bluuebunny/crossref_metadata_2025 huggingface dataset:
EFFICIENT RECONFIGURABLE MANCHESTER ADDERS FOR LOW-POWER MEDIA PROCESSING
Authors: CORSONELLO PASQUALE , PERRI STEFANIA
Published: April 2005

A new highly reconfigurable Manchester adder for low-power media signal processing is presented. The proposed circuit can be run-time partitioned. Its 64-bit version performs one 64-, two 32-, four 16-, or eight 8-bit additions. When the AMS 0.35 mm 2-poly 3-metal 3.3 V CMOS (CSD) process is used to produce a layout, an energy dissipation of only 78 pJ and a worst propagation delay of about 10.2 ns are obtained. The novelty demonstrated in this letter is that the introduction of dummy bit positions along the carry-path can be avoided using on-purpose dynamic logic stages.
AB INITIO CALCULATIONS OF INTERMOLECULAR INTERACTION POTENTIALS OF FULLERENE-FRAGMENTS SYSTEMS
Authors: KITA YUKIUMI , WAKO KEI , OKADA ISAMU , TACHIKAWA MASANORI
Published: April 2005

We have performed the ab initio molecular orbital calculations for combinations of the fullerene-fragments as the models of the nonbonding interaction of C 60 dimer at the preferred configurations in the simple cubic phase. The intermolecular interaction potentials have been calculated using several basis sets with MP2 level of the electron correlation energy and the basis set superposition error correction. The strong dispersion attractions that is dominant in the van der Waals interaction has been found for the combinations of the fullerene-fragments. The equilibrium intermolecular distances obtained are in good agreement with the corresponding experimental value. The repulsive region of the intermolecular interaction calculated by ab initio method is found to be express by an atom–atom interaction potential with an anisotropic exponential type repulsive term, which is less steep than the conventional Lennard–Jones type potential.
AB INITIO PATH INTEGRAL STUDY ON ISOTOPE EFFECT OF AMMONIA MOLECULE
Authors: TACHIKAWA MASANORI , SHIGA MOTOYUKI
Published: April 2005

We have applied ab initio path integral molecular dynamics simulation to study the quantum feature and proton/deuteron isotope effect of ammonia molecule. This method treats all the rotational and vibrational degrees of freedom fully quantum mechanically, while the potential energies of the respective molecular configurations are calculated "on the fly" using ab initio quantum chemical approach. The differences on the geometry and the electronic structure between NH 3 and ND 3 molecules are investigated in detail.
THEORETICAL TRANSITION PROBABILITIES FOR THE $\tilde{A}^{2}A_{1} -\tilde{X}^{2}B_{1}$ SYSTEM OF H2O+ AND D2O+ AND RELATED FRANCK–CONDON FACTORS BASED ON GLOBAL POTENTIAL ENERGY SURFACES
Authors: TOKUE IKUO , YAMASAKI KATSUYOSHI , MINAMINO SATOSHI , NANBU SHINKOH
Published: April 2005

To elucidate the ionization dynamics, in particular the vibrational distribution, of H 2 O +(Ã) produced by photoionization and the Penning ionization of H 2 O and D 2 O with He *(2 3S) atoms, Franck–Condon factors (FCFs) were given for the [Formula: see text] ionization, and the transition probabilities were presented for the [Formula: see text] emission. The FCFs were obtained by quantum vibrational calculations using the three-dimensional potential energy surfaces (PESs) of [Formula: see text] and [Formula: see text] electronic states. The global PESs were determined by the multi-reference configuration interaction calculations with the Davidson correction and the interpolant moving least squares method combined with the Shepard interpolation. The obtained FCFs exhibit that the [Formula: see text] state primarily populates the vibrational ground state, as its equilibrium geometry is almost equal to that of [Formula: see text], while the bending mode (ν2) is strongly enhanced for the H 2 O +(Ã) state; the maximums in the population of H 2 O + and D 2 O + are approximately v2 = 11–12 and 15–17, respectively. These results are consistent with the distributions observed by photoelectron spectroscopy. Transition probabilities for the [Formula: see text] system of H 2 O + and D 2 O + show that the bending progressions consist primarily of the [Formula: see text] emission, with combination bands from the (1, v′2 = 4–8, 0) level being next most important.
A NEW ORBITAL INTERACTION ANALYSIS SYSTEM "LUMMOX" AND IT'S APPLICATION OF PHOSPHINE-PALLADIUM COMPLEXES
Authors: YAMANAKA MASAHIRO , SHIGA AKINOBU
Published: April 2005

A new orbital interaction analysis system, "LUMMOX", is based on two theories of "Paired Interacting Orbital (PIO)" and "Localized Frontier Orbital (LFO)", which have been developed by Fujimoto et al. LUMMOX can readily estimate the reactivity of an interacting system A–B of various sizes with the same A by comparing with the same number of the interacting orbitals. By applying LUMMOX, we report herein the primary orbital interaction on the phosphine-palladium complexes ( PF 3 Pd , PH 3 Pd , PMe 3 Pd , PPh 3 Pd ) continuously changes from the donative to back-donative interaction.
DYNAMICS OF SIMPLE FLUIDS CONFINED IN CYLINDRICAL PORE: EFFECT OF PORE SIZE
Authors: KIM HYUNGJUN , CHO CHUL HEE , LEE EOK KYUN
Published: April 2005

