bluuebunny/crossref_metadata_2025 huggingface dataset:
Four‐angle saturation transfer (FAST) method for measuring creatine kinase reaction rates in vivo
Authors: Bottomley Paul A. , Ouwerkerk Ronald , Lee Ray F. , Weiss Robert G.
Published: August 2002

A new fast method of measuring kinetic reaction rates for two‐site chemical exchange is described. The method employs saturation transfer magnetic resonance spectroscopy (MRS) and acquisition of only four spectra under partially saturated, high signal‐to‐noise ratio (SNR) conditions. In two acquisitions one of the exchanging species is saturated; the other two employ a control saturation. Each pair of acquisitions is applied with two different flip angles, and the equilibrium magnetization, relaxation times, and reaction rates are calculated therefrom. This four‐angle saturation transfer (FAST) method is validated theoretically using the Bloch equations modified for two‐state chemical exchange. Potential errors in the rate measurements due to the effects of exchange are evaluated for creatine kinase (CK) metabolism modeled for skeletal and heart muscle, and are found to be <5% for forward CK flux rates of 0.05 ≤ kf ≤ 1.0 s–1, and up to a 90% depletion of phosphocreatine (PCr). The effect of too much or too little saturating irradiation on FAST appears to be comparable to that of the conventional saturation transfer method, although the relative performance deteriorates when spillover irradiation cuts the PCr signal by 50% or more. “FASTer” and “ FASTest” protocols are introduced for dynamic CK studies wherein [PCr] and/or kf changes. These protocols permit the omission of one or two of the four acquisitions in repeat experiments, and the missing information is recreated from initial data via a new iterative algorithm. The FAST method is validated empirically in phosphorus (31P) MRS studies of human calf muscle at 1.5 T. FAST measurements of 10 normal volunteers yielded the same CK reaction rates measured by the conventional method (0.29 ± 0.06 s–1) in the same subjects, but an average of seven times faster. Application of the FASTer algorithm to these data correctly restored missing information within seven iterations. Finally, the FAST method was combined with 1D spatially localized 31P MRS in a study of six volunteers, yielding the same kf values independent of depth, in total acquisition times of 17–39 min. These timesaving FAST methods are enabling because they permit localized measurements of metabolic flux, which were previously impractical due to intolerably long scan times. Magn Reson Med 47:850– 863, 2002. © 2002 Wiley‐Liss, Inc.
Rapid cine MRI of the human heart using reconstruction by estimation of lines and inhibition of fold‐in
Authors: Rehwald Wolfgang G. , Kim Raymond J. , Judd Robert M.
Published: August 2002

A fast imaging method is described that yields an approximately six‐fold acquisition time reduction relative to conventional techniques. The method involves: 1) acquisition of every sixth k‐space line; 2) shifting of acquired k‐space lines between odd and even frames; and 3) a single‐frame correction image. Reconstruction is achieved by temporal interpolation for k‐space lines not acquired combined with subtraction of stationary fold‐in artifacts. Seven patients with heart disease and one volunteer were evaluated. SNR was measured in myocardium and the ventricular cavity for both the conventional and new technique. The method is best suited for fast imaging of moving objects confined to a small region within a larger stationary object, such as the heart within the thoracic cavity. It can be implemented in cine and functional imaging sequences and, in principle, in perfusion sequences. Magn Reson Med 47:844–849, 2002. © 2002 Wiley‐Liss, Inc.
Dynamic imaging with multiple resolutions along phase‐encode and slice‐select dimensions
Authors: Panych Lawrence P. , Zhao Lei , Jolesz Ferenc A. , Mulkern Robert V.
Published: August 2002

An implementation is reported of an imaging method to obtain MUltiple Resolutions along Phase‐encode and Slice‐select dimensions (MURPS), which enables dynamic imaging of focal changes using a graded, multiresolution approach. MURPS allows one to trade spatial resolution in part of the volume for improved temporal resolution in dynamic imaging applications. A unique method of Hadamard slice encoding is used, enabling the varying of the phase encode and slice resolution while maintaining a constant effective TR throughout the entire 3‐D volume. MURPS was implemented using a gradient‐recalled echo sequence, and its utility was demonstrated for MR temperature monitoring. In this preliminary work, it has been shown that changes throughout a large volume can be effectively monitored in times that would normally only permit dynamic imaging in one or a very few slices. Magn Reson Med 45:940–947, 2001. © 2001 Wiley‐Liss, Inc.
Hyperechoes
Authors: Hennig Juergen , Scheffler Klaus
Published: August 2002

A novel spin‐echo‐based refocusing strategy called a hyperecho mechanism is introduced by which the full coherence of magnetization submitted to a sequence of arbitrary RF pulses can be reinstalled. First implementations illustrate the potential of hyperecho formation—especially for Rapid Acquisition with Relaxation Enhancement (RARE) imaging, in which the full image intensity can be retrieved using a fraction of the RF power of a fully refocused sequence. The contribution of stimulated echo pathways to the hyperecho signal leads to an increased signal intensity at a given refocusing time for tissues with T1 > T2. For identical T2 contrast, longer echo times have to be used. Further possibilities for using hyperechoes in gradient‐echo sequences and for spin selection are discussed. Magn Reson Med 46:6–12, 2001. © 2001 Wiley‐Liss, Inc.
Direct comparison of 3D spiral vs. Cartesian gradient‐echo coronary magnetic resonance angiography
Authors: Börnert Peter , Stuber Matthias , Botnar René M. , Kissinger Kraig V. , Koken Peter , Spuentrup Elmar , Manning Warren J.
Published: August 2002

