bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous1H PFG‐NMR and confocal microscopy of monolayer cell cultures: Effects of apoptosis and necrosis on water diffusion and compartmentalization
Authors: Minard Kevin R. , Holtom Gary R. , Kathmann Loel E. , Majors Paul D. , Thrall Brian D. , Wind Robert A.
Published: August 2004

We induced apoptosis and necrosis in monolayer cultures of Chinese hamster ovary cells using okadaic acid and hydrogen peroxide (H2O2), respectively, and examined the effect on water diffusion and compartmentalization using pulsed‐field‐gradient (PFG)1H‐NMR and simultaneous confocal microscopy. In PFG experiments characterized by a fixed diffusion time (<4.7 ms) and variableb‐values (0–27000 s/mm2),1H‐NMR data collected with untreated cells exhibited multiexponential behavior. Analysis with a slow‐exchange model revealed two distinct cellular water compartments with different apparent diffusion coefficients (ADCs; 0.56, 0.06 × 10−3mm2/s) and volume fractions (0.96 and 0.04). During the first 12 hr of necrosis or apoptosis, the amount of water in the smallest compartment increased twofold before significant changes in cell density or plasma membrane integrity occurred. Over the same period, water content in the largest compartment decreased by a factor of >2 in apoptotic cells, in accordance with observed cell shrinkage, and changed little in necrotic counterparts, where only slight swelling was evident. These results indicate that PFG1H‐NMR serves as a sensitive indicator of early cell death in monolayer cultures, and can be used to distinguish apoptosis from necrosis. Measurements of restricted diffusion and water exchange are presented to elucidate the compartment origins and justify the model assumptions. Magn Reson Med 52:495–505, 2004. © 2004 Wiley‐Liss, Inc.
High‐pass‐low‐pass (HP‐LP) reconstruction of CINE phase‐contrast MRI
Authors: Kerwin W.S.
Published: August 2004

A new interpretation of CINE phase‐contrast (PC) MRI is presented in which flowing blood is shown to induce separate high‐ and low‐temporal‐frequency components in the resulting image sequence. The flow velocities can then be extracted from the ratio of these two components, independently of any unknown phase offset. This interpretation leads to new insights into improving temporal resolution, eliminating noise, and reducing acquisition time in PC imaging. A specific example explored in this article uses a technique related to unaliasing by Fourier‐encoding the overlaps using the temporal dimension (UNFOLD) to acquire PC velocity measurements at 54–68 time points in the cardiac cycle, all within a single breath‐hold of <20 s. In experimental studies, these techniques were shown to yield improved signal‐to‐noise ratios (SNRs) in a flow phantom and cerebrospinal fluid (CSF) flow studies, and to resolve the formation of a flow vortex during left ventricular (LV) filling in humans. Magn Reson Med 52:566–574, 2004. © 2004 Wiley‐Liss, Inc.
Pulsatile motion effects on 3D magnetic resonance angiography: Implications for evaluating carotid artery stenoses
Authors: Al‐Kwifi Osama , Kim Jae K. , Stainsby Jeff , Huang Yuexi , Sussman Marshall S. , Farb Richard I. , Wright Graham A.
Published: August 2004

In‐plane carotid artery motion during a 3D MR angiography (MRA) scan can significantly degrade the resulting image resolution. This study characterizes the effect of cardiac pulsatility on 3D contrast‐enhanced (CE) MRA with elliptical centric acquisitions using a point‐spread function (PSF) analysis. Internal carotid artery (ICA) motion was collected from volunteers and patients using both MR and ultrasound (US) scans. After measuring the carotid artery motion displacement, a simulation was performed which calculated the blurring effects for three different protocols: nongated and two different cardiac gating schemes. The motion sensitivity of each protocol was evaluated for different spatial resolutions. The selection of optimal imaging parameters for a given scan time was investigated. The final results showed that cardiac‐gated acquisitions only over a limited region of k‐space high spatial frequencies are more time‐efficient than cardiac gating for the entire k‐space, as it allows for higher resolutions to be achieved and for capturing the arterial phase with low spatial frequencies. Selecting the optimal gating parameters depends directly on the motion characteristics of each individual. Our initial clinical experience is presented, and the need for a real‐time tool that characterizes motion behavior for each individual as a prescan protocol is discussed. Magn Reson Med 52:605–611, 2004. © 2004 Wiley‐Liss, Inc.
Flow‐gated phase‐contrast MRI using radial acquisitions
Authors: Thompson Richard B. , McVeigh Elliot R.
Published: August 2004

Phase‐contrast (PC) MRI is a noninvasive method for imaging blood and tissue velocity. PC experiments are typically segmented into many cardiac cycles in order to obtain sufficient spatial and temporal resolution, and thus require a gating signal to properly combine the data from multiple cardiac cycles. Although the surface electrode ECG is the gating waveform of choice for cardiovascular MRI, alternative gating methods are required for fetal cardiac imaging (due to the unavailability of fetal ECG signals) and for cases of ECG contamination via the strong magnetic fields within the MR scanner. This study demonstrates the feasibility of using imaging data from flow‐encoded MRI experiments to derive times for cardiac gating. An undersampled radial k‐space acquisition method is used to measure an image‐derived flow‐gating waveform in real‐time, from which the gating times are derived. These gating times are used to reconstruct a conventional gated‐segmented image series by combining the real‐time data from multiple heartbeats. Flow‐gated PC experiments were performed on five normal volunteers with slice prescriptions in four anatomic regions. The standard deviation (SD) of the difference between the flow‐gating and ECG gating times ranged from 5 ms to 12 ms. Magn Reson Med 52:598–604, 2004. Published 2004 Wiley‐Liss, Inc.
In vivo measurement and imaging of tumor oxygenation using coembedded paramagnetic particulates
Authors: Ilangovan Govindasamy , Bratasz Anna , Li Haiquan , Schmalbrock Petra , Zweier Jay L. , Kuppusamy Periannan
Published: August 2004

