bluuebunny/crossref_metadata_2025 huggingface dataset:
On-Line Processing of Unidirectional Fiber Composites Using Radiative Heating: I. Model
Authors: Chern Bih-Cherng , Moon Tess J. , Howell John R.
Published: July 2003

Thermal radiation is a clean, flexible, efficient and effective means to supply energy to process a composite on-line. Radiative transfer in high-fiberdensity, unidirectional composites is complex, if analyzed completely. A detailed thermal model for on-line processing of unidirectional fiber composites by surface or volumetric radiative heating is presented. The physical geometry and imposed thermal and radiative boundary conditions correspond to a unidirectional, hoop-wound cylinder. In-situ (or continuous) curing of thermosets or on-line consolidation of thermoplastics is represented by the inclusion or omission, respectively, of the exothermic, chemical energy release term in the energy equation. Numerical results are presented for the temperature and degree of cure of graphite/epoxy and glass/epoxy cylinders. The effects of: surface or volumetric radiative heat flux; radiant-source emissive power level and efficiency; radiative emission from the composite; exothermic, chemical energy release; radiation’s angle of incidence; and independent and dependent scattering in the composite’s interior are presented. Validation of the model is presented in Part II of this paper, as well as recommended manufacturing process windows for process parameters, such as radiant-source emissive power level and winding speed. Part II also includes surface and volumetric radiative properties of unidirectional graphite/epoxy and glass/epoxy composites that were used in the numerical simulations.
Static Characterization of Carbon–Carbon Brake Disk
Authors: Yoo Jae-Seok , Oh Se-Hee , Kim Chun-Gon , Hong Chang-Sun , Kim Kwang-Soo
Published: July 2003

The material properties of a carbon–carbon brake disk were measured bystatic tests. The static strength was tested for each slot in a carbon–carbon rotor disk which is the stress critical part of a carbon–carbon brake system during operation. A loading fixture was designed for the static strength test of a single carbon–carbon rotor disk. To simulate the real dynamic system in a static condition, the friction surface of the rotor disk was clamped and static load was applied to a slot in the circumferential direction of the rotor disk. The described failure mechanism of the brake disk can be described as a sequence of the multiple matrix cracks at the contact surface of the rotor slot, subsequent delaminations from the cracked contact surface, and the final fracture at the notch of the slot. To investigate the mechanical behavior upon the different slot shapes, FE analysis was used. The rotor with slots of the acute sliding angle had the smallest Tsai–Wu failure index.
A Novel Procedure for Identification of 3D Moisture Diffusion Parameters on Thick Composites: Theory, Validation and Experimental Results
Authors: Pierron F. , Poirette Y. , Vautrin A.
Published: July 2003

This paper presents a novel method for the identification of the parameters governing Fickian moisture diffusion in composite materials. In the first part of the manuscript, the theoretical background is given and closed-form solutions are produced for 3D Fickian diffusion. Then, the different existing identification alternatives are reviewed and a novel procedure is proposed that takes advantage of all the gravimetric curve data points instead of just initial slope and saturation. The method relies on the solution of an optimization problem. In the second part of the paper, validation of this identification technique is performed from simulated gravimetric curves. The main advantage of the method when compared to previously published materials is that diffusion coefficients and saturation level can be identified from gravimetric curves obtained from unsaturated coupons. This is particularly useful when considering thick coupons that will take a long time to saturate or when non-Fickian diffusion mechanisms occur after some time. Finally, the method is applied to experimental results obtained from glass/epoxy composites. It is shown that although the diffusion of moisture in the composite is basically non-Fickian, it can be considered Fickian up to about 10 days and that these data are sufficient to retrieve the 3D diffusion coefficients as well as the Fickian saturation level.
Mold Fill Time and Void Reduction in Resin Transfer Molding Achieved by Articulated Tooling
Authors: Choi Jun H. , Dharan C. K.H.
Published: July 2003

Tool articulation is proposed as a means to improve mold fill time and to reduce void generation in resin transfer molding (RTM). Following a brief review of conventional RTM and a discussion of the limitations on the factors that control fluid flow through porous media, the articulated tool concept is described. The sequence of motion of an articulated segmented mold necessary for consolidation, void removal and accelerated fluid flow through a fibrous preform is described. An analysis of the process using a fiber preform with orthotropic permeability is outlined from which mold fill time is obtained. This is compared with conventional RTM mold fill times using typical resin properties and fiber volume fractions. In addition, void reduction in the articulated process relative to conventional RTM is investigated. For the conservative assumptions used in the analysis, the articulated process demonstrates an improvement by a factor of at least five in mold fill time compared with conventional RTM, accompanied by reduced void generation.
Pneumatic Characterization of Composite Materials
Authors: Tsai Cho-Liang , Cheng Ming-Chang , Hwang Shun-Fa , Tsai Yi-Shiun
Published: July 2003

