bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of anomalous estimates of tensor‐derived quantities in diffusion tensor imaging
Authors: Koay Cheng Guan , Carew John D. , Alexander Andrew L. , Basser Peter J. , Meyerand M. Elizabeth
Published: March 2006

The diffusion tensor is typically assumed to be positive definite. However, noise in the measurements may cause the eigenvalues of the tensor estimate to be negative, thereby violating this assumption. Negative eigenvalues in diffusion tensor imaging (DTI) data occur predominately in regions of high anisotropy and may cause the fractional anisotropy (FA) to exceed unity. Two constrained least squares methods for eliminating negative eigenvalues are explored. These methods, the constrained linear least squares method (CLLS) and the constrained nonlinear least squares method (CNLS), are compared with other commonly used algebraic constrained methods. The CLLS tensor estimator can be shown to be equivalent to the linear least squares (LLS) tensor estimator when the LLS tensor estimate is positive definite. Similarly, the CNLS tensor estimator can be shown to be equivalent to the nonlinear least squares (NLS) tensor estimator when the NLS tensor estimate is positive definite. The constrained least squares methods for eliminating negative eigenvalues are evaluated with both simulations and in vivo human brain DTI data. Simulation results show that the CNLS method is, in terms of mean squared error for estimating trace and FA, the most effective method for correcting negative eigenvalues. Magn Reson Med, 2006. Published 2006 Wiley‐Liss, Inc.
Iterative blind deconvolution in magnetic resonance brain perfusion imaging
Authors: Grüner Renate , Taxt Torfinn
Published: March 2006

In first pass magnetic resonance brain perfusion imaging, arterial input functions are used in the deconvolution of the observed contrast concentrations to obtain quantitative hemodynamic parameters. Ideally, arterial input functions should be measured in each imaged voxel to eliminate the effects of delay and dispersion of the contrast agent from the injection site. An approach based on iterative blind deconvolution with the Richardson–Lucy algorithm is proposed for the simultaneous estimation of voxel‐specific arterial input functions and voxel‐specific tissue residue functions. An extended contrast concentration model was used to separate the first pass bolus from additional recirculation and leakage signals. The extended model was evaluated using in vivo data. Computer simulations examined the feasibility of iterative blind deconvolution in perfusion imaging. Preliminary in vivo results from a patient with fibromuscular dysplasia showed territories with delayed/dispersed arterial input functions that coincided with the location of territories supplied by collateral circulation as described from the complete radiologic examination. Higher flow values and shorter mean transit times compared to conventional methods were obtained in these areas, suggesting that the effects of dispersion were minimized. The in vivo estimated arterial input functions visualized the patient's blood supply patterns as a function of time. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Quantification of the shape of fiber tracts
Authors: Batchelor P. G. , Calamante F. , Tournier J.‐D. , Atkinson D. , Hill D. L. G. , Connelly A.
Published: March 2006

The fiber tracts generated using diffusion MRI are usually simply displayed and assessed visually for a specific clinical or medical research purpose. This paper proposes computational techniques that can be used to study the shape of the tracts and make interindividual comparisons. These methods make use of fundamental geometric invariants, such as curvatures and torsions, or Fourier descriptors, together with the link of a pair of curves. Intersubject comparisons only require that the starting and ending points of the tracts can be defined and do not require point‐by‐point correspondences such as obtained using image registration. Principal component analysis‐based shape analysis is also investigated. The invariants are tested on simulations and in vivo datasets, and the scale dependence and noise sensitivity of the measures are assessed. The potential for these techniques to be used in neuroscience research and clinical applications is demonstrated. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.
Using real options analysis to value reoptimization options in the shifting bottleneck heuristic
Authors: Yeung Thomas G. , Mason Scott J.
Published: March 2006

The reoptimization procedure within the shifting bottleneck (SB) involves reevaluation of all previously scheduled toolgroup subproblems at each iteration of the SB heuristic. A real options analysis (ROA) model is developed to value the option to reoptimize in the SB heuristic, such that reoptimization only occurs when it is most likely to lead to a schedule with a lower objective function. To date, all ROA models have sought to value options financially (i.e., in terms of monetary value). The ROA model developed in this paper is completely original in that it has absolutely no monetary basis. The ROA methodologies presented are shown to greatly outperform both full and no reoptimization approaches with respect to both computation time and total weighted tardiness. © 2006 Wiley Periodicals, Inc. Naval Research Logistics, 2006
Acquired coagulation factor inhibitors in children after topical bovine thrombin exposure
Authors: Savage William J. , Kickler Thomas S. , Takemoto Clifford M.
Published: March 2006

Acquired inhibitors of coagulation factors, particularly to factor V (FV) and thrombin, after topical bovine thrombin exposure may result in clinically important coagulopathies. While bovine thrombin is commonly used in pediatric patients for surgical hemostasis, the reported cases of acquired inhibitors in children are few. We report two cases of children who developed factor inhibitors after bovine thrombin exposure. One child developed a FV inhibitor at 3 months of age after exposure to bovine thrombin during cardiac surgery. The inhibitor resolved with intravenous immunoglobulin (IVIG) and steroids. The other child developed concomitant FV and bovine thrombin inhibitors after cardiac surgery at age 11 years. The presence of these inhibitors complicated post‐operative anti‐coagulation management, but the inhibitors were transient. In addition to these two cases, we identified all the pediatric patients with bovine thrombin‐induced inhibitors who were reported in the world's literature, and reviewed their clinical characteristics. These cases underscore the fact that bovine thrombin can be antigenic in infants and children and can result in significant coagulopathies. Pediatr Blood Cancer 2007;49:1025–1029. © 2006 Wiley‐Liss, Inc.
Memory deficits in long‐term survivors of childhood brain tumors may primarily reflect general cognitive dysfunctions
Authors: Reimers Tonny Solveig , Mortensen Erik Lykke , Schmiegelow Kjeld
Published: March 2006

Background

To analyze the impact of potential predictors on memory performance in survivors of childhood brain tumors and to examine whether deficits in memory after radiotherapy (RT) should be considered part of a more global mental dysfunction.

