bluuebunny/crossref_metadata_2025 huggingface dataset:
An Intelligent Coherent Approach to Cooperation between TCP and ATM Congestion Control Algorithms—Modeling and Simulation Analysis
Authors: Yu Qing , Hoang Doan B.
Published: July 2003

The combination of transmission control protocol (TCP) and asynchronous transfer mode (ATM) to deliver transport services may incur significant performance penalties due to the interaction of congestion control algorithms of TCP and ATM. In this paper, the authors examine two control categories (explicit window adaptation [EWA] and ACK bucket control [ABC]) and their representative schemes. In particular, they propose the fair intelligent EWA scheme for EWA and the fair intelligent ABC scheme for ABC. The key idea is to combine the feedback information from the receiver, from the ATM network, and from the local information at edge device intelligently to explicitly/implicitly control the TCP rate. The authors present simulation results to show that their schemes can control the buffer occupancy at edge device efficiently and can carry the benefits of ABR end-to-end, resulting in significant improvement in throughput, fairness, packet loss rate, and end-to-end delay for TCP connections. Both schemes are transparent to TCP, requiring no modifications in the ATM networks except at the network edge device. Importantly, they allow TCP to be used with any underlying network, not just ATM, as long as the network is capable of providing explicit feedback information concerning the availability of bandwidth.
Performance Evaluation of Multimedia Services in Cellular Networks
Authors: Fazekas Péter , Imre Sándor , Telek Miklós
Published: July 2003

In this paper, a new analytical method is presented for analyzing cellular networks with connections that change their transmission rate during the session. The method is based on a Markovian model of a single base station and an approximate recursive formula following from the Markov model. This formula is applicable for calculating call level system parameters rapidly with reasonable error. Two simple admission control strategies are also presented and investigated. The accuracy of the proposed approximate method is verified by computer simulations.
Agent-based Planning and Simulation of Combined Rail/Road Transport
Authors: Gambardella Luca Maria , Rizzoli Andrea E. , Funk Petra
Published: July 2003

A simulation model of the flow of intermodal terminal units (ITUs) among inland intermodal terminals is presented. The intermodal terminals are interconnected by rail corridors. Each terminal serves a user catchment area via a road network. The terminal is modelled as a set of platforms that are served by a number of gantry cranes and front lifters. Given the schedule of train connections among the terminals, an agent-based system, the intermodal transport planner (ITP), books ITUs on trains and assigns trucks to deliver them to the source terminal and to pick them up in the destination terminal. The terminal and rail corridor simulation software has been implemented as a discrete event simulation model, using MODSIM III as development tool. The ITP has been implemented on the basis of the TELETRUCK system. This research has been developed within the PLATFORM project, funded by the Directorate General VII of the European Community.
Simulation of a Multiagent System for Retail Inventory Control: A Case Study
Authors: Signorile Robert
Published: July 2003

The supply chain of a manufacturing enterprise is a worldwide network of suppliers, factories, warehouses, distribution centers, and retailers through which raw materials are acquired, transformed, and delivered to customers. Supply chain functions must operate in a coordinated manner to optimize performance. But the dynamics of the enterprise and the market make this difficult: materials do not arrive on time, production facilities fail, and employees are ill, causing deviations from the plans. In some cases, these events may be dealt with locally. In other cases, the problem cannot be locally contained, and modifications across many functions are required. This paper describes the use of agent technology to improve performance within important aspects of supply chain management. A supply chain model will be designed and implemented in ZUES. Through simulation on different configurations of the model, the impact of information sharing and coordination on supply chain performance will be analyzed.
A Discrete-Continuous Combined Modeling Approach for Supply Chain Simulation
Authors: Lee Young Hae , Cho Min Kwan , Kim Yun Bae
Published: July 2003

Supply chain management (SCM)is a strategic paradigm to coordinate cash, material, and information flows from raw material to customer. Supply chain simulation (SCS)is a strong and popular tool for designing, evaluating, and optimizing the structure of supply chains, and it requires an important task to estimate the effect of the planning to coordinate such flows in SCM. Stochastic natures existing in the supply chain can be analyzed efficiently using simulation. One uses discrete-event simulation to model a supply chain in general. However, the nature of the supply chain system is neither completely discrete nor continuous; both aspects must be considered together in developing an SCS model. In this paper, a framework of discrete-continuous combined modeling for supply chain simulation is proposed. Equations for the continuous aspects of a supply chain in this framework are included, and a simple example of the SCS model using this equation is presented.
A Simulation-based Method for the Process to Allow Continuous Tracking of Quality, Cost, and Time
Authors: Goel S. , Strong D. R. , Richards N. , Goel N. C.
Published: July 2003

A simulation-based methodology is developed for continuously tracking and analyzing the quality of product, associated cost, and time during the manufacturing process. In particular, the metal-to-metal bonding process related to the prefit stage is selected for the study, in which required mating conditions for detail parts that make up the bonded assembly are critical. Finally, the results of the model allow the optimal condition to the supply-chain network and identification of problems that affect the quality and productivity of manufactured goods in a factory on a continuous basis.
FELT: A Far Future Event List Structure Optimized for Calendar Queues
Authors: Hui Timothy Chee-Kin , Thng Ian Li-Jin
Published: July 2003

