bluuebunny/crossref_metadata_2025 huggingface dataset:
Microsphere‐induced embolic stroke: An MRI study
Authors: Mayzel‐Oreg Orna , Omae Tsuyoshi , Kazemi Mark , Li Fuhai , Fisher Marc , Cohen Yoram , Sotak Christopher H.
Published: May 2004

Despite the many studies of the middle cerebral artery occlusion (MCAO) model, efficient therapy for stroke is still lacking, emphasizing the need for further development and characterization of experimental stroke models. In the present study, the rather unexplored multifocal microsphere‐induced stroke model in rats was characterized by multiparametric MRI. We induced microembolic infarction in a group of Sprague‐Dawley rats by injecting a dose of about 1000 50‐μm polyethylene microspheres intracranially from the external carotid artery. Diffusion‐, perfusion‐, and T2‐weighted MRI were used to evaluate the infarct development during and following the first 3 hr after microsphere injection (N = 20). The animals were also imaged at 12‐hr (N = 8), 24‐hr (N = 17), and 48‐hr (N = 5) time points. After the final imaging time point, the brains were removed and sectioned into 2‐mm‐thick slices, and infarct volumes were measured by 2,3,4‐triphenyltetrazolium chloride (TTC) staining. From calculated apparent diffusion coefficient (ADC) maps, a volume of reduced ADC appeared 0.5–1.0 hr postinjection, and by the 3‐hr time point the volume of ADC reduction had increased to a size of 5% ± 1% (mean ± SEM) of the brain hemisphere. The lesion volume increased significantly (P < 0.01) to 16% ± 2% of the hemisphere volume at the 12‐hr time point, while at 24 hr the lesion (15% ± 2% of the hemisphere) was also significantly larger (P < 0.001) than at 3 hr. The perfusion deficit resulting from the microsphere injection was immediate, going from a cerebral blood flow index (CBFi) of 74% ± 3% at the time of microsphere injection to 68% ± 2% of the contralateral mean at 3 hr (P < 0.05), to 55% ± 4% of the contralateral values at 12 hr (P < 0.05), and to 57% ± 2% of the contralateral mean at 24 hr (P < 0.001). The lesion development in the microsphere‐induced stroke model was found to be slower than in the MCAO model, and continued up to the 24–48‐hr time point. Magn Reson Med 51:1232–1238, 2004. © 2004 Wiley‐Liss, Inc.
High‐resolution fast spin echo imaging of the human brain at 4.7 T: Implementation and sequence characteristics
Authors: Thomas David L. , De Vita Enrico , Roberts Steven , Turner Robert , Yousry Tarek A. , Ordidge Roger J.
Published: May 2004

In this work, a number of important issues associated with fast spin echo (FSE) imaging of the human brain at 4.7 T are addressed. It is shown that FSE enables the acquisition of images with high resolution and good tissue contrast throughout the brain at high field strength. By employing an echo spacing (ES) of 22 ms, one can use large flip angle refocusing pulses (162°) and a low acquisition bandwidth (50 kHz) to maximize the signal‐to‐noise ratio (SNR). A new method of phase encode (PE) ordering (called “feathering”) designed to reduce image artifacts is described, and the contributions of RF (B1) inhomogeneity, different echo coherence pathways, and magnetization transfer (MT) to FSE signal intensity and contrast are investigated. B1 inhomogeneity is measured and its effect is shown to be relatively minor for high‐field FSE, due to the self‐compensating characteristics of the sequence. Thirty‐four slice data sets (slice thickness = 2 mm; in‐plane resolution = 0.469 mm; acquisition time = 11 min 20 s) from normal volunteers are presented, which allow visualization of brain anatomy in fine detail. This study demonstrates that high‐field FSE produces images of the human brain with high spatial resolution, SNR, and tissue contrast, within currently prescribed power deposition guidelines. Magn Reson Med 51:1254–1264, 2004. © 2004 Wiley‐Liss, Inc.
Observation of significant signal voids in images of large biological samples at 11.1 T
Authors: Beck Barbara L. , Jenkins Kelly , Caserta Jim , Padgett Kyle , Fitzsimmons Jeffrey , Blackband S.J.
Published: May 2004

Proton MRI of large biological samples were obtained on an 11.1 T / 40 cm instrument. Images were obtained of a fixed human brain and a large piece of fresh beef. The proton MR images demonstrate severe distortions within these conductive samples, indicative of shortened electrical wavelengths and wave behavior within the sample. These observations have significant implications with respect to the continuing evolution of MR to higher magnetic field strengths on large samples, particularly on humans. Magn Reson Med 51:1103–1107, 2004. © 2004 Wiley‐Liss, Inc.
Navigator gating and volume tracking for double‐triggered cardiac proton spectroscopy at 3 Tesla
Authors: Schär Michael , Kozerke Sebastian , Boesiger Peter
Published: May 2004

Respiratory motion compensation based on navigator echoes for double‐triggered cardiac proton spectroscopy at 3.0T is presented. The navigators measure the displacement of the liver–lung interface during free breathing. This information allows for double triggering on a defined window within the respiratory cycle and on a defined trigger delay after the R‐wave based on the ECG. Furthermore, it allows the excitation volume to be shifted by the determined respiratory displacement within the defined window in real‐time (volume tracking). Static and motion phantom experiments were performed in this study, and it was demonstrated that volume tracking permits the suppression of signal from tissue next to the localized volume. However, triggering on a defined respiratory position is still necessary to achieve high spectral quality, because shimming and water suppression calibration are only optimal for a small window of the respiratory cycle. Single‐volume spectra obtained in the myocardial septum of healthy subjects are presented. Magn Reson Med 51:1091–1095, 2004. © 2004 Wiley‐Liss, Inc.
Method for reduced SAR T1ρ‐weighted MRI
Authors: Wheaton Andrew J. , Borthakur Arijitt , Corbo Matthew , Charagundla Sridhar R. , Reddy Ravinder
Published: May 2004