While 3D thin‐slab coronary magnetic resonance angiography (MRA) has traditionally been performed using a Cartesian acquisition scheme, spiral k‐space data acquisition offers several potential advantages. However, these strategies have not been directly compared in the same subjects using similar methodologies. Thus, in the present study a comparison was made between 3D coronary MRA using Cartesian segmented k‐space gradient‐echo and spiral k‐space data acquisition schemes. In both approaches the same spatial resolution was used and data were acquired during free breathing using navigator gating and prospective slice tracking. Magnetization preparation (T2 preparation and fat suppression) was applied to increase the contrast. For spiral imaging two different examinations were performed, using one or two spiral interleaves, during each R‐R interval. Spiral acquisitions were found to be superior to the Cartesian scheme with respect to the signal‐to‐noise ratio (SNR) and contrast‐to‐noise‐ratio (CNR) (both P < 0.001) and image quality. The single spiral per R‐R interval acquisition had the same total scan duration as the Cartesian acquisition, but the single spiral had the best image quality and a 2.6‐fold increase in SNR. The double‐interleaf spiral approach showed a 50% reduction in scanning time, a 1.8‐fold increase in SNR, and similar image quality when compared to the standard Cartesian approach. Spiral 3D coronary MRA appears to be preferable to the Cartesian scheme. The increase in SNR may be “traded” for either shorter scanning times using multiple consecutive spiral interleaves, or for enhanced spatial resolution. Magn Reson Med 46:789–794, 2001. © 2001 Wiley‐Liss, Inc.
EPR oxygen mapping (EPROM) of engineered cartilage grown in a hollow‐fiber bioreactor
Authors: Ellis Scott J. , Velayutham M. , Velan S. Sendhil , Petersen Erik F. , Zweier Jay L. , Kuppusamy Periannan , Spencer Richard G.S.
Published: August 2002

A novel electron paramagnetic resonance (EPR)‐based oxygen mapping procedure (EPROM) is applied to cartilage grown in a single‐, hollow‐fiber bioreactor (HFBR) system. Chondrocytes harvested from the sterna of 17‐day‐old chick embryos were inoculated into an HFBR and produced hyaline cartilage over a period of 4 weeks. Tissue oxygen maps were generated according to the EPROM technique (Velan et al., Magn Reson Med 2000;43:804–809) by making use of the line‐broadening effects of oxygen on the signal generated from nitroxide spin probes. In addition, the effect on oxygen consumption of the addition of cyanide to the tissue was investigated. Cyanide is a potent inhibitor of oxidative phosphorylation, and accordingly, given the constant provision of oxygen to the tissue, it would be expected to increase oxygen levels within the HFBR. The EPROM measurements showed a significant increase in oxygen concentration in the cartilage after the addition of cyanide. In contrast to other methods for studying oxygen in cartilage, EPROM can provide direct, noninvasive visualization of local concentrations in three dimensions. Magn Reson Med 46:819–826, 2001. © 2001 Wiley‐Liss, Inc.
Gd‐DTPA2–‐enhanced MRI of femoral knee cartilage: A dose‐response study in healthy volunteers
Authors: Tiderius Carl J. , Olsson Lars E. , de Verdier Hans , Leander Peter , Ekberg Olle , Dahlberg Leif
Published: August 2002

The negatively charged contrast agent Gd‐DTPA2– distributes inversely to the cartilage fixed charged density. This enables structural cartilage examinations by contrast‐enhanced MRI. In line with the development of a clinically applicable protocol for such examinations, this study describes the temporal pattern of Gd‐DTPA2– distribution in femoral knee cartilage at three different doses in healthy volunteers. Nineteen volunteers (ages 21–28 years) were examined with a 1.5T MRI system. Quantitative relaxation rate measurements were made in weight‐bearing central parts of femoral cartilage using sets of five turbo inversion recovery images with different inversion times. The cartilage was analyzed before and four times (1–4 h) after an intravenous injection of Gd‐DTPA2– at single, double, and triple doses: 0.1, 0.2, and 0.3 mmol/kg body weight, respectively. The increase in R1 postcontrast was linearly dose‐related at all times. The highest R1 values were registered at 2 and 3 h postcontrast, suggesting 2 h to be optimal in the clinical situation. The triple dose indicated a subtle compartmental difference in men, with higher contrast distribution medially than laterally. Results suggest that the triple dose is needed to detect minor cartilage matrix differences. Magn Reson Med 46:1067–1071, 2001. © 2001 Wiley‐Liss, Inc.
Intravascular lymphomatosis
Authors: Oei Melina E. , Kraft George H. , Sarnat Harvey B.
Published: August 2002

Intravascular lymphomatosis, also known as endovascular lymphoma or angiotropic large cell lymphoma, is a rare malignancy typically diagnosed at autopsy. We describe a case in which the diagnosis was made at an early stage. Specific electrodiagnostic findings suggested concomitant polyneuropathy and myopathy. Suspicion of a paraneoplastic syndrome during electrodiagnostic testing prompted muscle biopsy, which revealed myopathy due to the direct infiltration of neoplastic cells. Resultant treatment with a standard chemotherapy regimen not only increased the patient's survival, but also improved neurological function. © 2002 Wiley Periodicals, Inc. Muscle Nerve 25:000–000, 2002
Deformations caused by the movements of shear and tensile faults
Authors: Sheu Guang Y.
Published: August 2002

Earlier solutions of deformations resulting from the movements of shear and tensile faults in a half space (Bull. Seismol. Soc. Amer. 1985; 75:1135, 1992; 82:1018) have been revised in view of cross‐anisotropic stress–strain relationships. The dislocation theory (Canad. J. Phys. 1958; 36:192) is reviewed and the displacement field due to a concentrated force in an anisotropic half space is solved analytically for developing the current research. A fault is simulated as a point source of strain nuclei in applying the dislocation theory.