We study the thermodynamic and dynamical properties of Weeks–Chandler–Anderson (WCA) fluids confined in a cylindrical pore by means of a canonical molecular dynamics simulation method. The pore model is an infinitely long cylinder consisted of a thermal wall and mimics a typical carbon nanotube. The thermodynamic properties are obtained for relatively high density fluids over a wide range of pore diameters at a given temperature. The size dependence of the self-diffusion coefficients in the cylindrical pore is also investigated. It is found that, as the pore diameter decreases, the potential energy and axial component of the pressure exhibit a sharp rise and the self-diffusion coefficient decreases. The observed behaviors can be understood in terms of the geometrical confinement and attenuation of transport induced by dispersive fluid-wall interaction. In addition, anomalous diffusion is observed at the pore size corresponding to twice the particle diameter.
Nedd4–2 isoforms differentially associate with ENaC and regulate its activity
Authors: Itani Omar A. , Stokes John B. , Thomas Christie P.
Published: April 2005

Mutations that disrupt a PY motif in epithelial Na+channel (ENaC) subunits increase surface expression of Na+channels in the collecting duct, resulting in greater Na+reabsorption. Nedd4 and Nedd4–2 have been identified as ubiquitin ligases that can interact with ENaC via its PY motifs to regulate channel activity. We recently reported that human Nedd4–2 (hNedd4–2) is expressed as many isoforms because of alternative promoter usage and/or variable splicing. To understand the relevance of hNedd4–2 isoforms for collecting duct Na+transport, we studied the interaction with ENaC and the intracellular localization and function of the following three naturally occurring hNedd4–2 isoforms: full-length Nedd4–2 (Nedd4–2), Nedd4–2 lacking the NH2-terminal C2 domain (Nedd4–2ΔC2), and Nedd4–2 lacking the C2 domain and WW domains 2 and 3 (Nedd4–2ΔWW2,3). Nedd4–2 and Nedd4–2ΔC2 associate with ENaC and robustly reduce Na+transport in Xenopus oocytes, whereas the interaction with and functional effect of Nedd4–2ΔWW2,3 on ENaC is weak. Nedd4–2 is expressed in the mouse collecting duct, and overexpression of Nedd4–2 reduces endogenous ENaC activity in a collecting duct cell line. This reduction in ENaC activity can be reversed early with exposure to dexamethasone, an effect that is associated with an increase in sgk1 abundance. The C2 domain is required to target Nedd4–2 to the plasma membrane in response to elevation of intracellular Ca2+concentration ([Ca2+]i) in MDCK cells, although it does not appear to mediate the inhibitory effect of [Ca2+]ion Na+transport. Our data illustrate that naturally occurring hNedd4–2 isoforms differentially associate with ENaC to regulate its activity.
Exaggerated response to adenosine in kidneys from high salt-fed rats: role of epoxyeicosatrienoic acids
Authors: Liclican Elvira L. , McGiff John C. , Pedraza Paulina L. , Ferreri Nicholas R. , Falck John R. , Carroll Mairead A.
Published: April 2005

Cytochrome P-450 (CYP)-dependent epoxyeicosatrienoic acids (EETs) dilate rat preglomerular microvessels when adenosine2Areceptors (A2AR) are stimulated. As high salt (HS) intake increases epoxygenase activity and adenosine levels, we hypothesized that renal adenosine responses would be greater in HS-fed rats. Male Sprague-Dawley rats were fed either HS (4.0% NaCl) or normal salt (NS; 0.4% NaCl) diet. On day 8, isolated kidneys were perfused with Krebs' buffer containing indomethacin (10 μM) and l-NAME (200 μM) and preconstricted to ∼150 mmHg with infusion of phenylephrine (10−7M). Renal effluents were extracted for analysis of eicosanoids by gas chromatography-mass spectrometry. Bolus injections of the stable adenosine analog 2-chloroadenosine (2-CA; 0.1–10 μg) resulted in dose-dependent dilation; at 10 μg, perfusion pressure (PP) was lowered to a greater extent in the kidneys of HS rats compared with NS rats (−60 ± 4 vs. −31 ± 8 mmHg; P < 0.05) and the area of response was increased (27 ± 6 vs. 9 ± 4 mm2; P < 0.05), as was EET release (132 ± 23 vs. 38 ± 18 ng; P < 0.05). HS treatment increased A2AR and CYP2C23 protein expression. A selective epoxygenase inhibitor, MS-PPOH (12 μM), significantly reduced the response to 2-CA in HS rats; PP, area of response, and EET release decreased by 40, 70, and 81%, respectively, whereas lesser changes were evident in NS kidneys. Thus the greater vasodilator response to 2-CA seen in kidneys obtained from HS-fed rats was mediated by increased EET release. As EETs are renal vasodilator and natriuretic eicosanoids, interactions between adenosine and EETs may contribute to the adaptive response to HS intake.
Developmental changes in airway and tissue mechanics in mice
Authors: Bozanich Elizabeth M. , Collins Rachel A. , Thamrin Cindy , Hantos Zoltán , Sly Peter D. , Turner Debra J.
Published: April 2005