A reduced specific absorption rate (SAR) version of the T1ρ‐weighted MR pulse sequence was designed and implemented. The reduced SAR method employs a partial k‐space acquisition approach in which a full power spin‐lock pulse is applied to only the central phase‐encode lines of k‐space, while the remainder of k‐space receives a low‐power spin‐lock pulse. Acquisition of high‐ and low‐power phase‐encode lines are interspersed chronologically to minimize average power deposition. In this way, the majority of signal energy in the central portion of k‐space receives full T1ρ‐weighting, while the average SAR of the overall acquisition can be reduced, thereby lowering the minimum safely allowable TR. The pulse sequence was used to create T1ρ maps of a phantom, an in vivo mouse brain, and the brain of a human volunteer. In the images of the human brain, SAR was reduced by 40% while the measurements of T1ρ differed by only 2%. The reduced SAR sequence enables T1ρ‐weighted MRI in a clinical setting, even at high field strengths. Magn Reson Med 51:1096–1102, 2004. © 2004 Wiley‐Liss, Inc.
p‐version of the generalized FEM using mesh‐based handbooks with applications to multiscale problems
Authors: Strouboulis Theofanis , Zhang Lin , Babuška Ivo
Published: May 2004

In this paper, we analyse the p‐convergence of a new version of the generalized finite element method (generalized FEM or GFEM) which employs mesh‐based handbook functions which are solutions of boundary value problems in domains extracted from vertex patches of the employed mesh and are pasted into the global approximation by the partition of unity method (PUM). We show that the p‐version of our GFEM is capable of achieving very high accuracy for multiscale problems which may be impossible to solve using the standard FEM. We analyse the effect of the main factors affecting the accuracy of the method namely: (a) The data and the buffer included in the handbook domains, and (b) The accuracy of the numerical construction of the handbook functions. We illustrate the robustness of the method by employing as model problem the Laplacian in a domain with a large number of closely spaced voids. Similar robustness can be expected for problems of heat‐conduction and elasticity set in domains with a large number of closely spaced voids, cracks, inclusions, etc. Copyright © 2004 John Wiley & Sons, Ltd.
Multi‐scale analysis and FE computation for the structure of composite materials with small periodic configuration under condition of coupled thermoelasticity
Authors: Feng Yong‐Ping , Cui Jun‐Zhi
Published: May 2004

The two‐scale asymptotic (TSA) expressions of the increment of temperature and the displacement for the structure of composite materials with small periodic configuration under coupled thermoelasticity condition are derived formally in this paper, especially, the two‐scale coupled relation between the increment of temperature and the displacements are set up. Then the approximate solutions and their error estimations are presented, and the multi‐scale finite element algorithm corresponding to TSA is described. Finally, simple numerical results evaluated by multi‐scale FE computation are shown. They demonstrate that the basic configuration and the increment of temperature strongly influence upon local strains and local stresses inside basic cell. Copyright © 2004 John Wiley & Sons, Ltd.
Adhesive element modelling and weighted static shape control of composite plates with piezoelectric actuator patches
Authors: Sun Dongchang , Tong Liyong
Published: May 2004

A novel finite element model is presented for static and dynamic analysis of composite plates integrated with a laminated piezoelectric layer, a host laminated composite plate and an adhesive layer between them. A new adhesive element is developed which includes both peel and shear effects in the adhesive layer based on first‐order shear deformation plate theory. The thin adhesive layer between the piezoelectric layer and the host plate is modelled by assuming that it carries constant shear and peel strains throughout its thickness. In addition, a weighted static shape control scheme for finding the optimal voltage distribution for static shape control is given. By selecting different weighting matrices, a variety of items such as displacements, slopes, curvatures, strains and even generalized forces, can be included in finding the optimal actuating voltage for static shape control. The present model is validated by comparing with those results available in the literature. The numerical results show that the weighted linear least method can give a satisfactory voltage distribution to best match the desired shape. Copyright © 2004 John Wiley & Sons, Ltd.
Comparison of regularization methods for solving the Cauchy problem associated with the Helmholtz equation
Authors: Marin L. , Elliott L. , Heggs P. J. , Ingham D. B. , Lesnic D. , Wen X.
Published: May 2004

In this paper, several boundary element regularization methods, such as iterative, conjugate gradient, Tikhonov regularization and singular value decomposition methods, for solving the Cauchy problem associated to the Helmholtz equation are developed and compared. Regularizing stopping criteria are developed and the convergence, as well as the stability, of the numerical methods proposed are analysed. The Cauchy problem for the Helmholtz equation can be regularized by various methods, such as the general regularization methods presented in this paper, but more accurate results are obtained by classical methods, such as the singular value decomposition and the Tikhonov regularization methods. Copyright © 2004 John Wiley & Sons, Ltd.
Procedures for approximate eigenproblem reanalysis of structures
Authors: Kirsch Uri , Bogomolni Michael
Published: May 2004

