Can tissue drug concentrations be monitored by microdialysis during or after isolated limb perfusion for melanoma treatment?

Isolated limb perfusion (ILP) with melphalan is used to treat recurrent melanoma. This study aimed to develop a microdialysis technique for melphalan tissue concentration measurement during ILP. The effects of melphalan concentration (50-600 mu g/ml), microdialysis flow rate (0.55-17.5 mu l/min), probe length (5-50 mm) and temperature (25-41.5 degrees C) on in vitro recovery were studied. In addition, in vivo recovery was measured in rat hindlimbs perfused with melphalan using 50 mm microdialysis probes implanted subcutaneously and into muscle. Both dialysate and tissue sample melphalan concentrations were determined by high performance liquid chromatography. The in vitro recovery of melphalan was not affected by melphalan concentration or temperature, but increased with probe length and decreased with flow rate. The melphalan concentrations in subcutaneous and muscle dialysates were not significantly different. A linear relationship was found between tissue dialysate concentrations and actual tissue concentrations of melphalan (r(2) = 0.97). Microdialysis is a potential method for tissue drug monitoring which may assist in the efficacious use of cytotoxics in human ILP. (C) 2000 Lippincott Williams & Wilkins.

Glucocorticoid receptors in human preadipocytes: regional and gender differences

Glucocorticoid excess causes visceral obesity and its accompanying insulin resistance, dyslipidemia and hypertension. Glucocorticoids enhance preadipocyte (PA) differentiation and increase their aromatase activity (oestrogen production) and there is regional variability in these PA processes. Therefore, we studied human PAs for the presence of, and any regional or gender differences in, glucocorticoid receptors (GRs). Confluent subcultured human subcutaneous (Sc) and visceral (Vis) PAs from both genders contained GRs as assessed by GR gene expression and specific glucocorticoid (dexamethasone) binding. The dissociation constant was similar to that of other human cells and there was no difference between Sc and Vis sites or between males and females. There was significantly less GR mRNA in Vis PAs compared with Sc PAs in females (P=0.008) but not in males. There was less glucocorticoid binding in Vis compared with Sc PAs in females, measured by maximal binding capacity (P=0.035) or single saturating dose glucocorticoid binding (Bssd) (P=0.019). There was no regional difference in specific glucocorticoid binding in males. There was a gender difference with fewer GRs in Vis PAs in females compared with males measured by Bssd (P=0.006). In summary, GRs are present in human PAs. There is a lower GR density in Vis compared with Sc PAs in females, and females have fewer GRs in Vis PAs compared with males. These differences are likely to affect regional aromatase activity and to contribute to the smaller visceral fat mass in females compared with males.

Hybrid modelling of coupled pore fluid-solid deformation problems

A hybrid formulation for coupled pore fluid-solid deformation problems is proposed. The scheme is a hybrid in the sense that we use a vertex centered finite volume formulation for the analysis of the pore fluid and a particle method for the solid in our model. The pore fluid formally occupies the same space as the solid particles. The size of the particles is not necessarily equal to the physical size of materials. A finite volume mesh for the pore fluid flow is generated by Delaunay triangulation. Each triangle possesses an initial porosity. Changes of the porosity are specified by the translations of the mass centers of particles. Net pore pressure gradients are applied to the particle centers and are considered in the particle momentum balance. The potential of our model is illustrated by means of a simulation of coupled fracture and fluid flow developed in porous rock under biaxial compression condition.

A numerical study of flexural buckling of foliated rock slopes

The occurrence of foliated rock masses is common in mining environment. Methods employing continuum approximation in describing the deformation of such rock masses possess a clear advantage over methods where each rock layer and each inter-layer interface (joint) is explicitly modelled. In devising such a continuum model it is imperative that moment (couple) stresses and internal rotations associated with the bending of the rock layers be properly incorporated in the model formulation. Such an approach will lead to a Cosserat-type theory. In the present model, the behaviour of the intact rock layer is assumed to be linearly elastic and the joints are assumed to be elastic-perfectly plastic. Condition of slip at the interfaces are determined by a Mohr-Coulomb criterion with tension cut off at zero normal stress. The theory is valid for large deformations. The model is incorporated into the finite element program AFENA and validated against an analytical solution of elementary buckling problems of a layered medium under gravity loading. A design chart suitable for assessing the stability of slopes in foliated rock masses against flexural buckling failure has been developed. The design chart is easy to use and provides a quick estimate of critical loading factors for slopes in foliated rock masses. It is shown that the model based on Euler's buckling theory as proposed by Cavers (Rock Mechanics and Rock Engineering 1981; 14:87-104) substantially overestimates the critical heights for a vertical slope and underestimates the same for sub-vertical slopes. Copyright (C) 2001 John Wiley & Sons, Ltd.