Procedure

We studied 126 patients with brain tumors diagnosed before the age of 15 years and treated January 1970 through February 1997 in Eastern Denmark. Sixty‐nine of the 126 patients had received RT. In addition to working memory and long‐term memory (LTM), general intelligence (IQ) was assessed.

Results

The mean test scores in nearly all memory tests were lower than expected from available norms. In multiple linear regression, treatment with RT, hemisphere tumor location, and hydrocephalus treated with a shunt at the time of diagnosis were found to be significant risk factors for memory deficits. When IQ was included as a covariate, RT did not significantly predict memory performance, while shunt and tumor location remained significant for several but not all tests.

Conclusion

These results suggest that in patients treated with RT, memory deficits primarily reflect a general cognitive dysfunction, and it is likely that these intelligence deficits may compromise the chances of success of special memory training. In contrast, memory deficits in non‐irradiated patients may to some degree reflect specific cognitive dysfunctions being most pronounced for patients treated with a shunt and for patients with hemispheric tumors. Pediatr Blood Cancer 2007;48:205–212. © 2006 Wiley‐Liss, Inc.
Hydroxyurea therapy lowers TCD velocities in children with sickle cell disease
Authors: Kratovil Tonya , Bulas Dorothy , Driscoll M. Catherine , Speller‐Brown Barbara , McCarter Robert , Minniti Caterina P.
Published: March 2006

Introduction

Hydroxyurea (HU) improves hematologic parameters and decreases adverse events in patients with sickle cell disease (SCD). HU has been proposed as an alternative to chronic transfusions for secondary stroke prevention. Transcranial doppler (TCD) is an accepted method of stroke risk stratification in patients with SCD. We sought to determine if HU affects TCD velocities in children with SCD.

Methods

A cohort of 24 children with HbSS with a baseline TCDi prior to HU and a follow‐up after at least 6 months of therapy was analyzed. Twenty‐four age‐matched children with HbSS formed the control group. Differences in hematologic parameters before and after HU therapy were evaluated.

Results

TCDi velocities decreased in the HU‐treated patients. The adjusted mean change in TCDi velocities was −13.0 cm/sec (95% CI −20.19, −5.92) in the HU‐treated group and +4.72 cm/sec (95% CI −3.24, 12.69) in the controls. Changes in TCDi between the two groups were statistically significant (P < 0.001). Changes in hematologic parameters were not predictive of changes in TCDi velocities in the treated patients. Four out of five patients with TCDi velocities >170 cm/sec had normalization of TCDi velocities on HU. Mean change was −34.75 cm/sec in this subgroup. No patients experienced cerebrovascular accidents (CVA) while on HU.

Conclusions

HU‐treated patients experienced statistically significant decreases in TCDi velocities compared to age‐matched controls. Changes in hematologic parameters were not predictive of changes in TCDi velocities in the treated group. The decrease in TCDi velocities is not a consequence of changes in hematologic values in patients treated with HU. Pediatr Blood Cancer © 2006 Wiley‐Liss, Inc.
Proteome analysis of multidrug resistance in vincristine‐resistant human gastric cancer cell line SGC7901/VCR
Authors: Yang Yi‐Xuan , Xiao Zhi‐Qiang , Chen Zhu‐Chu , Zhang Gui‐Ying , Yi Hong , Zhang Peng‐Fei , li Jian‐Ling , Zhu Guo
Published: March 2006

In order to elucidate the mechanisms of multidrug resistance (MDR) of vincristine‐resistant human gastric carcinoma cell line SGC7901/VCR, 2‐DE was used to separate the total proteins of SGC7901/VCR and its parental cell line SGC7901. PDQuest software was applied to analyze 2‐DE images, and the differential protein spots were identified by both MALDI‐TOF‐MS and ESI‐Q‐TOF‐MS. Then the differential expressional levels of partially identified proteins were determined by Western blot analysis and real‐time RT‐PCR. Furthermore, the association of heat shock protein (HSP27), one of the highly expressed proteins in sgc7901/vcr, with MDR was analyzed using antisense inhibition of HSP27. In this study, the well‐resolved, reproducible 2‐DE patterns of SGC7901/VCR and SGC7901 were established, and yielded about 1100 protein‐spots each. All the 24 differential proteins between the two cell lines were identified, and the differential expression levels of the partial proteins were confirmed. The suppression of HSP27 expression by HSP27 antisense oligonucleotides could enhance vincristine chemosensitivity in sgc7901/vcr and induce the cells to exhibit apoptotic morphological features after vincristine treatment. The differentially expressed proteins could be divided into six groups based on their functions: calcium‐binding proteins, chaperones, proteins involved in drug detoxification or repair of DNA damage, metabolic enzymes, proteins related to cellular structure, and proteins relative to signal transduction, some of which may contribute to MDR of human gastric carcinoma cell line SGC7901/VCR. These data will be valuable for further study of the mechanisms of MDR in human gastric cancer.
Ligand profiling and identification technology for searching bioactive ligands
Authors: Baek Moon‐Chang , Kim Sun‐Jin , Yea Kyungmoo , Kim Youndong , Lee Byung‐Dae , Kim Jaeyoon , Lee Hae‐Jeong , Kang Mee‐Hee , Choi Sun‐Kyu , Kim Jong‐In , Lee Taehoon G. , Suh Pann‐Ghill , Ryu Sung Ho
Published: March 2006