In vibration mode superposition analysis, the main computational effort is spent in the solution of the eigenproblem. In reanalysis procedures this solution must be repeated for each change in the design. It is shown in this study how the combined approximations method can be used to improve the efficiency of some common iterative procedures. These procedures can then be used for efficient eigenproblem reanalysis. Solution of the reduced eigenproblem by the combined approximations method is first demonstrated. Procedures based on inverse iteration, inverse iteration with shifts, and subspace iteration are then considered. Some numerical examples show that high accuracy is achieved for very large changes in the design. In cases where higher accuracy is required, additional terms of the approximations may be considered. Copyright © 2004 John Wiley & Sons, Ltd.
Bifurcation points and bifurcated branches by an asymptotic numerical method and Padé approximants
Authors: Boutyour E. H. , Zahrouni H. , Potier‐Ferry M. , Boudi M.
Published: May 2004

The aim of this work is to develop a reliable and fast algorithm to compute bifurcation points and bifurcated branches. It is based upon the asymptotic numerical method (ANM) and Padé approximants. The bifurcation point is detected by analysing the poles of Padé approximants or by evaluating, along the computed solution branch, a bifurcation indicator well adapted to ANM. Several examples are presented to assess the effectiveness of the proposed method, that emanate from buckling problems of thin elastic shells. Especially problems involving large rotations are discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Studies of the strong coupling and weak coupling methods in FSI analysis
Authors: Zhang Qun , Hisada Toshiaki
Published: May 2004

The weak coupling methods in fluid–structure interaction analysis are newly classified into three types; the weak coupling method for solving structures with interfaces, the weak coupling method for solving fluids with interfaces, and the weak coupling method for solving both fluids and structures with interfaces. The consistent added matrices of these weak coupling methods are derived from the condensation of the strong coupling formulation. Some approximations for the consistent added matrices, which can avoid the matrix coupling, are proposed. The reasons for convergence difficulty in the weak coupling methods are clarified. A number of numerical results are presented to investigate the convergence properties and computational efficiency of these methods. Copyright © 2004 John Wiley & Sons, Ltd.
Truncation error and stability analysis of iterative and non‐iterative Thomas–Gladwell methods for first‐order non‐linear differential equations
Authors: Kavetski Dmitri , Binning Philip , Sloan Scott W.
Published: May 2004

The consistency and stability of a Thomas–Gladwell family of multistage time‐stepping schemes for the solution of first‐order non‐linear differential equations are examined. It is shown that the consistency and stability conditions are less stringent than those derived for second‐order governing equations. Second‐order accuracy is achieved by approximating the solution and its derivative at the same location within the time step. Useful flexibility is available in the evaluation of the non‐linear coefficients and is exploited to develop a new non‐iterative modification of the Thomas–Gladwell method that is second‐order accurate and unconditionally stable. A case study from applied hydrogeology using the non‐linear Richards equation confirms the analytic convergence assessment and demonstrates the efficiency of the non‐iterative formulation. Copyright © 2004 John Wiley & Sons, Ltd.
An adaptive least squares mixed finite element method for the stress‐displacement formulation of linear elasticity
Authors: Cai Zhiqiang , Korsawe Johannes , Starke Gerhard
Published: May 2004

A least‐squares mixed finite element method for linear elasticity, based on a stress‐displacement formulation, is investigated in terms of computational efficiency. For the stress approximation quadratic Raviart‐Thomas elements are used and these are coupled with the quadratic nonconforming finite element spaces of Fortin and Soulie for approximating the displacement. The local evaluation of the least‐squares functional serves as an a posteriori error estimator to be used in an adaptive refinement algorithm. We present computational results for a benchmark test problem of planar elasticity including nearly incompressible material parameters in order to verify the effectiveness of our adaptive strategy. For comparison, conforming quadratic finite elements are also used for the displacement approximation showing convergence orders similar to the nonconforming case, which are, however, not independent of the Lamé parameters. © 2004 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2005
High‐order numerical methods for one‐dimensional parabolic singularly perturbed problems with regular layers
Authors: Clavero C. , Gracia J. L. , Jorge J. C.
Published: May 2004

In this work we construct and analyze some finite difference schemes used to solve a class of time‐dependent one‐dimensional convection‐diffusion problems, which present only regular layers in their solution. We use the implicit Euler or the Crank‐Nicolson method to discretize the time variable and a HODIE finite difference scheme, defined on a piecewise uniform Shishkin mesh, to discretize the spatial variable. In both cases we prove that the numerical method is uniformly convergent with respect to the diffusion parameter, having order near two in space and order one or 3/2, depending on the method used, in time. We show some numerical examples which illustrate the theoretical results, in the case of using the Euler implicit method, and give better numerical behaviour than that predicted theoretically, showing order two in time and order N−2log2N in space, if the Crank‐Nicolson scheme is used to discretize the time variable. Finally, we construct a numerical algorithm by combining a third order A‐stable SDIRK with two stages and a third‐order HODIE difference scheme, showing its uniformly convergent behavior, reaching order three, up to a logarithmic factor. © 2004 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2005
Rhabdomyolysis with HMG‐CoA reductase inhibitors and gemfibrozil combination therapy
Authors: Chang Jennie T. , Staffa Judy A. , Parks Mary , Green Lanh
Published: May 2004

Context

Elevated total cholesterol (total‐C) and low‐density lipoprotein cholesterol (LDL‐C) levels are established risk factors for cardiovascular disease (CVD). HMG‐CoA reductase inhibitors (statins) are effective cholesterol‐lowering drugs that are commonly prescribed to treat this condition. These drugs are often combined with another class of drugs, fibric acid derivatives, to lower both cholesterol and triglyceride levels. Rhabdomyolysis is a known, rare serious side effect of statin monotherapy and of statin‐fibrate combination therapy.