Residues of zeta-cypermethrin in bovine tissues and milk following pour-on and spray application

The depletion of zeta-cypermethrin residues in bovine tissues and milk was studied. Beef cattle were treated three times at 3-week intervals with 1 ml 10 kg(-1) body weight of a 25 g litre(-1) or 50 g litre(-1) pour-on formulation (2.5 and 5.0 mg zeta-cypermethrin kg(-1) body weight) or 100 mg kg(-1) spray to simulate a likely worst-case treatment regime. Friesian and Jersey dairy cows were treated once with 2.5 mg zeta-cypermethrin kg(-1) in a pour-on formulation. Muscle, liver and kidney residue concentrations were generally less than the limit of detection (LOD = 0.01 mg kg(-1)). Residues in renal-fat and back-fat samples from animals treated with 2.5 mg kg(-1) all exceeded the limit of quantitation (LOQ = 0.05 mg kg(-1)), peaking at 10 days after treatment. Only two of five kidney fat samples were above the LOQ after 34 days, but none of the back-fat samples exceeded the LOQ at 28 days after treatment. Following spray treatments, fat residues were detectable in some animals but were below the LOQ at all sampling intervals. Zeta-cypermethrin was quantifiable (LOQ = 0.01 mg kg(-1)) in only one whole-milk sample from the Friesian cows (0.015 mg kg(-1), 2 days after treatment). In whole milk from Jersey cows, the mean concentration of zeta-cypermethrin peaked 1 day after treatment, at 0.015 mg kg(-1), and the highest individual sample concentration was 0.025 mg kg(-1) at 3 days after treatment. Residues in milk were not quantifiable beginning 4 days after treatment. The mean concentrations of zeta-cypermethrin in milk fat from Friesian and Jersey cows peaked two days after treatment at 0.197 mg kg(-1) and 0.377 mg kg(-1), respectively, and the highest individual sample concentrations were 2 days after treatment at 0.47 mg kg(-1) and 0.98 mg kg(-1), respectively. (C) 2001 Society of Chemical Industry.

A method for the design of MRI radiofrequency coils based on triangular and pulse basis functions

This paper presents a numerical technique for the design of an RF coil for asymmetric magnetic resonance imaging (MRI) systems. The formulation is based on an inverse approach where the cylindrical surface currents are expressed in terms of a combination of sub-domain basis functions: triangular and pulse functions. With the homogeneous transverse magnetic field specified in a spherical region, a functional method is applied to obtain the unknown current coefficients. The current distribution is then transformed to a conductor pattern by use of a stream function technique. Preliminary MR images acquired using a prototype RF coil are presented and validate the design method. (C) 2002 Elsevier Science B.V. All rights reserved.

Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: The health ABC study

Background. A decline in muscle mass and muscle strength characterizes normal aging. As clinical and animal studies show it relationship between higher cytokine levels and low muscle mass, the aim of this study was to investigate whether markers, of inflammation are associated with muscle mass and strength in well-functioning elderly persons. Methods. We Used baseline data (1997-1998) of the Health, Aging, and Body Composition (Health ABC) Study on 3075 black and white men and women aged 70-79 years. Midthigh muscle cross-sectional area (computed tomography), appendicular muscle mass (dual-energy x-ray ab absorptiometry). isokinetic knee extensor strength (KinCom). and isometric inip strength were measured. plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were assessed by enzyme-linked immunosorbent assay (ELISA). Results. Higher cytokine levels were generally associated with lower muscle mass and lower muscle strength. The most consistent relationship across the gender and race groups was observed for IL-6 and grip strength: per SD increase in IL-6, grip strength was 1.1 to 2.4 kg lower (p < .05) after adjustment for age, clinic Site. health status, medications, physical activity. smoking. height. and body fat. Ail overall measure of elevated cytokine level was created by combining the levels of IL-6 and TNF-alpha. With the exception of white men, elderly persons having high levels of IL-6 (> 1.80 pg/ml) as well as high levels of TNF-alpha (> 3.20 pg/ml) had a smaller muscle area, less appendicular mass. a lower knee extensor strength. and a lower grip strength compared to those with low levels of both cytokines. Conclusions. Higher plasma concentrations of IL-6 and TNF-alpha are associated with lower muscle mass and lower muscle strength in well-functioning older men and women. Higher cytokine levels. as often observed in healthy older persons. may contribute to the loss Of muscle mass and strength that accompanies aging.