Most studies using mice to model human lung diseases are carried out in adults, although there is emerging interest in the effects of allergen, bacterial, and viral exposure early in life. This study aims to characterize lung function in BALB/c mice from infancy (2 wk) through to adulthood (8 wk). The low-frequency forced oscillation technique was used to obtain impedance data, partitioned into components representing airway resistance, tissue damping, tissue elastance, and hysteresivity (tissue damping/tissue elastance). Measurements were made at end-expiratory pause (transrespiratory system pressure = 2 cmH2O) and during relaxed slow expiration from 20 to 0 cmH2O. Airway resistance decreased with age from 0.63 cmH2O·ml−1·s at 2 wk to 0.24 cmH2O·ml−1·s at 8 wk ( P < 0.001). Both tissue damping and tissue elastance decreased with age ( P < 0.001) from 2 to 5 wk, then plateaued through to 8 wk ( P < 0.001). This pattern was seen both in measurements taken at end-expiratory pause and during expiration. There were no age-related changes seen in hysteresivity when measured at end-expiratory pause, but the pattern of volume dependence did differ with the age of the mice. These changes in respiratory mechanics parallel the reported structural changes of the murine lung from the postnatal period into adulthood.
Sensitivity of Auditory Cortical Neurons to the Locations of Leading and Lagging Sounds
Authors: Mickey Brian J. , Middlebrooks John C.
Published: April 2005

We recorded unit activity in the auditory cortex (fields A1, A2, and PAF) of anesthetized cats while presenting paired clicks with variable locations and interstimulus delays (ISDs). In human listeners, such sounds elicit the precedence effect, in which localization of the lagging sound is impaired at ISDs ≲10 ms. In the present study, neurons typically responded to the leading stimulus with a brief burst of spikes, followed by suppression lasting 100–200 ms. At an ISD of 20 ms, at which listeners report a distinct lagging sound, only 12% of units showed discrete lagging responses. Long-lasting suppression was found in all sampled cortical fields, for all leading and lagging locations, and at all sound levels. Recordings from awake cats confirmed this long-lasting suppression in the absence of anesthesia, although recovery from suppression was faster in the awake state. Despite the lack of discrete lagging responses at delays of 1–20 ms, the spike patterns of 40% of units varied systematically with ISD, suggesting that many neurons represent lagging sounds implicitly in their temporal firing patterns rather than explicitly in discrete responses. We estimated the amount of location-related information transmitted by spike patterns at delays of 1–16 ms under conditions in which we varied only the leading location or only the lagging location. Consistent with human psychophysical results, transmission of information about the leading location was high at all ISDs. Unlike listeners, however, transmission of information about the lagging location remained low, even at ISDs of 12–16 ms.
Current Issues in Anticoagulation
Authors: Agnelli Giancarlo
Published: April 2005

Anticoagulation therapy with unfractionated heparin, low-molecular-weight heparins and oral vitamin K antagonists is currently the mainstay of treatment and prevention of thromboembolic disorders (such as deep vein thrombosis, pulmonary embolism and stroke prevention in patients with atrial fibrillation). Although these therapies have proven benefits, they also have important limitations that result in their underuse in routine clini- cal practice. Consequently, many patients identified by guidelines as requiring anticoagulant therapy receive no or inadequate treatment. Heparins require parenteral administration and pose the risk of heparin-induced thrombocytopenia. Vitamin K antagonists have a narrow separation of antithrombotic and haemorrhagic effects and numerous food and drug-drug interactions, and require frequent coagulation monitoring and dose adjustment to ensure effective antithrombotic protection while minimizing the risk of bleeding complications. In response to these limitations, several new anticoagulants have recently been developed, including selective factor Xa inhibitors such as fondaparinux and ximelagatran, the first oral agent in the new class of direct thrombin inhibitors and the first new oral anticoagulant for almost 60 years. Ximelagatran possesses many of the properties of an ideal agent for anticoagulation therapy. With its oral formulation, consistent and predictable pharmacological profile and no coagulation monitoring, ximelagatran has the potential to increase the use and duration of anticoagulation treatment in thromboembolic disorders and to reduce the burden associated with long-term management.
The Role of Ximelagatran in the Treatment of Venous Thromboembolism
Authors: Schulman Sam
Published: April 2005

Clinical-based evidence demonstrates that long-term oral anticoagulant therapy with the vitamin K antagonists is highly effective for the secondary prevention of venous thromboembolism (VTE). However, owing to fear of bleeding complications and the inconvenience of coagulation monitoring, many patients do not receive the required duration of treatment. This can lead to a high incidence of recurrent VTE events and has prompted the evaluation of alternative treatment strategies and the development of new anticoagulants for VTE management. For patient groups in which it is particularly difficult to maintain the target intensity of anticoagulation, low-molecular-weight heparin (LMWH) has been found to significantly reduce the risk of recurrent VTE without increasing bleeding risk. The parenteral administration of LMWH, however, is a drawback for long-term use in the outpatient setting. Long-term warfarin use at a lower intensity (international normalized ratio [INR] 1.5–2.0) has also been assessed as a possible strategy to reduce bleeding complications and the need for monitoring, but results were disappointing when compared with conventional-intensity warfarin (INR 2.0–3.0). New therapies in development that may potentially offer a more favourable benefit-risk profile and greater consistency and predictability of response include the synthetic pentasaccharides, fondaparinux and idraparinux. These par enterally administered indirect factor Xa inhibitors have a predictable pharmacokinetic profile, allowing use without coagulation monitoring. Fondaparinux to date has only been evaluated in the initial treatment (5–7 days) of symptomatic deep vein thrombosis. In contrast, idraparinux, with its longer half-life (80 h) allowing once-weekly parenteral dosing, has the potential for long-term treatment and is currently being assessed in phase III trials for the secondary prevention of VTE. Currently, the most promising new therapeutic option is the first of the oral direct thrombin inhibitors, ximelagatran. The THRombin Inhibitor in VEnous thromboembolism (THRIVE) clinical trial programme has demonstrated that this agent is as effective as standard therapy for the acute treatment (THRIVE Treatment) and secondary prevention (THRIVE lll) of VTE events and is well tolerated when used for 6 months or over extended periods up to 1.5 years. Furthermore, with oral administration, fixed dosing and no requirement for anticoagulation monitoring, ximelagatran has the potential to facilitate optimal use and duration of VTE treatment by overcoming the limitations of current agents.
Computer-Assisted Phenotype Characterization for Genetic Research in Psychiatry
Authors: Fangerau Heiner , Ohlraun Stephanie , Granath Ralf O. , Nöthen Markus M. , Rietschel Marcella , Schulze Thomas G.
Published: April 2005