Objective

To examine Food and Drug Administration's (FDA's) postmarketing database for cases of rhabdomyolysis in relation to monotherapy and combination use and calculate reporting rates for this event.

Design

Domestic cases of statin‐ and statin/gemfibrozil‐associated rhabdomyolysis were culled from FDA's database and reviewed. Rhabdomyolysis was defined by CPK ≥ 10 000 IU/L, myopathic signs and symptoms and clinical diagnosis of rhabdomyolysis. Reporting rates, consisting of number of reported cases/number of prescriptions for each drug, were then calculated to determine whether the reporting of rhabdomyolysis cases was commensurate with extent of use of each statin in the population.

Setting

Cases were obtained from the FDA adverse event reporting system (AERS) database.

Patients

NA.

Main Outcome Measures

Number of rhabdomyolysis cases were evaluated, along with outcomes, such as renal failure, dialysis and death.

Results

Of 866 total reported cases, 482 (56%) were associated with monotherapy and 384 (44%) related to combination therapy. More than 80% of reported cases for each drug resulted in hospitalization for renal failure and dialysis. 80 patients expired from events related directly to rhabdomyolysis. Reporting rates for all statins, except for cerivastatin, were similar and much lower than 1 per 100 000 prescriptions. The cerivastatin‐reporting rate was much higher at 4.24/100 000 prescriptions.

Conclusions

Rhabdomyolysis is a rare, serious side effect of statin monotherapy and of statin‐fibrate combination therapy. Clinicians need to remain cognizant of this potential adverse event and discuss signs and symptoms of muscle toxicity with patients in order improve the benefits‐to‐risks of treating dyslipidemia with statins. Copyright © 2004 John Wiley & Sons, Ltd.
A proteomic approach to analyze salt‐responsive proteins in rice leaf sheath
Authors: Abbasi Fida Mohammad , Komatsu Setsuko
Published: May 2004

To examine the response of rice to salt stress, changes in protein expression were analyzed using a proteomic approach. To investigate dose‐ and time‐dependent responses, rice seedlings were exposed to 50, 100 and 150 mM NaCl for 6 to 48 h. Proteins were extracted from leaf sheath and separated by two‐dimensional polyacrylamide gel electrophoresis. Eight proteins showed 1‐ to 3‐fold up‐regulation in leaf sheath, in response to 50 mM NaCl for 24 h. Among these, three proteins were unidentified (LSY081, LSY262 and LSY363) while five proteins were identified as fructose bisphosphate aldolases, photosystem II (PSII) oxygen evolving complex protein, oxygen evolving enhancer protein 2 (OEE2) and superoxide dismutase (SOD). The maximum expression levels of seven proteins were at 24 h. Their expression declined after 48 h of 50 mM NaCl treatment. In contrast, SOD maintained its elevated expression throughout these conditions. The increased expression of proteins seen in the 50 mM NaCl treatment group was less pronounced in the groups receiving 100 or 150 mM NaCl for 24 h. The expression of SOD was a common response to cold, drought, salt and abscisic acid (ABA) stresses while the expression of LSY081, LSY363 and OEE2 was enhanced by salt and ABA stresses. LSY262 was expressed in leaf sheath and root, while fructose bisphosphate aldolases, PSII oxygen evolving complex protein and OEE2 were expressed in leaf sheath and leaf blade. LSY363 was expressed in leaf sheath but was below the level of detection in leaf blade and root. These results indicate that specific proteins expressed in specific regions of rice show a coordinated response to salt stress.
Copolymerization of allyl butyl ether with acrylates via controlled radical polymerization
Authors: Venkatesh Rajan , Vergouwen Frank , Klumperman Bert
Published: May 2004

The atom transfer radical polymerization (ATRP) and reversible addition–fragmentation chain transfer (RAFT) of acrylates (methyl acrylate and butyl acrylate) with allyl butyl ether (ABE) were investigated. Well‐defined copolymers containing almost 20 mol % ABE were obtained with ethyl‐2‐bromoisobutyrate as an initiator. Narrow molar mass distributions (MMDs; polydispersity index ≤ 1.3) were obtained from the ATRP experiments, and they suggested conventional ATRP behavior, with no peculiarities caused by the incorporation of ABE. The comparable free‐radical (co)polymerizations resulted in broad MMDs. Increasing the fraction of ABE in the monomer feed led to an increase in the level of incorporation of ABE in the copolymer, at the expense of the overall conversion. Similarly, RAFT copolymerizations with S,S′‐bis(α,α′‐dimethyl‐α″‐acetic acid)trithiocarbonate also resulted in excellent control of the polymerization with a significant incorporation of ABE within the copolymer chains. The formation of the copolymer was confirmed with matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOF MS). From the obtained MALDI‐TOF MS spectra for the ATRP and RAFT systems, it was evident that several units of ABE were incorporated into the polymer chain. This was attributed to the rapidity of the cross‐propagation of ABE‐terminated polymeric radicals with acrylates. This further indicated that ABE was behaving as a comonomer and not simply as a chain‐transfer agent under the employed experimental conditions. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3271–3284, 2004
Influence of carboxyl‐terminated (butadiene‐co‐acrylonitrile) loading on the mechanical and thermal properties of cured epoxy blends
Authors: Thomas Raju , Abraham Jacob , Thomas P Selvin , Thomas Sabu
Published: May 2004