Data (Terr. Atmos. Oceanic Sci. 2000; 11(3):591, 631) that were used to study the Chi‐Chi earthquake (ML=7.3; 1999/9/21 AM 1:47) are introduced to compare the solution with the isotropic results. Results indicate that the anisotropy of stress–strain relationships does affect the results of predicted deformations. Copyright © 2001 John Wiley & Sons, Ltd.
Performance of Jacobi preconditioning in Krylov subspace solution of finite element equations
Authors: Lee F.‐H. , Phoon K.K. , Lim K.C. , Chan S.H.
Published: August 2002

This paper examines the performance of the Jacobi preconditioner when used with two Krylov subspace iterative methods. The number of iterations needed for convergence was shown to be different for drained, undrained and consolidation problems, even for similar condition number. The differences were due to differences in the eigenvalue distribution, which cannot be completely described by the condition number alone. For drained problems involving large stiffness ratios between different material zones, ill‐conditioning is caused by these large stiffness ratios. Since Jacobi preconditioning operates on degrees‐of‐freedom, it effectively homogenizes the different spatial sub‐domains. The undrained problem, modelled as a nearly incompressible problem, is much more resistant to Jacobi preconditioning, because its ill‐conditioning arises from the large stiffness ratios between volumetric and distortional deformational modes, many of which involve the similar spatial domains or sub‐domains. The consolidation problem has two sets of degrees‐of‐freedom, namely displacement and pore pressure. Some of the eigenvalues are displacement dominated whereas others are excess pore pressure dominated. Jacobi preconditioning compresses the displacement‐dominated eigenvalues in a similar manner as the drained problem, but pore‐pressure‐dominated eigenvalues are often over‐scaled. Convergence can be accelerated if this over‐scaling is recognized and corrected for. Copyright © 2002 John Wiley & Sons, Ltd.
Partial unilateral ureteral obstruction in rats
Authors: Wen Jian Guo
Published: August 2002

This review comprises an overview of the current knowledge on experimental partial unilateral ureteral obstruction (PUUO) and a summary of our latest original experimental PUUO studies in rats. Neonatal PUUO is the type of obstruction that is most often encountered in pediatric clinical practice. However, the pathogenesis of PUUO is still incompletely understood. Most of our knowledge on PUUO has been derived from experimental studies in a variety of animal models. Although progress has been made, the natural history of congenital hydronephrosis is still incompletely described. The effects on kidney functions of long‐term urinary tract obstruction, especially PUUO, have been less intensively studied. Recently, we created models with mild and severe PUUO in young rats by embedding the upper one fourth or the upper two thirds of the left ureter into the psoas muscle, respectively. Thereafter, the technique was used to create mild and severe PUUO in newborn rats and magnetic resonance imaging studies showed that both mild and severe obstruction caused a time‐dependent decrease in renal blood flow. Compensatory increase in total kidney volume and renal vein blood flow in contralateral non‐obstructed kidneys was not detectable when functional deterioration in the partially obstructed kidneys was present. Finally, we investigated the dynamic changes in renal relative signal intensity (RSI) of gadolinium‐diethylenetriamine pentaacetic acid (Gd‐DTPA) using magnetic resonance imaging in rats with partial, complete unilateral ureteral obstruction and sham‐operated controls. The results showed that changes in Gd‐DTPA RSI are compatible with the known physiological and anatomical changes in kidneys in response to ureteral obstruction and useful for distinguishing an obstructed from a non‐obstructed collecting system and also for differentiating a partially obstructed from a completely obstructed collecting system. Neurourol. Urodynam. 21:231–250, 2002. © 2002 Wiley‐Liss, Inc.
Urinary dysfunction in Brown‐Séquard syndrome
Authors: Sakakibara Ryuji , Hattori Takamichi , Uchiyama Tomoyuki , Yamanishi Tomonori
Published: August 2002

Brown‐Séquard syndrome (BS) is a rare but well documented condition of the spinal cord hemisection, comprising hemiparesis with crossed superficial sensory disturbance. However, little is known of micturitional function in BS, although some patients with BS are troubled with severe voiding difficulty and urinary incontinence. We performed urinary questionnaire and urodynamic studies in eight patients with BS, including seven men and one woman, mean age of 41 years. Detailed questionnaire showed that five of the eight patients (63%) had micturitional symptoms, including voiding difficulty in three, urinary retention in two, urinary frequency in two and urge urinary incontinence in one. Urodynamic abnormalities were noted in all five patients with micturitional symptoms, including post‐micturition residuals in four (average 149 mL), high urethral closure pressure in two, increased bladder volume at first sensation in one, detrusor hyperreflexia in four, detrusor areflexia on voiding in three and unrelaxing sphincter on voiding in four. Three asymptomatic patients showed normal urodynamic finding. Micturitional symptoms were more common in patients with severe motor paresis (100%) than in those with mild motor paresis (40%), and there was no relation between micturitional disturbance with superficial or deep sensory disturbance. A combination of treatments for the underlying disorders with α‐adrenergic blocking agent and clean, intermittent self‐catheterization ameliorated the urinary dysfunction in all patients together with neurological dysfunction. In conclusion, micturitional disturbance was not uncommon in our patients with BS, particularly in those with severe motor paresis, which could ameliorate by appropriate therapies. Neurourol. Urodynam. 20:661–667, 2001. © 2001 Wiley‐Liss, Inc.
Development of a low‐cost flow meter to grade the maximum flow rate
Authors: Pel J.J.M. , van Mastrigt R.
Published: August 2002