We introduce a new methodology named ligand profiling and identification for effective discovery of bioactive ligands such as peptide hormones. This technology was developed from a new concept of parallel column chromatography and active fraction profiling by nano‐LC MS. Traditional methods use sequential column chromatography, and thus are inevitably limited by the low abundance of the peptide of interest and by a low yield due to the many column steps. Using this new technology, insulin was successfully identified and diarginylinsulin, a minor intermediate form of insulin, was unexpectedly also identified simultaneously from 100 mg of porcine pancreatic tissue. This integrative technology could be used to search for various low‐abundance peptides (or bioactive molecules) rapidly and simultaneously, by applying this to the later stages of traditional sequential purification.
The HUPO Brain Proteome Project Jamboree: Centralised summary of the pilot studies
Authors: Hamacher Michael , Stephan Christian , Blüggel Martin , Chamrad Daniel , Körting Gerhard , Martens Lennart , Müller Michael , Hermjakob Henning , Parkinson David , Dowsey Andrew , Reidegeld Kai A. , Marcus Katrin , Dunn Michael J. , Meyer Helmut E. , Apweiler Rolf
Published: March 2006

The Bioinformatics Committee of the HUPO Brain Proteome Project (HUPO BPP) meets regularly to execute the post‐lab analyses of the data produced in the HUPO BPP pilot studies. On January 9–11, 2006 the members as well as invited analysts came together at the European Bioinformatics Institute in Hinxton, UK for the pilot studies jamboree. The results of the reprocessing were presented and tasks forces were initiated to compile, to interpret and to summarise the data obtained.
Dr. Hans‐Joachim Kraus receives a Wiley Pacesetter Award
Authors: Dunn Michael J.
Published: March 2006

No abstracts.
Effect of the dynamic absorptance of a metallic target surface on pulsed laser ablation
Authors: Li Li , Zhang Duanming , Li Zhihua , Guan Li , Tan Xinyu , Liu Dan , Fang Ranran
Published: March 2006

A theoretical model of pulsed laser ablation (PLA) considering the dynamic absorptance of a target surface is proposed. First, the expression for the dynamic absorptance as a function of irradiation time and incident laser intensity is derived. The incident laser intensity is assumed to be expressed by a Gauss function, which more closely approaches the actual case. The heat conduction equation considering the dynamic absorptance and the Gaussian distribution of laser intensity is then set up. Using tungsten as an example, the evolution of the absorptance with irradiation time and intensity before melting and after melting is numerically simulated, as well as the evolution of temperature with time. In addition, the evolution of melt depth with time is given. The effects of the dynamic absorptance on PLA are investigated in detail, especially for the evolution of temperature with time for the melt layer. Results show the dynamic absorptance affects the simulated results markedly, and its effects on the target temperature after melting become stronger than those before melting. A comparison of the calculated results with experimental data shows that the dynamic absorptance plays an important role during PLA. (© 2006 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Effect of chitosan coating and vacuum packaging on the quality of refrigerated grilled pork
Authors: Yingyuad Songchai , Ruamsin Sompoch , Reekprkhon Dhaweerat , Douglas Supaporn , Pongamphai Suwassa , Siripatrawan Ubonrat
Published: March 2006

The effects of chitosan coating and vacuum packaging on the quality and shelf‐life of retail packaged grilled pork in a PVDC/nylon pouch during refrigerated storage at 2 ± 1°C were investigated. Grilled pork without chitosan coating and packaged in 100% air was used as the control sample. Firmness, pH, colour, peroxide values, microbial population and shelf‐life (as determined by sensory characteristics) of the samples were determined during the storage. The results showed that colour, peroxide values and microbial population coincided with sensory characteristics. The delayed growth of microbes in vacuum packaging can be attributed to inhibition by low levels of O2. Chitosan coating was shown to minimize oxidation, as reflected by the peroxide values, colour changes and microbial counts of the samples. Vacuum‐packaged chitosan‐coated grilled pork showed negligible microbial growth and was found to be organoleptically acceptable throughout the storage period. Chitosan coating along with vacuum packaging provided a type of active packaging to maintain quality and extend the shelf‐life of grilled pork. Copyright © 2006 John Wiley & Sons, Ltd.
CNS Permeability of Drugs Predicted by a Decision Tree
Authors: Andres Claudia , Hutter Michael C.
Published: March 2006

To predict the ability of drug‐like molecules to penetrate the Central Nervous System (CNS), a decision tree was generated. This algorithm was designed to make a straight forward yes/no decision about the permeability of the blood‐brain barrier for a given substance, based on the numerical criteria of a large variety of molecular descriptors. The decision tree achieved a prediction accuracy of 96% for the 186 compounds of the training set and 84% for the test set comprising 38 molecules. We found that CNS+drugs are predicted with a higher accuracy (>94%) than CNS‐ substances (>89%).
Utilization of nanoscale zero‐valent iron for source remediation—A case study
Authors: Henn Keith W. , Waddill Dan W.
Published: March 2006