Tumor tissue oxygenation is an important parameter that is positively correlated to the chemo‐ or radiation treatment outcome of certain tumors. Hence, methods to accurately and noninvasively determine the concentration of oxygen (pO2) in tumors will be valuable. In this study, electron paramagnetic resonance (EPR) spectroscopy, utilizing microcrystalline particulates of lithium phthalocyanine (LiPc), was used to perform repeated measurements of pO2 as a function of tumor growth. We permanently embedded the particulates in the tumor by coimplanting them with RIF‐1 tumor cells during inoculation in mice. This procedure enabled repeated measurements of oxygen concentration in the tumor to be obtained for >2 weeks during its growth phase. The particulates were stable and nontoxic to the tumor cells. Both an in vitro clonogenic assay and an in vivo tumor growth rate examination in C3H mice showed no apparent effect on cell proliferation or tumor growth rate. The measurements indicated that the pO2 of the tumor decreased exponentially with tumor growth and reached hypoxic levels (∼4 mmHg) within 4 days after inoculation of the tumor cells. Spatial EPR imaging revealed a nonuniform distribution of the embedded particulates, which were localized mainly in the middle of the tumor volume. Oxygen mapping of the tumor, obtained by spectroscopic EPR imaging, showed significant variation of pO2 within the tumor. In summary, EPR spectroscopy and imaging with an embedded oximetry probe enabled accurate and repeated measurements of pO2 to be obtained in growing tumors under nonperturbing conditions. Magn Reson Med 52:650–657, 2004. © 2004 Wiley‐Liss, Inc.
Persistent contrast enhancement by sterically stabilized paramagnetic liposomes in murine melanoma
Authors: Bertini Ivano , Bianchini Francesca , Calorini Lido , Colagrande Stefano , Fragai Marco , Franchi Alessandro , Gallo Oreste , Gavazzi Cinzia , Luchinat Claudio
Published: August 2004

In the present research, we investigated the use of paramagnetic liposomes as contrast agents (CAs) for the detection of solid tumors. The liposomes were sterically stabilized by a polyethylene glycol (PEG) coating, and their size was constrained to ∼100 nm. Dimyristoyl‐sn‐glycero‐3‐phosphoethanolamine‐N‐diethylene‐triaminepentaacetate (DMPE‐DTPA) was used as the gadolinium‐carrying fatty acid chain. The relaxation properties were characterized through nuclear magnetic relaxation dispersion (NMRD) measurements, and analyzed with the use of theories and computer programs that are adequate for slowly rotating systems. Their relaxivity at 1.5 T was found to be acceptable for in vivo use. We then tested the liposomes against B16‐F10 murine melanomas using standard T1‐weighted schemes at 1.5 T, and concentrations corresponding to 0.03 mmol/kg of gadolinium (i.e., three to six times lower than the concentration of the small gadolinium complexes in clinical use). The blood half‐life was found to be 120 ± 20 min. The experiments show a good contrast enhancement in the tumor (33% ± 22%) 2 hr after administration, a further increase (43 ± 27%) 20 hr after administration, and a decrease (25% ± 14%) 54 hr after administration. High persistence of the CA was also observed in the liver and intestine, as expected in a hepatobiliar excretion pathway. Magn Reson Med 52:669–672, 2004. © 2004 Wiley‐Liss, Inc.
Three‐dimensional diffusion tensor microscopy of fixed mouse hearts
Authors: Jiang Yi , Pandya Kumar , Smithies Oliver , Hsu Edward W.
Published: August 2004

The relative utility of 3D, microscopic resolution assessments of fixed mouse myocardial structure via diffusion tensor imaging is demonstrated in this study. Isotropic 100‐μm resolution fiber orientation mapping within 5.5° accuracy was achieved in 9.1 hr scan time. Preliminary characterization of the diffusion tensor primary eigenvector reveals a smooth and largely linear angular rotation across the left ventricular wall. Moreover, a higher level of structural hierarchy is evident from the organized secondary and tertiary eigenvector fields. These findings are consistent with the known myocardial fiber and laminar structures reported in the literature and suggest an essential role of diffusion tensor microscopy in developing quantitative atlases for studying the structure–function relationships of mouse hearts. Magn Reson Med 52:453–460, 2004. © 2004 Wiley‐Liss, Inc.
Simultaneous magnetoencephalography and SQUID detected nuclear MR in microtesla magnetic fields
Authors: Volegov Petr , Matlachov Andrei N. , Espy Michelle A. , George John S. , Kraus Robert H.
Published: August 2004

A system that simultaneously measures magnetoencephalography (MEG) and nuclear magnetic resonance (NMR) signals from the human brain was designed and fabricated. A superconducting quantum interference device (SQUID) sensor coupled to a gradiometer pickup coil was used to measure the NMR and MEG signals. 1H NMR spectra with typical Larmor frequencies from 100–1000 Hz acquired simultaneously with the evoked MEG response from a stimulus to the median nerve are reported. The single SQUID gradiometer was placed approximately over the somatosensory cortex of a human subject to noninvasively record the signals. These measurements demonstrate, for the first time, the feasibility of simultaneous MRI and MEG. NMR in the microtesla regime provides narrow linewidths and the potential for high spatial resolution imaging, while SQUID sensors enable direct measurement of neuronal activity with high temporal resolution via MEG. Magn Reson Med 52:467–470, 2004. © 2004 Wiley‐Liss, Inc.
Perturbation method for magnetic field calculations of nonconductive objects
Authors: Jenkinson Mark , Wilson James L. , Jezzard Peter
Published: August 2004