A mixture of epoxy with liquid nitrile rubber, carboxyl‐terminated (butadiene‐co‐acrylonitrile) (CTBN) was cured under various temperatures. The cured resin was a two‐phase system, where spherical rubber domains were dispersed in the matrix of epoxy. The morphology development during cure was investigated by scanning electron microscope (SEM). There was slight reduction in the glass transition temperature of the epoxy matrix (Tg) on the addition of CTBN. It was observed that, for a particular CTBN content, Tg was found to be unaffected by the cure temperature. Bimodal distribution of particles was noted by SEM analysis. The increase in the size of rubber domains with CTBN content is due probably to the coalescence of the rubber particles. The mechanical properties of the cured resin were thoroughly investigated. Although there was a slight reduction in tensile strength and young's modulus, appreciable improvements in impact strength, fracture energy, and fracture toughness were observed. Addition of nitrile rubber above 20 parts per hundred parts of resin (phr) made the epoxy network more flexible. The volume fraction of dispersed rubbery phase and interfacial area were increased with the addition of more CTBN. A two‐phase morphology was further established by dynamic mechanical analysis (DMA). © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 2531–2544, 2004
Effect of crosslinking on intermolecular interactions in thermosetting blends of epoxy resin with poly(ethylene oxide)
Authors: Hu Lindi , Lü Han , Zheng Sixun
Published: May 2004

The miscibility and intermolecular‐specific interactions in thermosetting blends of epoxy resin (ER) with poly(ethylene oxide) (PEO) cured with various amounts of 1,3,5‐tridroxybenzene (THB) were investigated by differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). The glass‐transition behavior indicated that all the blends were miscible and had homogeneous amorphous phases; FTIR showed that there were the intermolecular hydrogen‐bonding interactions between crosslinked ER and PEO. However, both the glass‐transition behavior and infrared spectroscopy also indicated that the intermolecular interactions were significantly reduced by the formation of crosslinked structures, which was shown by comparing the experimental results of poly(hydroxyether of bisphenol A) (PH)/PEO and ER/PEO blends cured with various amounts of the curing agent. In ER/PEO blends the intermolecular hydrogen‐bonding interactions were much weaker than the self‐association of hydroxyls of ER, which was in marked contrast to the interactions in PH/PEO blends. In ER/PEO blends with various amounts of the curing agent, the intermolecular interactions between epoxy polymers and PEO were reduced with an increasing degree of crosslinking. The results were interpreted in terms of the effect of crosslinking on the intermolecular interactions, such as steric shielding, the screening effect, and chain connectivity resulting from the formation of the three‐dimensional crosslinked network, which could reduce the intermolecular hydrogen‐bonding interactions among hydroxyls of ER versus ether oxygen atoms of PEO. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 2567–2575, 2004
Respiratory illness in children attending daycare
Authors: Dales Robert E. , Cakmak Sabit , Brand Kevin , Judek Stan
Published: May 2004

Daycare attendance has been associated with an increased occurrence of respiratory illness, but little is known about which children are at particular risk. Our objectives were to determine the association between the incidence of respiratory illness and attendance in daycare, and to determine if the risk is modified by selected sociodemographic factors. Using a prospective study design, 185 newborns in Prince Edward Island, Canada, were recruited between January 1997–March 2000. They were followed for 2 years or until the end‐date of the study in September 2000. Information on daycare attendance and respiratory illness was collected twice monthly by telephone interviews of the parent. Comparing those who were ever in daycare more than 1 day per week (daycare group) to those who were not, the association between daycare and illness was stronger among children 15 months of age compared to those less than 3 months of age (P < 0.001), and stronger among those without siblings than those with siblings (P < 0.001). Among those not in daycare, family income was inversely related to the proportion of days with an illness episode: 9.8% (CI, 6.0, 13.6) if family income was <$30,000 vs. 5.2% (CI, 4.1, 6.3) if ≥$30,000 (P = 0.003). However, in the daycare group, income did not influence illness, with respective values of 14.6% (CI, 12.4, 16.8) vs. 13.2% (CI, 12.1, 14.3) (P = 0.21). In conclusion, younger children and those with siblings may be less susceptible to illness associated with daycare, and daycare attendance may negate a protective effect of higher income on respiratory illness. Pediatr Pulmonol. 2004; 38:64–69. © 2004 Wiley‐Liss, Inc.
Clinical value of obtaining sputum and cough swab samples following inhaled hypertonic saline in children with cystic fibrosis
Authors: Ho S.A. , Ball R. , Morrison L.J. , Brownlee K.G. , Conway S.P.
Published: May 2004

Prompt detection and treatment of lower respiratory tract infection are essential in the management of patients with cystic fibrosis (CF), who often have signs or symptoms of respiratory infection without any pathogens being isolated from sputum or cough swab specimens. The aims of this study were to assess the efficacy and clinical value of obtaining sputum and oropharyngeal cough swab samples following induction with hypertonic saline (HS) in this group of patients. Forty‐three outpatients with CF, mean age 7.2 years (range, 1.8–12.9 years), were recruited over a 2‐year period. Nebulized salbutamol was administered, followed by 6% HS. Sputum was preferentially obtained before and after HS induction if possible. If the patient was not able to expectorate, oropharyngeal cough swabs were taken instead. Four patients were able to expectorate sputum before and 19 after HS induction. The procedure was tolerated in 41 of 43 patients. Pathogens were isolated from 13 patients' HS‐induced samples, but not from their corresponding preinduced specimens, and 4 patients' preinduced specimens cultured organisms which were not identified from their HS‐induced samples. Significant changes were made in the management of 13 (30.2%) patients directly resulting from the positive culture of pathogens only from HS‐induced samples. Cultures from oropharyngeal cough swab or expectorated sputum specimens following inhalation of HS provide additional microbiological information which is of clinical value and may lead to changes in patient management. Pediatr Pulmonol. 2004; 38:82–87. © 2004 Wiley‐Liss, Inc.
Longitudinal study of oxidative status in 312 cystic fibrosis patients in stable state and during bronchial exacerbation
Authors: Lagrange‐Puget Marie , Durieu Isabelle , Ecochard René , Abbas‐Chorfa Fatima , Drai Jocelyne , Steghens Jean‐Paul , Pacheco Yves , Vital‐Durand Denis , Bellon Gabriel
Published: May 2004