The dimensional change of some composite materials induced by ambient air pressure change was discovered and dubbed pneumatic strain in 2000. This pneumatic behavior closely resembles hygric behavior, and pneumatic strain is proportional to the ambient air pressure change by the coefficients of the pneumatic expansion. A method termed the suspension method was employed in this work to characterize the pneumatic behavior of unidirectional T700 carbon/epoxy composite laminate and other materials, such as Kevlar 49 fiber, aluminum plate, aluminum foil, paper, celluloid sheet and pure epoxy plate. Longitudinal and transverse pneumatic strains of T700 carbon/epoxy composite lamina induced by 1 atm air pressure change were measured. The results also indicated that Kevlar 49 fiber and aluminum have no pneumatic behavior, while paper, celluloid film and epoxy plate do have pneumatic behavior. Two major contributions of this work are verifying the effectiveness of suspension method for the pneumatic characterizing and discovering more materials having pneumatic behavior.
Experimental Characterization of the Influence of Tackifier Material on Preform Permeability
Authors: Estrada Gonzalo , Vieux-Pernon Céline , Advani Suresh G.
Published: July 2003

Liquid composite molding processes use both simple and complex sets of preforms to produce high-performance composite parts. To produce these parts, binder materials known as tackifiers are used to shape the fabrics into complicated preforms prior to the resin injection. Tackifier materials enhance the formability and handling operations of dry reinforcements, and become an integral part of the composite laminate. A commercial tackifier was employed to form fiberglass preforms. Various preforms were prepared with different concentrations of the tackifier, and the effect on the permeability was studied. A permeability work-cell was used to continuously measure the permeability of the tackified preform for different fiber volume fractions. An analytical model based on a unit cell definition in combination with microscopic images was used to predict the permeability of tackified preforms. A comparison between the experimental measurement and the predicted results show the deficiencies in the unit cell approach to model permeability of preforms containing low concentrations of tackifiers.
Design and Process for Preformed Woven, Knitted, and Braided Thermoplastic Composite Reinforced Arrester
Authors: Ramani Karthik , Dai Heming
Published: July 2003

A new process and associated designs were developed for electrical arresters. When an abnormal voltage surge occurs, the arrester explodes due to the energy released. The composite shell provides the protection needed to prevent the broken arrester fragments from being expunged. Preformed woven, knitted, and braided composite shells, consisting of commingled polypropylene (PP) and E-glass yarn, were fabricated and consolidated in order to reinforce electrical arresters. A braided composite shell, composed of dry glass yarn and neat PP yarn, was designed, processed, and tested to investigate the effect of venting. This braided design allowed the energy released to be vented in the area between glass fiber bundles. Experimental results demonstrate that the woven and braided shells performed better than the knitted shell. A theoretical analysis based on the composite mechanics theory was performed in order to explain the experimental results.
Domestic Political Accountability and the Escalation and Settlement of International Disputes
Authors: HUTH PAUL K. , ALLEE TODD L.
Published: July 2003

A political accountability model is developed to explain how the accountability of incumbent democratic leaders to domestic political opposition influences the diplomatic and military policies of governments. The model is situated within the democratic peace literature and compared with existing theoretical work. Empirically, the hypotheses are tested on a new data set of 348 territorial disputes for the period from 1919 to 1995. Each dispute is divided into three separate stages so that hypotheses about the initiation and outcome of both negotiations and military confrontations, and opposing patterns of war and dispute settlement, can be tested. Results provide strong support for a number of hypotheses concerning the importance of electoral cycles and the strength of opposition parties in explaining patterns of both conflictual and cooperative behavior by democratic states.
Collective Self-Esteem and Africultural Coping Styles in African American Adolescents
Authors: Constantine Madonna G. , Donnelly Peter C. , Myers Linda James
Published: July 2003

The authors examine the relationships between dimensions of collective self-esteem and Africultural coping styles in a sample of African American adolescents. They found that African American adolescents with higher public collective self-esteem (i.e., the belief that others feel positively about their cultural group) reported greater use of spiritual-centered Africultural coping styles to deal with stressful situations. Results also revealed that higher importance to identity collective self-esteem (i.e., the belief that their cultural group is an important part of their self-concept) was related to greater use of collective coping strategies among African American adolescents.
Building State Capacity from the Inside Out: Parties of Power and the Success of the President’s Reform Agenda in Russia
Authors: Smyth Regina
Published: July 2003

In contrast to his predecessor Boris Yeltsin, Russia’s President Vladimir Putin continues to successfully neutralize legislative opposition and push his reform agenda through the State Duma. His success is due in large part to the transformation of the party system during the 1999 electoral cycle. In the face of a less polarized and fragmented party system, the Kremlin-backed party of power, Unity, became the foundation for a stable majority coalition in parliament and a weapon in the political battle to eliminate threatening opponents such as Yuri Luzhkov’s Fatherland-All Russia and the Communist Party of the Russian Federation.
Concurrent Evaluation of Web Cache Replacement and Coherence Strategies
Authors: Belloum A. S.Z. , Hertzberger L. O.
Published: July 2003

When studying Web cache replacement strategies, it is often assumed that documents are static. Such an assumption may not be realistic, especially when large-size caches are considered. Because of the strong correlation between the efficiency of the cache replacement strategy and the real state of the cached documents, one may expect dramatic changes of the cache performance when there is a possibility of hits on out-of-date documents. The authors’ aim in this study is to outline using simulation the impact of some cache coherence techniques such as the invalidation protocol, the TTL-based strategies, and prefetching on the efficiency of the cache replacement strategies. Using a simple cache model, they will show that the cache hits recorded when using some replacement strategies are more likely to be performed on out-of-date documents. They will show also the impact of the workload used on the outcome of the simulation.
A Second-Order Approximation for DEVS Simulation of Continuous Systems
Authors: Kofman Ernesto
Published: July 2003