Inhomogeneous magnetic fields produce artifacts in MR images including signal dropout and spatial distortion. A novel perturbative method for calculating the magnetic field to first order (error is second order) within and around nonconducting objects is presented. The perturbation parameter is the susceptibility difference between the object and its surroundings (for example, ∼10 ppm in the case of brain tissue and air). This method is advantageous as it is sufficiently accurate for most purposes, can be implemented as a simple convolution with a voxel‐based object model, and is linear. Furthermore, the method is simple to use and can quickly calculate the field for any orientation of an object using a set of precalculated basis images. Magn Reson Med 52:471–477, 2004. © 2004 Wiley‐Liss, Inc.
Effects of inductive coupling on parallel MR image reconstructions
Authors: Ohliger Michael A. , Ledden Patrick , McKenzie Charles A. , Sodickson Daniel K.
Published: August 2004

Theoretical arguments and experimental results are presented that characterize the impact of inductive coupling on the performance of parallel MRI reconstructions. A simple model of MR signal and noise reception suggests that the intrinsic amount of spatial information available from a given coil array is unchanged in the presence of inductive coupling, as long as the sample remains the dominant source of noise for the coupled array. Any loss of distinctness in the measured coil sensitivities is compensated by information stored in the measured noise correlations. Adjustments to the theory are described to account for preamplifier noise contributions. Results are presented from an experimental system in which preamplifier input impedances are systematically adjusted in order to vary the level of coupling between array elements. Parallel image reconstructions using an array with four different levels of coupling and an acceleration factor up to six show average SNR changes of −7.6% to +7.5%. The modest changes in overall SNR are accompanied by similarly small changes in g‐factor. These initial results suggest that moderate amounts of inductive coupling should not have a prohibitive effect on the use of a given coil array for parallel MRI. Magn Reson Med 52:628–639, 2004. © 2004 Wiley‐Liss, Inc.
Visualization of β‐amyloid plaques in a transgenic mouse model of Alzheimer's disease using MR microscopy without contrast reagents
Authors: Lee Sang‐Pil , Falangola Maria F. , Nixon Ralph A. , Duff Karen , Helpern Joseph A.
Published: August 2004

The visualization of β‐amyloid plaque deposition in brain, a key feature of Alzheimer's disease (AD), is important for the evaluation of disease progression and the efficacy of therapeutic interventions. In this study, β‐amyloid plaques in the PS/APP transgenic mouse brain, a model of human AD pathology, were detected using MR microscopy without contrast reagents. β‐Amyloid plaques were clearly visible in the cortex, thalamus, and hippocampus of fixed brains of PS/APP mice. The distribution of plaques identified by MRI was in excellent agreement with those found in the immunohistological analysis of the same brain sections. It was also demonstrated that image contrast for β‐amyloid plaques was present in freshly excised nonfixed brains. Furthermore, the detection of β‐amyloid plaques was achieved with a scan time as short as 2 hr, approaching the scan time considered reasonable for in vivo imaging. Magn Reson Med 52:538–544, 2004. © 2004 Wiley‐Liss, Inc.
Susceptibility weighted imaging (SWI)
Authors: Haacke E. Mark , Xu Yingbiao , Cheng Yu‐Chung N. , Reichenbach Jürgen R.
Published: August 2004

Susceptibility differences between tissues can be utilized as a new type of contrast in MRI that is different from spin density, T1‐, or T2‐weighted imaging. Signals from substances with different magnetic susceptibilities compared to their neighboring tissue will become out of phase with these tissues at sufficiently long echo times (TEs). Thus, phase imaging offers a means of enhancing contrast in MRI. Specifically, the phase images themselves can provide excellent contrast between gray matter (GM) and white matter (WM), iron‐laden tissues, venous blood vessels, and other tissues with susceptibilities that are different from the background tissue. Also, for the first time, projection phase images are shown to demonstrate tissue (vessel) continuity. In this work, the best approach for combining magnitude and phase images is discussed. The phase images are high‐pass‐filtered and then transformed to a special phase mask that varies in amplitude between zero and unity. This mask is multiplied a few times into the original magnitude image to create enhanced contrast between tissues with different susceptibilities. For this reason, this method is referred to as susceptibility‐weighted imaging (SWI). Mathematical arguments are presented to determine the number of phase mask multiplications that should take place. Examples are given for enhancing GM/WM contrast and water/fat contrast, identifying brain iron, and visualizing veins in the brain. Magn Reson Med 52:612–618, 2004. © 2004 Wiley‐Liss, Inc.
Intracellular manganese ions provide strong T1 relaxation in rat myocardium
Authors: Nordhøy Wibeke , Anthonsen Henrik W. , Bruvold Morten , Brurok Heidi , Skarra Sissel , Krane Jostein , Jynge Per
Published: August 2004

The efficacy of manganese ions (Mn2+) as intracellular (ic) contrast agents was assessed in rat myocardium. T1 and T2 and Mn content were measured in ventricular tissue excised from isolated perfused hearts in which a 5‐min wash‐in with 0, 30, 100, 300, or 1000 μM of Mn dipyridoxyl diphosphate (MnDPDP) was followed by a 15‐min wash‐out to remove extracellular (ec) Mn2+. An inversion recovery (IR) analysis at 20 MHz revealed two T1 components: an ic and short T1‐1 (650–251 ms), and an ec and longer T1‐2 (2712–1042 ms). Intensities were about 68% and 32%, respectively. Tissue Mn content correlated particularly well with ic R1‐1. A two‐site water‐exchange analysis of T1 data documented slow water exchange with ic and ec lifetimes of 11.3 s and 7.5 s, respectively, and no differences between apparent and intrinsic relaxation parameters. Ic relaxivity induced by Mn2+ ions in ic water was as high as 56 (s mM)−1, about 8 times and 36 times higher than with Mn2+ aqua ions and MnDPDP, respectively, in vitro. This value is as high as any reported to date for any synthetic protein‐bound metal chelate. The increased rotational correlation time (τR) between proton and electron (Mn2+) spins, and maintained inner‐sphere water access, might make ic Mn2+ ions and Mn2+‐ion‐releasing contrast media surprisingly effective for T1‐weighted imaging. Magn Reson Med 52:506–514, 2004. © 2004 Wiley‐Liss, Inc.
Evaluation of internal MRI coils using ultimate intrinsic SNR
Authors: Çelik Haydar , Eryaman Yiǧitcan , Altıntaş Ayhan , Abdel‐Hafez I.A. , Atalar Ergin
Published: August 2004