Calendar queues (CQ) are often employed in discrete event simulators to store pending events. They can achieve O(1) access time as long as the CQ resizes often enough to ensure that events are not skewed but evenly distributed in the queue structure. However, a resize operation would involve creating a new CQ structure and then moving each item from the old CQ to the new CQ before discarding the old CQ. Hence, such resizes can be costly if the size of the queue is very large. This article proposes a new secondary queuing structure that complements the primary CQ structure. Known as FELT (far future event leaf tree), the secondary FELT structure is a lazy queue (i.e., semisorted) structure that manages events that are considered to be too far away to be considered in the primary CQ structure. The FELT structure is shown to be far superior than the dynamic lazy calendar queue.
Investment Decisions of International Mining Firms: Policy Approaches
Authors: O’Regan Bernadette , Moles Richard
Published: July 2003

The tools and techniques of system dynamics method are applied to the complex problem of understanding those factors that affect the flow of international mineral investment funds. The main deliverable is a simulation model developed in Powersim in the system dynamics tradition. The model, comprising more than 180 variables, provides a means of examining the effectiveness of varied environmental, fiscal, and corporate policies on the flow of investment funds and mineral resources among a number of simulated mining firms and competing countries.
Simulation-Based Performance Comparisons of Routing Protocols for Mobile Ad Hoc Networks
Authors: Boukerche Azzedine
Published: July 2003

An ad hoc network is a collection of wireless mobile hosts forming a temporary network without the aid of any established infrastructure or centralized administration. Because of the limited range of each host’s wireless transmission, to communicate with hosts outside its transmission range, a host needs to enlist the aid of its nearby hosts in forwarding packets to the destination. A routing protocol for ad hoc networks is executed on every host and is therefore subject to the limit of the resources at each mobile host. In this paper, the authors focus on on-demand schemes, studying and comparing the performance of three routing protocols: AODV, CBRP, and DSR. Results indicate that despite its improvement in reducing route request packets, CBRP has a higher overhead than DSR because of its periodic hello messages, while AODV’s end-to-end packet delay is the shortest when compared to DSR and CBRP.
Design and Simulation of a Distributed Dynamic Clustering Algorithm for Multimode Routing in Wireless Ad Hoc Networks
Authors: McDonald A. Bruce , Znati Taieb F.
Published: July 2003

This article presents analysis of the design and simulation of a new class of environmentally aware clustering algorithms for wireless ad hoc networks. The clustering algorithm establishes an adaptive self-organizing arrangement that enables multimode routing strategies. Multimode operation is needed to enhance scalability and robustness. In the present case, clustering is based on a criterion that enforces an upper bound on the probability of path failure within a cluster over time. The result is an adaptive hybrid routing strategy that dynamically balances routing overhead against routing optimality. The clustering algorithm unifies the routing strategies according to localized and time-varying mobility characteristics. A simulation model was developed to validate the effectiveness of the clustering algorithm and demonstrate the multimode routing behavior. Results show that the algorithm adapts effectively to node mobility and achieves relatively consistent overhead regardless of network size and mobility.
A Simulation Study of IPv6 to ATM Flow-Mapping Techniques
Authors: Basu Kashinath , Ball Frank , Kouvatsos Demetres D.
Published: July 2003

This paper presents a simulation study into the problem of conveying Internet protocol (IP) packets over an asynchronous transfer mode (ATM) network in cases where quality of service (QoS) is an important consideration. The main focus of the work is on mapping IP packet flows onto ATM cell streams, particularly for the purpose of maintaining the QoS requirements of continuous media (audio and video) traffic. Simulation models of two different flow-mapping scenarios are described, and results of an evaluation of the flow-mapping process are presented. These results are also used to validate an analytical solution to the problem, which has been developed in a separate but related piece of work.
Design and Simulation of a New Queuing Architecture for Large-Scale ATM Switches
Authors: Guizani Mohsen , Al-Fuqaha Ala Isam
Published: July 2003

The authors study the different buffering techniques used in the literature to solve the contention problem in asynchronous transfer mode (ATM) switching architectures. The objective of this study is to determine the buffer requirements needed to achieve a given quality of service (e.g., a given cell loss probability). On the basis of this study, the authors propose a combined central and output queuing (CCOQ) technique to be used in designing large-scale ATM switches. Also, a general design technique for an N× N large-scale ATM switch is proposed with a suitable CCOQ buffer size to reduce both the cell loss probability and the complexity of the memory modules. The switch has to be designed such that it can be implemented using the smallest number of VLSI chips possible. It should be also reliable for commercial use. The switch should support multicast and priority control functions.
A Simulation Study of Epoch Load Sharing in Distributed Systems
Authors: Karatza Helen D. , Hilzer Ralph C.
Published: July 2003