We developed an inexpensive flow meter to grade the maximum flow rate of individuals at locations other than the clinical setting. This flow meter consists of a funnel connected to a collecting tube with several exit ports. Urine directed into this tube flows through one or more ports and is collected in a measuring cup to measure the voided volume. The number of ports emitting the liquid is a measure for the flow rate. We made four experimental models to test and compare some of the physical properties. One of these models was selected as a prototype and was tested in five healthy volunteers. All volunteers voided repeatedly in a standard rotating disk flow meter and in this prototype to test its accuracy. The response time of the experimental models depended on the outlet resistance of the exit ports and the volume of the collecting tube. In two models, this time was comparable with that of currently used volume‐based electronic flow meters (∼2 seconds). In healthy volunteers, the maximum flow rates graded with the selected prototype and those measured with the rotating disk flow meter showed good agreement (difference=0.4 ± 2.6 mL/s; mean ± SD). The low‐cost flow meter may be used repeatedly to grade the maximum flow rate at private and familiar locations (for example, at home), which may increase the accuracy of evaluating the urinary stream in patients with lower urinary tract symptoms. Neurourol. Urodynam. 21:48–54, 2002. © 2002 Wiley‐Liss, Inc.
Service differentiation using a multi‐level RED mechanism
Authors: Aweya James , Ouellette Michel , Montuno Delfin Y.
Published: August 2002

This paper describes a multi‐level active queue management scheme that combines packet classification and random early detection (RED) capabilities to provide differentiated performance characteristics for different classes of service. The proposed RED scheme uses a simple control‐theoretic algorithm to randomly discard packets with a load‐dependent probability when a buffer in a router gets congested. Copyright © 2002 John Wiley & Sons, Ltd.
Forked end: a novel transmembrane protein involved in neuromuscular specificity in drosophila identified by gain‐of‐function screening
Authors: Umemiya Takeshi , Takasu Etsuko , Takeichi Masatoshi , Aigaki Toshiro , Nose Akinao
Published: August 2002

The Drosophila neuromuscular connectivity provides an excellent model system for studies on target recognition and selective synapse formation. To identify molecules involved in neuromuscular recognition, we conducted gain‐of‐function screening for genes whose forced expression in all muscles alters the target specificity. We report here the identification of a novel transmembrane protein, Forked end (FEND), encoded by the fend gene, by the said screening. When the FEND expression was induced in all muscles, motoneurons that normally innervate muscle 12 formed ectopic synapses on a neighboring muscle 13. The target specificity of these motoneurons was also altered in the loss‐of‐function mutant of fend. During embryonic development, fend mRNA was detected in a subset of cells in the central nervous system and in the periphery. These results suggest that FEND is a novel axon guidance molecule involved in neuromuscular specificity. © 2002 Wiley Periodicals, Inc. J Neurobiol 51: 205–214, 2002
On the solution of large Sylvester‐observer equations
Authors: Calvetti D. , Lewis B. , Reichel L.
Published: August 2002

The design of a Luenberger observer for large control systems is an important problem in Control Theory. Recently, several computational methods have been proposed by Datta and collaborators. The present paper discusses numerical aspects of one of these methods, described by Datta and Saad (1991). Copyright © 2001 John Wiley & Sons, Ltd.
A numerically scalable domain decomposition method for the solution of frictionless contact problems
Authors: Dureisseix D. , Farhat C.
Published: August 2002

We present a domain decomposition method with Lagrange multipliers for solving iteratively frictionless contact problems. This method, which is based on the FETI method and therefore is named here the FETI‐C method, incorporates a coarse contact system that guides the iterative prediction of the active zone of contact. We demonstrate numerically that this method is numerically scalable with respect to both the problem size and the number of subdomains. Copyright © 2001 John Wiley & Sons, Ltd.
An algorithm and a method to search bifurcation points in non‐linear problems
Authors: Chambon R. , Crochepeyre S. , Charlier R.
Published: August 2002

This paper is devoted to a numerical method able to help the determination of the bifurcation threshold in non‐linear time‐independent continuum mechanic problems. First, some theoretical results about uniqueness are recalled. In the framework of the large‐strain assumption, the differences between the classical finite‐step problem and the rate problem are presented. An iterative algorithm able to solve the rate problem is given. Using different initializations, it is seen in some numerical experiments that it is possible with this algorithm to get different solutions when the underlying mathematical problem solved does not enjoy a uniqueness property. The constitutive equations used have been chosen to be simple enough to deduce some theoretical knowledge about the corresponding uniqueness problems. Finally, a method is given which is able in some case to give an upper bound of the bifurcation threshold. Copyright © 2001 John Wiley & Sons, Ltd.
Time‐ and space‐adaptive methods applied to localization phenomena in empty and saturated micropolar and standard porous materials
Authors: Ehlers W. , Ellsiepen P. , Ammann M.
Published: August 2002