The upper bounds of the signal‐to‐noise ratio (also known as the “ultimate intrinsic signal‐to‐noise ratio” (UISNR)) for internal and external coils were calculated. In the calculation, the body was modeled as a dielectric cylinder with a small coaxial cylindrical cavity in which internal coils could be placed. The calculated UISNR values can be used as reference solutions to evaluate the performance of internal MRI coils. As examples, we evaluated the performance of a loopless antenna and an endourethral coil design by comparing their ISNR with the UISNR. Magn Reson Med 52:640–649, 2004. © 2004 Wiley‐Liss, Inc.
Catheter tracking and visualization using 19F nuclear magnetic resonance
Authors: Kozerke Sebastian , Hegde Sanjeet , Schaeffter Tobias , Lamerichs Rolf , Razavi Reza , Hill Derek L.
Published: August 2004

This work presents an investigation into catheter visualization and localization using 19F nuclear magnetic resonance (NMR) in conjunction with proton imaging. For this purpose, the imaging capabilities of a standard system were extended to allow for 19F excitation and signal detection. Two modes of operation were implemented: 1) a real‐time tracking mode that provides tip tracking and automatic slice position updates interleaved with real‐time, interactive proton imaging; and 2) a non‐real‐time catheter length visualization mode in which the entire length of a catheter can be assessed. Initial phantom experiments were conducted with the use of an angiographic balloon catheter filled with the blood substitute perfluorooctylbromide (PFOB). Using limited bandwidth excitation centered at the resonances of the CF2 groups of PFOB, we found that sufficient signal could be received to facilitate tip tracking during catheter motion and length visualization for various catheter configurations. The present approach is considered a promising alternative to existing methods, which either are associated with safety concerns (if active markers are employed) or suffer from insufficient, direction‐dependent contrast (if passive visualization is used). Furthermore, our approach enables visualization of the entire length of the catheter. The proposed method provides a safe technique that, unlike electrical or optical devices, does not require modification of commercially available catheters. Magn Reson Med 52:693–697, 2004. © 2004 Wiley‐Liss, Inc.
Fat fractions and spectral T2 values in vertebral bone marrow in HIV‐ and non‐HIV‐infected men: A 1H spectroscopic imaging study
Authors: Mulkern Robert V. , Huang Jeannie , Vajapeyam Sridhar , Packard Alan B. , Oshio Koichi , Grinspoon Steven
Published: August 2004

Fat fractions and spectral T2 values of fat and water within the vertebral marrow of non‐HIV‐ and HIV‐infected men were measured with the use of a Carr‐Purcell‐Meiboom‐Gill (CPMG) line scan spectroscopic imaging sequence. The fat fraction for the HIV‐infected men (0.29 ± 0.08) was significantly lower (P < 0.05, Student's unpaired t‐test) than the fat fraction found in non‐HIV‐infected men (0.40 ± 0.12). The mean water and fat T2 values did not differ between the two groups, and did not show any systematic dependence on fat fraction over the wide range of fat fractions encountered in this study. The marrow water and fat T2 values measured with the CPMG approach were markedly longer than the spectral T2 values reported by other groups using the more common point‐resolved spectroscopy (PRESS) and stimulated‐echo acquisition mode (STEAM) acquisitions. Proton spectroscopic studies of vertebral marrow revealed differences between non‐HIV‐ and HIV‐infected men that may prove useful for studying the effects of this disease and/or antiretroviral agents on body composition. Magn Reson Med 52:552–558, 2004. © 2004 Wiley‐Liss, Inc.
Non‐linear finite element analysis of large amplitude sloshing flow in two‐dimensional tank
Authors: Cho J. R. , Lee H. W.
Published: August 2004

This paper is concerned with the accurate and stable finite element analysis of large amplitude liquid sloshing in two‐dimensional tank under the forced excitation. The sloshing flow is formulated as an initial‐boundary‐value problem based upon the fully non‐linear potential flow theory. The flow velocity field is interpolated from the velocity potential with second‐order elements according to least square method, and the free surface conditions are tracked by making use of the direct time differentiation and the predictor–corrector method. Meanwhile, the liquid mesh is adapted such that the incompressibility condition is strictly satisfied. The accuracy and stability of the numerical method introduced are verified from the comparison with the existing reference solutions. As well, the numerical results are compared with those obtained by the linear theory with respect to the liquid fill height and the excitation amplitude. Copyright © 2004 John Wiley & Sons, Ltd.
A fast algorithm for three‐dimensional electrostatics analysis: fast Fourier transform on multipoles (FFTM)
Authors: Ong E. T. , Lee K. H. , Lim K. M.
Published: August 2004

In this paper, we propose a new fast algorithm for solving large problems using the boundary element method (BEM). Like the fast multipole method (FMM), the speed‐up in the solution of the BEM arises from the rapid evaluations of the dense matrix–vector products required in iterative solution methods. This fast algorithm, which we refer to as fast Fourier transform on multipoles (FFTM), uses the fast Fourier transform (FFT) to rapidly evaluate the discrete convolutions in potential calculations via multipole expansions. It is demonstrated that FFTM is an accurate method, and is generally more accurate than FMM for a given order of multipole expansion (up to the second order). It is also shown that the algorithm has approximately linear growth in the computational complexity, implying that FFTM is as efficient as FMM. Copyright © 2004 John Wiley & Sons, Ltd.
Wind field simulation for structural engineering purposes
Authors: Rossi Riccardo , Lazzari Massimiliano , Vitaliani Renato
Published: August 2004