A director theory for visco-elastic folding instabilities in multilayered rock

A model for finely layered visco-elastic rock proposed by us in previous papers is revisited and generalized to include couple stresses. We begin with an outline of the governing equations for the standard continuum case and apply a computational simulation scheme suitable for problems involving very large deformations. We then consider buckling instabilities in a finite, rectangular domain. Embedded within this domain, parallel to the longer dimension we consider a stiff, layered beam under compression. We analyse folding up to 40% shortening. The standard continuum solution becomes unstable for extreme values of the shear/normal viscosity ratio. The instability is a consequence of the neglect of the bending stiffness/viscosity in the standard continuum model. We suggest considering these effects within the framework of a couple stress theory. Couple stress theories involve second order spatial derivatives of the velocities/displacements in the virtual work principle. To avoid C-1 continuity in the finite element formulation we introduce the spin of the cross sections of the individual layers as an independent variable and enforce equality to the spin of the unit normal vector to the layers (-the director of the layer system-) by means of a penalty method. We illustrate the convergence of the penalty method by means of numerical solutions of simple shears of an infinite layer for increasing values of the penalty parameter. For the shear problem we present solutions assuming that the internal layering is oriented orthogonal to the surfaces of the shear layer initially. For high values of the ratio of the normal-to the shear viscosity the deformation concentrates in thin bands around to the layer surfaces. The effect of couple stresses on the evolution of folds in layered structures is also investigated. (C) 2002 Elsevier Science Ltd. All rights reserved.

Incorporation of bovine dry blood plasma into biscuit flour for the production of pasta

Spray-dried blood plasma (DBP) (10.9 g/100 g [w/w] nitrogen) was added to medium-protein biscuit flour (1.4 g/100 g N) during pasta manufacture. High-protein durum semolina (2.0 g/100 g N) Was used to produce the control pasta. Sensory data indicated that the addition of DBP produced pasta with significantly better colour intensity and acceptability. aroma intensity, flaN our intensity. textural strength, texture acceptability, aftertaste intensity, aftertaste acceptability. and overall acceptability The DBP/biscuit flour formulation that gave the optimum balance between pasta protein content and organoleptic acceptability contained 2.2 g/100 g DBP. A higher content of DBP resulted in increased protein levels, but these pasta formulations, ere less acceptable organoleptically. (C) 2002 Swiss Society of Food Science and Technology. Published by Elsevier Science Ltd. All rights reserved.

Longevity and stability of cratonic lithosphere: Insights from numerical simulations of coupled mantle convection and continental tectonics

[1] The physical conditions required to provide for the tectonic stability of cratonic crust and for the relative longevity of deep cratonic lithosphere within a dynamic, convecting mantle are explored through a suite of numerical simulations. The simulations allow chemically distinct continents to reside within the upper thermal boundary layer of a thermally convecting mantle layer. A rheologic formulation, which models both brittle and ductile behavior, is incorporated to allow for plate-like behavior and the associated subduction of oceanic lithosphere. Several mechanisms that may stabilize cratons are considered. The two most often invoked mechanisms, chemical buoyancy and/or high viscosity of cratonic root material, are found to be relatively ineffective if cratons come into contact with subduction zones. High root viscosity can provide for stability and longevity but only within a thick root limit in which the thickness of chemically distinct, high-viscosity cratonic lithosphere exceeds the thickness of old oceanic lithosphere by at least a factor of 2. This end-member implies a very thick mechanical lithosphere for cratons. A high brittle yield stress for cratonic lithosphere as a whole, relative to oceanic lithosphere, is found to be an effective and robust means for providing stability and lithospheric longevity. This mode does not require exceedingly deep strength within cratons. A high yield stress for only the crustal or mantle component of the cratonic lithosphere is found to be less effective as detachment zones can then form at the crust-mantle interface which decreases the longevity potential of cratonic roots. The degree of yield stress variations between cratonic and oceanic lithosphere required for stability and longevity can be decreased if cratons are bordered by continental lithosphere that has a relatively low yield stress, i.e., mobile belts. Simulations that combine all the mechanisms can lead to crustal stability and deep root longevity for model cratons over several mantle overturn times, but the dominant stabilizing factor remains a relatively high brittle yield stress for cratonic lithosphere.

Anisotropic convection model for the earth's mantle

The paper presents a theory for modeling flow in anisotropic, viscous rock. This theory has originally been developed for the simulation of large deformation processes including the folding and kinking of multi-layered visco-elastic rock (Muhlhaus et al. [1,2]). The orientation of slip planes in the context of crystallographic slip is determined by the normal vector - the director - of these surfaces. The model is applied to simulate anisotropic mantle convection. We compare the evolution of flow patterns, Nusselt number and director orientations for isotropic and anisotropic rheologies. In the simulations we utilize two different finite element methodologies: The Lagrangian Integration Point Method Moresi et al [8] and an Eulerian formulation, which we implemented into the finite element based pde solver Fastflo (www.cmis.csiro.au/Fastflo/). The reason for utilizing two different finite element codes was firstly to study the influence of an anisotropic power law rheology which currently is not implemented into the Lagrangian Integration point scheme [8] and secondly to study the numerical performance of Eulerian (Fastflo)- and Lagrangian integration schemes [8]. It turned out that whereas in the Lagrangian method the Nusselt number vs time plot reached only a quasi steady state where the Nusselt number oscillates around a steady state value the Eulerian scheme reaches exact steady states and produces a high degree of alignment (director orientation locally orthogonal to velocity vector almost everywhere in the computational domain). In the simulations emergent anisotropy was strongest in terms of modulus contrast in the up and down-welling plumes. Mechanisms for anisotropic material behavior in the mantle dynamics context are discussed by Christensen [3]. The dominant mineral phases in the mantle generally do not exhibit strong elastic anisotropy but they still may be oriented by the convective flow. Thus viscous anisotropy (the main focus of this paper) may or may not correlate with elastic or seismic anisotropy.