A pilot‐scale study was performed using a palladium‐catalyzed and polymer‐coated nanoscale zero‐valent iron (ZVI) particle suspension at the Naval Air Station in Jacksonville, Florida. A total of 300 pounds of nanoscale ZVI particle suspension was injected via a gravity feed and recirculated through a source area containing chlorinated volatile organic compounds (VOCs). The recirculation created favorable mixing and distribution of the iron suspension and enhanced the mass transfer of sorbed and nonaqueous constituents into the aqueous phase, where the contaminants could be reduced. Between 65 and 99 percent aqueous‐phase VOC concentration reduction occurred, due to abiotic degradation, within five weeks of the injection. The rapid abiotic degradation processes then yielded to slower biological degradation as subsequent decreases in ‐elimination parameters were observed—yet favorable redox conditions were maintained as a result of the ZVI treatment. Post‐treatment analyses revealed cumulative reduction of soil contaminant concentrations between 8 and 92 percent. Aqueous‐phase VOC concentrations in wells side gradient and downgradient of the source were reduced up to 99 percent and were near or below applicable regulatory criteria. These reductions, coupled with the generation of innocuous by‐products, indicate that nanoscale ZVI effectively degraded contamination and reduced the mass flux from the source, a critical metric identified for source treatment.
A summary of this project was recently presented at the US EPA Workshop on Nanotechnology for Site Remediation in Washington, D.C., on October 21–22, 2005. This case study supplied evidence that nanoscale zero valent iron, an emerging remediation technology, has been implemented successfully in the field. More information about this workshop and this presentation can be found at www.frtr.gov/nano/index.htm. © 2006 Wiley Periodicals, Inc.
Remediation of acid mine drainage leachate by a physicochemical and biological treatment‐train approach
Authors: Ngwenya Elvis G. , Walsh Maud , Metosh‐Dickey Caroline A. , Portier Ralph J.
Published: March 2006

Biological and physicochemical approaches were utilized in a treatment train for acid mine dis charge (AMD) waters. Anaerobic bioreactors, chemical precipitation reactors, and biopolymer chelation reactors, operated in static, semicontinuous, and continuous flow modes, removed significant quantities of metals and sulfates associated with AMD water. Static tests indicated accept able copper removal via precipitation by generation of hydrogen sulfide in anaerobic reactors. However, low pH affected the biopolymer coating in the chelation reactor, resulting in loss of bed surface. Corrections of AMD to pH > 7 resulted in some metal precipitationprior to biopolymer treatment. A series of static semicontinuous tests at pH 5.0 provided improved metal and sulfate removal. Copper (Cu+) was reduced to trace concentrations, while manganese (Mn+), although reduced, proved to be the most recalcitrant of the metals. © 2006 Wiley Periodicals, Inc.
Field performance of a fan‐driven spray evaporator
Authors: Flach Gregory P. , Sappington Frank C. , Dixon Kenneth L.
Published: March 2006

An emerging evaporation technology uses a powerful axial fan and high‐pressure spray nozzles to propel a fine mist into the atmosphere at high air and water flow rates. Commercial units have been deployed at several locations in North America and worldwide since the mid‐1990s, typically in arid or semiarid climates. A commercial spray evaporator was field tested at the U.S. Department of Energy's Savannah River Site in South Carolina to develop quantitative performance data under relatively humid conditions. A semiempirical correlation was developed from eight tests from March through August 2003. For a spray rate of 250 L/min (66 gpm) and continuous year‐round operation at the Savannah River Site, the predicted average evaporation rate is 48 L/min (13 gpm). © 2006 Washington Savannah River Company
Non‐parametric inference of adverse events under informative censoring
Authors: Nishikawa Masako , Tango Toshiro , Ogawa Makiko
Published: March 2006

In long‐term treatments or in treatments associated with frequent severe adverse events (AEs) such as those for oncology, it is important to know the probability of occurrence of AEs over time and their severity. However, some patients discontinue treatment and drop out of the clinical trial. Assumption that the drop‐outs are non‐informative is not always true and are not validated by data.

We propose a method of applying competing risk analysis by defining events of ‘occurrence of AE’ and ‘drop‐out prior to AE’. We focus on one AE at a time. We distinguish obvious non‐informative censoring from other censorings that may not be non‐informative. Therefore, our approach does not need an independent assumption for drop‐outs. The cumulative incidence function estimator (CIFE) for the AE by severity can be obtained by treating the degree of severity as a competing risk within the AE. We also propose a non‐parametric estimator of CIF for sequential occurrence of the same AE by forming a subset of subjects with prior occurrence(s) of the same AE and by applying Wang and Wells' estimator. We give a very simple formulation of the cumulative joint incidence function estimator (CJIFE) for subjects who drop out of the clinical trial after having suffered from the AE at least one time. We evaluate the performance of Pepe's variance estimator for CJIFE with small samples by simulations. We find that it works well with a sample size more than 100. A useful graphical presentation for CIFEs and CJIFE is shown. Copyright © 2006 John Wiley & Sons, Ltd.
Estimating the response rate in the presence of measurement error
Authors: Qu Yongming , Kulkarni Pandurang M. , Sanger Todd M.
Published: March 2006

In clinical research, it is often of interest to estimate the response rate (i.e. the proportion of subjects who achieve a clinically meaningful threshold) for a particular variable. The standard estimator of the response rate is generally biased in the presence of measurement error. The estimation accounting for the measurement error utilizing fully nonparametric (NP) methods is complicated and may not be efficient. Therefore, we propose a model‐based approach assuming a parametric model for the true value and only the first few moments for the measurement error. The estimator for the true response rate and the variance for the estimator are derived. An innovative method using bootstrap simulation is proposed to check the model assumption. Simulations show that the proposed estimator outperforms a fully NP estimator if the model assumption for X holds. This method is applied to address a commonly occurring question in osteoporosis regarding response to treatment in terms of longitudinal changes in bone mineral density (BMD). Bootstrap simulations showed that the model utilized is appropriate. The proposed method can also be applied in other fields of clinical research. Copyright © 2006 John Wiley & Sons, Ltd.
Revisiting the relation between change and initial value: a review and evaluation
Authors: Tu Yu‐Kang , Gilthorpe Mark S.
Published: March 2006