This paper offers a survey of the issue of wind velocity modelling and simulation; the theme is studied considering stationary multivariate stochastic process, according to the prescribed cross‐spectral density matrix. It also analyses extension to generation of vector fields and compares AR, ARMA and Shinozuka–Deodatis approaches in application to both small and real size examples. A number of ‘quality indices’ are chosen and used to assess the performance of the different numerical procedures. Wavelets are used together with standard Fourier transform in the process of checking the quality of the signals generated. Finally, the present study provides some guidelines concerning the optimal parameters to be chosen for the application of AR and ARMA procedures and a comment on the numerical efficiency of the different generation algorithms. Copyright © 2004 John Wiley & Sons, Ltd.
Shape optimization for radar cross sections by a gradient method
Authors: Bondeson A. , Yang Y. , Weinerfelt P.
Published: August 2004

A gradient method for optimization of shape and materials for radar cross section (RCS) reduction is derived from Maxwell's equations. The method uses the adjoint problem and finds the derivatives of the RCS with respect to all design parameters from a single solution of the scattering problem. The method is tested in two‐dimensional test problems to minimize the RCS in specified angular intervals at a single frequency, and finds configurations with strongly reduced RCS in a small number of iterations. In the absence of other constraints, the optimal shapes of perfectly electrically conducting (PEC) scatterers have sharp corners pointing in the directions where the RCS is minimized and shapes optimized at a single or small number of frequencies exhibit corrugations with about half the wavelength of the incident wave. The corrugations can be suppressed by means of penalty functions, and this gives only moderate increases of the RCS. After such regularization, the optimal shapes agree well with expectations from geometrical optics; they have almost flat surfaces whose normals lie outside the intervals chosen for RCS optimization, and sharp edges at locations where the surface normal points into the intervals in which the RCS is minimized. Shape optimization of PEC wing profiles aiming at both good aerodynamical properties and low RCS show give conflicting requirements on the shape. Copyright © 2004 John Wiley & Sons, Ltd.
Multidisciplinary topology optimization solved as a Nash game
Authors: Habbal Abderrahmane , Petersson Joakim , Thellner Mikael
Published: August 2004

In the present work, multidisciplinary optimization is formulated in the game theory framework. We choose a coupled heat transfer—thermoelastic system as the case study for which a topology design approach is developed. The multidisciplinary optimization problem is solved as a non‐cooperative game and we determine a Nash equilibrium. The game has two players and the parameterization of the design domain is such that the design variables describe the material density and a parameter which influences the heat flow by convection to the surrounding fluid. The first player controls the structure and the second player controls the temperature distribution in the structure. For the second player, we present mathematical proof of existence of a discrete valued optimal solution and it is concluded that no regularization of the suboptimization problem is needed. We present two numerical examples which illustrate the proposed methodology. One of the examples is also solved by weighting the objectives to a scalar valued objective function and the result is compared with the Nash game solution. Copyright © 2004 John Wiley & Sons, Ltd.
Shape functions for polygonal domains with interior nodes
Authors: Malsch Elisabeth Anna , Dasgupta Gautam
Published: August 2004

The presented formulation follows in a series of publications which outline a method for constructing test functions which satisfy essential edge conditions exactly. The method promises a complete solution, satisfying all of the requirements of a Ritz coordinate function. The influence of interior points on the domain solution is included in this construction. Similar to conformal bubble functions, the test functions are zero along the boundary and single valued only at the points they describe. Unlike the bubble function construction, the interior points can be located at any desired point in the domain. The resulting set of trial functions can satisfy the required global conditions including the exact reproduction of constant and linear fields. Copyright © 2004 John Wiley & Sons, Ltd.
Die Geschichte der Östrogene: “Etwa ein Molekül wie das Morphin”
Authors: Meyer Ulrich
Published: August 2004

Es erscheint heute selbstverständlich, dass die Funktionen des menschlichen Organismus gleichermaßen durch Nervensystem und hormonelle Regelkreise gesteuert werden, indes erfolgte die Aufklärung dieser Zusammenhänge keineswegs gleichzeitig.
Neue Selektive Estrogenrezeptor‐Modulatoren: Me‐too‐SERMs?
Authors: Holzgrabe Ulrike
Published: August 2004

Die pharmakologischen Effekte aller vorgestellten Stilben–Derivate und Analoga sind trotz großer struktureller Ähnlichkeit nicht generell verschieden, aber genügend unterschiedlich groß, um einerseits ein unterschiedliches Nebenwirkungsprofil zu zeigen und andererseits verschiedene Therapieziele zu rechtfertigen. Da zumeist in Vergleich zu den Ausgangsverbindungen wie Tamoxifen ein günstigeres Nebenwirkungsspektrum erzielt wurde, kann man die neuen Verbindungen als “me‐better” einstufen. Die Zukunft, d.h. die klinischen Studien, müssen zeigen, welches SERM für die Behandlung von Brustkrebs und welches zur Therapie der Osteoporose eingesetzt werden kann. Die SERMs werden die “Hormontherapie” nicht ersetzen, aber sie stellen eine gute Alternative für Frauen dar, bei denen die Hormonersatztherapie kontraindiziert ist oder die ihre Nebenwirkungen nicht tolerieren.
Pharmakologie der Estrogene: Komplexe Wirkmechanismen – facettenreiche Wirkbilder
Authors: Mohr K.
Published: August 2004