Psychiatric disorders differ from other complex phenotypes in their lack of objectively assessable biological markers that contribute to the establishment of a research diagnosis for genetic studies. To nevertheless allow for the delineation of genetically meaningful diagnostic entities for psychiatric genetic research, comprehensive phenotype characterization procedures are required. It is widely agreed that these should include the standardized assessment of life-time clinical symptomatology, sociodemographic, and environmental factors. Data should be based on several sources, i.e. diagnostic interviews with probands and their relatives as well as a thorough review of medical records, and final assignment of diagnosis should follow robust algorithms (i.e. best-estimate procedures, consensus diagnosis). Here, we outline a practical implementation of such a phenotype characterization strategy, including patient recruitment, study enrolment procedures, comprehensive diagnostic assessment, and data management. We argue that successful psychiatric phenotype characterization requires flexible tools. For this purpose, we have developed a computer-assisted phenotype characterization inventory, built around the backbone of a relational database. It allows for the straightforward assessment of symptoms, automated error checks and diagnostic assignment, easily manageable data storage and handling, and flexible data transfer between various research centers even across language barriers, while at the same time keeping up with the highest standards for the protection of sensitive patient data.
Defining the Phenotype in Human Genetic Studies: Forward Genetics and Reverse Phenotyping
Authors: Schulze Thomas G. , McMahon Francis J.
Published: April 2005

The definition of phenotypes for genetic study is a challenging endeavor. Just as we apply strict quality standards to genotype data, we should expect that phenotypes meet consistently high standards of reproducibility and validity. The methods for achieving accurate phenotype assignment in the research setting – the ‘research diagnosis’ – are different from the methods used in clinical diagnosis in the patient care setting. We evaluate some of the main challenges of phenotype definition in human genetics, and begin to outline a set of standards to which phenotypes used in genetics studies may aspire with the goal of increasing the quality and reproducibility of linkage and association studies. Revisiting the traditional phenotype definitions through a focus on familial components and heritable endophenotypes is a time-honored approach. Reverse phenotyping, where phenotypes are refined based on genetic marker data, may be a promising new approach. The stakes are high, since the success of gene mapping in genetically complex disorders hinges on the ability to delineate the target phenotype with accuracy and precision.
Quantifying the Percent Increase in Minimum Sample Size for SNP Genotyping Errors in Genetic Model-Based Association Studies
Authors: Kang Sun Jung , Finch Stephen J. , Haynes Chad , Gordon Derek
Published: April 2005

Kang et al. [Genet Epidemiol 2004;26:132–141] addressed the question of which genotype misclassification errors are most costly, in terms of minimum percentage increase in sample size necessary (%MSSN) to maintain constant asymptotic power and significance level, when performing case/control studies of genetic association in a genetic model-free setting. They answered the question for single nucleotide polymorphisms (SNPs) using the 2 × 3 χ2 test of independence. We address the same question here for a genetic model-based framework. The genetic model parameters considered are: disease model (dominant, recessive), genotypic relative risk, SNP (marker) and disease allele frequency, and linkage disequilibrium. %MSSN coefficients of each of the six possible error rates are determined by expanding the non-centrality parameter of the asymptotic distribution of the 2 × 3 χ2 test under a specified alternative hypothesis to approximate %MSSN using a linear Taylor series in the error rates. In this work we assume errors misclassifying one homozygote as another homozygote are 0, since these errors are thought to rarely occur in practice. Our findings are that there are settings of the genetic model parameters that lead to large total %MSSN for both dominant and recessive models. As SNP minor allele approaches 0, total %MSSN increases without bound, independent of other genetic model parameters. In general, %MSSN is a complex function of the genetic model parameters. Use of SNPs with small minor allele frequency requires careful attention to frequency of genotyping errors to insure that power specifications are met. Software to perform these calculations for study design is available, and an example of its use to study a disease is given.
Incorporating Individual Error Rate into Association Test of Unmatched Case-Control Design
Authors: Hao Ke , Wang Xiaobin
Published: April 2005