The relation between initial disease status and subsequent change following treatment has attracted great interest in clinical research. However, statisticians have repeatedly warned against correlating/regressing change with baseline due to two methodological concerns known as mathematical coupling and regression to the mean. Oldham's method and Blomqvist's formula are the two most often adopted methods to rectify these problems. The aims of this article are to review briefly the proposed solutions in the statistical and psychological literature, and to clarify the popular misconception that Blomqvist's formula is superior to Oldham's method. We argue that this misconception is due to a failure to recognize that the heterogeneity of individual responses to treatment is a source of regression to the mean in the analysis of the relation between change and initial value. Furthermore, we demonstrate how each method actually answers different research questions, and how confusion arises when this is not always understood. Copyright © 2006 John Wiley & Sons, Ltd.
Attitudes to Genetic Testing for Deafness: The Importance of Informed Choice
Authors: Guillemin Marilys , Gillam Lynn
Published: March 2006

With recent progress in the identification of genes for deafness, it is highly likely that genetic testing, including pre‐natal testing, for deafness will become more widely available. In a context where there are concerns about pre‐natal testing, and where many in the Deaf community contest the understanding of deafness as a disability, it is important to examine the attitudes of Deaf/deaf people toward genetic testing. This qualitative study employed in‐depth interviews to investigate the views about genetic testing for deafness of 19 participants, who were identified as functionally deaf or hearing impaired, or as belonging to the Deaf community. The key findings are that participants were generally supportive of genetic testing for deafness but only when full information about all relevant aspects of deafness is given to prospective users of genetics services. Participants emphasized informed choice, stating that information about medical and technological options for deaf people should be provided, together with information about communication, education, and the experience of being deaf. Although there was less support for pre‐natal diagnosis and termination of pregnancy for deafness, most participants nonetheless felt that individual choice was important and that pre‐natal diagnosis should be made available to those who wanted to use it.
Twin Gestation Pregnancies: Genetic Counseling and Testing Experience
Authors: Peters Kathryn F. , Saltsman Brian M. , Petrill Stephen A.
Published: March 2006

We report on the prenatal genetic counseling and testing experience in 343 pregnancies with twin or higher multiple gestations. By self‐report, 8% (27/343) parents of these pregnancies reported meeting with a genetic counselor, and 23% (79/343) elected prenatal genetic testing. The most common testing procedures elected were maternal serum analyte screening and amniocentesis to identify fetuses with aneuploidy or neural tube defects. Use of prenatal genetic testing was correlated with advanced maternal age. No association was found between use of genetic testing and use of OI/ART or the length of time needed to conceive. Forty percent (11/27) of those who met with a genetic counselor opted to decline prenatal testing/screening. These data suggest that although clients with multiple gestation pregnancies would likely benefit from genetic counseling, many are not availing themselves of this service. Implications of these data for the genetic counseling profession are discussed.
Thymosin β4 and AcSDKP inhibit the proliferation of HL‐60 cells and induce their differentiation and apoptosis
Authors: Huang Wei Qi , Wang Bao He , Wang Qi Ru
Published: March 2006

Our previous works have shown that bone marrow stromal cells secrete thymosin β4 (Tβ4) and AcSDKP. Tβ4 and AcSDKP are existed in the conditioned medium of bone marrow endothelial cells. They exerted inhibitory effects on hematopoietic cells and then had protective effect on the early hematopoietic cells, which were cultured in the presence of hematopoietic stimulators.

Thymosin β4 consists of 43 peptides with a molecular weight of 4963. It contains at its N‐terminal end the sequence of the acetylated tetrapeptide Ac‐N‐Ser‐Asp‐Lys‐Pro (AcSDKP). This study was performed to evaluate the effect of Tβ4 and AcSDKP on the growth of HL‐60 cells. It was showed that Tβ4 (10−11–10−7 mol/L) and AcSDKP (10−11–10−7 mol/L) had the dose‐dependent inhibitory effect on the proliferation of HL‐60 cells. Based on cell morphology and NBT reduction, Tβ4 and AcSDKP induced differentiation of HL‐60 cells. Morphologic and DNA fragment analysis proved that Tβ4 and AcSDKP induced apoptosis of HL‐60 cells. In order to analyze the mechanism of the effects of Tβ4 and AcSDKP, intracellular free Ca2+ concentration ([Ca2+]i) of HL‐60 leukemic cells was tested and Atlas cDNA Expression Array was performed. The results showed that Tβ4 and AcSDKP could increased [Ca2+]i by stimulating the release of Ca2+ from intracellular Ca2+ pool. Moreover, AcSDKP could also elicit a potent extracelluar calcium influx in HL‐60 cells. Tβ4 could also change apoptotic‐related gene expression in leukemic cells, and resulted in the inhibition of proliferation and induction of differentiation and apoptosis of leukemic cells.
Lipid peroxidation and antioxidant status in blood and tissue of malignant breast tumor and benign breast disease
Authors: Gönenç Aymelek , Erten Derya , Aslan Sabahattin , Akıncı Melih , Şimşek Bolkan , Torun Meral
Published: March 2006