In this article, based on the methodology of discrete event simulation of continuous systems via quantized state systems (QSS), a new second-order approximation, called second-order quantized state systems (QSS2), is proposed. This new approximation, which satisfies the same stability and convergence properties that were deduced for QSS in previous works, also allows reducing the number of calculations with respect to the former method. It is shown that in the particular case of linear time-invariant (LTI) systems, the QSS2 can be exactly represented by a DEVS model, and in nonlinear systems, an approximated DEVS model can be also obtained. For the LTI case, a closed formula giving the necessary quantization that allows achieving a bound in the error during the whole simulation is deduced. This formula, which stands for both QSS and QSS2 approaches, also proves that for any quantization, the error is always bounded.
A-CMSI: An Airport-Common Modeling and Simulation Infrastructure Using High-Level Architecture
Authors: Adelantado Martin , Deman Thibault
Published: July 2003

The airport-common modeling and simulation infrastructure (A-CMSI) is both a modeling and execution environment aimed at experimenting with and validating solutions for improving airport ground movements. The infrastructure is currently built by integrating a set of existing or newly designed simulators, each specialized for a different component of the simulated airport system. The infrastructure provides a Java graphical user interface (GUI) allowing for the description of the expected simulation conditions and interaction with the simulation execution. Both integration and collaborative design are achieved using the Department of Defense’s high-level architecture (HLA). This paper discusses the facilities offered by the GUI and presents the architecture of the airport modeling and simulation infrastructure being developed. The authors then focus on the usefulness of HLA in both collaborative design and joint experimentation domains.
Design and Modeling of an Interval-based ABR Flow Control Protocol
Authors: Chen Wenfeng , Mouftah Hussein T.
Published: July 2003

A novel flow control protocol is presented for Availability Bit Rate (ABR) service in Asynchronous Transfer Mode (ATM) networks. This scheme features periodic explicit rate feedback that enables precise allocation of link bandwidth and buffer space on a hop-by-hop basis to guarantee maximum throughput, minimum cell loss, and high resource efficiency. With the inclusion of resource management cell synchronization and consolidation algorithms, this protocol is capable of controlling point-to-multipoint ABR services within a unified framework. The authors illustrate the modeling of single ABR connection, the interaction between multiple ABR connections, and the constraints applicable to flow control decisions. A loss-free flow control mechanism is presented for high-speed ABR connections using a fluid traffic model. Supporting algorithms and ATM signaling procedures are specified, in company with linear system modeling, numerical analysis, and simulation results, which demonstrate its performance and cost benefits in high-speed backbone networking scenarios.
TCP Explicit Congestion Notification over ATM-UBR: A Simulation Study
Authors: Djemame K. , Kara M.
Published: July 2003

The enhancement of Transmission Control Protocol’s (TCP’s) congestion control mechanisms using Explicit Congestion Notification (ECN) over Asynchronous Transfer Mode (ATM) networks is overviewed. TCP’s congestion control is enhanced so that congestion is indicated by not only packet losses as is currently the case but an agent implemented at the ATM network’s edge as well. The novel idea uses EFCI (Explicit Forward Congestion Indication) bits (available in every ATM cell header) to generalize the ECN response to the UBR (Unspecified Bit Rate) service, notify congestion, and adjust the credit-based window size of the TCP. The authors’ simulation experiments show that TCP ECN achieves significantly lower cell loss, packet retransmissions, and buffer utilization, and exhibits better throughput than (non-ECN) TCP Reno.
Analytic and Simulation Modeling for AAL2 Connection Admission Control
Authors: Petr David W. , Vaddi Gopi K. , Vatte Raghushankar R. , Sreepathi-Komanduri Sampath
Published: July 2003

Fine time-scale simulation and analysis are combined with coarse time-scale simulation in the design and performance evaluation of connection admission control (CAC) techniques applied to connections that utilize the asynchronous transfer mode (ATM) Adaptation Layer Type 2 (AAL2). Fine time-scale (packet-level) simulation and then analytical modeling are used to determine the AAL2-level connection load that can be supported by a given ATM-level connection capacity, under a delay tail quality of service (QoS) specification. Self-configuring CAC for AAL2 with load estimation (SCALE) is introduced, which uses ATM signaling to establish and release ATM-level connections as necessary to support a set of AAL2-level connections. Using the results of the earlier analytical modeling, coarse time-scale (connection-level) simulation experiments demonstrate SCALE parameter trade-offs and confirm that SCALE can be an effective solution to the large time-of-day load variations expected from a set of AAL2 connections.
GRIDS-SCF: An Infrastructure for Distributed Supply Chain Simulation
Authors: Taylor Simon J. E. , Sudra Rajeev , Janahan Tharumasegaram , Tan Gary , Ladbrook John
Published: July 2003