This paper examines load sharing in distributed systems. It proposes a special load-sharing method, referred to as epoch load sharing. With this policy, load is evenly distributed among distributed processors, with job migration only at the end of predefined intervals. The time interval between successive load sharing is called an epoch. The authors compare the performance of epoch job migration with other traditional load-sharing methods. The objective is to reduce the number of times that global system information is needed to make allocation decisions while achieving good overall performance and fairness in individual job service. The impact of the variability in migration cost and job service demand is also examined. Simulation results indicate that for specific workloads, epoch job migration can combine good performance with a moderate scheduling overhead.
“If there is a Better Intercultural Plan in any School System in America, I Do Not Know where it is”
Authors: Pak Yoon K.
Published: July 2003

This article explores the relatively unknown history of the San Diego City Schools’ attempts at intercultural reform after World War II and how educators responded to the specific needs of students and community members in the wake of racial, ethnic, and religious tensions on the West Coast. The 3-year intercultural program was one of the first of its kind in California and became a template for those in Los Angeles and San Francisco to follow. How the program developed, what was instituted in the classrooms, and the conservative political resistance faced by school leaders is examined.
Black Milwaukee’s Challenge to the Cycle of Urban Miseducation
Authors: Span Christopher M.
Published: July 2003

Milwaukee’s two African American Immersion schools—public schools that infused African and African American themes into the state’s prescribed curriculum—officially opened in 1990 and 1991. Inner-city African American residents and school officials in Milwaukee prompted the call for their establishment. It was hoped that these African-centered schools would serve as a model for the city’s public school system to effectively combat the disparaging statistics associated with African American students. Needless to say, the proposition was controversial but at the same time historically significant. Black Milwaukee’s call for schools, reflective of their culture and educational expectations, was not a spur-of-the-moment proposal; it was a response to the city’s continued inability to effectively educate African American children. Arguably, it was an initiative more than 40 years in the making. Accordingly, Milwaukee’s African American Immersion schools can be seen as a beginning and an end for inner-city Black Milwaukeeans. The schools were a beginning because they signified a new direction of educational reform in the city, one specific to the educational needs of inner-city African American children. Concomitantly, the establishment of these two African American Immersion schools can be seen as an end result of more than two generations of struggle for equitable opportunities and school reform in Milwaukee.
Black Student Empowerment and Chicago
Authors: Danns Dionne
Published: July 2003

Current school reform efforts in Chicago have gained national attention, but little is known about the struggle for educational reform that took place in the 1960s. Black students, surrounded by the organizing in their communities and the events shaping the civil rights and Black Power movements, moved to correct the injustices they experienced at their schools in 1968. After several protests at individual schools, students organized citywide boycotts demanding community control, Black administrators, more Black history courses, and various other school improvements. Their protests led to increased Black administrators and increased Black history courses. The most significant accomplishment was the organized efforts to improve their education.
The “Simmie” Side of Life
Authors: REILING DENISE M.
Published: July 2003

In this article, an analysis has been provided of the counterintuitive affective response Old Order Amish youth make to unique cultural prescriptions for adolescent deviance, which have been constructed by adult Amish culture. Data reported on were gathered as part of a larger ethnographic study and through more than 60 in-depth interviews on this particular topic. Evidence was found that supports the basic principles of Terror Management Theory, although in an unexpected and indirect fashion. Rather than function as a specialized cultural-anxiety buffer against fear generated by the contemplation of mortality, as Terror Management Theory would predict, the deviance prescribed for youth culture produces high levels of anxiety and depression for Amish youth. In this cultural context, youth find existential value in adult, not youth, culture.
Correlates of Gun Involvement and Aggressiveness among Adolescents
Authors: DING CODY S. , NELSEN EDWARD A. , LASSONDE CYNTHIA T.
Published: July 2003

This study examined adolescents' aggressiveness in relation to their experiences, beliefs, and attitudes concerning gun use. It also investigated family composition, relationships with parents, and emotionality as correlates of gun involvement and aggressiveness. A self-report questionnaire was given to 334 students, 167 females and 167 males, in a junior high school in upstate New York. Correlation coefficients and regression analyses revealed that males who had more experience with guns reported reacting more violently to frustration and also admitted to having participated in greater numbers of violent incidents. Girls who indicated that they were alienated from and dissatisfied with their mothers felt generally more upset and unhappy, reacted angrily to frustration, and more often expressed aggression toward persons and objects. Both boys and girls whose families owned and used guns tended to believe that gun use had innocuous effects.
“Not Under My Roof!”
Authors: WHITE NAOMI ROSH
Published: July 2003

Young people are staying at home for longer periods. This study explores how this extended period of living with parents is experienced by young people. In what sense is the parental home also “home” to coresident young adult offspring? How are these constructed meanings of home related to young people's sense of autonomy and the structure of power relations in the family? The findings showed that the concept of home is a core organizing symbol in the discourse about the experience of coresidence with parents, linking the social, emotional, and physical dimensions of the domestic environment with the young person's developing sense of self. The meaning of home is connected to perceived rights to make decisions about how the household might operate, the division of labor within its confines, and the tenor of relationships between its members.
Internet Technology Use by American Convention and Visitors Bureaus
Authors: Yuan Yu-Lan , Gretzel Ulrike , Fesenmaier Daniel R.
Published: July 2003

