parameters measured. Third, the caloric difference between the subject groups [the highest fructose consumers (seven or more servings per week) had twice the calorie intake of the no-fructose group (zero servings per week)] cannot be ignored as a far simpler explanation for the few observed differences reported by the authors. This is especially

compelling because the fructose increment in moderate consumers versus zero consumers could not have exceeded 15% of the total energy, whereas that check details for the highest consumers could have been as low as 5% (calculated from Table 1 of their article). Thus, rather than proposing reduced fructose intake as the solution for NAFLD patients at risk for liver fibrosis, Abdelmalek

et al. should recommend that these patients eat less of everything. The experimental design of Li et al.2 provided rats adlibitum access to selleck kinase inhibitor 10% (wt/vol) fructose in water with or without curcumin or pioglitazone and standard rat chow. The data in Fig. 1 of their article show that the fructose rats consumed approximately 1650 mL of fluid per week (236 mL/day), which is equivalent to 94 kcal/day from fructose. For perspective, this would be like feeding a 70-kg human more than 5200 g of fructose per day (21,000 kcal/day). From the combination of such a highly exaggerated exposure and a lack of a suitable nonfructose carbohydrate control, we can conclude only that (1) this study does not prove a meaningful role for fructose in the development of hepatic steatosis at typical intake levels (45 g/day or 180 kcal/day3), and (2) the curcumin therapy solution proposed by Li et al. has academic interest but is likely unnecessary in humans. Because Abdelmalek et al.1 and Li et al.2 have failed to demonstrate a unique effect for fructose in patients with NAFLD or NASH, respectively, they are left with two solutions in search of a problem. John S. White Ph.D. Potential conflict of interest: John S. White is the president of White Technical Research and is a consultant to the food and beverage industry in the area of nutritive sweeteners.

Cytotoxicity was assessed by alanine and aspar-tate aminotransferase, lactate dehydrogenase, water-soluble tetrazolium salt 1 proliferation and caspase-3 activity assays. Small animal imaging by dynamic

contrast-enhanced-MRI and choline PET was performed. Results. In both cell lines, artesunate dose dependently reduced cell viability and proliferation (from 50 micromolar: p<0.05). This reduction was enhanced by hypoxia (from 12.5 micromolar: p<0.01). Moreover, artesunate downregulated the secretion of VEGF and placental growth factor in vitro (both p<0.05) and in vivo (both p<0.01). In the mouse model for HCC, artesunate decreased vessel density and tumor burden (both p<0.05). No apparent hepatotox-icity or mortality was observed. In vitro and in vivo activation of the PKR-like endoplasmic reticulum kinase pathway (resp. p<0.05 and p<0.01) together with decreased ATP-binding cassette transporter G2 expression (resp. ABT-263 p<0.01 and p<0.05) by artesunate

was demonstrated. Conclusions. These observations exhibit the potential of artesunate as a safe treatment of HCC optionally combined with current hypoxia-inducing therapies such as transarterial embolization or sorafenib. As a low-cost drug, artesunate might be of particular interest for the developing countries with high incidence of HCC. Disclosures: Isabelle Colle – Advisory Committees or Review Panels: MSD, Janssen, MSD, Gilead; Patent Held/Filed: Trombogenics; Speaking and Teaching: BMS, Janssen The following people have nothing to disclose: Yves-Paul Vandewynckel, Debby Laukens, Anja M. Geerts, Louis Libbrecht, Eliene Bogaerts, Cisplatin manufacturer Lindsey Devisscher, Annelies Paridaens,

Xavier Verhelst, Christian Vanhove, Benedicte Descamps, Sophie Janssens, Bart Lambrecht, Christophe Van Steenkiste, Hans Van Vlier-berghe Background/Aim: Aptamers check details are small synthetic oligonu-cleotides that bind to protein targets with high specificity and affinity. AS1411 is the first nucleic acid aptamer in clinical development for cancers. AS1411 binds to the protein nucle-olin, which is over-expressed in the cytoplasm and on the surface of cancer cells. Glypican-3 (GPC3), a cell surface protein that is highly expressed in hepatocellular carcinoma (HCC), has emerged as a candidate therapeutic target. We aimed to investigate the therapeutic potential of aptamers for HCC by evaluating AS1411 effect on HCC cell growth and by confirming the affinity and specificity of GPC3 aptamer in HCC cells. Methods: Human HCC cell lines (Huh-7, SNU 761 cells) and human cholangiocarcinoma (CCA) cell lines (KMBC, Witt cells) were used. Cell growth was assessed using MTS assay and cell death signaling was explored by immunoblot analysis. Fluorescence-activated cell sorting was performed to evaluate the affinity and specificity of GPC3 aptamers in HCC cells.