Within the context of supply chain simulation, this paper introduces the generic runtime infrastructure for distributed simulation as a novel infrastructure for distributed supply chain simulation that promotes user transparency and extensible service provision. These are discussed with regard to a distributed simulation of a supply chain model (federation) GRIDS-SCF and a case study on supply chain simulation from the automotive industry. The main aim of this work is to provide industry with a business benefit from distributed simulation by making it possible to connect and reuse previously developed models in a supply chain while minimizing technological intervention (additional technological skills required) with the end user simulationist. It is suggested that this approach may pave the way for distributed supply chain simulation that emphasizes simulation methodology rather than technology.
Evaluation of Tug Escort Schemes Using Simulation of Drifting Tankers
Authors: Merrick Jason R. W.
Published: July 2003

The ability of tug escort vessels to save oil-laden tankers that become disabled in Prince William Sound, Alaska, is tested using a simulation of the drift path of the tankers. Tug escort schemes are intended to save tankers that have lost steering or propulsion by attaching a line and either holding the tanker from running aground until a repair can be made or towing the tanker to port. The ability of an escort tug to save disabled tankers depends on its position at the time of the accident; the location, speed, and direction of the tanker at the time of the failure; and the wind and current conditions that changed dynamically during a save attempt. To accurately test the save capability of a proposed escort scheme, a simulation of Prince William Sound is created that models dynamic changes in environmental conditions and thus the movement of the tanker.
Simulating Effects of Fiber Crimp, Flocculation, Density, and Orientation on Structure Statistics of Stochastic Fiber Networks
Authors: Scharcanski J. , Dodson C. T. J. , Clarke R. T.
Published: July 2003

The Neyman-Scott process is adapted to the problem of simulating the statistical properties of stratified stochastic fibrous materials. The simulations suggest a relationship between the mean number of fibers per zone and mean voids, independent of the nature of the stochastic fibrous structure: the characteristic shape of the transfer function curve persists whether or not the structure contains crimped fibers or if it is random or flocculated, isotropic or anisotropic. This could be an important universal effect. The mean and standard deviation turn out to be positively related for some fiber network parameters, such as mean voids, fiber density, and mean number of fiber bounds. Also, the simulations suggest that fiber crimp has a higher impact on isotropic structures. As crimp is increased, isotropic structures tend to present smaller mean voids, higher mean number of fibers per zone, and higher total number of bonds per fiber than anisotropic structures.
An Active Networks Simulation Environment
Authors: Rao Dhananjai M. , Wilsey Philip A.
Published: July 2003

The steady increase in size and complexity of communication networks, coupled with growing needs and demands, has motivated the development of active networks. Active networking techniques embed computational capabilities into conventional networks, thereby massively increasing the complexity and customization of the computations that are performed with a network. One of the most effective techniques for studying and analyzing active networks is computer-based simulation, but customized and flexible tools are required to ease effective use of simulations. In an endeavor to address these diverse issues, an Active Networks Simulation Environment (ANSE) has been developed. ANSE provides an environment for modeling, parallel simulation, and Web-based simulation of active networks. This paper presents the issues involved in the design and development of ANSE and the results obtained from the experiments conducted to evaluate the effectiveness of ANSE. Studies indicate that ANSE provides an effective environment for modeling and simulation of large-scale active networks.
“Making Democracy Real”
Authors: Johnson Lauri
Published: July 2003

This article examines how an interracial coalition of radical teachers from the Teachers Union of New York City and community activists from the Citywide Citizens Committee on Harlem promoted Black history and intercultural curriculum materials and worked side-by-side with parents for school reform in the New York City schools during the 1930s and early 1940s. Their efforts to develop more culturally responsive schools in Harlem and Bedford-Stuyvesant were derailed by the late 1940s in the wake of the red-baiting of progressive scholars and teacher union activists during the cold war era.
Exploring the Utility of Social Control Theory for Youth Development
Authors: HUEBNER ANGELA J. , BETTS SHERRY C.
Published: July 2003

The purpose of this study was to examine the utility of social control theory's “attachment” and “involvement” bonds as protective factors to examine gender differences in reports of delinquency and academic achievement in a sample of 7th to 12th graders. Attachment bonds were operationalized as attachment to parents, to nonparent adults, and to peers; involvement bonds were operationalized as time spent in various school- and non-school-based activities. It was expected that, with respect to delinquency and academic achievement, attachment bond variables would be more protective for females than the involvement bond variables, whereas the involvement bond variables would be more protective for males than the attachment bond variables. The findings suggest that although several of the involvement bond variables of social control theory are predictive of both delinquency and academic achievement for both genders, only the attachment bond variables provide such an overall protective function for females. Implications for theory and practice are discussed.
Risk and Protective Factors Associated with Gang Involvement among Urban African American Adolescents
Authors: LI XIAOMING , STANTON BONITA , PACK ROBERT , HARRIS CAROLE , COTTRELL LESLEY , BURNS JAMES
Published: July 2003

Data from 349 urban African American youth were analyzed to explore whether the differences in exposure to violence, resilience, and distress symptoms between gang members and nonmembers resulted from the risk behaviors in which youth participated or from the gang membership itself. Youth with current or past gang membership documented higher levels of risk involvement, lower levels of resilience, higher exposure to violence, and higher distress symptoms. These associations persisted even after controlling for age, gender, or risk involvement. This study provides evidence that gang membership itself may be associated with increased risk and ill-effects on psychological well-being and that strong family involvement and resiliency protect against gang involvement.
Race Differences in Strains Associated with Suicidal Behavior among Adolescents
Authors: WATT TONI TERLING , SHARP SUSAN F.
Published: July 2003