Adoption and diffusion theories are used to explain key factors affecting the use of Internet technology by American convention and visitors bureaus. Organizational properties, leader characteristics, and technology-activity fit are assumed to determine the extent and length of information technology (IT) use. A survey conducted among American convention and visitors bureaus indicates that bureaus can be classified into five adopter groups (laggards, sophisticated followers, knowledge adopters, early light adopters, and late light adopters), which follow two different paths of technology implementation and use. Bureaus along these paths differ substantially in terms of their use of applications, their perceptions of IT, and the impacts of IT on their activities. Education and knowledge of bureau leaders and the perceived usefulness of IT also affect the bureaus’ potential to become knowledge adopters.
To Look or Book: An Examination of Consumers’ Apprehensiveness toward Internet Use
Authors: Susskind Alex M. , Bonn Mark A. , Dev Chekitan S.
Published: July 2003

In a series of three studies, a two-factor measure of apprehension toward Internet use was developed and tested among three independent samples of consumers. The relationship between general Internet apprehensiveness (GIA) and transactional Internet apprehensiveness (TIA) was examined in concert with the relationship between consumers’ online information seeking, purchasing intentions, and behaviors. Results indicated that (1) a two-factor measure of GIA and TIA demonstrated construct validity across three independent samples of potential Internet users, (2) GIA is more strongly related to perceptions of Internet use for information seeking compared to online purchasing, and (3) TIA is more strongly related to perceptions of online purchasing activities and reported online purchasing behavior compared with perceptions of online information-seeking behavior. Implications for management practice and further research are presented.
Forecasting the Demand for International Business Tourism
Authors: Kulendran Nada , Witt Stephen F.
Published: July 2003

Previous research in the area of tourism demand modeling and forecasting has paid little attention to business tourism. This study provides the most comprehensive comparison to date of the accuracy of modern forecasting methods in the context of international business tourism demand forecasting. Seven forecasting models are examined, including the error correction model and various structural time-series and autoregressive integrated moving average (ARIMA) models. The empirical results show that relative forecasting performance is highly dependent on the length of forecasting horizon, that adding explanatory variables to the structural time-series model does not improve forecasting performance, and that testing for unit roots is likely to yield reasonably accurate results under certain conditions.
Examining Welcome Center Visitors’ Travel and Information Behaviors: Does Location of Centers or Residency Matter?
Authors: Pennington-Gray Lori , Vogt Christine
Published: July 2003

The purpose of this study was to examine the role of welcome center location and residency of visitors in serving different vacation market segments. Data from all 13 Michigan welcome centers were analyzed to examine the relationship between center location and residency, and other consumer travel characteristics. Results indicated in-state travelers were more likely to visit interior welcome centers (than border), and out-of-state travelers were more likely to visit border welcome center locations (than interior). For trip purpose and timing of the visit in relation to the trip, location and residency effects were found. A residency effect was found for selected types of information search and accommodation types. The location of state-managed information centers appears to play a role in the type of traveler served, thus suggesting interior and border welcome centers are an important element of a state’s tourism marketing program and information network.
Segmenting the Japanese Tour Market to Turkey
Authors: Sirakaya Ercan , Uysal Muzaffer , Yoshioka Carlton F.
Published: July 2003

In recent years, as a newly emerged tourism destination and moderately developed country, Turkey has enjoyed increased visitation from abroad, including Japan. However, there has not been a systematic research effort to understand the travel behavior of Japanese visitors to Turkey. The purpose of this exploratory study was to segment Japanese travelers to Turkey using travel motivations as part of travel behavior descriptors. Theoretical and practical contributions of the motivation factors are discussed within the framework of Iso-Ahola’s arousal theory. The article concludes with marketing and management implications as suggested by the study findings.
Adapting Herzberg: A Conceptualization of the Effects of Hygiene and Motivator Attributes on Perceptions of Event Quality
Authors: Crompton John L.
Published: July 2003

Herzberg suggested that job satisfaction was a function of two types of conditions that he termed hygiene or dissatisfier and motivator or satisfier attributes. This article suggests that these same conditions may contribute to explaining levels of visitor satisfaction with an event. Hygiene attributes are the generic infrastructure elements that form the platform or foundation on which a meaningful event is developed. If their quality is below a given threshold, then dissatisfaction will result, but they have little potential for creating satisfaction with an event. They are a necessary but not a sufficient condition for visitor satisfaction. Satisfaction only results from visitor interaction with the motivator attributes that are the distinctive features of the event that attract people to it.
The Louisiana Tax Free Shopping Program for International Visitors: A Case Study
Authors: Dimanche Frédéric
Published: July 2003

The strong relationship between tourism and shopping has long been pointed out, but the tourism literature has largely ignored the issues of duty-free or tax-free shopping, either from an economic or from a marketing perspective. This research note proposes a case study of the only state-sponsored tax-free shopping program in the United States. The analysis puts the Louisiana Tax Free Shopping Program in its historical context, describes the program’s achievements in its 10-year existence, presents Louisiana international tourists’ shopping behavior, then examines the economic impact claims that are made by the program. Results show that tax-free shopping is an incentive that increases tourists’ propensity to buy retail goods. Marketing and policy recommendations are made to conclude this research note.
The Use of Repertory Grid Analysis to Elicit Salient Short-Break Holiday Destination Attributes in New Zealand
Authors: Pike Steven
Published: July 2003