Objectives: Genotyping error commonly occurs and could reduce the power and bias statistical inference in genetics studies. In addition to genotypes, some automated biotechnologies also provide quality measurement of each individual genotype. We studied the relationship between the quality measurement and genotyping error rate. Furthermore, we propose two association tests incorporating the genotyping quality information with the goal to improve statistical power and inference. Methods: 50 pairs of DNA sample duplicates were typed for 232 SNPs by BeadArray technology. We used scatter plot, smoothing function and generalized additive models to investigate the relationship between genotype quality score (q) and inconsistency rate (ĩ) among duplicates. We constructed two association tests: (1) weighted contingency table test (WCT) and (2) likelihood ratio test (LRT) to incorporate individual genotype error rate (Εi), in unmatched case-control setting. Results: In the 50 duplicates, we found q and ĩ were in strong negative association, suggesting the genotypes with low quality score were more likely to be mistyped. The WCT improved the statistical power and partially corrects the bias in point estimation. The LRT offered moderate power gain, but was able to correct the bias in odds ratio estimation. The two new methods also performed favorably in some scenarios when Εi was mis-specified. Conclusions: With increasing number of genetic studies and application of automated genotyping technology, there is a growing need to adequately account for individual genotype error rate in statistical analysis. Our study represents an initial step to address this need and points out a promising direction for further research.
Issues in Association Analysis: Error Control in Case-Control Association Studies for Disease Gene Discovery
Authors: Ott Jurg
Published: April 2005

Several sources of errors are discussed. While genotyping errors have little effect on power in case-control association studies, they tend to strongly increase false positive results in TDT type tests unless occurrence of errors is allowed for in the analysis (e.g., TDTae test). Disregarding non-genetic risk factors is shown to lead to a form of hidden heterogeneity, which can strongly reduce power. Stratification of data into more homogeneous subgroups is advocated as a simple solution to allowing for non-genetic risk factors such as socio-economic status and food preferences.
Optimal Selection of SNP Markers for Disease Association Studies
Authors: Halldórsson Bjarni V. , Istrail Sorin , De La Vega Francisco M.
Published: April 2005

Genetic association studies with population samples hold the promise of uncovering the susceptibility genes underlying the heritability of complex or common disease. Most association studies rely on the use of surrogate markers, single-nucleotide polymorphism (SNP) being the most suitable due to their abundance and ease of scoring. SNP marker selection is aimed to increase the chances that at least one typed SNP would be in linkage disequilibrium (LD) with the disease causative variant, while at the same time controlling the cost of the study in terms of the number of markers genotyped and samples. Empirical studies reporting block-like segments in the genome with high LD and low haplotype diversity have motivated a marker selection strategy whereby subsets of SNPs that ‘tag’ the common haplotypes of a region are picked for genotyping, avoiding typing redundant SNPs. Based on these initial observations, a plethora of ‘tagging’ algorithms for selecting minimum informative subsets of SNPs has recently appeared in the literature. These differ mostly in two major aspects: the quality or correlation measure used to define tagging and the algorithm used for the minimization of the final number of tagging SNPs. In this review we describe the available tagging algorithms utilizing a 3-step unifying framework, point out their methodological and conceptual differences, and make an assessment of their assumptions, performance, and scalability.
Local Anesthesia Reduces Pain Associated with Transrectal Prostatic Biopsy
Authors: Trucchi Alberto , De Nunzio Cosimo , Mariani Simone , Palleschi Giovanni , Miano Lucio , Tubaro Andrea
Published: April 2005

Introduction: To test the hypothesis that periprostatic block could completely relief prostatic biopsy-associated pain. Materials and Methods: Patients scheduled for transrectal ultrasound guided prostate biopsy were randomized (1:1:1 ratio) to no analgesia (group A), endorectal enema of 1% lidocaine gel (group B) or transrectal periprostatic block (group C). All patients underwent 10 core TRUS-guided biopsy. After the procedure, a ten visual analogue pain score (VAS) from 0 = no discomfort to 10 = severe pain was administered to the biopsied patients and a global estimation of pain associated with the procedure was obtained. The study design included interim analysis of pain score after the first 60 patients were enrolled. Kruskal-Wallis test for unpaired data was used for statistical analysis. Data are presented as mean, median (range). Results: Sixty patients were enrolled between May 2003 and December 2003 and all patients were evaluable. Mean and median age was 68.5 and 69 (range 53–82) years, respectively. Mean and median PSA was 86.8 and 9 ng/ml (range 0.58–4.111), respectively. No major side effects were observed. Patients in group A scored at VAS a median 4, mean 5.5 ± 2.3 (range 3–10). Patients in group B scored a median 4, mean 5.5 ± 2.7 (range 3–10) (p = 0.237). Patients receiving periprostatic injections of carbocaine (group C) scored a median 0, mean 0.5 ± 0.8 (range 0–2). The level of pain reported by this group of patients was significantly different from those reported by patients who performed prostatic biopsy without anesthesia or with intrarectal anesthetic jelly (p = 0.00001). In the periprostatic block group 65% of patients referred no pain after the procedure (VAS = 0) while all patients in the other groups experience some degree of pain. Conclusion: The use of bilateral periprostatic block is a very effective and useful technique, well tolerated by the patient, which almost completely abolishes the pain and discomfort associated with the prostatic biopsy procedure.
Experience with Primary Urethral Carcinoma from the Blackfoot Disease-Endemic Area of South Taiwan: Increased Frequency of Bulbomembranous Adenocarcinoma?
Authors: Tsai Yuh-Shyan , Yang Wen-Horng , Tong Yat-Ching , Lin Johnny S.N. , Pan Chen-Ching , Tzai Tzong-Shin
Published: April 2005