Cytotoxicity was assessed by alanine and aspar-tate aminotransferase, lactate dehydrogenase, water-soluble tetrazolium salt 1 proliferation and caspase-3 activity assays. Small animal imaging by dynamic

contrast-enhanced-MRI and choline PET was performed. Results. In both cell lines, artesunate dose dependently reduced cell viability and proliferation (from 50 micromolar: p<0.05). This reduction was enhanced by hypoxia (from 12.5 micromolar: p<0.01). Moreover, artesunate downregulated the secretion of VEGF and placental growth factor in vitro (both p<0.05) and in vivo (both p<0.01). In the mouse model for HCC, artesunate decreased vessel density and tumor burden (both p<0.05). No apparent hepatotox-icity or mortality was observed. In vitro and in vivo activation of the PKR-like endoplasmic reticulum kinase pathway (resp. p<0.05 and p<0.01) together with decreased ATP-binding cassette transporter G2 expression (resp. buy Pembrolizumab p<0.01 and p<0.05) by artesunate

was demonstrated. Conclusions. These observations exhibit the potential of artesunate as a safe treatment of HCC optionally combined with current hypoxia-inducing therapies such as transarterial embolization or sorafenib. As a low-cost drug, artesunate might be of particular interest for the developing countries with high incidence of HCC. Disclosures: Isabelle Colle – Advisory Committees or Review Panels: MSD, Janssen, MSD, Gilead; Patent Held/Filed: Trombogenics; Speaking and Teaching: BMS, Janssen The following people have nothing to disclose: Yves-Paul Vandewynckel, Debby Laukens, Anja M. Geerts, Louis Libbrecht, Eliene Bogaerts, Enzalutamide clinical trial Lindsey Devisscher, Annelies Paridaens,

Xavier Verhelst, Christian Vanhove, Benedicte Descamps, Sophie Janssens, Bart Lambrecht, Christophe Van Steenkiste, Hans Van Vlier-berghe Background/Aim: Aptamers selleck chemical are small synthetic oligonu-cleotides that bind to protein targets with high specificity and affinity. AS1411 is the first nucleic acid aptamer in clinical development for cancers. AS1411 binds to the protein nucle-olin, which is over-expressed in the cytoplasm and on the surface of cancer cells. Glypican-3 (GPC3), a cell surface protein that is highly expressed in hepatocellular carcinoma (HCC), has emerged as a candidate therapeutic target. We aimed to investigate the therapeutic potential of aptamers for HCC by evaluating AS1411 effect on HCC cell growth and by confirming the affinity and specificity of GPC3 aptamer in HCC cells. Methods: Human HCC cell lines (Huh-7, SNU 761 cells) and human cholangiocarcinoma (CCA) cell lines (KMBC, Witt cells) were used. Cell growth was assessed using MTS assay and cell death signaling was explored by immunoblot analysis. Fluorescence-activated cell sorting was performed to evaluate the affinity and specificity of GPC3 aptamers in HCC cells.