Repertory grid analysis was developed almost 50 years ago, but its application in destination image research has been rare. The technique was used to identify 17 attributes deemed salient to New Zealanders, when differentiating domestic short-break holiday destinations. These were then compared to those attributes used in 84 previous destination studies, as well as with results from personal interviews with tourism practitioners. A number of differences between the repertory grid findings and practitioner opinion confirmed the value of seeking consumer input when developing attribute lists for use in structured surveys. While both the repertory grid findings and practitioner opinion showed a general consistency with the range of 100+ attributes used in the literature, key differences highlighted the importance of the New Zealand domestic travel context. The article attempts to demonstrate the efficacy of repertory grid, an economical technique that has been underused by tourism market researchers.
Low-Level Violence
Authors: Dupper David R. , Meyer-Adams Nancy
Published: July 2003

A largely neglected aspect of school violence is low-level, underlying violence in schools that includes bullying, peer sexual harassment, victimization based on sexual orientation, and the psychological maltreatment of students by teachers. Low-level violence angers and alienates many students and contributes to a hostile school environment. This article examines the extent of low-level violence in U.S. public schools and its impact on students’ school performance. The authors argue that the one way of reducing low-level violence in schools is to create a more positive school culture and climate. Guidelines for preventing or minimizing low-level violence in schools are presented.
Friends, Family, and Neighborhood
Authors: Williams Trina R. , Davis Larry E. , Saunders Jeanne , Williams James Herbert
Published: July 2003

This study examines the relationship between academic performance and a number of contextual factors for African American freshmen in an urban setting. Living arrangements, relatives and friends’ religiosity, exposure to academic success, and neighborhood perceptions were analyzed to investigate their impact on intention to complete school, grade point average (GPA), and number of suspensions. Results indicate that gender, church attendance by peers, and percentage of relatives completing high school were significant in predicting positive academic outcomes. Perception of neighborhood deterioration was inversely related to intention for school completion and GPA. School suspensions were positively related to perception of neighborhood deterioration. Implications for interventions are discussed.
Disciplinary Challenges
Authors: Mukuria Gathogo
Published: July 2003

This article explores and compares the role of principals in predominantly African American urban middle schools with suspension rates. This study compares how principals in schools with low and high suspension rates differ in addressing disciplinary challenges. The selection of the principals was based on a purposeful sampling technique. Data were collected through observations, interviews, and document analysis. The findings indicate several factors contributing to lower suspension rates including high parental involvement, structured environment, schoolwide discipline programs, and mutual respect among students and teachers. Contrarily, schools with high suspension rates have ineffective use of these attributes.
Political Revisions
Authors: NORRIS ANDREW
Published: July 2003

But play, you must,

A tune beyond us, yet ourselves,

A tune upon the blue guitar

Of things exactly as they are.

— Wallace Stevens
Drug Interaction Studies with Repaglinide: Repaglinide on Digoxin or Theophylline Pharmacokinetics and Cimetidine on Repaglinide Pharmacokinetics
Authors: Hatorp Vibeke , Thomsen Mikael S.
Published: July 2003

Drug interaction studies were carried out to ensure that hypoglycemia due to inhibition of repaglinide elimination or chronic hyperglycemia due to inhibition of repaglinide absorption was avoided. Conversely, the effects of repaglinide on the pharmacokinetics of drugs with only a narrow margin between effective and toxic concentrations, such as digoxin or theophylline, were determined. The studies reported here compared monotherapy with combined therapies in healthy volunteers. There were no significant differences between the pharmacokinetic parameters of repaglinide when given as monotherapy and when administered concurrently with cimetidine. Similarly, the coadministration of repaglinide and digoxin did not influence the pharmacokinetics of digoxin administered alone. When repaglinide was coadministered with theophylline, the only pharmacokinetic change was that the peak plasma theophylline concentration was slightly reduced. No direct drug‐drug interactions were found in these studies, suggesting that repaglinide may be coprescribed with cimetidine, digoxin, or theophylline at the dosage used for monotherapy.
Drug Interaction between Cimetidine and Timolol Ophthalmic Solution: Effect on Heart Rate and Intraocular Pressure in Healthy Japanese Volunteers
Authors: Ishii Yoko , Nakamura Koichi , Tsutsumi Kimiko , Kotegawa Tsutomu , Nakano Shigeyuki , Nakatsuka Kazuo
Published: July 2003