In cystic fibrosis (CF), there is an imbalance in the oxidant/antioxidant system, leading to oxidative damage. The aim of this study was to assess antioxidant‐scavenger deficiencies and lipid peroxide variations in three clinical situations (stable status, acute exacerbation, and after intravenous antibiotic treatment). The objective was also to correlate oxidative stress with age, nutritional status, and respiratory function. The study included prospectively 312 consecutive patients and 53 controls. Antioxidants (vitamin A, vitamin E, carotenoids, and glutathione) and oxidative markers (malondialdehyde and lipid peroxides) were measured in plasma. Regression analyses were performed. Antioxidant levels were lower in CF patients than in controls. These levels decreased during acute exacerbation and increased after antibiotic treatment. Carotenoid levels were not modified by infection or age. Only vitamin A and carotenoid levels were positively correlated to body mass index. Antioxidant levels were correlated to forced expiratory volume at 1 sec. Lipid peroxidation markers were lower in patients than in controls. Their levels decreased during infection, and increased after antibiotic treatment. Impaired lung function was correlated with elevated malondialdehyde levels. In conclusion, this study demonstrates antioxidant deficiency in a very large cohort of CF patients. Carotenoid and vitamin E deficiencies occur early in the course of the disease. Antioxidants decrease with bronchial infection. By contrast, nutritional disorders did not modify antioxidant levels during acute exacerbations. Thus, pulmonary disorders rather than nutritional disorders seem to be essential in the imbalance of the oxidant/antioxidant system. Results concerning glutathione and oxidative‐marker levels highlighted the fact that their plasma values do not reflect oxidative stress in the respiratory tract. Pediatr Pulmonol. 2004; 38:43–49. © 2004 Wiley‐Liss, Inc.
Effect of DNase on exercise capacity in cystic fibrosis
Authors: Barker Michael , Franke Egbert , Böhle Martin , Pfannenstiel Claus , Heimann Gerhard
Published: May 2004

DNase can reduce viscosity and facilitate expectoration of airway secretions in cystic fibrosis (CF) lung disease. We evaluated its effect on exercise performance in relation to resting pulmonary function. Fifteen sputum‐producing CF patients (aged 9–28 years; FEV1 22–83% predicted) performed spirometry, body plethysmography, nitrogen washout, and incremental cardiopulmonary exercise testing before and after 8 weeks of first‐time treatment with daily inhaled rhDNase. Most subjects reported increased amounts and fluidity of sputum. The effect on objective parameters was heterogeneous, without statistical significance. Groupwise, FEV1 increased by 6% without correlation to baseline values; individual patients gained up to 40%. Indices of hyperinflation and air trapping were slightly raised. Maximal workload and oxygen uptake (V′O2) increased by up to 20% in a number of patients. The treatment effect on V′O2 was neither related to baseline levels of pulmonary function and exercise capacity nor to the change in FEV1. Ventilatory equivalents for oxygen and carbon dioxide during exercise were slightly but insignificantly lower after DNase treatment; minimal O2 saturation was unaffected. We conclude that improvement of exercise performance with DNase is restricted to a subgroup of CF patients and may not be predicted or identified by spirometry and subject report alone. Pediatr Pulmonol. 2004; 38:70–74. © 2004 Wiley‐Liss, Inc.
Symptoms, lung function, and β2‐adrenoceptor polymorphisms in a birth cohort followed for 10 years
Authors: Wilson Nicola M. , Lamprill Jane R. , Mak Judith C.W. , Clarke Jane R. , Bush Andrew , Silverman Michael
Published: May 2004

As little is known about the natural history of bronchial responsiveness and the development of wheezing symptoms in early childhood, a cohort of children at risk of allergy, whose lung function and bronchial responsiveness had been measured in the neonatal period, was followed prospectively for 10 (SD, 0.8) years in order to determine the role of neonatal measurements on wheezing history and later lung function. A potential role for beta‐2 adrenoceptor (β2AR) polymorphisms in these relationships was also sought as a secondary objective. Of the original 73 children, wheezing history was available in 65 (89%), and 49 (67%) attended the laboratory for physiological measurements and genotyping of β2AR. Wheezing was categorized as occurring 1) only before the fourth birthday, 2) after the fourth birthday, or 3) never. No relation was seen between neonatal and later lung function. However, neonatal bronchial responsiveness predicted subsequent FEV1 (P = 0.03). Increased neonatal bronchial responsiveness was associated with transient wheeze <4 years but not with later wheeze. Neonatal V′maxFRC was reduced in those possessing Gln27 or Arg16 alleles, but there was no effect of β2AR polymorphisms on FEV1 at 10 years. Wheeze after 4 years of age was typical of classical asthma, as it was strongly related to atopy and bronchial responsiveness at age 10. In conclusion, we confirmed the association of neonatal bronchial responsiveness with both early wheezing and later lung function. We also showed an influence of polymorphisms at both aa16 and aa27 on neonatal lung function. Wheezing beyond 4 years, typical of classical asthma, was unrelated to early measurements of lung function or bronchial responsiveness. Pediatr Pulmonol. 2004; 38:75–81. © 2004 Wiley‐Liss, Inc.
Pulmonary arterial hypertension in children
Authors: Rosenzweig Erika Berman , Widlitz Allison C. , Barst Robyn J.
Published: May 2004