SIPPET is currently ongoing and, to date, 270 (target 300) patients from 21 countries across four continents have been recruited. A major strength of SIPPET is that it is a pragmatic trial (Table 2). Although RCTs are the underlying basis of evidence-based medicine, strict inclusion and exclusion criteria mean Ipatasertib that patient populations frequently do not accurately reflect

the type of patients who are treated in everyday practice. In contrast, pragmatic trials aim to reflect the variation among patients observed in everyday clinical practice [20]. Pragmatic trials also allow for the application of different treatments to different patients; in this manner, it is the management protocol rather than individual treatment that is the subject of investigation [20]. For example, patients in SIPPET can be treated with prophylaxis which is used widely in Europe but, to generate a result that would apply worldwide, the study protocol also allows for patients to be treated on demand. Among the limitations of SIPPET is the inclusion of patients minimally exposed to blood components who may have a degree of underlying immunological

response relating to their previous product. Moreover, in a check details pragmatic trial not all risk factors can be strictly balanced such as use of prophylaxis vs. on demand treatment, treatment intensity and the presence of danger signals. It is hoped that these issues may be overcome by sample size, as this is the largest RCT conducted to date in haemophilia. SIPPET is an independent study organized and conducted by the Angelo Bianchi Bonomi Hemophilia and Thrombosis Center in Milan, Italy. Some major problems that have been encountered during the course of the trial can be summed up in two categories: high costs and local/international click here over-regulation

(Table 3). The challenges of meeting the high costs of conducting a study such as SIPPET are further complicated by the difficulties encountered in obtaining independent funding. Arguably, the single biggest issue in conducting SIPPET has been the competition for patients with trials of recombinant products in PUPs organized and supported by the pharmaceutical industry. The issue of whether the source of FVIII concentrate (plasma-derived or recombinant) affects the incidence of inhibitor development in PUPs remains unsettled. It is anticipated that the results of the ongoing randomized, controlled SIPPET study will help clarify this issue. Meanwhile, there is solid evidence to indicate that switching among FVIII products does not influence inhibitor risk in PUPS or PTPs with haemophilia A. Q. SHI E-mail: [email protected] Although the association between von Willebrand factor (VWF) and FVIII has been investigated for decades, the effect of VWF on the reactivity of anti-FVIII antibodies (inhibitors) remains controversial.

24 In HCC, CD44 is also an important marker used in combination with other CSC markers to better define the surface phenotype of liver CSCs. For the aforementioned markers, including CD133 and CD90, cells co-expressing either of these markers and CD44

present a more aggressive phenotype than cells with a positive expression of either CD133 or CD90 alone. Yang et al. showed that CD44+ cells developed tumor nodules in immunodeficient mice faster than CD44- cells, whereas lung metastases were only observed in immunodeficient mice transplanted with CD90+CD44+ cells.23 In another study, CD44 was found to be preferentially expressed in a CD133+ population in four HCC cell lines, including Huh7, SMMC-7721, MHCC-LM3 and MHCC-97L. CD133+CD44+ cells exhibit enhanced selleck chemical abilities to form tumors, are chemoresistant and express a higher level of “stemness”-associated genes, as compared with their CD133+CD44-

counterparts.25 EpCAM is present in the embryonic liver, bile duct epithelium and proliferating bile ductules in the cirrhotic liver, but it is absent in normal adult hepatocytes.26 An elevated expression of EpCAM was first identified in premalignant hepatic tissues; therefore, this surface protein was suggested to be an early biomarker for HCC.27 Following a cDNA microarray analysis on a clinical cohort of primary HCC tissue, EpCAM+ HCC was linked with the gene signature and the molecular pathway of hepatic progenitor

cells, whereas genes expressed in EpCAM- HCC cells were associated with mature hepatocyte functions.26 These two subtypes Wnt inhibitor of HCC were further stratified into four groups with features resembling different hepatic lineages, and they showed prognostic differences based on the expression of alpha fetoprotein (AFP).26,28 EpCAM+ HCC cells selleck compound have also been shown to be highly invasive and tumorigenic, in comparison with their EpCAM- counterparts.28 Recently, a novel cell surface marker, CD13, was identified for potentially dormant and semi-quiescent CSCs in HCC. Haraguchi et al. found that CD13 was commonly enriched in an SP population sorted from Huh7, PLC/PRF/5 and Hep3B cells by gene expression microarray analysis. CD13 was selected as a putative marker to enrich the semi-quiescent liver CSCs because of its predominant distribution during the G1/G0 phase.29 This result suggested that CD13+ cells represent the dormant or slow-growing population that is believed to account for the chemoresistant capacity in HCC. Researchers then assessed the tumorigenic potential of CD13 with two other liver CSC markers, CD133 and CD90. The results clearly showed that the CD13+CD133+ and CD13+CD90- fractions in Huh7 and PLC/PRF/5 cell lines, respectively, initiated tumor formation effectively in limiting-dilution and serial transplantation assays.