Localization phenomena, as e.g. shear bands, occur as a result of local concentrations of plastic strains in small bands of finite width. The reason for this behaviour lies in the basic properties of elasto‐plastic frictional materials, where variations of the Lode angle together with the non‐associated plastic dilatation result in local softening effects. Proceeding from non‐viscous empty porous materials, it is well known that the computation of shear bands reveals an ill‐posed problem. To overcome this behaviour, two different regularization strategies are considered, which are (1) the inclusion of independent rotational degrees of freedom (micropolar formulation) and (2) the inclusion of viscosity effects (standard formulation) by taking into consideration viscoplastic properties of the solid matrix or a viscous pore‐fluid, respectively. The numerical treatment furthermore proceeds from time‐ and space‐adaptive strategies to refine and to coarsen both the time step and the mesh size. Considering quasi‐static problems, the space discretization yields a DAE system of index 1 in the time domain which can be successfully treated by SDIRK methods, thus allowing for an efficient estimation of the time error and, as a consequence, for an adaptive time‐step control. In the space domain, the present investigation proceeds from an error indicator of Zienkiewicz‐Zhu type, where smoothened values of the L2‐norms of characteristic quantities are compared to the respective discrete values. The efficiency of this procedure is demonstrated by the computation of the biaxial experiment on an empty and a liquid‐saturated porous soil material and of the slope failure problem of a fluid‐saturated soil. Copyright © 2001 John Wiley & Sons, Ltd.
Some nonconforming mixed box schemes for elliptic problems
Authors: Croisille Jean‐Pierre , Greff Isabelle
Published: August 2002

In this article, we introduce three schemes for the Poisson problem in 2D on triangular meshes, generalizing the FVbox scheme introduced by Courbet and Croisille [1]. In this kind of scheme, the approximation is performed on the mixed form of the problem, but contrary to the standard mixed method, with a pair of trial spaces different from the pair of test spaces. The latter is made of Galerkin‐discontinuous spaces on a unique mesh. The first scheme uses as trial spaces the P1 nonconforming space of Crouzeix‐Raviart both for u and for the flux p = ∇u. In the two others, the quadratic nonconforming space of Fortin and Soulie is used. An important feature of all these schemes is that they are equivalent to a first scheme in u only and an explicit representation formula for the flux p = ∇u. The numerical analysis of the schemes is performed using this property. © 2002 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 18: 355–373, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/num.10003
Adequacy of finite difference schemes for convection‐diffusion equations
Authors: Shapira Yair
Published: August 2002

Finite difference schemes for the numerical solution of singularly perturbed convection problems on uniform grids are studied in the limit case where the viscosity and the meshsize approach zero at the same time. The present error estimates are given in terms of order of magnitude in the above limit process and are useful in a priori choosing adequate schemes and meshsizes for boundary‐layer problems and problems with closed characteristics. Published 2002 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 18: 280–295, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/num.10007
Acrylate terpolymer in fabrication of medicated skin patches
Authors: Mare Vibha S. , Bharti Prasad V. , Vavia Pradeep R.
Published: August 2002

An acrylate based pressure sensitive adhesive (PSA) was synthesized to design a drug‐in‐adhesive (DIA) type transdermal therapeutic system (TTS) for nitroglycerin used in the treatment of angina pectoris. 2‐Ethylhexyl acrylate (EHA), methyl methacrylate (MMA) and acrylic acid (AA) were used to synthesize the PSA by free radical solution polymerization. The effects of reaction time, reaction temperature, initiator concentration and solvent on polymerization were studied. The synthesized terpolymer was characterized by 1H‐NMR, FT‐IR, differential scanning calorimetry (DSC) and gel permeation chromatography (GPC) and also evaluated for intrinsic viscosity, refractive index, peel strength, moisture uptake and skin irritation potential. The PSA was used to develop DIA type patches of nitroglycerin. The patches were cast using solvent evaporation technique and dried at controlled temperature. The patches were evaluated for thickness uniformity, weight variation, peel strength and moisture pick‐up. The percent drug content and in vitro drug release was determined by high pressure liquid chromatography (HPLC) method. On the basis of in vitro release profile, patches were selected for in vitro skin permeation studies. The developed formulation TP‐1 (K = 24.892 mcg/cm2/hr) followed zero‐order rate kinetics and showed better skin permeation rate in comparison to the marketed TTS (MTTS) (K = 17.413 mcg/cm2/hr). TP‐1 was subjected to stability testing for a period of 1 year according to ICH guidelines. The patches were found to be stable and an expiry date of 2 years was predicted with storage at 25 °C or below. Copyright © 2001 John Wiley & Sons, Ltd.
Preparation of polyaniline conductive composites with diene‐rubber or polyphenylacetylene
Authors: Cataldo Franco , Maltese Paolo
Published: August 2002

We describe the preparation of polyaniline (PANI‐EB) by aniline oxidation with KIO3 and the purification of the resulting dedoped polymer by an acetone extraction step to eliminate undesired by‐products from polyaniline, which could generate some safety concerns in the application and use of PANI. Excellent homogeneous and electrically conducting composite films can be prepared from chloroform solutions of purified PANI doped with camphorsulfonic acid in presence of cis‐1,4‐polybutadiene as the film‐forming agent. These films have been characterized by FT‐IR and UV‐VIS‐NIR spectroscopy. A method to synthesisze PANI directly doped with dodecylbenzenesulfonic acid (DBSA) is also reported. DBSA‐doped‐PANI was then used to prepare composites with polyphenylacetylene (PPA) by growing homogeneous films from chloroform solution. These films were conductive and were studied by FT‐IR and UV‐VIS‐NIR spectroscopy. In view of the application of these composites as gas sensors or in “electronic noses”, a short discussion is presented about the criteria used in the selection of the chemical nature of the host polymer where doped PANI is included to confer electrical conductivity. The interaction between the molecules to be detected and the polymeric sensing surface is discussed in terms of physisorption, chemisorption and charge‐transfer‐complex formation. Copyright © 2001 John Wiley & Sons, Ltd.
Amnion rupture sequence in a first trimester missed abortion
Authors: Philipp Tom , Kalousek Dagmar K.
Published: August 2002