Objectives: To describe and compare primary urethral carcinomas in South Taiwan with those in the USA and to explore the influence of chronic arsenic exposure. Methods: From 1988 to 2001, there were 21 pathologically proven primary urethral carcinomas diagnosed and treated at our hospital (14 males, 7 females). Seven of 14 male patients were chronically exposed to arsenic in drinking water for an average of 23 years. We compared our cases to three studies in the USA (80 males, 179 females), and analyzed the influence of chronic arsenic exposure by onset age, histology, staging, and outcome. Results: Male patients with localized tumors had better survival compared to those with advanced tumors (p = 0.0045 in males, p = 0.07 in females). In comparison to the three studies in the USA, there was an unusual higher frequency of bulbomembranous adenocarcinoma at our center (43 vs. 18%, 2 and 0%, respectively, p < 0.0001), particularly among those with chronic arsenic exposure (73 vs. 14%, p = 0.031). Conclusions: In South Taiwan, there was a high frequency of bulbomembranous urethral adenocarcinoma, which might be associated with chronic arsenic exposure. Although the implications of such an observation are minimal owing to its rarity, it is worth exploring.
Necrotic Pancreatic Graft Causing Acute Urinary Retention
Authors: Laven Brett A. , Rapp David E. , Avila Desiderio , O’Connor R. Corey , Bales Gregory T.
Published: April 2005

Urologic complications are frequently encountered after pancreas transplantation with a graft duodenocystostomy. Urinary infections, hematuria, and irritative voiding symptoms are some of the most frequent complications with a bladder-drained pancreas allograft. While voiding dysfunction is common in these patients due to underlying neuropathy, to our knowledge, we report the first case of obstructive uropathy in a female due to retained necrotic graft material.
EBER Expression of Pure Urinary Bladder Lymphoepithelioma-Like Carcinoma in Two Unique Asian Patients
Authors: Chen Kuan-Chou , Chiang Han-Sun , Fang Chia-Lang
Published: April 2005

We describe the 2 unique Asian cases of pure urinary bladder lymphoepithelioma-like carcinoma (LELCA). One patient had metastatic pelvic lymphoadenopathy and the other with superficial tumor. The EBER in situ hybridization both showed negative results despite racial or geographical factors might influence the peculiar susceptibility of individuals of Asian ancestry to Epstein-Barr virus-associated lymphoepithelioma-like carcinoma. The 2 patients were treated pertinently with satisfactory outcomes and intravesical BCG instillation is performed to prevent superficial LELCA recurrence rationally.
Pure Squamous Cell Carcinoma after Intravesical BCG Treatment
Authors: Yurdakul Talat , Avunduk Mustafa Cihat , Piskin Mehmet Mesut
Published: April 2005

Besides the commonly seen side effects of intravesical BCG instillations, very rare complications have been reported including new tumor formation other than transitional cell carcinoma of the bladder. Here we report the first case of pure squamous cell carcinoma formation in a BCG-treated patient with pure transitional cell carcinoma.
Efficacy, Tolerability, and Safety of Lanthanum Carbonate in Hyperphosphatemia: A 6-Month, Randomized, Comparative Trial versus Calcium Carbonate
Authors: Hutchison A.J. , Maes B. , Vanwalleghem J. , Asmus G. , Mohamed E. , Schmieder R. , Backs W. , Jamar R. , Vosskühler A.
Published: April 2005

Background/Aims: Hyperphosphatemia is an important clinical consequence of renal failure, and its multiple adverse systemic effects are associated with significantly increased risks of morbidity and mortality in dialysis patients. Existing oral phosphate binders have not permitted control of serum phosphate within currently accepted guidelines. This study compares lanthanum carbonate with calcium carbonate for control of serum phosphate in hemodialysis patients. Methods: In this European multicentre study, 800 patients were randomised to receive either lanthanum or calcium carbonate and the dose titrated over 5 weeks to achieve control of serum phosphate. Serum levels of phosphate, calcium and parathryoid hormone were followed over the following 20 weeks. Results: Around 65% of patients in each group achieved phosphate control, but in the calcium carbonate group this was at the expense of significant hypercalcemia (20.2% of patients vs. 0.4%). Consequently, calcium x phosphate product tended to be better controlled in the lanthanum group. Conclusion: This 6-month study demonstrates that serum phosphate control with lanthanum carbonate (750–3,000 mg/day) is similar to that seen with calcium carbonate (1,500–9,000 mg/day), but with a significantly reduced incidence of hypercalcemia. Lanthanum carbonate is well tolerated and may be more effective in reducing calcium x phosphate product than calcium carbonate.
A Retrospective Series of Long-Term Survivors of Metastatic Breast Cancer in Complete Remission
Authors: Amoroso Vito , Valcamonico Francesca , Simoncini Edda , Ardighieri Laura , Grisanti Salvatore , Vassalli Lucia , Marpicati Patrizia , Lucini Laura , Ferrari Vittorio D. , Rangoni Giovanni , Marini Giovanni
Published: April 2005

Aim: To describe clinical features, treatment modalities and long-term outcome of patients with overt metastatic breast cancer in complete remission for more than 5 years. Patients and Methods: A retrospective survey of 12 patients who were referred to a single institution from 1982 to 1995. Results: The majority of the long-term survivors had a good performance status, endocrine-responsive disease and a single metastatic site. Ten patients had received chemotherapy, 8 patients hormone therapy, and 2 patients had been treated with surgery followed by systemic therapies. At a median follow-up of 11.7 years, 10 of the 12 patients were still in complete remission. The median duration of complete remission was 9.2 years (range 5.0–15.7 years). Conclusions: This case series confirms that only a few metastatic breast cancer patients could potentially be cured with multidisciplinary treatments.
First-Line Treatment with Irinotecan and Raltitrexed in Metastatic Colorectal Cancer
Authors: Aparicio Jorge , Vicent José M. , Maestu Inmaculada , Bosch Carles , Galán Antonio , Busquier Isabel , Llorca Cristina , Garcerá Salvador , Campos Juan M. , López-Tendero Pedro , Balcells Miquel
Published: April 2005