Pulmonary arterial hypertension is a serious progressive condition with a poor prognosis if not identified and treated early. Because the symptoms are nonspecific and the physical findings can be subtle, the disease is often diagnosed in its later stages. Remarkable progress has been made in the field of pulmonary arterial hypertension over the past several decades. The pathology is now better defined, and significant advances have occurred in understanding the pathobiologic mechanisms. Risk factors have been identified, and the genetics have been characterized. Advances in technology allow earlier diagnosis as well as better assessment of disease severity. Therapeutic modalities such as new drugs, e.g., epoprostenol, treprostinil, and bosentan, and surgical/interventional options, e.g., transplantation and atrial septostomy, which were unavailable several decades ago, have had a significant impact on prognosis and outcome. Thus, despite our inability to cure pulmonary arterial hypertension, advances in medical treatments over the past two decades have resulted in significant improvement in outcomes for children with various forms of pulmonary arterial hypertension. This report is a review the current state of the art for pulmonary arterial hypertension in 2004, with an emphasis on childhood pulmonary arterial hypertension and specific recommendations for current practice and future directions. Pediatr Pulmonol. 2004; 38:2–22. © 2004 Wiley‐Liss, Inc.
PCD and RP: X‐linked inheritance of both disorders?
Authors: Krawczyński Maciej R. , Witt Michał
Published: May 2004

A Caucasian, seven‐generation family of Polish origin with apparently X‐linked inheritance of coexisting retinitis pigmentosa (RP) and primary ciliary dyskinesia (PCD), with 14 identified males affected with RP and 14 obligate healthy female carriers, is presented. To our knowledge, four of the RP‐affected males were diagnosed with PCD. The cases might imply the presence of one of the PCD loci, influencing neither laterality nor fertility, within the X‐chromosome. Pediatr Pulmonol. © 2004 Wiley‐Liss, Inc.
Conformational study of fragments of envelope proteins (gp120: 254–274 and gp41: 519–541) of HIV‐1 by NMR and MD simulations
Authors: Kanyalkar Meena , Srivastava Sudha , Saran Anil , Coutinho Evans
Published: May 2004

The envelope proteins, gp120 and gp41 of HIV‐1, play a crucial role in receptor (CD4+ lymphocytes) binding and membrane fusion. The fragment 254–274 of gp120 is conserved in all strains of HIV and, as a part of the full gp120 protein, behaves as ‘immunosilent’, but as an individual fragment it is ‘immunoreactive’. When this fragment binds to its receptor, it activates the fusion domain of gp41 allowing viral entry into the host CD4+ cells. The conformation of fragment 254–274 of the gp120 domain and fragment 519–541 of the gp41 domain was studied by NMR and MD simulations. The studies were carried out in three varied media—water, DMSO‐d6 and hexafluoroacetone (HFA). The fusogenic nature of the gp41 domain peptide was investigated by 31P NMR experiments with model bilayers prepared from dimyristoyl‐L‐α‐phosphatidylcholine (DMPC). The solvent was seen to exert a major effect on the structure of the two peptides. Fragment (254–274) of gp120 in DMSO‐d6 had a type I β‐turn around the tetrad Val9‐Ser10‐Thr11‐Gln12 while in HFA a helical structure spanning the region Ile5 to Gln12 was seen with the remaining part of the peptide in a random coil structure. It is possible that the β‐turn may constitute an initiation site for the formation of the helix. In water at pH 4.5, the peptide adopted a β‐sheet. The NMR results for fragment 519–541 of gp41 are conclusive of a β‐sheet structure in DMSO‐d6, a conformation which may help in insertion into the membrane, a notion also put forward by others. The 31P NMR studies of DMPC vesicles with this fragment show its fusogenic nature, promoting fusion of unilamellar vesicles to larger agglomerates like multilamellar ones. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.
Conformational analysis of peptide analogues of silkmoth chorion protein segments using CD, NMR and molecular modelling
Authors: Benaki Dimitra C. , Mikros Emmanuel , Hamodrakas Stavros J.
Published: May 2004

Silkmoth proteins secreted from the follicular cells that surround the oocyte form a large extracellular assembly which is important for protecting and sustaining the structure of the oocyte and the developing embryo. These proteins have been classified into two major families (A and B). Sequence analysis showed conservation of a central domain containing long stretches of six amino acid residue repeats in both families, which have been suggested to be organized in β‐sheet structures. In this work NMR and CD spectra, as well as molecular calculations, have been used to investigate the conformational properties of two synthetic peptides (A and B), analogues of parts of the central domain of silkmoth chorion proteins of the A and B families, respectively. These peptides consist of three tandem repeats of the six‐residue basic motif. Analysis of CD spectra of the two peptides in aqueous solutions and mixtures with organic solvents revealed β‐sheet and turn structural elements with a percentage higher than 40%. NOESY spectra at low temperatures (263–273 K) show sequential nOe connectivities (i, i+1), indicative of a relative flexibility. The presence of H Ni‐HNi+1 cross‐peaks and medium Hαi‐HNi+1 connectivities, chemical shift deviations and temperature coefficient data provide, for the first time, experimental evidence that local folded structures around Gly residues occur in peptide segments of chorion proteins in solution. Simulated annealing calculations were used to examine the conformational space of the peptides and to probe the initial steps of amyloid fibril formation in the case of chorion proteins. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.
A combinatorial approach to the synthesis of cystine based organogelators
Authors: Matteucci Mizio , Bhalay Gurdip , Bradley Mark
Published: May 2004