Changes in the levels of malondialdehyde (MDA), nitrate and nitrite (as an index of nitric oxide production), lipid hydroperoxide (LOH), total antioxidant capacity (TAC), lipids (total cholesterol and triglycerides) and lipoproteins (HDL‐ and LDL‐cholesterol) were estimated in breast cancer patients (n = 15) and benign breast disease (n = 15). Serum and tissue MDA levels were found to be decreased in breast cancer patients compared to the benign group (p < 0.05). In contrast, nitrate and nitrite levels were increased in serum and tissue of the cancer group compared to benign breast disease patients (p < 0.05). Compared to the benign group, tissue TAC levels were elevated in the breast cancer patient group (p < 0.05). Total cholesterol and HDL‐cholesterol were elevated in the benign group compared with cancer patients (p < 0.05). These findings support the hypothesis that lipid peroxidation in serum and tissue of benign breast disease is greater than in breast cancer. However, the enhanced levels of nitric oxide may be in response to inflammation in patients with breast cancer. Total antioxidant status is lower in benign tissue than in cancerous tissue, probably to compensate for this elevated free radical production.
Src homology 2 domain of overexpressed Lyn kinase is responsible for the acceleration of granulocyte colony‐stimulating factor‐induced neutrophilic nuclear lobulation
Authors: Oka Naomi , Suzuki Akiko , Omura Tomomi , Sakai Hiroshi , Murakami Hiroshi
Published: March 2006

We have previously shown that the overexpression of a Src family kinase, Lyn, and its kinase‐negative form, LynKN, in a granulocyte progenitor cell line, GM‐I62M, accelerates neutrophilic nuclear lobulation when the cells are cultured in the presence of granulocyte colony‐stimulating factor. In this study, we investigated the role of the Src homology 2 (SH2) and SH3 domains of Lyn in the accelerated induction of nuclear lobulation. In contrast to wild‐type Lyn, the overexpression of its SH2 domain mutant did not induce the accelerated nuclear morphological changes, but the overexpressed SH3 domain mutant had the same effects as wild‐type Lyn. Therefore, the SH2 domain of Lyn is responsible for the accelerated induction of neutrophilic nuclear lobulation upon G‐CSF stimulation.
Decrease in plasma B‐type natriuretic peptide early after initiation of cardiac resynchronization therapy predicts clinical improvement at 12 months
Authors: Kubánek Miloš , Málek Ivan , Bytešník Jan , Frídl Petr , Riedlbauchová Lucie , Karasová Ludmila , Lánská Véra , Kautzner Josef
Published: March 2006

Background

Decrease in neurohormonal activation during pharmacotherapy for chronic heart failure (CHF) is associated with haemodynamic and clinical improvement. We tested the hypothesis that changes in neurohormonal activation after initiation of cardiac resynchronization therapy (CRT) predict its long‐term clinical effect.

Methods

The study group included 43 patients with CHF (37 males, mean age 62±9 years, NYHA class 3.2±0.4, QRS duration 195±24 ms) who underwent successful implantation of a CRT system. Pharmacotherapy remained stable during the first 3 months of follow‐up. Plasma levels of B‐type natriuretic peptide (BNP) and big endothelin‐1 (big ET‐1) were evaluated before and 3 months after implantation. Clinical, echocardiographic and exercise parameters were monitored for a mean period of 25.8±6.7 months.

Results

At 12 months of follow‐up 13 non‐responders were identified (no improvement in NYHA class (n=10), urgent heart transplantation (n=2) and death due to progressive heart failure (n=1)). CRT resulted in a significant reduction in neurohormone levels (BNP 345.4±346 vs. 267.7±320.8 pg/ml, p<0.01, big ET‐1 3.11±1.50 vs. 2.50±1.56 fmol/ml p<0.05), especially in responders. Percentage change in BNP level was a stronger predictor of long‐term clinical improvement than clinical, echocardiographic and exercise parameters at 3 months of follow‐up.

Conclusions

Percentage change in plasma BNP levels from baseline to 3 months was the strongest predictor of long‐term response to CRT and may have potential to predict outcome.
Thalidomide attenuates the development of fibrosis during post‐infarction myocardial remodelling in rats
Authors: Yndestad Arne , Vinge Leif Erik , Bjørnerheim Reidar , Ueland Thor , Wang Jacob E. , Frøland Stig S. , Attramadal Håvard , Aukrust Pål , Øie Erik
Published: March 2006

Background

Inflammation plays a pathogenic role in the development of heart failure (HF). The aim of this study was to examine the effect of treatment with the immunomodulating drug thalidomide in a rat model for post‐myocardial infarction (MI) HF.

Methods

Rats were subjected to MI by left coronary artery ligation or sham‐operated. Seven days after surgical intervention rats were randomised to treatment with thalidomide or vehicle for 8 weeks.

Results

Our main findings were: (i) thalidomide treatment did not affect cardiac function or the hypertrophic response, as determined by haemodynamic measurements and heart chamber weights, respectively. (ii) HF rats treated with thalidomide had a minor reduction in septum and relative wall thickness (p<0.05), indicating an anti‐remodelling effect. (iii) Thalidomide appeared to have immunostimulatory effects on the myocardium as evident by increased MIP‐1α gene expression (p<0.05). (iv) Treating HF rats with thalidomide reduced myocardial collagen content, as assessed by markedly decreased levels of hydroxyproline (~ 40% reduction; p<0.05), accompanied by lower TGF‐β1 gene expression (p<0.05).

