The utility of measuring the corpus callosal angle (CA) for the diagnosis of idiopathic normal pressure hydrocephalus (INPH) was investigated. Three-dimensional magnetic resonance imaging (MRI) was performed in 34 INPH patients, 34 Alzheimer's disease (AD) patients, and 34 normal control (NC) subjects. Measurement of the CA on the coronal MR images of the posterior commissure perpendicular to the anteroposterior commissure plane was performed for all subjects. The CA of the INPH group (mean +/- SD, 66 +/- 14 degrees) was significantly smaller than those of the AD (104 +/- 15 degrees) and NC (112 +/- 11 degrees) groups. When using the threshold of the mean - 2SD value of the NC group (= 90 degrees), an accuracy of 93%, sensitivity of 97%, and specificity of 88% were observed for discrimination of INPH from AD patients. Measuring the CA helps in differentiating INPH patients from AD and normally aged subjects.

Background and Purpose Systemic hypertension has long been considered as a risk factor of aneurysmal rupture. However, a causal link between systemic hypertension and the development of aneurysmal rupture has not been established. In this study, using a mouse model of intracranial aneurysm rupture, we examined the roles of systemic hypertension in the development of aneurysmal rupture. Methods Aneurysms were induced by a combination of deoxycorticosterone acetate (DOCA)-salt induced hypertension and a single injection of elastase into the cerebrospinal fluid in mice. Anti-hypertensive treatment was started six days after aneurysm induction. Aneurysmal rupture was detected by neurological symptoms and confirmed by the presence of intracranial aneurysm with subarachnoid hemorrhage. Hydralazine (direct vasodilator) or the discontinuation of the DOCA-salt treatment was used to assess the roles of systemic hypertension. Captopril (angiotensin converting enzyme inhibitor) or losartan (angiotensin II type 1 receptor antagonist) was used to assess the roles of the local renin-angiotensin system in the vascular wall. Results Normalization of blood pressure by hydralazine significantly reduced the incidence of ruptured aneurysms and the rupture rate. There was a dose dependent relationship between the reduction of blood pressure and the prevention of aneurysmal rupture. Captopril and losartan were able to reduce the rupture rates without affecting systemic hypertension induced by DOCA-salt treatment. Conclusions Normalization of blood pressure after aneurysm formation prevented aneurysmal rupture in mice. In addition, we found that the inhibition of the local renin-angiotensin system independent from the reduction of blood pressure can prevent aneurysmal rupture.

BackgroundAlterations in TNF-α expression have been associated with cerebral aneurysms, but a direct role in formation, progression, and rupture has not been established.MethodsCerebral aneurysms were induced through hypertension and a single stereotactic injection of elastase into the basal cistern in mice. To test the role of TNF-α in aneurysm formation, aneurysms were induced in TNF-α knockout mice and mice pretreated with the synthesized TNF-α inhibitor 3,6′dithiothalidomide (DTH). To assess the role of TNF-α in aneurysm progression and rupture, DTH was started 6 days after aneurysm induction. TNF-α expression was assessed through real-time PCR and immunofluorescence staining.ResultsTNF-α knockout mice and those pre-treated with DTH had significantly decreased incidence of aneurysm formation and rupture as compared to sham mice. As compared with sham mice, TNF-α protein and mRNA expression was not significantly different in TNF-α knockout mice or those pre-treated with DTH, but was elevated in unruptured and furthermore in ruptured aneurysms. Subarachnoid hemorrhage (SAH) occurred between 7 and 21 days following aneurysm induction. To ensure aneurysm formation preceded rupture, additional mice underwent induction and sacrifice after 7 days. Seventy-five percent had aneurysm formation without evidence of SAH. Initiation of DTH treatment 6 days after aneurysm induction did not alter the incidence of aneurysm formation, but resulted in aneurysmal stabilization and a significant decrease in rupture.ConclusionsThese data suggest a critical role of TNF-α in the formation and rupture of aneurysms in a model of cerebral aneurysm formation. Inhibitors of TNF-α could be beneficial in preventing aneurysmal progression and rupture.

Background and Purpose-Intracerebral hemorrhage, induced by recombinant tissue plasminogen activator (rtPA) in ischemic stroke, is attributable to the increased activity of matrix metalloproteinase-9 (MMP-9). Patients with acute infarct benefit from the neuroprotective drug edaravone, a free radical scavenger. We examined the mechanisms by which edaravone may help to suppress rtPA-induced brain hemorrhage. Methods-Male Wistar rats weighing 250 to 280 g were subjected to 3-hour transient middle cerebral artery occlusion (MCAO) and divided randomly into 3 groups. Immediately after reperfusion, 1 group was intravenously injected with 10 mg/kg rtPA, another with rtPA plus 3 mg/kg edaravone, and the 3rd group received no treatment. We assessed the hemorrhage volume and the activity of MMP-9 in the brain 24 hours postischemia. We also studied the activity of MMP-9, its mRNA expression, and nuclear factor-kappa B (NF-B) activity in rtPA-stimulated human microvascular endothelial cells (HBECs). Results-The degree of hemorrhage and the level of endothelial cell-derived MMP-9 were elevated in rats treated with rtPA alone and attenuated in rats treated with rtPA plus edaravone. In rtPA-stimulated HBECs, edaravone suppressed the activity and mRNA expression of MMP-9 in a dose-dependent manner. Edaravone also inhibited NF-B activation. Conclusions-We demonstrate that edaravone inhibits rtPA-induced cerebral hemorrhage in the ischemic brain of rats via the inhibition of MMP-9 expression in vivo, which is substantiated by inhibition of MMP-9 expression and NF-B activation in HBECs. Edaravone may render thrombolytic therapy safer for the administration of rtPA in patients with ischemic stroke.

