Computer Aided Detection and measurement of peripheral artery disease.

Computer-Aided Tomography Angiography (CTA) images are the standard for assessing Peripheral artery disease (PAD). This paper presents a Computer Aided Detection (CAD) and Computer Aided Measurement (CAM) system for PAD. The CAD stage detects the arterial network using a 3D region growing method and a fast 3D morphology operation. The CAM stage aims to accurately measure the artery diameters from the detected vessel centerline, compensating for the partial volume effect using Expectation Maximization (EM) and a Markov Random field (MRF). The system has been evaluated on phantom data and also applied to fifteen (15) CTA datasets, where the detection accuracy of stenosis was 88% and the measurement accuracy was with an 8% error.

Outcomes of optic nerve sheath decompression for nonarteritic ischemic optic neuropathy.

Efficacy of optic nerve sheath decompression (ONSD) in treating non-arteritic ischemic optic neuropathy (NAION) is not clear. We retrospectively analyzed the records of 91 patients with NAION, who were examined during a two-year period, and compared the final Snellen visual acuities of eyes treated with ONSD with those of eyes that did not have surgery. Seven of 18 eyes with ONSD (39%) demonstrated increased visual acuity of two or more lines; whereas 23 of 71 eyes without surgery (32%) had increased acuity. The ONSD group and no surgery group were further subdivided into eyes with progressive visual loss and nonprogressive visual loss. No statistically significant differences in visual outcome between groups were found. We did not find the high frequency of visual improvement that has been reported in some studies of ONSD for NAION.

The Determinants of Exit in Argentina: Core and Peripheral Regions

This paper analyses the regional determinants of exit in Argentina. We find evidence of a dynamic revolving door by which past entrants increase current exits, particularly in the peripheral regions. In the central regions, current and past incumbents cause an analogous displacement effect. Also, exit shows a U-shaped relationship with respect to the informal economy, although the positive effect is weaker in the central regions. These findings point to the existence of a core-periphery structure in the spatial distribution of exits. Key words: firm exit, count data models, Argentina JEL: R12; R30; C33

Evaluation of peripheral arterial bypass grafts with multi-detector row CT angiography: comparison with duplex US and digital subtraction angiography.

PURPOSE: To assess the technical feasibility of multi-detector row computed tomographic (CT) angiography in the assessment of peripheral arterial bypass grafts and to evaluate its accuracy and reliability in the detection of graft-related complications, including graft stenosis, aneurysmal changes, and arteriovenous fistulas. MATERIALS AND METHODS: Four-channel multi-detector row CT angiography was performed in 65 consecutive patients with 85 peripheral arterial bypass grafts. Each bypass graft was divided into three segments (proximal anastomosis, course of the graft body, and distal anastomosis), resulting in 255 segments. Two readers evaluated all CT angiograms with regard to image quality and the presence of bypass graft-related abnormalities, including graft stenosis, aneurysmal changes, and arteriovenous fistulas. The results were compared with McNemar test with Bonferroni correction. CT attenuation values were recorded at five different locations from the inflow artery to the outflow artery of the bypass graft. These findings were compared with the findings at duplex ultrasonography (US) in 65 patients and the findings at conventional digital subtraction angiography (DSA) in 27. RESULTS: Image quality was rated as good or excellent in 250 (98%) and in 252 (99%) of 255 bypass segments, respectively. There was excellent agreement both between readers and between CT angiography and duplex US in the detection of graft stenosis, aneurysmal changes, and arteriovenous fistulas (kappa = 0.86-0.99). CT angiography and duplex US were compared with conventional DSA, and there was no statistically significant difference (P >.25) in sensitivity or specificity between CT angiography and duplex US for both readers for detection of hemodynamically significant bypass stenosis or occlusion, aneurysmal changes, or arteriovenous fistulas. Mean CT attenuation values ranged from 232 HU in the inflow artery to 281 HU in the outflow artery of the bypass graft. CONCLUSION: Multi-detector row CT angiography may be an accurate and reliable technique after duplex US in the assessment of peripheral arterial bypass grafts and detection of graft-related complications, including stenosis, aneurysmal changes, and arteriovenous fistulas.

Ulnar Nerve Transposition at the Elbow under Local Anesthesia: A Patient Satisfaction Study.