A solid‐phase approach was used to prepare 20 cystine amide derivatives with disulfide bond formation resulting from an intra‐site reaction between neighbouring cysteine residues. Library members were screened as potential organogelators in a range of solvent mixtures and resulted in the identification of a potent gelator able to rigidify water/DMSO mixtures at concentrations as low as 1.3 mM. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.
Peptides and multiple antigen peptides from Schistosoma mansoni glyceraldehyde 3‐phosphate dehydrogenase: preparation, immunogenicity and immunoprotective capacity in C57BL/6 mice
Authors: Vepr̆ek Pavel , Jez̆ek Jan , Velek Jir̆í , Tallima Hatem , Montash Mona , Ridi Rashika El
Published: May 2004

Four monoepitopic MAPs (MAP A, B, C and E) and one bis‐diepitopic MAP B‐E derived from the primary sequence of Schistosoma mansoni glyceraldehyde 3‐phosphate dehydrogenase, previously tested in BALB/c mice, were examined for their immunogenicity and protective capacity in C57BL/6 mice. Despite multimerization into MAPs, MAP A and MAP C were poorly immunogenic. In contrast to BALB/c mice, MAP E was non‐immunogenic in C57BL/6 mice. Peptide B in the form of MAP B or bis‐diepitopic MAP B‐E elicited immune responses in C57BL/6 mice that were associated with a significant decrease in worm burden.

The MAPs were prepared by the stepwise solid‐phase peptide synthesis using Boc/Bzl chemistry, successfully purified on the RP‐HPLC column and characterized by RP‐HPLC, HPCE and MALDI‐TOF MS techniques. A general strategy for MAPs purification is discussed here and the purification of MAP B and MAP E is documented in detail. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.
Synthesis and characterization of a chimeric peptide derived from fasciculin that inhibits acetylcholinesterase
Authors: Falkenstein Roberto J. , Gornalusse Germán G. , Peña Clara
Published: May 2004

Fasciculins are peptides isolated from mamba (Dendroaspis) venoms which exert their toxic action by inhibiting acetylcholinesterase (AChE). They contain a characteristic triple stranded antiparallel β‐sheet formed by residues 22–27, 34–39 and 48–53. A chimeric peptide named Fas‐C, encompassing most of these sequences was synthesized using SPPS/Boc‐chemistry and characterized chemically, structurally and functionally. Fas‐C has two disulfide bridges, formed sequentially using dual cysteine protection.

SDS‐PAGE patterns, HPLC profiles and MS proved the peptide identity. Circular dichroism indicated the presence of 13.6% and 41.6% of β‐sheet and β‐turn, respectively, comparable to values observed in the native toxin. An inhibitory effect on eel AChE was displayed by the peptide (Ki71.6 ± 18.3 µ M), although not reaching the affinity level of the parent native toxin (Ki 0.3 nM). It is confirmed that the principal binding region of fasciculin to AChE resides within loop II. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd.
Anti‐plasmodial activity of some Kenyan medicinal plant extracts singly and in combination with chloroquine
Authors: Muregi F. W. , Chhabra S. C. , Njagi E. N. M. , Lang'at‐Thoruwa C. C. , Njue W. M. , Orago A. S. S. , Omar S. A. , Ndiege I. O.
Published: May 2004

Sixty organic and aqueous extracts of eleven plants used for the control of malaria by local communities in Kisii District, Kenya were screened for in vitro anti‐plasmodial activity. The plants selection was based on existing ethnobotanical information and interviews with local communities. The extracts were tested against chloroquine sensitive and resistant laboratory adapted strains of Plasmodium falciparum. The study revealed that 63.6% of the plants were active (IC50 ≤ 100 µg/mL). Extracts of four plants, Ekebergia capensis, Stephania abyssinica, Ajuga remota and Clerodendrum myricoides gave IC50 values below 30 µg/mL against both chloroquine sensitive and resistant P. falciparum strains. Combination of extracts of E. capensis and C. myricoides with chloroquine against the multi‐drug resistant P. falciparum isolate (V1/S) revealed synergistic effect. The plants which showed activity may be useful as sources for novel anti‐plasmodial compounds. Copyright © 2004 John Wiley & Sons, Ltd.
Antioxidant and free radical scavenging activities of 5,7,3′‐trihydroxy‐3,6,4′‐trimethoxyﬂavone from Brickellia veronicaefolia
Authors: Pérez G. R. M. , Vargas S. R. , Martinez M. F. J. , Cordova R. I.
Published: May 2004

The antioxidant and antiradical activities of 5,7,3′‐trihydroxy‐3,6,4′‐trimethoxyﬂavone or centaureidin isolated and characterized from Brickellia veronicaefolia were elucidated by heat‐induced oxidation in a β‐carotene and linoleic acid system and by the 1,1‐diphenyl‐2‐picrylhydrazyl decoloration test. The centaureidin (32.1%) exhibited antioxidative activity less than that of BHT (95.5%) and α‐tocopherol (95.9%) on oxidation in a β‐carotene and linoleic acid system. A moderate antiradical effect (47.6%) compared with BHT (96.7%) and α‐tocopherol (94.6%) in DPPH decoloration test was found. Copyright © 2004 John Wiley & Sons, Ltd.