We report the diagnosis of amnion rupture sequence made by sonography and fetoscopy during the first trimester of gestation in a case of missed abortion. The investigation revealed a demised fetus with the characteristics of 9 weeks of development. The early fetus had an amnion adhesion at the tip of the nose and strands of amnion wrapped around the terminal phalanges of both feet. No defects in addition to the face and limb involvement were identified. The karyotype was normal: 46,XX. In the reported case, fetoscopy allowed confirmation of the sonographic diagnosis of an amnion rupture sequence in the first trimester of gestation and consequently helped to clarify the cause of abortion in this case of early fetal demise. Copyright © 2001 John Wiley & Sons, Ltd.
Hydrops fetalis in three male fetuses of a female with incontinentia pigmenti
Authors: Dufke Andreas , Vollmer Brigitte , Kendziorra Heidemarie , Mackensen‐Haen Susanne , Orth Ulrike , Orlikowsky Thorsten , Gal Andreas
Published: August 2002

Objectives

Careful investigation of hydrops fetalis (HF) is important with regard to genetic counselling and prenatal diagnosis. HF is known to be associated with various genetic disorders. To date there has been only one report of a male fetus in whom incontinentia pigmenti (IP) was associated with generalised oedema. We describe a family who had a girl with clinical signs of IP after three consecutive miscarriages of three male fetuses due to HF.

Results

Molecular genetic analysis showed a mutation in the NEMO/IKKχ gene in the girl and the mother, which confirmed the diagnosis of IP in both cases. In the two fetuses that could be investigated, inheritance of the affected maternal X chromosome could be demonstrated retrospectively by linkage analysis.

Conclusion

The present findings suggest that IP might be an X‐linked dominant trait causing HF in male fetuses. In cases of recurrent HF in male fetuses, minimal signs of IP in the maternal line should therefore be carefully investigated in order to be able to perform mutational analysis and to offer appropriate genetic counselling. Copyright © 2001 John Wiley & Sons, Ltd.
Split‐hand/split‐foot malformation with paternal mutation in the p63 gene
Authors: Witters Ingrid , Van Bokhoven Hans , Goossens A. , Van Assche Frans‐André , Fryns Jean‐Pierre
Published: August 2002

We report the prenatal diagnosis at 16 weeks' gestation of bilateral split‐hand/split‐foot malformation (SHSFM) with severe lobster claw deformity of hands and feet in a male fetus without associated malformations. A minor manifestation of SHSFM was present in the father with only mild bilateral foot involvement (syndactyly I–II; cleft II–III; left cutaneous syndactyly III–IV).

 Mutation analysis of the p63 gene on chromosome 3q27 showed a missense mutation 577A→G (predicting amino acid substitution K193E) in the father. This mutation has not been reported so far in SHSFM but resembles the previously reported 580A→G (predicting amino acid substitution K194E) in a family with SHSFM. Copyright © 2001 John Wiley & Sons, Ltd.
Association between congenital foot anomalies and gestational age at amniocentesis
Authors: Yoon G. , Chernos J. , Sibbald B. , Lowry R.B. , Connors G. , Simrose R. , Bernier F.P.
Published: August 2002

Objectives

Our objectives were to confirm the reported association between early amniocentesis and congenital foot anomalies as well as to report, for the first time, on the outcome of amniocenteses performed during the 13th and 14th weeks of gestation.

Methods

We conducted a triple cohort retrospective study of 4457 amniocenteses. Cohort definitions: early amniocentesis (EA), 11 weeks and 0/7 days to 12 weeks to 6/7 days; early midtrimester amniocentesis (EMA), 13 weeks and 0/7 days to 14 weeks and 6/7 days; and midtrimester amniocentesis (MA), 15 weeks and 0/7 days to 19 weeks and 6/7 days. Outcome measures were obtained by searching the Alberta Congenital Anomalies Surveillance System (ACASS) database for children born with foot anomalies represented by International Classification of Diseases version 9 (ICD‐9) codes 754.5, 754.6 and 754.7.

Results

Incidences of congenital foot anomalies were: EA 11/980 (1.1%), EMA 11/2515 (0.4%), and MA 1/962 (0.1%). There is a significant difference between the EA and EMA cohorts (p=0.019) and between the EA and MA cohorts (p=0.003); however, these data suggest there is no difference between EMA and MA cohorts (p=0.11).

Conclusions

Our incidence of congenital foot anomalies of 1.1% for women who underwent EA is similar to previously reported data, which further validates this association; however, our data also suggest that the foot anomaly risk may be limited to amniocenteses performed before the 13th week of gestation. Copyright © 2001 John Wiley & Sons, Ltd.
Minor sonographic signs of trisomy 21 at 15–20 weeks' gestation in fetuses born without malformations: a prospective study
Authors: Viora E. , Errante G. , Bastonero S. , Sciarrone A. , Campogrande M.
Published: August 2002

A prospective study was performed on 2119 pregnancies that underwent genetic amniocentesis. Indications for amniocentesis were either maternal age (⩾35) or triple‐test results (risk⩾1/380).

The study covered a 36‐month period and assessed the prevalence of minor ultrasound markers both in fetuses with Down syndrome and normal control fetuses at 15–19 week' gestation.