Biochemical analysis of cerebrospinal

fluid (CSF) found increased concentrations of orexinA and corticotropin-releasing factor in patients with MOH. The levels of both hormones correlated with the amount of monthly drug intake.[42] Patients overusing triptans had CSF glutamate levels lower than those in patients with chronic migraine without medication overuse, but higher than those in nonheadache controls.[43] The anatomical, functional, and biochemical studies described above demonstrate the dysfunction of the endogenous pain control system, probably selleck chemicals llc 5-HT- or endocannabinoid-dependent, in patients with MOH. Alteration of this control system may increase cortical excitability and facilitate pain perception. However, because several changes are also observed in chronic migraine patients without medication overuse, these changes may simply reflect the worsening of headache and may not imply much about the pathogenesis of MOH. The primary objective of preclinical studies is to determine how chronic medication affects the trigeminal Talazoparib concentration nociceptive system and other brain areas involved in headache pathogenesis. Preclinical evidence shows that chronic exposure to opiates can facilitate the nociceptive process. Upregulation of CGRP has been observed in dorsal

root ganglia after prolonged exposure to morphine.[44, 45] Sustained morphine exposure affects spinal glutamatergic transmission. Enhancement of glutamate release[46] and downregulation of spinal glutamate transporters[47] has been found after sustained morphine exposure. Expansion of cutaneous receptive click here fields and lower thresholds of dura-sensitive medullary dorsal horn neurons was observed in rats receiving sustained infusion of morphine.[48] Another mechanism underlying chronic opiate-mediated

nociceptive exacerbation has been proposed as the activation of a toll-like receptor-4 on glial cells, resulting in a proinflammatory state.[49] This evidence indicates that chronic opiate exposure can lead to a persistent pronociceptive trigeminal neural adaptation.[50] Prolonged exposure to triptans produces comparable changes in the sensory system. Enhancement of the CGRP and NO systems has been observed in animals treated with triptans. Chronic sumatriptan exposure produces long-lasting cutaneous tactile allodynia. This change corresponds with an increased number of CGRP-positive dural afferent neurons in the TG. Exposure to triptans increases CGRP levels in the blood after challenge by a nitric oxide donor.[51] CGRP can increase expression of the TRPV1 receptor, thus facilitating the nociceptive process.[52] In addition to increasing CGRP levels, chronic triptan exposure can increase the expression of neuronal nitric oxide synthase (nNOS) in the TG neurons innervating the dura in rats.

Methods: Mouse liver AS were studied by electron microscopy. Transcriptome analysis in AS cell lines vs. normal liver sinusoidal endothelial cells (LSEC) from control and Notch1 K〇 mice without AS including gene set enrichement analysis (GSEA) were performed. In one AS cell line the effects of selleck chemicals llc treatment with increasing sorafenib concentrations (1-20 μM) were analyzed. Time-lapse microscopy of sorafenib exposed AS cells grown on matrigel was analyzed. Cell proliferation was monitored using the real-time cell analyser system xCELLigence. Cell viability and intracellular signalling were assessed by flow cytometry and western

blotting. Results: In the transitional zone between tumor and normal tissue, ultrastructural features varied from normal to dysplastic endothelial cells selleck screening library with prominent nucle-oli and Weibel Palade bodies. Transcriptome analysis showed massive changes in gene expression identifying FGFRs, TGFβ, met proto-oncogene, PlGF, and VEGF-A as potential drivers in malignant transformation of hepatic AS. Moreover, GSEA revealed that six of the top 20 upregulated chemical and genetic perturbation gene sets were related to myc targets (FDR<0. 25). C-myc is a downstream transcription factor target of the Raf/MEK/ERK pathway, which can be blocked