Rising adolescent suicide rates have prompted scholars and practitioners to identify predictive strains. Resulting profiles of suicidal adolescents often assume that a single model is applicable to all adolescent subgroups. Although scholars have repeatedly suggested that suicidal processes may vary for Blacks and Whites, few researchers have examined race differences in suicidal correlates. No studies have tested for process differences by race among adolescents specifically. This study examines social strains contributing to suicidal behavior among adolescents by race. Results support the presence of process differences and delineate the specific nature of these differences. Results hold theoretical and interventionist implications for the contextual nature of suicide among adolescents.
Winter Tourist Segments in Austria: Identifying Stable Vacation Styles Using Bagged Clustering Techniques
Authors: Dolnicar Sara , Leisch Friedrich
Published: July 2003

Market segmentation is a very popular and broadly accepted way of increasing profitability. The number of reports published on a posteriori market segmentation studies has rapidly increased since Haley’s milestone publication on benefit segmentation in 1968. Nevertheless, it is common practice to use a single segmentation base only and to run a single calculation of a single algorithm, which dramatically increases the chance of building an entire marketing plan on a random solution of the algorithm chosen. The application presented constructs winter vacation styles based on guest survey data, avoiding both weaknesses mentioned before. Through the replicative framework provided by bagged clustering, potentially suboptimal random solutions are avoided. Independent partitioning of vacation activities and travel motives leads to more holistic segments. By looking for over and underrepresentation of all combinations of the behavioral and psychographic segmentation, vacation styles are identified and studied in detail.
Integrating Community into the Classroom
Authors: Langhout Regina Day , Rappaport Julian , Simmons Doretha
Published: July 2003

This article is about the tensions faced in facilitating the relationship between teachers and community members while working toward a community garden project. The authors adopt an ecological model for effective classroom-community collaboration and discuss how this process unfolded in the current setting. Two classroom projects serve as exemplars of culturally relevant classroom-community collaboration. The garden project is evaluated through classroom-community collaboration models. This evaluation includes a discussion of common and disparate goals of teachers and community members and how differences are navigated in the current milieu.
Reexamining Anthropology and Education
Authors: Tapia Javier
Published: July 2003

Many educational programs that incorporate ethnic minority students’ culture into the curriculum rely on a fragmented view of culture. These perspectives emphasize symbolic and ideational aspects of culture. As such, they ignore students’ economic conditions that influence schooling. This study provides detailed data from two Latino households to show that a deeper understanding of students’ lives requires an investigation of household members’ survival and economic practices. It also shows that household studies provide a deeper understanding of students’ culture and daily practices that cannot be obtained from reading books, as is common in many educational programs.
Disrupting the Logic of Home-School Relations
Authors: Abrams Laura S. , Gibbs Jewelle Taylor
Published: July 2003

Through in-depth interviews with 10 mothers from diverse ethnocultural and socioeconomic groups the authors explore issues of parent roles, access to power, and practices of inclusion and exclusion at an urban elementary school that is undergoing comprehensive school reform. They apply a theory of social and cultural reproduction to assess the potential for school reformstrategies to disrupt traditional patterns of parent marginalization within public schools. The analysis suggests that school interventions seeking to change established practices and ideologies concerning parent involvement can become contested terrain, mediating power relations between parent groups and exposing competing needs and concerns about children’s education.
Unusually Low Clearance of Two CYP3A Substrates, Alprazolam and Trazodone, in a Volunteer Subject with Wild‐Type CYP3A4 Promoter Region
Authors: von Moltke Lisa L. , Tran Thanh Huu , Cotreau Monette M. , Greenblatt David J.
Published: July 2003

A healthy 40‐year‐old Caucasian male volunteer displayed unusually low clearance and long elimination half‐life of alprazolam and trazodone, two CYP3A substrate drugs, following single‐dose oral administration in clinical pharmacokinetic studies. Genomic DNA isolated from the individual's peripheral blood was subjected to polymerase chain reaction amplification and subsequent sequence analysis of a 592 base‐pair segment upstream from the CYP3A coding region. The analysis revealed no variation from wild‐type in the nucleotide present at position −290, previously suggested to influence expression and/or activity of CYP3A. The functional significance of this promoter region mutation is unclear and requires further evaluation.
Optimization of Oral Etoposide Dosage in Elderly Patients with Non‐Hodgkin's Lymphoma Using the Fraction of Dose Absorbed Measured for Each Patient
Authors: El‐Yazigi Adrian , Ezzat Adnan , Berry John , Raines Dale A. , Yusuf Ahmed , Al‐Rawithi Sameer , Legayada Erlinda S.
Published: July 2003