Systemic adverse effects of timolol ophthalmic solution given at usual therapeutic doses have been well characterized. Timolol is partially metabolized by cytochrome P450 (CYP) 2D6. Cimetidine inhibits the activity of cytochrome P450, including CYP2D6, leading to reduced systemic clearance of concomitant drugs. Coadministration of cimetidine has been speculated to affect the pharmacological effects of timolol ophthalmic solution, resulting in increased blood concentration. To evaluate whether administration of cimetidine with timolol ophthalmic solution increased the degree of beta‐blockade, 12 healthy Japanese male volunteers ages 19 to 26 received cimetidine (400 mg), an oral placebo, timolol maleate 0.5% (0.05 mL to each eye), or placebo eye drops in a randomized, double‐blind, Latin‐square design. The oral drug alone was given for 3 days, and on the 4th day, eye drops were applied after oral drug administration. At baseline and 1, 3, and 6 hours after eye drop administration, blood pressure and heart rate (HR) were measured before and after exercise. Intraocular pressure (IOP) was measured at rest. A visual analog scale (VAS) was used to assess subjective bodily feelings in exercise tolerance after every physical exercise. The exercise HR, exercise systolic blood pressure (SBP), and resting SBP were reduced following timolol with and without cimetidine compared with the placebo (p < 0.01, respectively). Administration of cimetidine with timolol ophthalmic solution resulted in additional reductions of the resting HR and IOP VAS detected a significant reduction in exercise tolerance from timolol ophthalmic solution (p < .05). In conclusion, administration of cimetidine with timolol ophthalmic solution increased the degree of beta‐blockade.
Relationship between Lymphocyte and Clinical Steroid Responsiveness in Focal Segmental Glomerulosclerosis
Authors: Briggs William A. , Gimenez Luis F. , Samaniego‐Picota Milagros , Choi Michael J. , Nadasdy Tibor , Eustace Joseph , Scheel Paul J.
Published: July 2003

A remission in nephrotic proteinuria with steroid treatment appears to favorably alter the natural history of focal segmental glomerulosclerosis (FSGS). It is not known why some patients have a favorable response to steroid treatment whereas others do not. Considering the possibility that differences in the pharmacodynamic responsiveness to steroids among patients might be one factor, the authors examined the relationship between the pretreatment suppressive effect of steroids on lymphocyte proliferation (% inhibition) in vitro and the short‐ and intermediate‐term responses of creatinine clearance (Clcr and/or nephrotic proteinuria (urine protein/creatinine ratio = Up/c in 13 patients with FSGS. There were significant correlations between % inhibition and the changes in Clcr at 3 (r = 0.92, p < 0.001) and 6 (r = 0.86, p < 0.01) months and the changes in Up/c at 3 months (r = −0.74, p = 0.02). Thus, the greater the pretreatment lymphocyte steroid sensitivity the greater the increase in Clcr or decrease in Up/c. The changes in these parameters could not be accounted for on the basis of steroid dose or histopathology The in vitro sensitivity of FSGS patients' lymphocytes to steroids may be of value in anticipating their clinical response to treatment.
Effects of Celecoxib, a Novel Cyclooxygenase‐2 Inhibitor, on Platelet Function in Healthy Adults: A Randomized, Controlled Trial
Authors: Leese Philip T. , Hubbard Richard C. , Karim Aziz , Isakson Peter C. , Yu Shawn S. , Geis G. Steven
Published: July 2003

Conventional nonsteroidal anti‐inflammatory drugs (NSAIDs) nonspecifically inhibit cyclooxygenase‐1 (COX‐1), an enzyme critical to normal platelet function, and COX‐2, which mediates inflammatory response mechanisms. Celecoxib, an antiarthritic agent that inhibits COX‐2 but spares COX‐1 at therapeutic doses, is expected to have minimal effects on platelet function. A double‐blind, randomized, placebo‐controlled study of 10 days' duration was conducted in 24 healthy adults to compare the effects on platelet function of a supratherapeutic dose of celecoxib (600 mg bid) with a standard dose of naproxen (500 mg bid), a conventional NSAID. Ex vivo platelet aggregation in response to standard agonists (collagen, arachidonate, or U46619 [a thromboxane A2 receptor agonist]), bleeding time, and serum thromboxane B2 (TxB2 level were measured. Unlike celecoxib or placebo, naproxen produced statistically significant reductions in platelet aggregation and serum TxB2 levels and increased bleeding time. The results indicate that even at supratherapeutic doses, celecoxib will not interfere with normal mechanisms of platelet aggregation and hemostasis, supporting the premise that celecoxib is COX‐1 sparing relative to conventional NSAIDs.
Baseline Pain and Response to Analgesic Medications in the Postsurgery Dental Pain Model
Authors: Averbuch M. , Katzper M.
Published: July 2003

In designing clinical trials for the treatment of acute pain, enrollment of patients with moderate to severe pain is recommended even when the desired indication is treatment of mild pain. To test this approach, the authors explored the results of two studies that had the same standard placebo‐controlled, parallel‐group design and that compared the study medication to a single dose of ibuprofen 400 mg. One study had 25 subjects, the other 50 in its ibuprofen arm. Subjects indicating moderate or severe pain (on a scale ranging from 0 = none, 1 = mild, 2 = moderate, 3 = severe) following a surgical extraction of two or more third molars were enrolled. There was a difference between the ibuprofen groups in these two studies in average baseline pain intensity (PI) (2.88 ± 0.33 vs. 2.26 ± 0.44). In the higher baseline group, PI decreased faster, achieving lower levels of PI that were maintained for the rest of the study period. The results of pain relief measurements paralleled those of PI. The authors conclude that including patients with a higher degree of baseline pain in the postoperative dental pain model has the potential to increase discrimination of analgesic properties of new drugs.
A Comparison of Fluoride Bioavailability from a Sustained‐Release NaF Preparation (Neosten) and Other Fluoride Preparations
Authors: Gitomer William L. , Sakhaee Khashayar , Pak Charles Y C.
Published: July 2003