by sorafenib, a multikinase inhibitor. Timelapse imaging showed that sorafenib treatment dramatically reduced migration of AS cells. Differences in filopodia dynamics were significant (p=0. 0201) after 6 h with a decrease in filopodia丨 extensions. Sorafenib inhibited cell proliferation in a time and dose-dependant manner, whereas the number of apoptotic cells was only slightly elevated with increasing concentrations. In addition, sorafenib suppressed ERK phosphorylation and expression of Cyclin D2 in the AS cell line. Conclusion: We identified Notch1 as LSEC tumor suppressor gene

and established selleck products three hepatic AS cell lines as a useful in vitro tool. Our data demonstrate antitumor activity of sorafenib in AS cells with potent inhibition of migration, filopodia formation, and cell proliferation, which support further evaluation of sorafenib as a novel treatment strategy. Disclosures: The following people have nothing to disclose: Sonja Rothweiler, Michael T. Dill, Luigi Terraciano, Zuzanna Makowska, Markus H. Heim, David Semela Background: Hepatitis C virus (HCV) has been reported to regulate cellular microRNAs (miRNAs). The HCV core protein is considered to be a potential oncoprotein in HCV-related hepatocellular carcinoma (HCV-HCC), but HCV core-regulated microRNAs are largely unknown. Our preliminary experiments revealed significantly down-regulated microRNA-152 (miR152) expression in HCV core protein-overexpressing HepG2 cells in comparison with the control Ad-EGFP infected HepG2 cells.

Diffusion tensor imaging (DTI) examines water motion in vivo. DTI changes in the corticospinal tract changes have been

correlated with sensorimotor deficits and postoperative improvement in patients with brain tumors,[1-3] and motor function in patients with ischemic strokes.[4, 5] We describe a patient with unilateral enlarged Virchow–Robin spaces in the thalamus and ventral midbrain. The patient did not have any motor symptoms despite compression of the adjacent corticospinal tract, abnormal diffusion tensor metrics, and abnormal tractography. A 54-year-old female with peritoneal and breast carcinomas presented with headaches, memory loss, and confusion. She had no signs or symptoms of motor weakness after complete neurological evaluation. MRI at 1.5 Tesla (Signa HDx, GE Medical Systems, Milwaukee, WI, USA) showed multiple brain metastases and edema distant from the motor cortices and corticospinal tracts. The patient had already received systemic AZD5363 cost chemotherapy and whole brain radiation therapy. Despite additional chemotherapy and stereotactic radiosurgery

to a right frontal lobe metastasis, the patient succumbed to her disease 18 months after diagnosis of the brain metastases. MRI also revealed cystic dilatations in the left thalamus and ventral midbrain adjacent to the corticospinal tract. (Fig 1A). These lesions followed cerebro-spinal fluid (CSF) intensity on all sequences including diffusion-weighted imaging (excluding dermoid or epidermoid), were in the brain (excluding http://www.selleckchem.com/products/R788(Fostamatinib-disodium).html arachnoid

cyst), and did not enhance (excluding cystic neoplasm or infection). Consistent with enlarged Virchow–Robin spaces along collicular and accessory collicular arteries,[6] comparison with prior studies showed them to be stable for >1 year and present before the brain metastases. DTI was acquired using a single-shot spin-echo echo-planar sequence with: TR/TE 13,500/100 ms, matrix 128 × 128, field of view (FOV) 240 mm, slice thickness 3 mm, b-value 1,000 s/mm2, and number of excitations (NEX) 1 in 25 noncollinear directions. Using DTI Studio v2.5,[7] fractional anisotropy (FA), mean diffusivity (MD), and directionally encoded color FA maps were generated (Fig 1B). Regions-of-interest (ROIs) were drawn around each corticospinal tract on axial slices selleck inhibitor in the posterior limb of the internal capsule and in the ventral midbrain. Values generated for each voxel within the ROIs were exported in Analyze format into Analysis of Functional Neuroimages,[8] and organized in histograms according to frequency of values per side. Comparisons were made between sides for proportion of FA > .8, distribution of FA, distribution of MD, longitudinal diffusivity (λ0), and radial diffusivity [(λ1+λ2)/2]. Statistical analysis was performed using two-sided Wilcoxon rank-sum nonparametric tests and two-sample tests of proportions (to compare the relative percentage of voxels >.8). Median FA and MD were .82 and 2.2 × 10−3 mm2/second as compared to .74 and 2.