Background Ulnar nerve decompression at the elbow traditionally requires regional or general anesthesia. We wished to assess the feasibility of performing ulnar nerve decompression and transposition at the elbow under local anesthesia. Methods We examined retrospectively the charts of 50 consecutive patients having undergone ulnar nerve entrapment surgery either under general or local anesthesia. Patients were asked to estimate pain on postoperative days 1 and 7 and satisfaction was assessed at 1 year. Results On day 1, pain was comparable among all groups. On day 7, pain scores were twice as high when transposition was performed under general anesthesia when compared with local anesthesia. Patient satisfaction was slightly increased in the local anesthesia group. These patients were significantly more willing to repeat the surgery. Conclusion Ulnar nerve decompression and transposition at the elbow can be performed under local anesthesia without added morbidity when compared with general anesthesia.

The effect of virtual reality on visual vertigo symptoms in patients with peripheral vestibular dysfunction: a pilot study.

Individuals with vestibular dysfunction may experience visual vertigo (VV), in which symptoms are provoked or exacerbated by excessive or disorientating visual stimuli (e.g. supermarkets). VV can significantly improve when customized vestibular rehabilitation exercises are combined with exposure to optokinetic stimuli. Virtual reality (VR), which immerses patients in realistic, visually challenging environments, has also been suggested as an adjunct to VR to improve VV symptoms. This pilot study compared the responses of sixteen patients with unilateral peripheral vestibular disorder randomly allocated to a VR regime incorporating exposure to a static (Group S) or dynamic (Group D) VR environment. Participants practiced vestibular exercises, twice weekly for four weeks, inside a static (Group S) or dynamic (Group D) virtual crowded square environment, presented in an immersive projection theatre (IPT), and received a vestibular exercise program to practice on days not attending clinic. A third Group D1 completed both the static and dynamic VR training. Treatment response was assessed with the Dynamic Gait Index and questionnaires concerning symptom triggers and psychological state. At final assessment, significant betweengroup differences were noted between Groups D (p = 0.001) and D1 (p = 0.03) compared to Group S for VV symptoms with the former two showing a significant 59.2% and 25.8% improvement respectively compared to 1.6% for the latter. Depression scores improved only for Group S (p = 0.01) while a trend towards significance was noted for Group D regarding anxiety scores (p = 0.07). Conclusion: Exposure to dynamic VR environments should be considered as a useful adjunct to vestibular rehabilitation programs for patients with peripheral vestibular disorders and VV symptoms.

Dysregulation of voltage-gated sodium channels by ubiquitin ligase NEDD4-2 in neuropathic pain.

Peripheral neuropathic pain is a disabling condition resulting from nerve injury. It is characterized by the dysregulation of voltage-gated sodium channels (Navs) expressed in dorsal root ganglion (DRG) sensory neurons. The mechanisms underlying the altered expression of Navs remain unknown. This study investigated the role of the E3 ubiquitin ligase NEDD4-2, which is known to ubiquitylate Navs, in the pathogenesis of neuropathic pain in mice. The spared nerve injury (SNI) model of traumatic nerve injury-induced neuropathic pain was used, and an Nav1.7-specific inhibitor, ProTxII, allowed the isolation of Nav1.7-mediated currents. SNI decreased NEDD4-2 expression in DRG cells and increased the amplitude of Nav1.7 and Nav1.8 currents. The redistribution of Nav1.7 channels toward peripheral axons was also observed. Similar changes were observed in the nociceptive DRG neurons of Nedd4L knockout mice (SNS-Nedd4L-/-). SNS-Nedd4L-/- mice exhibited thermal hypersensitivity and an enhanced second pain phase after formalin injection. Restoration of NEDD4-2 expression in DRG neurons using recombinant adenoassociated virus (rAAV2/6) not only reduced Nav1.7 and Nav1.8 current amplitudes, but also alleviated SNI-induced mechanical allodynia. These findings demonstrate that NEDD4-2 is a potent posttranslational regulator of Navs and that downregulation of NEDD4-2 leads to the hyperexcitability of DRG neurons and contributes to the genesis of pathological pain.