This study was undertaken to investigate the pharmacokinetics of etoposide for optimizing its oral dosage in elderly patients with non‐Hodgkin's lymphoma (NHL) using the fraction of dose absorbed calculated from the data generated from first oral and intravenous doses in the same patient. Twenty‐three NHL patients (ages 61–95 years) entered this study. Each received 50 mg/m2 of etoposide by 1‐hour IV infusion, which was repeated every 24 hours for 5 days. The second cycle commenced on day 21, with etoposide being administered by mouth at a dose as close to 50 mg/m2 as possible. Serial blood samples were collected and analyzed for etoposide by HPLC. The fraction of dose absorbed (F) was calculated as F = (AUCor/AUCiv)(Div/Dor), and etoposide was then given orally for the following 20 days at a daily dose equivalent to Dor/F. After 1 week free of etoposide administration, a second cycle of oral etoposide at the adjusted dose was given for 21 days. The mean ± SD values for t1/2β, tmax, Cmax, CLTor, and MRT observed following the first oral dose were 8.98 ± 4.84 h, 1.39 ± 0.96 h, 0.083 ± 0.046 mg • L−1/mg•m−2, 1.89 ± 1.2 L•h−1/m2, and 10.37 ± 2.76 h, respectively, and those observed following the first intravenous dose were 8.05 ± 5.11 h, 1.57 ± 0.17 h, 0.142 ± 0.043 mg•L−1/mg•m−2, 1.25 ± 0.44 L • h−1/m2, and 7.69 ± 1.53 h, respectively. The mean ± SD of F was 0.80 ± 0.34. The data obtained indicate that optimization of etoposide oral dosage using F yielded good clinical results while keeping the morbidity at a level that is similar to that of the IV administration.
Acute Encephalopathy Due to Aluminum Toxicity Successfully Treated by Combined Intravenous Deferoxamine and Hemodialysis
Authors: Nakamura Hidefumi , Rose Peter G. , Blumer Jeffrey L. , Reed Michael D.
Published: July 2003

Acute aluminum intoxication is uncommon in clinical practice but can be fatal. This limited experience is reflected in the paucity of data assessing a viable approach to the treatment of these patients. In this report, the authors describe the clinical course and successful, pharmacokinetic‐based deferoxamine‐hemodialysis treatment regimen of a patient with severe aluminum encephalopathy following alum bladder irrigation. The combined use of deferoxamine and appropriately timed hemodialysis appears to be a very reasonable means of treating patients with severe acute aluminum intoxication.
Dose‐Proportional Pharmacokinetics of Risedronate on Single‐Dose Oral Administration to Healthy Volunteers
Authors: Mitchell David Y. , Eusebio Rachelle A. , Sacco‐Gibson Nancy A. , Pallone Karen A. , Kelly Sandra C. , Nesbitt John D. , Brezovic Christopher P , Thompson Gary A. , Powefl James H.
Published: July 2003

Risedronate is a pyridinyl bisphosphonate approved for the treatment of Paget's disease (US‐FDA) and in development for the treatment and prevention of osteoporosis. This study examined risedronate pharmacokinetics and tolerability after oral administration using a randomized, double‐blind, parallel‐group design. Healthy male and female volunteers (n = 22–23 subjects per dose) received a single oral dose of 2.5, 5, or 30 mg risedronate. Serum and urine samples were collected for 72 and 672 hours, respectively, and risedronate concentrations were determined by ELISA. Safety was evaluated by monitoring adverse events, clinical laboratory measurements, vital signs, and electrocardiograms. Mean Cmax (0.41, 0.94, and 5.1 ng/mL for 2.5, 5, and 30 mg, respectively), AUC (1.8, 3.9, and 21 ng•h/mL for 2.5, 5, and 30 mg, respectively), and urinary excretion (22, 63, and 260 μg for 2.5, 5, and 30 mg, respectively) were dose proportional, and there were no significant differences in tmax or CLR among the three doses. All doses were well tolerated; no serious adverse events occurred, and all but one of the adverse events were mild or moderate in severity. There was no evidence of an acute phase reaction occurring after oral administration of risedronate.
Higher Incidence of Elevated Body Temperature or Increased C‐Reactive Protein Level in Asthmatic Children Showing Transient Reduction of Theophylline Metabolism
Authors: Yamaguchi Akiko , Tateishi Tomonoh , Okano Yu‐ji , Matuda Takeshi , Akimoto Yasuko , Miyoshi Tomoko , Kobayashi Shinichi , Koitabashi Yasushi
Published: July 2003

The authors investigated whether theophylline metabolism is decreased in asthmatic patients and what condition may be related to its reduction. Fifty‐two children with asthma were given 15 mg/kg/day aminophylline intravenously at a constant rate. Blood and spot urine samples were collected at 24 hours, 48 hours, and 72 hours after beginning infusion. The ratio of plasma theophylline concentration at 72 hours to that at 24 hours (C72h/C24h) varied from 0.42 to 1.51 (average 0.894). Plasma theophylline concentration of patients with lower C72h/C24h than average reduced significantly, while the concentration of those with higher C72h/C24h remained unchanged. The urinary ratio of the sum of the metabolites to theophylline was significantly increased in the patients with the lower ratio. Among the demographic characteristics examined, significant difference was found only in the incidence of patients with C‐reactive protein (CRP) of 0.5 mg/dl or greater or patients with a fever of 37.5°C or greater when admitted. Acute febrile illness accompanied by increased CRP level may affect theophylline metabolism.
Cerebrospinal Fluid Pharmacokinetics of Cefpodoxime Proxetil in Piglets
Authors: Abdel‐Rahman Susan M. , Maxson Suzanne , Teo Charles , Hubbard Amanda E. , Kearns Gregory L.
Published: July 2003