Der molekulare Wirkungsmechanismus von Estrogenrezeptor‐Liganden ist komplex. Dies führt zu substanzspezifisch facettenreichen Wirkbildern und differenzierten klinischen Anwendungen.
Die WHI‐Studie und mehr: Große Klinische Studien
Authors: Dören Martina
Published: August 2004

Die “Wechseljahre” sind keine Krankheit, sondern eine natürliche Lebensphase, die den Zeitpunkt der letzten Blutung, die Menopause, mit einschließt. Physiologische Prozesse bedürfen per se nicht einer medizinischen Behandlung. Bis zu einem Drittel aller Frauen haben im Klimakterium keine oder nur diskrete Beschwerden. Eine Hormontherapie ist nicht geeignet, um die Alterung der Haut, Haarausfall oder Trockenheit der Augen zu behandeln sowie als negativ empfundene Veränderungen der Sexualität zu verbessern, kontrollierte Studien mit Wirkungsnachweis fehlen.

Die Indikation zur Hormontherapie bei vasomotorischen Beschwerden ist gemeinsam mit der Frau nach ausführlicher Differentialdiagnose zu stellen, wenn Frauen medizinische Hilfe auf dem Boden einer gemeinsamen Entscheidungsfindung (shared‐decision‐making) wegen Wechseljahrbeschwerden in Anspruch nehmen wollen:

˙unter vorrangiger Berücksichtigung des Wirksamkeitsnachweises für die betreffende Symptomatik,

˙der individuell empfundenen Schwere der Symptome,

˙des Lebensumfeldes und

˙möglicher Risiken (insbesondere kardiovaskuläres und karzinogenes Risiko).

Bei Frauen mit vorzeitiger (prämaturer) Menopause gelten im Prinzip die gleichen Grundsätze. Eine Therapie bis zum etwa 50. Lebensjahr mag hier in Anlehnung an den Median des natürlichen Menopausealters begründet erscheinen. Allerdings fehlen leider aussagefähige klinische Studien.
Wann ist eine Hormontherapie sinnvoll?: PROS und CONS
Authors: Hadji Peyman
Published: August 2004

Eine HT sollte nur bei Vorliegen einer Indikation verordnet werden. Dabei steht die Behandlung des klimakterischen Beschwerdekomplexes mit Hitzewallungen, Schweißausbrüchen, Schlafstörungen sowie atrophischen Veränderungen im Vordergrund. Für diese Indikation gibt es zur HT keine wirksame Alternative. Im Rahmen der WHI–Studie ist die Wirksamkeit der HT zur primären Prävention osteoporosebedingter Schenkelhals– und Wirbelkörperfrakturen eindeutig belegt. Unter einer Estrogen–Monotherapie über ca. 7 Jahre hat sich im Rahmen der WHI‐Studie (0, 6 mg CCE im Vergleich zu Placebo) kein erhöhtes Risiko für Brustkrebs oder kardiovaskuläre Erkrankungen mit Ausnahme thromboembolischer Erkrankungen bei gleichzeitiger Reduktion osteoporosebedingter Schenkelhalsfrakturen gezeigt. Bei prädisponierten Frauen besteht jedoch im Rahmen einer Kombinationstherapie ein – wenn auch sehr geringes – zusätzliches Risiko für venöse thromboembolische Erkrankungen und Schlaganfälle im ersten Jahr der Einnahme sowie für das Mammakarzinom nach einer mehr als 5jährigen Behandlung. Vor jeder Indikationsstellung ist eine ausführliche Beratung der Patientin sowie eine individuelle Risiko‐Nutzen‐Analyse, besonders bei langfristiger Anwendung, erforderlich.
Phytotherapie bei Wechseljahresbeschwerden: Stand der Forschung
Authors: Osmers Rüdiger , Kraft Karin
Published: August 2004

Neben der Hormontherapie werden Nahrungsergänzungsmittel und Phytotherapeutika zur Behandlung des klimakterischen Syndroms eingesetzt. Phytoestrogene (Soja, Rotklee) sind einer Placebobehandlung bei der Therapie klimakterischer Beschwerden kaum überlegen, erscheinen hingegen wirksam zur Osteoporosevorbeugung. Es mehren sich allerdings Zweifel an der Sicherheit der Isoflavonpräparate.
Die Wirksamkeit der Traubensilberkerze ist durch kontrollierte klinische Studien belegt. Sie ist der HT ebenbürtig und zeichnet sich, bei einem langsameren Wirkungseintritt, gegenüber der HT durch eine bessere Verträglichkeit aus. Es existieren Hinweise auf einen osteoprotektiven Effekt, der in weiteren Langzeitstudien bestätigt werden muss. Cimicifuga‐Präparate können an estrogenresponsivem Gewebe, wie Brust und Uterus, als sicher angesehen werden. Patientinnen, die eine HT ablehnen oder nicht anwenden dürfen, steht mit den Cimicifuga‐Präparaten eine wirksame und gut verträgliche Alternative zur Verfügung.
Estrogene – Spielwiese für Galeniker: Viele Wege führen zum Ziel
Authors: Daniels Rolf
Published: August 2004

Estrogene sind ein gutes Beispiel dafür, wie sich durch galenische Maßnahmen die Eigenschaften eines potenten Wirkstoffs optimieren lassen. Unter Beachtung der jeweiligen Vorzüge und Nachteile sollte es bei der breiten Palette an verfügbaren Darreichungsformen gelingen, für jede Patientin ein kostengünstiges Therapieregime mit optimalem Nutzen‐Risiko‐Verhältnis zu finden.
Hormontherapie: Beratung in der Apotheke: Hinweise für den Apotheken‐Alltag
Authors: Martin Eric
Published: August 2004