Only fetuses with normal karyotype or trisomy 21 were considered.

Six minor sonographic markers were considered: nuchal thickness, pyelectasia, femur observed/expected and humerus observed/expected ratios, bowel echogenicity, and choroid plexus cysts. One or more ultrasound soft markers were present in 23 out of 33 fetuses with Down syndrome (70%) and in 572 out of 2069 normal fetuses (28%). Copyright © 2001 John Wiley & Sons, Ltd.
Preimplantation genetic diagnosis (PGD), a collaborative activity of clinical genetic departments and IVF centres
Authors: Geraedts Joep P. M. , Harper Joyce , Braude Peter , Sermon Karen , Veiga Anna , Gianaroli Luca , Agan Noelle , Munné Santiago , Gitlin Sue , Blenow Elisabeth , de Boer Kylie , Hussey Nicole , Kanavakis Emmanuel , Lee Soo‐Huan , Viville Stéphane , Krey Lewis , Ray Pierre , Emiliani Serena , Hsien Liu Yung , Vermeulen Stefan
Published: August 2002

An Erratum has been published for this article in Prenatal Diagnosis 22 (5) 2002, 451.

Preimplantation genetic diagnosis (PGD) requires the combined efforts of geneticists and workers in the field of reproductive medicine. This was studied on the basis of a questionnaire, sent to 35 members of the PGD Consortium of the European Society of Human Reproduction and Embryology (ESHRE). A reply was obtained from 20 centres. They represent the majority of activities in the field of PGD in the world.

It is obvious that many of the activities (in vitro fertilisation, embryo culture and biopsy) take place in IVF units while others (counselling and diagnosis) are the responsibility of genetic diagnostic centres. The distances between both units vary considerably.

In all but one centre sex determination is offered. Aneuploidy screening is offered in 13 out of 20 centres. PGD of translocations and other structural chromosome abnormalities is offered in all but one centre. The number of monogenic diseases offered varies considerably.

In comparison to prenatal diagnosis PGD is more expensive. The majority of these costs are due to the IVF or ICSI procedure. The charges for PGD vary between about € 600 and € 4000. In 16 out of 20 centres the parents to be must sign an informed consent form. Copyright © 2001 John Wiley & Sons, Ltd.
Preimplantation genetic diagnosis for familial amyloidotic polyneuropathy (FAP)
Authors: Carvalho F. , Sousa M. , Fernandes S. , Silva J. , Saraiva M. J. , Barros A.
Published: August 2002

Preimplantation genetic diagnosis (PGD) was developed more than a decade ago to offer an alternative to prenatal diagnosis for couples at risk of transmitting an inherited disease to their offspring. Portuguese‐type familial amyloidotic polyneuropathy (FAP type I), is an autosomal dominant disease presenting an inherited mutation in the gene encoding the plasma protein transthyretin (TTR). We here report the first protocol for single‐cell detection of the Met30 mutation in FAP type I and its application to PGD. A nested PCR reaction for exon 2 of the TTR gene was developed. The PCR product was then analysed by restriction enzyme analysis and SSCP allowing the detection of the point mutation. Ten clinical cycles were performed in seven couples. From the 93 metaphase II (MII) injected oocytes, 82 were normally fertilized and 78 were biopsied. A positive signal in the nested PCR reaction was obtained in 61 blastomeres, corresponding to a DNA amplification efficiency of 78.2%. No allele dropout (ADO) or contamination were detected. A biochemical pregnancy was obtained in three cases and a clinical pregnancy in one couple is actually in normal evolution. Copyright © 2001 John Wiley & Sons, Ltd.
Detection of Jarcho–Levin syndrome at 12 weeks' gestation by nuchal translucency screening and three‐dimensional ultrasound
Authors: Hull Andrew D. , James Gina , Pretorius Dolores H.
Published: August 2002

Jarcho–Levin syndrome (JLS) or spondylothoracic dysotosis causes early newborn death from respiratory insufficiency. Prenatal diagnosis is possible using fetal ultrasound, but requires a high level of suspicion and definitive diagnosis may be delayed well into the second trimester. We present a case in which a combination of three‐dimensional ultrasound and measurement of nuchal translucency thickness allowed successful detection of recurrent JLS at 12 weeks' gestation. Copyright © 2001 John Wiley & Sons, Ltd.
Mesomelic campomelia, polydactyly and Dandy–Walker cyst in siblings
Authors: Guschmann Michael , Horn Denise , Entezami Michael , Urban Maik , Hänel Susanne , Kunze Jürgen , Vogel Martin
Published: August 2002

The present report describes two fetuses, one female and one male, with thus far undescribed skeletal malformations. The mother was a gravida 2, para 0. Both pregnancies were terminated in the second trimester because of multiple congenital anomalies diagnosed ultrasonographically resembling a short rib‐polydactyly syndrome. Both fetuses were found to have postaxial hexadactyly of the hands and feet, marked bilateral campomelia of the forearm and shank bones, and a Dandy–Walker cyst. In addition, the fourth ventricle was dilated in the first sibling and the second sibling had an inverse intestinal malrotation. A literature search failed to reveal similar observations. Copyright © 2001 John Wiley & Sons, Ltd.
How large studies may mislead: the HOPE Study
Authors: Taylor Roy
Published: August 2002