Cefpodoxime is an oral third‐generation cephalosporin used for the treatment of acute upper‐respiratory tract infections caused by susceptible bacteria in children. Although not indicated for the treatment of bacterial meningitis, it is used to treat other infections produced by organisms associated with meningitis and may obscure the result of cerebrospinal fluid (CSF) cultures in children who develop meningitis while receiving oral antibiotics if sufficient concentrations are achieved in the CSF. This study evaluated the disposition of cefpodoxime and penetration into CSF in piglets. Fifteen Landacre‐Camborough cross piglets (10–20 days old) received cefpodoxime proxetil oral suspension (10 mg/kg). Repeated plasma and CSF samples were collected over 24 hours, for quantitation of cefpodoxime by HPLC. Pharmacokinetic analysis was performed on both plasma and CSF data. The plasma concentration versus time data for cefpodoxime were best characterized using a one‐compartment model with first‐order absorption. The mean (± SD) pharmacokinetic parameters for Cmax, tmax, and AUC0‐∞ were 23.3 ± 12.9 mg/L, 3.9 ± 1.4 h, and237 ± 129 mg/L•h, respectively. CSF/plasma ratios for AUC90‐∞, demonstrated a mean cefpodoxime penetration of approximately 5%. CSF penetration of cefpodoxime was evident following a single oral dose of cefpodoxime proxetil suspension. Despite the small percentage of total cefpodoxime dose distributing into the CSF, the resultant concentrations approached or exceeded the MIC90 for many bacterial pathogens considered susceptible to cefpodoxime. Accordingly, clinicians should use caution in the interpretation of CSF cultures in patients who develop clinical signs and symptoms consistent with meningitis and who have been previously treated with cefpodoxime.
Cirrhosis Does Not Affect the Pharmacokinetics and Pharmacodynamics of Clopidogrel
Authors: Slugg Peter H. , Much David R. , Smith William B. , Vargas Ramon , Nichola Peter , Necciari Jose
Published: July 2003

Clopidogrel, a new platelet ADP receptor antagonist used for the prevention of vascular ischemic events, is converted to an active metabolite via the cytochrome P450 system. Patients with cirrhosis may not metabolize drugs normally and may, in addition, have a number of defects in the coagulationsystem. To assess the effect of cirrhosis on the pharmacokinetics and pharmacodynamics of clopidogrel, the authors performed an open‐label, parallel‐group study of 12 patients with Child‐Pugh Class A or B cirrhosis and 12 matched controls. All 24 subjects received clopidogrel 75 mg PO QD for 10 days. Pharmacokinetics of clopidogrel and the major metabolite SR 26334 were analyzed on Days 1 and 10; pharmacodynamics were assessed by the inhibition of ADP‐induced platelet aggregation and by bleeding time prolongation factor. Pharmacokinetic analysis of clopidogrel was limited due to low plasma concentrations arising from rapid hydrolysis to SR26334. The Cmax at SS for clopidogrel was higher in cirrhotics than in normals. However, exposures to the metabolite SR 26334, as measured by AUC(tau), were comparable. At Day 10, there was not a statistically significant difference in mean inhibition of platelet aggregation (49.2% ± 38.6% in cirrhotics vs. 66.7% ± 7.5% in normals) or in bleeding time prolongation factor (1.64 ± 0.49 in cirrhotics vs. 1.54 ± 0.87 in normals) between groups. No significant adverse events, including bleeding events, were reported. In conclusion, there were no significant differences in the pharmacokinetics and pharmacodynamics of clopidogrel in this group of subjects with cirrhosis and matched normals. Therefore, no dos age adjustment of clopidogrel is required in patients with Child‐Pugh Class A or B cirrhosis.
Acetaminophen Controlled‐Release Sprinkles versus Acetaminophen Immediate‐Release Elixir in Febrile Children
Authors: Wilson John T. , Helms Richard , Pickering Bretten D. , Donahue Lori , Brown R. Don
Published: July 2003

Current acetaminophen (APAP) formulations approved for antipyretic use in children require up to five doses/day, which compromise compliance and risk breakthrough fever over 4 hours after dosing. A total of 112 evaluable febrile children received oral APAP‐equivalent doses of either one dose of APAP controlled release (CR) as sprinkles on apple sauce or one dose q 4 hours × 2 of APAP immediate‐release (IR) elixir in an 8‐hour, double‐blind, double‐dummy, randomized, multicenter study. Prior or concurrent antibiotic use did not significantly affect either the magnitude or the pattern of temperature reduction during the 8‐hour observation period. Significantly greater aural temperature reductions were found with APAP‐CR than with APAP‐IR at 4 and 5 hours. However, the 8‐hour AUCs of temperature reduction were not significantly different between treatments. Pharmacokinetic/pharmacodynamic modeling of APAP was performed in 8 patients with values in both treatments similar to previous results, except for expected differences in AUC0‐∞. Similar 8‐hour temperature reduction for APAP‐CR (one dose) and APAP‐IR (two doses) demonstrates the efficacy of APAP‐CR as an antipyretic in children 2 to 11 years of age. A decrease in the number of APAP daily doses and the prolonged antipyretic effect of APAP‐CR may assist those who care for febrile children at home.
Antiplatelet Effects of MK‐852, a Platelet Fibrinogen Receptor Antagonist, in Healthy Volunteers
Authors: Greenberg Howard E. , Wissel Paul , Barrett Jeffrey , Barchowsky Aaron , Gould Robert , Farrell Daniel , Panebianco Deborah , Hand Elizabeth , Gillen Lisa , Goldberg Michael R. , Bjornsson Thorir D.
Published: July 2003

