An image-based modeling framework for patient-specific computational hemodynamics

We present a modeling framework designed for patient-specific computational hemodynamics to be performed in the context of large-scale studies. The framework takes advantage of the integration of image processing, geometric analysis and mesh generation techniques, with an accent on full automation and high-level interaction. Image segmentation is performed using implicit deformable models taking advantage of a novel approach for selective initialization of vascular branches, as well as of a strategy for the segmentation of small vessels. A robust definition of centerlines provides objective geometric criteria for the automation of surface editing and mesh generation. The framework is available as part of an open-source effort, the Vascular Modeling Toolkit, a first step towards the sharing of tools and data which will be necessary for computational hemodynamics to play a role in evidence-based medicine.     

Monoamines modulate the electrically-evoked efflux of 3H-choline from slices of guinea pig nucleus basalis magnocellularis

The influence exerted by monoamines on acetylcholine release was studied in electrically stimulated slices of guinea pig nucleus basalis magnocellularis (nbM) prelabelled with ³H-choline (3H-Ch).Noradrenaline, 30 M, and clonidine, 1 M, reduced the evoked ³H-Ch efflux by about 50%, but phenylephrine, 100 M. did not; idazoxan, 0.1 M. but not prazosin, 1 M, antagonized these effects. pointing to the involvement of alpha₂ receptors. Apomorphine, 1 or 30 M. reduced ³H-Ch efflux from nbM slices as well. The effect was shared by quinpirole, 1 or 10 M, but not by 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benz-azepine (SKF 38393). 10 M, and was antagonized by sulpiride, 1 M, but not by R-(+)-8-chloro-2,3,4,5-tetra-hydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol (SCH 23390). 1 M, suggesting the involvement of the D₂ receptor subtype.5-hydroxytryptamine (5-HT) 0.3–30 M, and alphamethyl-5-HT, 10 M, significantly increased ³H-Ch efflux from nbM slices; the 5-HT₂ antagonist ritanserin, 1 M. prevented this response. 2-methyl-5-HT, 1–30 M, inhibited the evoked ³H-Ch efflux and its effect was prevented by the 5-HT₃ antagonist 1H,3,5H-tropan-3-yl-3,5-dichlorobenzoate (MDL 72222). 1 M.These findings indicate that i) catecholamines inhibit nbM neurons through alpha₂ and D₂ receptors and that ii) a complex serotonergic modulation of cholinergic function exists in the nbM, involving the activation of various receptor subtypes. which can mediate opposite responses. Correspondence to: A. Siniscalchi at the above address     

A comparison of skinfold anthropometry and dual-energy X-ray absorptiometry for the evaluation of body fat in cirrhotic patients

BACKGROUND AND AIMS: Skinfold anthropometry has been used to evaluate the nutritional status in cirrhosis. Such estimates are based on the calculations which derive from healthy subjects and may not apply to cirrhotic patients. We aimed to calculate the limits of agreement between Skinfold anthropometry (SA) and dual-energy X-ray absorptiometry (DXA) in estimating body fat in cirrhotics. METHODS: Forty cirrhotic patients were studied by both methods. The limits of agreement were estimated by the Bland and Altman method. RESULTS: Percentage body fat was similar when measured by DXA and SA (29.6 +/- 9.2 vs 28.9 +/- 7.5 %). Body fat mass was also similar (20.3 +/- 8.4 vs 20.3 +/- 7.7 kg). The limits of agreement between DXA and SA measurements were -7.04 (95%CI: -9.55 to -5.2) +8.56 (95%CI: +10.7 to +6.4.) in the assessment of percentage body fat and -5.32 (95%CI: -6.77 to -3.87) +5.24 (95%CI: +3.79 to +6.69) in the assessment of fat mass. CONCLUSION: Percentage body fat can be evaluated by SA or DXA with a difference of less then 5% in the majority of cirrhotic patients without overt fluid retention. This result is important when considering the large applicability of SA.     

Probing the binding of indolactam-V to protein kinase C through site-directed mutagenesis and computational docking simulations.

Protein kinase C (PKC) comprises a family of ubiquitous enzymes transducing signals by the lipophilic second messenger sn-1, 2-diacylglycerol (DAG). Teleocidin and its structurally simpler congener indolactam-V (ILV) bind to PKC with high affinity. In this paper, we report our computational docking studies on ILV binding to PKC using an automatic docking computer program, MCDOCK. In addition, we used site-directed mutagenesis to assess the quantitative contribution of crucial residues around the binding site of PKC to the binding affinity of ILV to PKC. On the basis of the docking studies, ILV binds to PKC in its cis-twist conformation and forms a number of optimal hydrogen bond interactions. In addition, the hydrophobic groups in ILV form "specific" hydrophobic interactions with side chains of a number of conserved hydrophobic residues in PKC. The predicted binding mode for ILV is entirely consistent with known structure-activity relationships and with our mutational analysis. Our mutational analysis establishes the quantitative contributions of a number of conserved residues to the binding of PKC to ILV. Taken together, our computational docking simulations and analysis by site-directed mutagenesis provide a clear understanding of the interaction between ILV and PKC and the structural basis for design of novel, high-affinity, and isozyme-selective PKC ligands.     

Physician integration into mass gathering medical care. The United States Air Show

INTRODUCTION: Limited information exists concerning physician staffing at mass gathering events. METHODS: A retrospective review of the preparation, planning, and provision of medical care for the United States Air Show was performed. Patient encounters from the air show for the years 1981-1991 also were evaluated. RESULTS: The frequency rate of overall encounters was 8.45 patients/10,000 spectators and hospital transport rate was 0.6/10,000 spectators. The majority of complaints were related to heat or minor injuries. During this period, emergency physicians played a vital role in both medical planning and on-site staffing. Emergency medicine residents also participated. A small patient population received direct benefit from on-site physician intervention. CONCLUSION: The on-site emergency physician is of benefit in event preplanning and reducing the burden on the EMS system during mass gathering events.     

Plasmodium vivax CS peptides display conformational preferences for folded forms in solution

Abstract: Spectroscopic techniques have been used to study the conformations of several synthetic peptides with sequences corresponding to the repeat regions of the circumsporozoite proteins of Plasmodium vivax, variants vk‐210 and vk‐247. As has previously been shown for P. falciparum, turn‐like folded conformations are observed, in rapid dynamic equilibrium with extended‐chain forms. These results are consistent with the known similarity of the structural, biosynthetic and immunological properties of the circumsporozoite proteins of different plasmodial species. Additionally, the observation of folded conformers provides a rationale for the effectiveness of these peptides as immunogens and potential vaccines.