Increased anandamide induced relaxation in mesenteric arteries of cirrhotic rats. Role of cannabinoid and vanilloid receptors

Background and aims: Anandamide is an endocannabinoid that evokes hypotension by interaction with peripheral cannabinoid CB1 receptors and with the perivascular transient receptor potential vanilloid type 1 protein (TRPV1). As anandamide has been implicated in the vasodilated state in advanced cirrhosis, the study investigated whether the mesenteric bed from cirrhotic rats has an altered and selective vasodilator response to anandamide. Methods: We assessed vascular sensitivity to anandamide, mRNA and protein expression of cannabinoid CB1 receptor and TRPV1 receptor, and the topographical distribution of cannabinoid CB1 receptors in resistance mesenteric arteries of cirrhotic and control rats. Results: Mesenteric vessels of cirrhotic animals displayed greater sensitivity to anandamide than control vessels. This vasodilator response was reverted by CB1 or TRPV1 receptor blockade, but not after endothelium denudation or nitric oxide inhibition. Anandamide had no effect on distal femoral arteries. CB1 and TRPV1 receptor protein was higher in cirrhotic than in control vessels. Neither CB1 mRNA nor protein was detected in femoral arteries. Immunochemistry showed that CB1 receptors were mainly in the adventitia and in the endothelial monolayer, with higher expression observed in vessels of cirrhotic rats than in controls. Conclusions: These results indicate that anandamide is a selective splanchnic vasodilator in cirrhosis which predominantly acts via interaction with two different types of receptors, CB1 and TRPV1 receptors, which are mainly located in perivascular sensory nerve terminals of the mesenteric resistance arteries of these animals.

Increased Presence of FOXP3+ Regulatory T Cells in Inflamed Muscle of Patients with Active Juvenile Dermatomyositis Compared to Peripheral Blood.

Juvenile dermatomyositis (JDM) is an immune-mediated inflammatory disease affecting the microvasculature of skin and muscle. CD4+CD25+FOXP3+ regulatory T cells (Tregs) are key regulators of immune homeostasis. A role for Tregs in JDM pathogenesis has not yet been established. Here, we explored Treg presence and function in peripheral blood and muscle of JDM patients. We analyzed number, phenotype and function of Tregs in blood from JDM patients by flow cytometry and in vitro suppression assays, in comparison to healthy controls and disease controls (Duchenne's Muscular Dystrophy). Presence of Tregs in muscle was analyzed by immunohistochemistry. Overall, Treg percentages in peripheral blood of JDM patients were similar compared to both control groups. Muscle biopsies of new onset JDM patients showed increased infiltration of numbers of T cells compared to Duchenne's muscular dystrophy. Both in JDM and Duchenne's muscular dystrophy the proportion of FOXP3+ T cells in muscles were increased compared to JDM peripheral blood. Interestingly, JDM is not a self-remitting disease, suggesting that the high proportion of Tregs in inflamed muscle do not suppress inflammation. In line with this, peripheral blood Tregs of active JDM patients were less capable of suppressing effector T cell activation in vitro, compared to Tregs of JDM in clinical remission. These data show a functional impairment of Tregs in a proportion of patients with active disease, and suggest a regulatory role for Tregs in JDM inflammation.

Role of the transcription factor sox4 in schwann cell development

Previous studies demonstrated that both Schwann cell differentiation and de-differentiation (in the situation of a nerve injury or demyelinating disease) are regulated by cell-intrinsic regulators including several transcription factors. In particular, the de-differentiation of mature Schwann cells is driven by the activation of multiple negative regulators of myelination including c-Jun, Notch, Sox-2 and Pax-3, all usually expressed in the immature Schwann cells and suppressed at the onset of myelination. In order to identify new negative regulators of myelination involved in the development of the peripheral nervous system (PNS) we analyzed the data from a previously performed transcriptional analysis of myelinating Schwann cells. Based on its transcriptional expression profile during myelination, Sox4, a member of the Sox gene family, was identified as a potential candidate. Previous studies demonstrated that prolonged Sox4 expression in oligodendrocytes maintains these cells in a premyelinating state, further suggesting its role as a negative regulator of myelination. Concomitantly, we observed upregulation of Sox4 mRNA and protein expression levels in the PNS of three different models of demyelinating neuropathies (Pmp22, Lpin1, and Scap KOs). To better characterize the molecular function of Sox4, we used a viral vector allowing Sox4 overexpression in cultured Schwann cells and in neuron-Schwann cell co-cultures. In parallel, we generated two transgenic lines of mice in which the overexpression of Sox4 is driven specifically in Schwann cells by the Myelin Protein Zero gene promoter. The preliminary data from these in vitro and in vivo experiments show that overexpression of Sox4 in PNS causes a delay in progression of myelination thus indicating that Sox4 acts as a negative regulator of Schwann cell myelination.