Estrogene sind wirksam bei der Behandlung postmenopausaler Beschwerden und bei der Prophylaxe der Osteoporose. Die fehlende Wirksamkeit bei der Primärprävention kardiovaskulärer Ereignisse sowie die mit der Hormontherapie verbundenen Risiken dürfen jedoch nicht dazu führen, dieses etablierte Therapieprinzip insgesamt in Frage zu stellen. Genauso bedenklich wie ein therapeutischer Nihilismus wäre das Propagieren der Phytoestrogen‐Nahrungsergänzungsmittel als “natürliche” Alternative. Rational begründet ist dagegen der Einsatz von Phytopharmaka auf der Basis definierter Cimicifuga‐Extrakte.
Die WHI‐Studie hat insgesamt kaum Überraschendes gebracht, bestehende Wissensdefizite zur Hormontherapie aber präzisiert. Weitere Untersuchungen insbesondere auch zu physiologischen Estrogenen und zu deren transdermalem Einsatz sind erforderlich. Bei den bekannten Risiken einer Hormontherapie stellen die Hormone nur einen Einflussfaktor dar. Eine Schlüsselrolle spielt in diesem Zusammenhang sicher das Rauchverhalten, einmal als eigenständiger Risikofaktor, zum anderen aufgrund seiner fundamentalen Einflüsse auf den Estrogenstoffwechsel und die Bildung toxischer bzw. mutagener Metabolite. Die bei Raucherinnen verminderte Estrogen‐Aktivität kann menopausale Beschwerden sowie das Herzkreislaufrisiko steigern. Das vermehrte Brustkrebsrisiko von Raucherinnen geht demgegenüber vermutlich auf die Induktion von Stoffwechselwegen zurück, die zur Bildung mutagener A‐Ring‐Metabolite führen.
Rätsel gelöst – warum Baldrian/Hopfen‐Extrakte schläfrig machen
Authors: Holzgrabe Ulrike
Published: August 2004

Kürzlich haben wir gelernt, dass Adenosin offensichtlich den Schlaf‐Wach‐Rhythmus steuert. Was liegt da näher, nicht nur nach Adenosin‐Analoga als potenzielle Schlafmittel zu suchen, sondern auch in pflanzlichen Arzneimitteln, die schon lange als Sedativa auf dem Markt sind. Baldrian und Hopfen (Abb. 1) stehen da an erster Stelle.
Nukleäre Rezeptoren – wachsendes Misstrauen gegenüber Tamoxifen
Authors: Dingermann Theo , Zündorf Ilse
Published: August 2004

Bei ungefähr 70 % aller Mammakarzinoma ist das Tumorwachstum abhängig von Estrogen und einem aktiven Estrogenrezeptor‐α (ER‐α). Daher ist es nur nahe liegend, dass Estrogenrezeptor – positive (ER+) Tumoren entweder über Hormonreduktion oder Anti‐Estrogene – vor allem Tamoxifen–behandelt werden.
Pilzinhaltsstoff gegen Arteriosklerose
Authors: Holzgrabe Ulrike
Published: August 2004

Schon häufig wurde an dieser Stelle über Naturstoffe berichtet, die ausgezeichnete antimikrobielle oder antivirale Eigenschaften aufwiesen. Heute soll von einem ringförmigen peptidischen Naturstoff die Rede sein, der als Leitstruktur für die Entwicklung neuer Arzneistoffe gegen Arteriosklerose genutzt wird.
Synthesis and characterization of micrometer‐sized homo and composite polyacrylonitrile particles of narrow size distribution on the basis of single‐step swelling of uniform polystyrene template microspheres
Authors: Boguslavsky Lior , Margel Shlomo
Published: August 2004

Polyacrylonitrile/polystyrene micrometer‐sized composite particles of narrow size distribution were prepared by a single‐step swelling of uniform polystyrene template microspheres with emulsion droplets of methylene chloride containing the monomer acrylonitrile and the initiator benzoyl peroxide. Methylene chloride was then evaporated carefully, followed by polymerization of acrylonitrile at 70 °C within the shrunken template particles. Polymerization of acrylonitrile also occurred at the particles' surface due to the interaction of surface polyacrylonitrile oligoradicals with acrylonitrile dissolved in the aqueous phase. Uniform polyacrylonitrile particles of higher surface area were formed by dissolving the template polystyrene polymer of the composite particles. Surface and bulk characterization of the particles were performed by methods such as FTIR, elemental analysis, TGA‐DSC, XRD, XPS, advancing contact angle, light microscope, SEM and cross‐sectional TEM. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4847–4861, 2004
Rod‐like polyelectrolyte adsorption onto charged surfaces in monovalent and divalent salt solutions
Authors: Cheng Hao , Olvera De La Cruz Monica
Published: August 2004

We analyze the adsorption of strongly charged polyelectrolytes onto weakly charged surfaces in divalent salt solutions. We include short‐range attractions between the monomers and the surface and between condensed ions and monomers, as well correlations among the condensed ions. Our results are compared with the adsorption in monovalent salt solutions. Different surface charge densities (σ), and divalent (m) and monovalent (s) salt concentrations are considered. When the Wigner‐Seitz cells diameter (2R) is larger than the length of the rod, the maximum amount of adsorption scales like nmax ∼ σ4/3 in both monovalent and divalent solutions. For homogeneously charged surfaces, the maximum adsorption occurs at s* ∼ σ2 when s* > ϕ, where ϕ is the monomer concentration, the counterpart for divalent salt solution, m* roughly scales as σ2.2 when m* > ϕ. The effective surface charge density has a maximum absolute value at m′ < m*. A discrete surface charge distribution and short‐range attractions between monomers and surface charge groups can greatly enhance surface charge inversion especially for high salt concentration. The critical salt concentration for adsorption in divalent salt solution roughly scales as mc ∼ bσ1.9, where b is the distance between two neighboring charged monomers. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 3642–3653, 2004
Health‐related quality of life in women previously treated for early‐stage breast cancer
Authors: Bardwell Wayne A. , Major Jacqueline M. , Rock Cheryl L. , Newman Vicky A. , Thomson Cynthia A. , Chilton Janice A. , Dimsdale Joel E. , Pierce John P.
Published: August 2004