The HOPE study is widely believed to indicate that anyone over the age of 55 years with a major cardiovascular risk factor should receive prophylactic therapy with ramipril but detailed inspection of the characteristics of the patient groups suggest problems of randomisation. There was a consistent over‐representation in the placebo group of patients with each of the most potent risk factors for cardiovascular events: previous history of myocardial infarction, peripheral vascular disease, previous stoke, angina, hypertension and elevated lipids. Moreover, there was an excess of males in the placebo group. The composite end point was of death from cardiovascular cause, myocardial infarction or stoke, and 651 patients in the ramipril group and 827 in the placebo group were affected. This gave an excess of primary endpoints in the placebo group of 176 cases. However, at baseline, there was an excess in the placebo group of individuals with previous ischaemic heart disease (95), peripheral vascular disease (119), previous stroke (13) and hypertension (69). Heart failure surprisingly occurred in similar numbers in the ramipril and placebo groups (81 vs. 79) respectively. The claim that this particular ACE inhibitor protects against cardiovascular disease is unfounded because of baseline imbalance in risk. Copyright © 2001 John Wiley & Sons, Ltd.
Causes of obesity
Authors: P.H. Wilding John
Published: August 2002

Obesity is an increasingly common problem that is recognised a disease by the WHO. It is a major risk factor for the development of type 2 diabetes because it causes insulin resistance and is associated with physical inactivity. Obesity develops when energy intake exceeds energy expenditure over a prolonged period of time, leading to an accumulation of body fat. Body weight is regulated by the hypothalamus, and there have been many recent advances in understanding of energy balance that might help understand why some individuals develop obesity, and lead to new treatments. Both genetic and environmental factors contribute to the development of obesity. The recent identification of rare single gene defects that cause severe early onset obesity, such as deficiency of the hormone leptin, demonstrate that genetic factors can be powerful determinates of body mass. However, obesity has been increasing rapidly throughout the world in the last two decades, so it seems unlikely that this change has a genetic basis. It seems more plausible that the increasing weight of most populations is an appropriate biological response to an abnormal environment, characterised by easy availability of cheap, energy dense food, coupled with a massive decline in physical activity levels in the population. The challenge in preventing type 2 diabetes is to reverse these trends, and help those already obese to adopt a lifestyle that encourages weight loss, including a healthy diet and greater physical activity. Copyright © 2001 John Wiley & Sons, Ltd.
Ulcer complications associated with anti‐inflammatory drug use. What is the extent of the disease burden?
Authors: Langman M. J. S.
Published: August 2002

Information on the intake of non‐steroidal anti‐inflammatory drugs (NSAIDs) and on aspirin taken regularly by patients with peptic ulcer bleeding aged 60 years and over was used in conjunction with data measuring the overall frequency of hospital admissions with ulcer bleeding in England and Wales to determine the annual burden of disease imposed by particular treatment strategies. Over 40% of the calculated 8528 episodes of ulcer bleeding in those aged 60 years and over, and over 40% of the estimated 981 deaths each year would seem to be causally related to the treatments. Substitution of the NSAID with the lowest associated risk would be expected to reduce the frequency of non‐aspirin NSAID‐associated episodes of ulcer bleeding, and deaths, each by over 70%. Use of the lowest conventional dose of regular prophylactic aspirin (75 mg) would also be expected to reduce the frequency of treatment‐related episodes, and deaths, by nearly 30%. Both strategies employed together would be expected to reduce NSAID and regular aspirin‐related bleeding ulcer admissions from 4121 to less than 2184, and deaths from 523 to less than 250. Substitution of completely safe anti‐inflammatory analgesics and anti‐platelet drugs would be expected to reduce admissions from 4121 to 1072, and deaths from 523 to 123. Copyright © 2001 John Wiley & Sons, Ltd.
Benzodiazepine use in patients hospitalized in a department of internal medicine: frequency and clinical correlates
Authors: Lagnaoui Rajaa , Moore Nicholas , Longy‐Boursier Maïté , Baumevieille Marie , Bégaud Bernard
Published: August 2002

Purpose

Misuse and overuse of benzodiazepines (BZD) are common. Several studies have shown that benzodiazepines are frequently used in hospitalized patients, but fewer studies have been conducted to investigate whether BZD use increases during the hospital stay or whether patients have already taken BZD before admission.

Objective

to assess the prevalence of benzodiazepine use in hospitalized patients and to determine characteristics associated with this use.

Methods

Prospective study over a 4‐month period based on all admissions to a department of internal medicine. The main outcome was the prevalence of benzodiazepine use at admission, during hospital stay and at discharge.

Results

Of 444 patients admitted, 147 (33%) used at least one benzodiazepine which was in 75% of the cases, short‐elimination half‐life BZD used as hypnotic. Of 105 (23.6%) patients using BZD at admission, 23 (5.2%) stopped BZD during hospital stay or when leaving hospital. The in‐hospital prevalence of BZD use was 30% (133 patients). In 28 (6.3%) patients without BZD at baseline, BZD was introduced during the hospital stay then stopped at discharge in 18 (4%) patients. The prevalence of BZD use at discharge was 23.9% (106 patients). In multivariate analyses, BZD use was significantly associated with number of drugs taken during hospitalization (OR:1.13; 95% CI: 1.03–1.24), and current neuropsychiatric diseases (OR:2.12; 95% CI: 0.86–5.23), but not with gender, age or length of stay.

Conclusion

Prevalence of BZD use appeared to be fairly high among hospitalized patients. There were very few new BZD users during hospital stay, most of whom were stopped at discharge. Most treatments were started before hospital, and continued during and after hospital stay without clear reevaluation. Copyright © 2001 John Wiley & Sons, Ltd.