Collectins, including surfactant proteins A (SP-A) and D (SP-D) and mannose binding lectin (MBL), are the important constituents of the innate immune system. Mycobacterium avium, a facultative intracellular pathogen, has developed numerous mechanisms for entering mononuclear phagocytes. In this study, we investigated the interactions of collectins with M. avium and the effects of these lectins on phagocytosis of M. avium by macrophages. SP-A, SP-D, and MBL exhibited a concentration-dependent binding to M. avium. The binding of SP-A to M. avium was Ca2+-dependent but that of SP-D and MBL was Ca2+-independent. SP-A and SP-D but not MBL enhanced the phagocytosis of FITC-labeled M. avium by rat alveolar macrophages and human monocyte-derived macrophages. Excess mannan, zymosan, and lipoarabinomannan derived from the M. avium-intracellular complex, significantly decreased the collectin-stimulated phagocytosis of M. avium. Enhanced phagocytosis was not affected by the presence of cycloheximide or chelation of Ca2+. The mutated collectin, SP-AE195Q, R197D exhibited decreased binding to M. avium but stimulated phagocytosis to a level comparable to wild-type SP-A. Enhanced phagocytosis by cells persisted even after preincubation and removal of SP-A or SP-D. Rat alveolar macrophages that had been incubated with SP-A or SP-D also exhibited enhanced uptake of 125I-mannosylated BSA. Analysis by confocal microscopy and flow cytometry revealed that the lung collectins up-regulated the cell surface expression of mannose receptor on monocyte-derived macrophages. These results provide compelling evidence that SP-A and SP-D enhance mannose receptor-mediated phagocytosis of M. avium by macrophages.

This paper describes a new computational method of fully automated anisotropic triangulation of a trimmed parametric surface. Given as input: (1) a domain geometry and (2) a 3 x 3 tensor field that specifies a desired anisotropic node-spacing, this new approach first packs ellipsoids closely in the domain by defining proximity-based interacting forces among the ellipsoids and finding a force-balancing configuration using dynamic simulation. The centers of the ellipsoids are then connected by anisotropic Delaunay triangulation for a complete mesh topology. Since a specified tensor field controls the directions and the lengths of the ellipsoids' principal axes, the method generates a graded anisotropic mesh whose elements conform precisely to the given tensor field.

As a part of ongoing efforts to develop computerized planning tools for cryosurgery, the current study focuses on developing an efficient numerical technique for bioheat transfer simulations. Our long-term goal is to develop a planning tool for cryosurgery that takes a 3D reconstruction of a target region, and suggests the best cryoprobe layout. Toward that goal, a planning algorithm, termed "force-field analogy," has been recently presented, based on a sequence of bioheat transfer simulations, which are by far the most computationally expensive part of the planning method. The objective in the current study is to develop a finite difference numerical scheme for bioheat transfer simulations, which reduces the overall run time of computerized planning, thereby making it clinically relevant. While the general concept of variable grid size and time intervals is not new, its application to the phase change problem of cryosurgery is the unique contribution of the current study.

Component layout plays an important role in the design and usability of many engineering products. The layout problem is also classified under the headings of packing, packaging, configuration, container stuffing, pallet loading or spatial arrangement in the literature. The problem involves the placement of components in an available space such that a set of objectives can be optimized while satisfying optional spatial or performance constraints. Whereas the technologies for circuit board and IC chip layout have advanced significantly during the past two decades and many commercial CAD tools have been available, the same is not to be said for three-dimensional mechanical layout methods and tools. While the number of components to be placed in a mechanical system is modest compared to that of a VLSI system, the increased combinatorial complexity over the two-dimensional layout problem and the geometric complexity of 3-D non-uniform components and container spaces make the mechanical layout synthesis a challenging task. Current tools available in practice to designers to aid in the general mechanical layout process mostly remain at the stages of physical or electronic models with the assistance of manual adjustment and visual feedback. The needs arising in the product layout and rapid prototyping for compact and complex products, quick turnaround time and efficient use of resources justify the development of effective layout synthesis methods for 3-D components of complex geometry. The difficulty in automating the mechanical and electro-mechanical layout process stems from 1) the modeling of the design objectives and constraints, 2) the efficient calculation of the objectives and constraints, 3) the identification of appropriate optimization search strategies. optimization search algorithm exploratory moves evaluations / simulations decision making accept, reject moves stop criteria topological connections attachment points route definition constraints non-overlap proximity alignment components geometric representation rigid body transformation design variables location orientation objectives packing density center of gravity configuration cost routing cost bracket cost performance constraints non-overlap proximity alignment constraints non-overlap proximity alignment components geometric representation rigid body transformation design variables location orientation objectives packing density center of gravity configuration cost routing cost bracket cost performance objectives packing density center of gravity configuration cost routing cost bracket cost performance optimization search algorithm exploratory moves evaluations / simulations decision making accept, reject moves stop criteria Figure 1. Major constituent parts for generic layout synthesis.