Conclusion

Although thalidomide had no effect on cardiac function, our results suggest that intervention with thalidomide may have beneficial effects in post‐MI HF by attenuating collagen accumulation and development of myocardial fibrosis.
‘Frequent’ ventricular bigeminy – A reversible cause of dilated cardiomyopathy. How frequent is ‘frequent’?
Authors: Shanmugam N. , Chua T.P. , Ward D.
Published: March 2006

An interesting development in the field of heart failure has been the link between frequent premature ventricular contractions and cardiomyopathy. We report a patient whose frequent ventricular bigeminy resulted in left ventricular impairment that resolved after the use of non‐contact mapping during radiofrequency ablation. A review of the literature regarding possible mechanisms is discussed. For the practicing clinician, the question of ‘frequent’ should be taken in context of symptoms and LV function. A single 24‐h Holter monitor may not truly reflect the ectopic load. We recommend that if there is associated LV dysfunction and a causal link to frequent PVCs then suppression with radiofrequency ablation is a safe and effective treatment strategy.
Inhibition of the HERG K+channel by the antifungal drug ketoconazole depends on channel gating and involves the S6 residue F656
Authors: Ridley John M. , Milnes James T. , Duncan Rona S. , McPate Mark J. , James Andrew F. , Witchel Harry J. , Hancox Jules C.
Published: March 2006

The mechanism ofhuman ether‐à‐go‐go‐related gene(HERG) K+channel blockade by the antifungal agent ketoconazole was investigated using patch‐clamp recording from mammalian cell lines. Ketoconazole inhibited whole‐cell HERG current (IHERG) with a clinically relevant half‐maximal inhibitory drug concentration (IC50) value of 1.7 μM. The voltage‐ and time‐dependent characteristics ofIHERGblockade by ketoconazole indicated dependence of block on channel gating, ruling out a significant role for closed‐state channel inhibition. The S6 HERG mutations Y652A and F656A produced ∼4‐fold and ∼21‐fold increases in IC50forIHERGblockade, respectively. Thus, ketoconazole accesses the HERG channel pore‐cavity on channel gating, and the S6 residue F656 is an important determinant of ketoconazole binding.
The synaptic vesicle protein 2C mediates the uptake of botulinum neurotoxin A into phrenic nerves
Authors: Mahrhold Stefan , Rummel Andreas , Bigalke Hans , Davletov Bazbek , Binz Thomas
Published: March 2006

Botulinum neurotoxins (BoNTs) inhibit neurotransmitter release by selectively cleaving core components of the vesicular fusion machinery. The synaptic vesicle proteins Synaptotagmin‐I and ‐II act as receptors for BoNT/B and BoNT/G. Here we show that BoNT/A also interacts with a synaptic vesicle protein, the synaptic vesicle glycoprotein 2C (SV2C), but not with the homologous proteins SV2A and SV2B. Binding of BoNT/A occurs at the membrane juxtaposed region preceding transmembrane domain 8. A peptide comprising the intravesicular domain between transmembrane domains 7 and 8 specifically reduces the neurotoxicity of BoNT/A at phrenic nerve preparations demonstrating the physiological relevance of this interaction.
N‐Myristoyltransferase 2 expression in human colon cancer: Cross‐talk between the calpain and caspase system
Authors: Selvakumar Ponniah , Smith-Windsor Erin , Bonham Keith , Sharma Rajendra K.
Published: March 2006

A number of viral and eukaryotic proteins which undergo a lipophilic modification by the enzyme N‐myristoyltransferase (NMT: NMT1 and NMT2) are required for signal transduction and regulatory functions. To investigate whether NMT2 contributes to the pathogenesis of colorectal carcinoma, we observed a higher expression of NMT2 in most of the cases of cancerous tissues compared to normal tissues (84.6% of cases; P
< 0.05) by Western blot analysis. Furthermore, protein–protein interaction of NMTs revealed that m‐calpain interacts with NMT1 while caspase‐3 interacts with NMT2. Our findings provide the first evidence of higher expression of NMT2 in human colorectal adenocarcinomas and the interaction of both forms of NMT with various signaling molecules.
SKILLED CARE AT BIRTH IN THE DEVELOPING WORLD: PROGRESS TO DATE AND STRATEGIES FOR EXPANDING COVERAGE
Authors: STANTON CYNTHIA , BLANC ANN K. , CROFT TREVOR , CHOI YOONJOUNG
Published: March 2006

Skilled attendance at delivery is one of the key indicators to reflect progress toward the Millennium Development Goal of improving maternal health. This paper assesses global progress in the use of skilled attendants at delivery and identifies factors that could assist in achieving Millennium Development Goals for maternal health. National data covering a substantial proportion of all developing country births were used for the estimation of trends and key differentials in skilled assistance at delivery. Between 1990 and 2000, the percentage of births with a skilled attendant increased from 45% to 54% in developing countries, primarily as a result of an increasing use of doctors. A substantial proportion of antenatal care users do not deliver with a skilled attendant. Delivery care use among antenatal care users is highly correlated with wealth. Women aged 35 and above, who are at greatest risk of maternal death, are the least likely to receive professional delivery care. Births in mid-level facilities appear to be a strategy that has been overlooked. More effective strategies are needed to promote skilled attendance at birth during antenatal care, particularly among poor women. Specific interventions are also needed to encourage older and high parity mothers to seek professional care at delivery.
Thermal behaviour of crustaceans
Authors: Lagerspetz Kari Y. H. , Vainio Liisa A.
Published: March 2006

Specific thermoreceptors or putative multimodal thermoreceptors are not known in Crustacea. However, behavioural studies on thermal avoidance and preference and on the effects of temperature on motor activity indicate that the thermosensitivity of crustaceans may be in the range 0.2–2°C. Work on planktonic crustaceans suggests that they respond particularly to changes in temperature by klinokinesis and orthokinesis. The thermal behaviour of crustaceans is modified by thermal acclimation among other factors. The acclimation of the critical maximum temperature is an example of resistance acclimation, while the acclimation of preference behaviour may be classified as capacity acclimation of some other function. In crustaceans, the use of the concepts stenothermy and eurythermy at the species level is questionable, and it is not possible to divide crustacean species into thermal guilds as suggested for fishes. Thermal preference behaviour contributes to fitness in different ways in different species, often by maximising the aerobic metabolic scope for activity. In crustaceans the peripheral nervous system seems to have retained the capacity for thermosensitivity and thermal acclimation independently of the central nervous system control of behaviour.
Eisenbrief – Aktuelle Empfehlungen zur Therapie der Eisenmangelanämie
Authors: Schaefer  , Huch  , Krafft
Published: March 2006