Twelve normal subjects completed a crossover study with sustained‐release sodium fluoride (Neosten, 11.3 mg F), monofluorophosphate (MFP, 10 mg F), and plain sodium fluoride (P‐NaF, 11.3 mg F). After each preparation was given with 400 mg calcium, serum fluoride (Fser was measured for 24 hours, and pharmacokinetic data were calculated. Fluoride absorption in the Neosten group, as measured by change in the area under the curve (ΔAUC] of Fser, was less than 33% of that in the MFP and P‐NaF treated groups. Both peak Fser (Cmax) and peak‐basal variation in the Neosten group were 25% that found in the other groups. t1/2 was nearly twofold greater after Neosten. MFP and P‐NaF showed greater bioavailability than Neosten and much higher Cmax that exceeded the toxic threshold of Fser (190 ng/ml). These findings could explain the ineffectiveness of MFP and P‐NaF observed in recent clinical trials.
Single‐Dose Pharmacokinetics of Repaglinide in Subjects with Chronic Liver Disease
Authors: Hatorp Vibeke , Walther Kirsten H. , Christensen Michael S. , Haug‐Pihale Gertraud
Published: July 2003

Repaglinide is a novel insulin secretagogue developed in response to the need for a fast‐acting, oral prandial glucose regulator for the treatment of type 2 (non‐insulin‐dependent) diabetes mellitus. Repaglinide is metabolized mainly in the liver; its pharmacokinetics may therefore be altered by hepatic dysfunction. This open, parallel‐group study compared the pharmacokinetics and tolerability of a single 4 mg dose of repaglinide in healthy subjects (n = 12) and patients with chronic liver disease (CLD) (n = 12). Values for AUC and Cmax were significantly higher in CLD patients compared with healthy subjects, and the MRT was prolonged in CLD patients. Values for tmax did not differ between the groups, but t1/2 was significantly prolonged in CLD patients compared with previously determined values in healthy subjects. AUC was inversely correlated with caffeine clearance in CLD patients but not in healthy subjects. Blood glucose profiles were similar in both groups. Adverse events (principally hypoglycemia) were similar in the two groups; none was serious. Repaglinide clearance is significantly reduced in patients with hepatic impairment; the agent should be used with caution in this group.
Pharmacokinetics and Safety of Duloxetine, a Dual‐Serotonin and Norepinephrine Reuptake Inhibitor
Authors: Sharma Amarnath , Goldberg Mark J. , Cerimele Benito J.
Published: July 2003

The pharmacokinetics and safety of duloxetine were evaluated in a single‐blind, placebo‐controlled, escalating multiple‐dose study in 12 healthy male subjects. In the treatment group (n = 8), duloxetine was administered orally at a starting dose of 20 mg twice daily (bid) and escalated at weekly intervals to 30 mg bid, then to 40 mg bid. The observed plasma concentration‐time data at all three dose levels were adequately described by a one‐compartment model with a first‐order absorption rate constant. The mean oral clearance, apparent volume of distribution, and half‐life values were 114 L/h (range: 44 to 218 L/h), 1943 L (range: 803 to 3531 L), and 12.5 h (range: 9.2 to 19.1 h), respectively. Somnolence, nausea, and dry mouth were observed following the initial dose, but they resolved with continuing drug administration. Duloxetine was not associated with clinically significant changes in blood pressure (BP) or heart rate (HR) measured in the standing position. However, in recumbent position, small increases in systolic (≤ 9 mmHg) and diastolic (≤ 5 mmHg) BP and small decreases in HR (≤ 6 beats/min) were observed. Abrupt discontinuation of duloxetine was associated with a small increase in mean HR (≤ 12beats/min). In 3 subjects, abrupt discontinuation was also associated with transient sleep disturbance. No clinically important changes in electrocardiograms, cardiac intervals, clinical laboratory tests, and neurological functions were observed. These results indicate that duloxetine exhibits linear pharmacokinetics with respect to dose and duration of treatment and that a multiple oral dose regimen starting at 20 mg bid and gradually escalating up to 40 mg bid was generally well tolerated.
Comparison of the Initial Hemodynamic Effects of Immediate‐Release versus Sustained‐Release Isosorbide‐5‐Mononitrate following Single Oral Doses
Authors: Trenk Dietmar , Hinder Markus , Stengele Eberhard , Bonn Rainer , Jähnchen Eberhard
Published: July 2003