Objectives: The combination of irinotecan and raltitrexed is safe and active in 5-fluorouracil-refractory, metastatic colorectal cancer (CRC), with the advantage of its convenient three-weekly schedule. The aim of this multicenter phase II study was to assess its efficacy and toxicity in first-line treatment. Methods: Between May 2000 and March 2001, 62 previously untreated patients received irinotecan (350 mg/m2) plus raltitrexed (3 mg/m2), with courses repeated every 21 days. Objective response was assessed every three courses, and treatment maintained until tumor progression or unacceptable toxicity. Results: A total of 331 cycles were administered, with a median of five cycles per patient (range, 1–16). Seventeen patients achieved a partial response and 2 a complete response, for an overall intention-to-treat response rate of 30% (95% confidence interval, 18–44%). The incidence of grade 3–4 toxicity per patient was diarrhea (27%), emesis (13%), anemia (12%), neutropenia (9%), and asthenia (7%). Three patients (5%) died from treatment-related adverse events (diarrhea plus neutropenia). The median potential follow-up is now 37 months. Median survival was 12.2 months, and median time to progression was 6.3 months. Conclusions: The combination of irinotecan plus raltitrexed is an easy comfortable schedule for patients with metastatic CRC, but both efficacy and toxicity results seem suboptimal for first-line treatment.
The Role of Neoadjuvant Chemotherapy in the Treatment of Advanced Ovarian Cancer
Authors: Pectasides Dimitrios , Farmakis Dimitrios , Koumarianou Anna
Published: April 2005

Primary cytoreductive surgery followed by chemotherapy represents the current standard treatment for patients with advanced ovarian cancer. Neoadjuvant chemotherapy followed by interval debulking surgery has been proposed as an alternative approach for the initial management of bulky ovarian cancer, aiming at the improvement of surgical efficiency and patients’ quality of life. According to the hitherto published studies, consisting mainly of retrospective observations, neoadjuvant chemotherapy followed by interval cytoreduction appears to improve the prognosis and quality of life in selected groups of patients. The survival outcome in these patients is similar to that of the conventional approach, or even better in some of the cases. Moreover, patients undergoing debulking surgery after having received neoadjuvant chemotherapy had a reduced perioperative morbidity compared to patients undergoing primary cytoreduction. Concurrently, neoadjuvant chemotherapy provides preoperative knowledge of tumor chemosensitivity, hence allowing the surgeon to choose appropriately aggressive treatment. However, until the results of prospective randomized trials become available, neoadjuvant chemotherapy followed by interval surgery should be applied only to individual cases and primarily in the context of clinical trials.
Alteration of Frequency Range for Binaural Beats in Acute Low-Tone Hearing Loss
Authors: Karino Shotaro , Yamasoba Tatsuya , Ito Ken , Kaga Kimitaka
Published: April 2005

The effect of acute low-tone sensorineural hearing loss (ALHL) on the interaural frequency difference (IFD) required for perception of binaural beats (BBs) was investigated in 12 patients with unilateral ALHL and 7 patients in whom ALHL had lessened. A continuous pure tone of 30 dB sensation level at 250 Hz was presented to the contralateral, normal-hearing ear. The presence of BBs was determined by a subjective yes-no procedure as the frequency of a loudness-balanced test tone was gradually adjusted around 250 Hz in the affected ear. The frequency range in which no BBs were perceived (FRNB) was significantly wider in the patients with ALHL than in the controls, and FRNBs became narrower in the recovered ALHL group. Specifically, detection of slow BBs with a small IFD was impaired in this limited (10 s) observation period. The significant correlation between the hearing level at 250 Hz and FRNBs suggests that FRNBs represent the degree of cochlear damage caused by ALHL.
Loss and Recovery of Sound-Evoked Otoacoustic Emissions in Young Chicks following Acoustic Trauma
Authors: Ipakchi Ramin , Kyin Tim , Saunders James C.
Published: April 2005

Young and adult chickens exhibit substantial inner-ear damage and post-exposure deterioration in cochlear nerve activity following exposure to intense sound. Both the structural and functional losses largely recover in both age groups within 2–4 weeks after exposure. However, some aspects of acoustic trauma differ between the young and adult chicken ear. Overstimulation in the young chick causes considerable post-exposure loss and then recovery of the steady-state endocochlear potential, while in the adult animal there is little post-exposure effect on this potential. Moreover, in adults there is post-exposure loss but little recovery in the distortion product otoacoustic emission (DPOAE). The present study explores the possibility of an age difference in the effects of overstimulation on the DPOAE by examining these emissions in young chicks following exposure to an intense pure tone. Chicks exposed to intense sound were formed into groups at 0 and 12 days of recovery, and these were complemented by two additional groups of age-matched controls. The cubic difference tone emission (the 2f1–f2 DPOAE component) was measured at 9 levels for 13 frequencies in all groups. Shortly after the exposure, the DPOAE reliably declined with the maximum loss at or above the exposure tone frequency. The exposed chicks examined 12 days after exposure showed complete recovery of the DPOAE. It would appear that 12 days of recovery sufficiently repaired inner ear damage to completely restore DPOAE production. This result is different from that in adult chicken and may be related to the greater severity of acoustic damage in the adult ear, a reduced susceptibility of the young ear to acoustic trauma, or the ability of the young animal to more successfully repair the inner ear.
Why Do Dialysis Patients Develop a Heart of Stone and Bone of China?
Authors: Martola Leena , Barany Peter , Stenvinkel Peter
Published: April 2005