Decrease in luteinizing hormone pulse frequency during a five-hour peripheral Ghrelin infusion in the ovariectomized rhesus monkey

RESUME : La ghrelin est un peptide sécrété par l'estomac jouant un rôle important dans le maintien de l'homéostasie énergétique. Ses taux plasmatiques sont augmentés durant des périodes prolongées de déficit nutritionnel. Une carence énergétique étant souvent associée à une inhibition de l'axe hypothalamo-hypophyso-ovarien, nous avons postulé que l'augmentation des taux circulant de ghrelin pourrait diminuer l'activité du générateur hypothalamique de pulsations de GnRH. Le protocole expérimental impliquait des singes rhésus adultes ovariectomisés (n=6) qui dans un premier temps recevaient durant 3 heures une perfusion de solution saline physiologique afin de mesurer la sécrétion pulsatile de LH à l'état basai. L'expérience se poursuivait alors durant 5 heures par une perfusion intraveineuse de ghrelin humaine (un bolus de 100-150µg suivi par 100-150µg/h) ou le maintien de la perfusion de solution saline physiologique. Des échantillons de sang étaient prélevés toutes les 15 minutes. La perfusion de ghrelin a augmenté ses taux plasmatiques de 2.9 fois par rapport aux valeurs de base. L'administration de ghrelin a significativement diminué la fréquence des pulsations de LH (de 0.89±0.07/h à l'état basai à 0.57±0.10/h durant la perfusion de ghrelin; p<0.05, moyenne±SEM), alors que la fréquence des pulsations de LH est restée inchangée durant la perfusion de solution physiologique. L'amplitude des pulsations de LH n'a pas été modifiée. La ghrelin a également stimulé de manière significative la sécrétion de cortisol et d'hormone de croissance, mais n'a toutefois pas eu d'effet sur la sécrétion de leptin. En conclusion, la ghrelin peut inhiber l'activité du générateur de pulsations de GnRH et pourrait ainsi contribuer à l'inhibition de l'axe de la reproduction observée durant des périodes de carence nutritionnelle, comme notamment chez les patientes souffrant d'anorexie mentale. La ghrelin peut également activer l'axe hypothalamo-hypophyso-surrénalien. Le lien dans cette situation entre l'activation de l'axe surrénalien et l'inhibition de l'axe de la reproduction reste à démontrer. ABSTRACT: Ghrelin, a nutrition-related peptide secreted by the stomach, is elevated during prolonged food deprivation. Because undernutrition is often associated with a suppressed reproductive axis, we have postulated that increasing peripheral ghrelin levels will decrease the activity of the GnRH pulse generator. Adult ovariectomized rhesus monkeys (n = 6) were subjected to a 5-h iv human ghrelin (100- to 150µg bolus followed by 100-150 µg/h) or saline infusion, preceded by a 3-h saline infusion to establish baseline pulsatile LH release. Blood samples were collected at 15-min intervals throughout the experiment. Ghrelin infusion increased plasma ghrelin levels 2.9-fold of baseline. Ghrelin significantly decreased LH pulse frequency (from 0.89 ± 0.07/h in baseline to 0.57 ± 0.10/h during ghrelin infusion; P<0.05, mean ± SEM), whereas LH pulse frequency remained unchanged during saline treatment. LH pulse amplitude was not affected. Ghrelin also significantly stimulated both Cortisol and GH release, but had no effect on leptin. We conclude that ghrelin can inhibit GnRH pulse activity and may thereby mediate the suppression of the reproductive system observed in conditions of undernutrition, such as in anorexia nervosa. Ghrelin also activates the adrenal axis, but the relevance of this to the inhibition of GnRH pulse frequency remains to be established.