In this double‐blind, randomized, placebo‐controlled crossover study, the authors investigated the initial time course of effects of isosorbide‐5‐mononitrate (IS‐5‐MN) on hemodynamic parameters in 15 healthy male volunteers after administering a single oral dose of either an immediate‐release formulation (IS‐5‐MN 20 mg) or of a sustained‐release formulation (IS‐5‐MN 50 mg). The latter formulation released 15 mg IS‐5‐MN immediately, while 35 mg of the dose was sustained release. The onset of effect on the a/b‐ratio of the finger pulse curve (20 minutes after administration) and on heart rate following orthostatic challenge (30 minutes) was not different following ingestion of either the immediate‐release or the sustained‐release formulation. Only the systolic blood pressure following orthostatic challenge was affected earlier after ingestion of the immediate‐release form of IS‐5‐MN (10 vs. 30 minutes). There was no statistically significant difference in the maximum effect on the measured hemodynamic parameters between the two formulations. There was no significant difference with respect to the effect per dose between both of the active treatments (i.e., IS‐5‐MN 20 mg immediate release and IS‐5‐MN 50 mg sustained release) within 6 hours after administration. The hemodynamic findings were consistent with the observed rates of the increase of plasma concentrations of IS‐5‐MN following both formulations. Thus, the administration of the sustained‐release formulation of IS‐5‐MN 50 mg caused similar maximum effects when compared with an immediate‐release formulation (20 mg). While the onset of effect of IS‐5‐MN on the a/b‐ratio of the finger pulse curve and on heart rate following orthostasis was similar after administration of either the immediate‐ or the sustained‐release formulation, the onset of effect of the sustained‐release formulation on systolic blood pressure orthostasis was determined slightly later. However, the latter difference seems to be of minor clinical relevance.
Information Overload in the Teaching of Pharmacology
Authors: Achike Francis I. , Ogle Clive W.
Published: July 2003

Medical students are usually drawn from the best of students, but it is not unusual to see these brilliant students fail their exams or even dismissed from medical school because of poor academic performance. Information overload has been recognized as one of the major contributing factors to this problem. The situation is expected to get worse, with the ever‐present technology‐induced exponential growth in information. In discussing this issue, the authors echo the concerns of several experts regarding the content overload of medical school curricula, particularly in pharmacology. It is the increasing awareness of this problem that led the Association of American Medical Colleges and the General Medical Council of Britain to promote the concept of a core curriculum for each of the principal disciplines in medicine. Several medical schools have adopted the concept and also the problem‐based learning approach, which focuses on ameliorating the complex problems associated with information growth in medical education. Based on the authors' experience as medical students, medical practitioners, and pharmacology teachers, they discuss the factors that contribute to information overload, from psychological and nonpsychological perspectives. Issues such as the design and structure of the curriculum, the quality of training and effectiveness of the teachers (clinically qualified vs. nonclinically qualified teachers), and the psychological preparedness of the students are discussed. The authors make suggestions for improvement.
Lack of Interaction between Lansoprazole and Propranolol, a Pharmacokinetic and Safety Assessment
Authors: Karol Michael D. , Locke Charles S. , Cavanaugh John H
Published: July 2003

Due to the prevalence of both gastrointestinal and cardiovascular diseases, it is likely that patients may be coprescribed gastric parietal cell proton pump inhibitors and beta‐adrenergic antagonists. Therefore, the objectives of this phase I study were to assess the potential effects of the coadministration of lansoprazole on the pharmacokinetics of propranolol and to evaluate the safety of propranolol with concomitant lansoprazole dosing. In a double‐blind fashion, 18 healthy male nonsmokers were initially randomized to receive either 60 mg oral lansoprazole, each morning for 7 days, or an identical placebo (period 1). On day 7, all subjects were concomitantly administered oral propranolol, 80 mg. After a minimum of 1 week following the last dose of either lansoprazole or placebo, subjects were crossed over to the opposite treatment for another 7 days (period 2). Subjects were again administered oral propranolol on day 7. During both treatment periods, blood samples for the determination of plasma propranolol and 4‐hydroxy‐propranolol were obtained just before the dose and at 0.5, 1, 2, 3, 4, 6, 8 12, 16, 20, and 24 hours postdose. Plasma propranolol and 4‐hydroxy‐propranolol concentrations were determined by using HPLC with fluorescence detection. The Cmax, tmax, AUCQ0‐∞, and t1/2 values for propranolol, as well as the AUC0‐∞ for 4‐hydroxy‐propranolol, were calculated and compared between the lansoprazole and placebo regimens. The mean age of the 15 subjects who successfully completed the study was 31 years (range: 24–38 years), and their average weight was 174.8 pounds (range: 145–203 pounds). There were no statistically significant differences between the lansoprazole and placebo regimens for the propranolol Cmax, tmax, AUC0‐∞, and t1/2 values. Also, there were no statistically significant differences between regimens for the 4‐OH‐propranolol AU0‐∞. Safety evaluations, which included adverse events, vital signs, clinical laboratory determinations, ECG, and physical examinations, revealed no unexpected clinically significant findings and did not suggest a drug‐drug interaction. In conclusion, lansoprazole does not significantly alter the pharmacokinetics of propranolol, suggesting that it does not interact with the CYP2D6‐ or CYP2C19‐mediated metabolism of propranolol. Modification of a propranolol dosage regimen in the presence of lansoprazole is not indicated, based on the pharmacokinetic analysis and the lack of a clinically significant alteration in the pharmacodynamic response.