Vascular calcification is a common complication of end-stage renal disease (ESRD). The mechanisms responsible are complex and have so far been considered to be mainly the result of a passive mechanism due to elevated PO4 levels and high Ca × PO4 ion product resulting in saturated plasma. However, recent results suggest that also other features, commonly observed in the uremic milieu, such as chronic inflammation, hyperleptinemia and a dysregulation of various mineral-regulating proteins might also contribute to an enhanced calcification process. Moreover, as an inverse relationship between vascular calcification and bone density has been documented in ESRD, it could be speculated that pathologically low bone remodelling (adynamic bone disease) associated with active vitamin D treatment and low parathyroid hormone (PTH) levels may predispose to ectopic calcification of vessels, valves and heart. As patients with vascular calcification have a higher intake of calcium-containing PO4 binders, novel, non-calcium containing PO4 binders may diminish the risk of progressive vascular calcification in this patient group. Further studies are needed to elucidate the respective role of chronic inflammation, hyperleptinemia and PTH-lowering therapies in this fatal complication of ESRD.
Chronic but Not Acute Hydrocortisone Treatment Shifts the Response to an Orthostatic Challenge towards Parasympathetic Activity
Authors: Nonell Annemarie , Bodenseh Stephanie , Lederbogen Florian , Kopf Daniel , Hamann Bettina , Gilles Maria , Deuschle Michael
Published: April 2005

Adrenocortical steroid hormones play a major role in the regulation of both action and metabolism of catecholamines. However, there is limited information on the effect of prolonged increase in plasma steroid hormone concentration on the sympathetic nervous system, which is the main source of norepinephrine. Using a double-blind, placebo-controlled cross-over design, we examined 20 male healthy volunteers after acute administration of 40 mg hydrocortisone or matching placebo as well as after a 1-week treatment with this steroid (daily dose, 40 mg) or placebo. Sympathetic nervous system activity was assessed by determination of overnight urinary norepinephrine and epinephrine secretion and by analysis of short-time heart rate variability (HRV) measures in the frequency domain. The low-frequency (LF) component of the HRV spectrum was considered to reflect both sympathetic and parasympathetic modulation and the high-frequency (HF) band vagal activity. HRV testing included the response to a mild cardiovascular challenge, orthostasis. After 1 subject had been excluded because of incompliance with the study medication, the data of 19 subjects were used for further analyses. Prolonged hydrocortisone treatment was associated with a significant shift of relative power from the LF to the HF band in the upright position, resulting in a significant decrease in the LF/HF ratio (placebo 6.77 ± 3.35 and hydrocortisone 4.72 ± 3.27; p < 0.05). No differences between groups were observed after acute steroid administration or after prolonged treatment in the supine position. Neither acute nor chronic hydrocortisone treatment resulted in significant changes in the overnight urinary catecholamine secretion. Our data suggest that prolonged but not acute hydrocortisone administration shifts the autonomic response to an orthostatic challenge towards parasympathetic activity.
Molecular Polymorphism of Native Gonadotropin-Releasing Hormone (GnRH) Is Restricted to Mammalian GnRH and [Hydroxyproline9] GnRH in the Developing Rat Brain
Authors: Gautron Jean-Pierre , Gras Christophe , Enjalbert Alain
Published: April 2005

Although chicken gonadotropin-releasing hormone (GnRH)-II is thought to occur in most animal species, its presence and that of two other variants (lamprey GnRH-III, salmon GnRH) is questionable in rodents. Here we report on the GnRH peptides present in the hypothalamus and the remaining brain of rat of both sexes during development. No immunoreactivity was detected in the elution zone of either native or hydroxylated forms of the above three variants in any of brain extracts chromatographed. The main peptides detected were mammalian GnRH (mGnRH) and m[hydroxyproline9]GnRH (mHypGnRH). In the hypothalamus, these peptides were associated with their free acid and precursor forms. N-terminal fragments from both native decapeptides ([1–5]GnRH) and mGnRH ([1–9]GnRH) were observed only in the hypothalamus. C-terminal fragments were detected in both tissues. The relative proportions of mGnRH and mHypGnRH showed no developmental changes in the remaining brain. The hypothalamic proportions of mHypGnRH were high on day 5, and decreased from day 15 onwards. The [Gly11]-precursor to mHypGnRH molar ratio was twofold lower than with the non-hydroxylated peptides. The mGnRH to [1–9]GnRH molar ratio increased in males but decreased in females during development. No sex-related differences were observed in the native decapeptide to [1–5]GnRH molar ratio. It was concluded that (1) chicken GnRH-II is not present in all mammals, (2) mGnRH and mHypGnRH are the main GnRH isoforms present in the rat brain, (3) the processing of [Gly11]-precursor into mHypGnRH occurs at a higher rate than that of mGnRH, and (4) the catabolism does not interfere with the developmental changes undergone by the mGnRH and mHypGnRH brain contents.