This study describes health‐related quality of life (HRQOL) in women previously treated for early stage breast cancer relative to general population and breast cancer norms. It also identifies correlates and multivariate predictors of physical and mental HRQOL. 2582 women who were up to four years post‐treatment for early stage breast cancer completed the RAND‐36 Health Survey and reported personal and cancer‐related information. Participants reported generally high HRQOL that was comparable to norms for women in the general population and other women with breast cancer. In multivariate analyses, better physical HRQOL was associated with fewer psychological symptoms, lower body mass index, better sleep quality, and more physical activity. Better mental HRQOL was associated with better sleep quality, fewer life events, less pain, and fewer gastrointestinal symptoms. Interventions targeting psychosocial symptoms, weight reduction, physical activity, sleep hygiene, and pain could result in improved HRQOL in these women. Copyright © 2003 John Wiley & Sons, Ltd.
Lung growth and function in children and adolescents with idiopathic pectus excavatum
Authors: Koumbourlis Anastassios C. , Stolar Charles J.
Published: August 2004

Patterns of lung growth and function were studied retrospectively in 103 patients (73 male and 30 female) with idiopathic pectus excavatum in order to determine: 1) the prevalence of restrictive lung defect and/or other lung function abnormalities; 2) the possible association between type of lung function abnormalities and age of the patient; and 3) whether the type of lung function is associated with other clinical conditions. Forty‐three patients (42%) were between 5–9 years of age; 36 (35%) were between 10–14 years; and 24 (23%) were between 15–19 years. Restrictive lung disease was detected only in 5 patients (5%), whereas 42 patients (41%) had evidence of obstructive pattern, and the remaining 56 patients (54%) had a normal pattern. The mean values for lung volume (total lung capacity (TLC) and/or forced vital capacity (FVC)) were lowest in the 10–14‐year group, whereas the mean values of the indices of lower airway function (forced expiratory volume at 1 sec (FEV1), FEV1/FVC, forced expiratory flow at 25–75% of forced vital capacity (FEF25–75), and FEF25–75/FVC) were higher in the younger group. Residual volume (RV) and RV/TLC were elevated in all age groups, but they declined toward normalization with increasing age. There were no significant differences between groups (stratified either by pattern of lung function or by age) with regard to their demographics or clinical characteristics (scoliosis, direction of sternal rotation, history of asthma/reactive airways disease, or exercise intolerance). We conclude that idiopathic pectus excavatum may be associated with a variety of lung function abnormalities (in particular, lower airway obstruction) even in the absence of overt clinical symptoms. There was no evidence of significant worsening of lung function with increasing age. Pediatr Pulmonol. 2004; 38:339–343. © 2004 Wiley‐Liss, Inc.
Structure–activity relationship study on human urotensin II
Authors: Guerrini Remo , Camarda Valeria , Marzola Erika , Arduin Marika , Calo Girolamo , Spagnol Martina , Rizzi Anna , Salvadori Severo , Regoli Domenico
Published: August 2004

The vasoactive cyclic undecapeptide urotensin‐II (U‐II) has been identified as an endogenous ligand for the G‐protein coupled receptor now referred to as the UT receptor. The U‐II/UT receptor system might be relevant for cardiovascular functions. A structure‐activity study of human U‐II investigating 31 peptides in the rat aorta bioassay is reported. Ala‐ and D‐scan investigations indicated that the sequence Phe6‐Trp7‐Lys8‐Tyr9 is essential for biological activity and that Lys8 and Tyr9 are particularly important. These two residues were substituted with a series of coded and non‐coded amino acids. These studies demonstrated that the positive charge of the primary aliphatic amine at position 8 and its relative spatial orientation is crucial for both receptor occupation and activation, while the only chemical requirement at position 9 is the presence of an aromatic moiety. Moreover, this study led to the identification of UT receptor partial agonists (compounds 23 and 24) which can be used as chemical templates for further investigations aimed at the identification of selective antagonists. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.
The use of remotely sensed data to detect channel hydromorphology; River Tummel, Scotland
Authors: Gilvear David J. , Davids Corine , Tyler Andrew N.
Published: August 2004

Colour aerial photography and multi‐spectral imagery acquired from airborne platforms for the River Tummel, Scotland, was used in conjunction with field survey to assess the feasibility of monitoring hydromorphology and human alteration within the river corridor. The study was undertaken to investigate the possibility of remotely sensing the physical status of a nation's rivers at the national scale to comply with the requirement of the European Water Framework Directive. Visual assessment and unsupervised and supervised automated classifications of the imagery were undertaken and compared with field survey data.

In the absence of overhanging vegetation canopies most features above the water line of interest were visible on the imagery. Below the water line, morphology and substrate composition together with bank materials on vertically cut banks are less easily detected. The overall accuracy of automated classification procedures, compared to field survey, was 60% for the colour aerial photography and 68% for the multi‐spectral imagery. Supervised classification was superior to unsupervised classification procedures. Sun glint on water surfaces and shadows caused by high banks, trees and buildings were observed as the cause of most misclassification of features.

Overall, the study demonstrates that remotely sensed digital imagery has the potential to allow panoptic mapping of river hydromorphology and human impacts. The possibilities and constraints, in light of the findings of this study, are discussed. In the context of new legislation which requires environmental protection agencies to have robust tools for monitoring the physical status, as part of meeting the objective of good ecological status, of rivers across an entire nation, remote sensing appears to provide a way forward. Copyright © 2004 John Wiley & Sons, Ltd.