MK‐852, a cyclic heptapeptide, is a potent platelet fibrinogen receptor antagonist When administered to normal healthy male subjects by 1 ‐ and 4‐hour constant rate intravenous infusions, it provides a generally well‐tolerated and reversible means of inhibition of platelet function. At infusion rates of 1 μg/kg/min for 1 hour and 0.44 μg/kg/min for 4 hours, respectively, MK‐852 extended baseline bleeding time by greater than 2.2‐fold and 2.6‐fold, inhibited ADP‐induced platelet aggregation by 76% and 69%, and inhibited collagen‐induced platelet aggregation by 65% and 67%, respectively. The pharmacokinetics of MK‐852 include an elimination half‐life of approximately 2 hours, total clearance of about 150ml/min, and volume of distribution of about 18 liters. Examination of the relationship between MK‐852 whole‐blood concentration in vitro and inhibition of platelet aggregation showed an EC50 of about 55 ng/ml and a Hill coefficient of 1.55. The infusions were generally well tolerated, with no study drug‐related changes in blood counts or biochemical profiles.
A Study Comparing the Clinical Pharmacokinetics, Pharmacodynamics, and Tolerability of Triamcinolone Acetonide HFA‐134a Metered‐Dose Inhaler and Budesonide Dry‐Powder Inhaler following Inhalation Administration
Authors: Argenti Domenick , Shah Bharti , Heald Donald
Published: July 2003

The impending phaseout of chlorofluorocarbons as propellants in pressurized metered‐dose inhalers used in the treatment of asthma has resulted in the development of alternative devices to deliver drug to the pulmonary airways. These alternative devices include metered‐dose inhalers using environmentally friendly hydroflurocarbon propellants and breath‐actuated dry‐powder inhalers. The purpose of this study was to compare the single‐ and multiple‐dose pharmacokinetics, pharmacodynamics, and tolerability of a newly developed hydroflurocarbon formulation of triamcinolone acetonide (Azmacort® HFA 225 mcg Inhalation Aerosol) to that of the dry‐powder formulation of budesonide (Pulmicort® Turbuhaler 200 mcg). This three‐way crossover study used 18 normal healthy subjects each receiving a 675 mcg dose of triamcinolone acetonide, 600 mcg dose of budesonide, or placebo twice a day for 5 days. Serial plasma samples were collected after the first and last dose of test medication for pharmacokinetic analysis. Pharmacodynamics were assessed by changes in hypothalamic‐pituitary‐adrenal axis function as measured by 8 a.m. serum cortisol, 24‐hour overnight serum cortisol AL/C(0.24), and 24‐hour urinary‐free cortisol after the last evening dose of test drug. Tolerability was assessed through physical examinations, vital signs, 12‐lead ECG, routine clinical labs, and adverse events recording. Both compounds were systemically absorbed. However, no significant drug accumulation was noted with chronic dosing. Chronic dosing did result in a statistically significant 20% reduction in basal 24‐hour serum cortisol AUC(0–24) for both compounds. There were no clinically significant abnormalities in physical examination, vital signs, 12‐lead ECG, or routine clinical labs noted during the study. Overall, the study drugs were well tolerated, with adverse events characterized as mild to moderate in severity.
Lack of Interaction between Tolcapone and Tolbutamide in Healthy Volunteers
Authors: Jorga Karin M. , Fotteler Bärbel , Gasser Rodolfo , Banken Ludger , Birnboeck Herbert
Published: July 2003

To assess the effect of tolcapone (an inhibitor of cytochrome P450 [CYP] 2C9 in vitro) on the pharmacokinetics and hypoglycemic effect of the CYP 2C9 substrate tolbutamide, 12 healthy male volunteers were randomized to receive a single dose of tolbutamide 500 mg plus either placebo or tolcapone 200 mg after an overnight fast and 30 minutes after the start of a 6.5‐hour 5% glucose infusion (150 mL/h). The participants crossed over to receive the alternative regimen after a washout period of at least 7 days. Tolcapone had no effect on the pharmacokinetics of tolbutamide or its metabolites and did not influence the effect of tolbutamide on plasma glucose concentrations. No serious adverse events or abnormal laboratory results or vital signs were reported. In conclusion, clinically relevant drug‐drug interactions between tolcapone and tolbutamide when given together in clinical practice appear unlikely.
Toxicity of Complementary Therapies: An Eastern Perspective
Authors: Tomlinson Brian , Chan Thomas Y. K. , Chan Juliana C. N. , Critchley Julian A.J.H. , But Paul P. H.
Published: July 2003

Chinese traditional medicine is used extensively in Chinese populations, and other Asian countries employ similar therapies. Herbal treatments have a major role in these systems, and although most have a well‐established safety record, occasional adverse effects are seen. Problems arise when toxic herbs are used in excessive doses, with improper preparation, or when they are substituted erroneously. There may also be adulteration with Western drugs or heavy metals, and interactions between herbs and Western drugs may also occur. It is always prudent to obtain a complete history of the use of herbal medications during any clinical assessment, particularly in Asian patients.