Most lymphoid organ dendritic cell types are phenotypically and functionally immature

Dendritic cells (DCs) have been thought to follow a life history, typified by Langerhans cells (LCs), with 2 major developmental stages: an immature stage that captures antigens in the periphery and a mature stage that presents those antigens in the lymphoid organs. However, a systematic assessment of the maturity of lymphoid organ DCs has been lacking. We have analyzed the maturity of the DC types found in the steady state in the spleen, lymph nodes (LNs), and thymus. The DCs that migrate into the iliac, mesenteric, mediastinal, or subcutaneous LNs from peripheral tissues were mature and therefore could not process and present newly encountered antigens. However, all the other DC types were phenotypically and functionally immature: they expressed low levels of surface major histocompatibility complex class 11 (MHC 11) and CD86, accumulated MHC 11 in their endosomes, and could present newly encountered antigens. These immature DCs could 1346 induced to mature by culture in vitro or by Inoculation of inflammatory stimuli in vivo. Therefore, the lymphoid organs contain a large cohort of immature DCs, most likely for the maintenance of peripheral tolerance, which can respond to infections reaching those organs and mature in situ. (C) 2003 by The American Society of Hematology.

Investment prioritization based on broadscale spatial budgeting to meet downstream targets for suspended sediment loads

On the basis of a spatially distributed sediment budget across a large basin, costs of achieving certain sediment reduction targets in rivers were estimated. A range of investment prioritization scenarios were tested to identify the most cost-effective strategy to control suspended sediment loads. The scenarios were based on successively introducing more information from the sediment budget. The relationship between spatial heterogeneity of contributing sediment sources on cost effectiveness of prioritization was investigated. Cost effectiveness was shown to increase with sequential introduction of sediment budget terms. The solution which most decreased cost was achieved by including spatial information linking sediment sources to the downstream target location. This solution produced cost curves similar to those derived using a genetic algorithm formulation. Appropriate investment prioritization can offer large cost savings because the magnitude of the costs can vary by several times depending on what type of erosion source or sediment delivery mechanism is targeted. Target settings which only consider the erosion source rates can potentially result in spending more money than random management intervention for achieving downstream targets. Coherent spatial patterns of contributing sediment emerge from the budget model and its many inputs. The heterogeneity in these patterns can be summarized in a succinct form. This summary was shown to be consistent with the cost difference between local and regional prioritization for three of four test catchments. To explain the effect for the fourth catchment, the detail of the individual sediment sources needed to be taken into account.

Evaluation of elastic modulus and hardness of thin films by nanoindentation

Simple equations are proposed for determining elastic modulus and hardness properties of thin films on substrates from nanoindentation experiments. An empirical formulation relates the modulus E and hardness H of the film/substrate bilayer to corresponding material properties of the constituent materials via a power-law relation. Geometrical dependence of E and H is wholly contained in the power-law exponents, expressed here as sigmoidal functions of indenter penetration relative to film thickness. The formulation may be inverted to enable deconvolution of film properties from data on the film/substrate bilayers. Berkovich nanoindentation data for dense oxide and nitride films on silicon substrates are used to validate the equations and to demonstrate the film property deconvolution. Additional data for less dense nitride films are used to illustrate the extent to which film properties may depend on the method of fabrication.

Hormone replacement therapy and breast cancer: estimate of risk: Education debate

The risk of breast cancer arises from a combination of genetic susceptibility and environmental factors. Recent studies show that type and duration of use of hormone replacement therapy affect a women's risk of developing breast cancer.1-7 The women's health initiative trial was stopped early because of excess adverse cardiovascular events and invasive breast cancer with oestrogen and progestogen.6 The publicity increased public awareness of the risks of hormone replacement therapy, and this was heightened by the publication of the million women study.2 However, the recently published oestrogen only arm of the women's health initiative trial suggests that this formulation may reduce the risk of breast cancer.8 To help make sense of the often confusing information,9 women and clinicians need individual rather than population risk data. We have produced estimates that can be used to calculate individual risk for women living up to the age of 79 and suggest the risk