Die Eisenmangelanämie ist eine häufige Komplikation bei chronisch kranken Patienten und in der Schwangerschaft. Der Eisenstatus lässt sich heute mittels Bestimmung von Serumferritin, Transferrinsättigung und gegebenenfalls von hypochromen Erythrozyten und Hämoglobingehalt der Retikulozyten (CHr) exakt und relativ unaufwendig charakterisieren. Die geringe Resorption und mangelnde Verträglichkeit limitieren in der Regel eine orale Eisensubstitution. In solchen Fällen bietet sich eine intravenöse Eisentherapie an, je nach Schweregrad der Anämie in Kombination mit rHuEPO (z.B. EPREX®/Epoetin alfa). Das in der Schweiz erhältliche Eisensaccharat (Venofer®) ermöglicht eine hochdosierte Eisensubstitution ohne Gefahr einer Anaphylaxie oder einer akuten Eisentoxizität.
Ist eine Teilanästhesie nur halb so schlimm? Regionalanästhesie versus Allgemeinanästhesie
Authors: Albrecht  , Filipovic
Published: March 2006

Die Wahl des Anästhesieverfahrens (Regional- oder Allgemeinanästhesie bzw. eine Kombination beider Verfahren) ist eine massgeschneiderte ärztliche Entscheidung. Sie wird von der Art des Eingriffes, der Erfahrung des Anästhesiearztes, vor allem aber auch den Begleiterkrankungen sowie den Wünschen und Ängsten des Patienten beeinflusst. In der Geburtshilfe vermochte die Einführung der Regionalanästhesie die Anästhesie-assoziierte Mortalität der Sectio caesarea markant zu senken. Entsprechend ist bei fehlenden Kontraindikationen die Regionalanästhesie für diesen Eingriff die Methode der Wahl. Hingegen sind in allen anderen chirurgischen Disziplinen die Regional- und die Allgemeinanästhesie einander hinsichtlich perioperativer Morbidität und Mortalität ebenbürtig. Bei grossen abdominellen und thorakalen Eingriffen werden Allgemein- und Regionalanästhesie häufig kombiniert und so ein synergistischer Effekt erzielt. Die Epiduralanästhesie wird vor der Einleitung der Allgemeinanästhesie eingelegt und intra- und postoperativ genutzt. Gegenüber einer alleinigen Allgemeinanästhesie kann damit eine verbesserte postoperative Schmerzkontrolle und eine Reduktion pulmonaler Komplikationen erreicht werden. Die perioperative Mortalität bleibt allerdings unbeeinflusst.
Spontanes Pneumomediastinum bei Asthma bronchiale
Authors: Wiesner  , Frey
Published: March 2006

Das Pneumomediastinum ist charakterisiert durch eine Luftansammlung im Mediastinum. Es entsteht meist infolge eines Thoraxtraumas. Ein spontanes Pneumomediastinum (sPM) tritt ohne eine erkennbare Ursache auf. Durch eine plötzliche Steigerung des intraalveolären Druckes (verursacht durch Husten oder körperliche Anstrengung) kommt es zur Alveolarruptur mit Übertritt von Luft über das bronchovaskuläre Bindegewebe ins Mediastinum. Das sPM ist eine seltene Komplikation des Asthma bronchiale, speziell bei jungen Männern. Wir stellen einen jungen Asthmapatienten mit einem sPM vor, bei dem zuerst eine allergische Reaktion diagnostiziert wurde, um auf diese seltene aber differentialdiagnostisch wichtige Symptomatik aufmerksam zu machen. Über das sPM ist in den letzten Jahren als zunehmendes Problem im Zusammenhang mit inhalativem Betäubungsmittelabusus berichtet worden.
Tako-Tsubo Kardiomyopathie (transient left ventricular apical ballooning) – eine wichtige Differentialdiagnose der akuten koronaren Herzkrankheit
Authors: Schneiter
Published: March 2006

Wir berichten über ein bisher wenig bekanntes Syndrom einer Form einer Kardiomyopathie, bei der es zu ausgeprägter Wandbewegungsstörung resp. Akinesie des linksventrikulären Apex sowie der midventrikulären Abschnitte kommt. Das Syndrom ist klinisch kaum von einem akuten Myokardinfarkt zu unterscheiden, das häufigste Symptom ist der akute Thoraxschmerz. Elektrokardiographisch finden sich ausgeprägte Repolarisationsstörungen bis hin zum Bild eines akuten ST-Hebungsinfarktes, ohne dass im Verlauf eine entsprechende myokardiale Nekrose im Sinne eines Makroinfarktes zu beobachten ist. Betroffen sind vorwiegend Frauen im mittleren oder höheren Alter, häufig lässt sich ein emotionaler oder physischer Trigger als möglicher auslösender Faktor in der Anamnese der Patientinnen eruieren. Die Prognose dieses seit knapp über zehn Jahren vorwiegend in Japan/Asien bekannten Krankheitsbildes ist in den meisten Fällen trotz dramatischer initialer Präsentation gut, bereits innerhalb von Stunden/Tagen kann sich die linksventrikuläre Kinetik vollständig normalisieren. Bisher ist dieses Krankheitsbild in der westlichen Welt kaum bekannt, die Prävalenz entsprechend unbekannt.