bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic and pharmacodynamic modeling of the antiplatelet and cardiovascular effects of cilostazol in healthy humans
Authors: Woo Su Kyung , Kang Won Ku , Kwon Kwang‐il 
Published: August 2002

ObjectiveCilostazol is an antiplatelet agent with vasodilating properties. It has been used to treat patients with peripheral ischemia, such as intermittent claudication. We used a pharmacokinetic‐pharmacodynamic model to analyze the relation between the plasma concentration of cilostazol, the inhibitory effect of the drug onplatelet aggregation, and the cardiovascular effects of the drug on healthy humans.MethodsA single oral dose of 100 mg cilostazol was administered to 20 healthy volunteers. Serial blood sampling and pharmacodynamic measurements were performed up to 48 hours thereafter. The effects of cilostazol on platelet aggregation, blood pressure, and heart rate were measured during the same period. The plasma concentration of cilostazol was measured with a validated HPLC method that entailed ultraviolet detection. The time courses of plasma cilostazol concentration, platelet aggregation, and cardiovascular effects were analyzed by means of pharmacokinetic‐pharmacodynamic modeling with the program ADAPT II.ResultsThe plasma concentration‐time course followed a 2‐compartment model. Mean peak concentration was775 ng/ml approximately 3.65 hours after administration of cilostazol. The maximal effect on platelet aggregation wasa 31.14% reduction 6.05 hours after administration. No significant difference in systolic blood pressure was found. The maximal increase in heart rate was 13.49%, whereas the maximal decrease in diastolic blood pressure was 29.51%. Both peak effects were detected approximately 6 hours after administration of the drug. Platelet aggregation and cardiovascular effects (change in diastolic blood pressure and heart rate) were analyzed with the effect‐link sigmoid maximal effect model.ConclusionThis pharmacokinetic‐pharmacodynamic model successfully described the relation between plasmaconcentration of cilostazol and the antiplatelet and cardiovascular effects of the drug.Clinical Pharmacology & Therapeutics (2002) 71, 246–252; doi: 10.1067/mcp.2002.122474
Impact of CYP2C9 amino acid polymorphisms on glyburide kinetics and on the insulin and glucose response in healthy volunteers
Authors: Kirchheiner Julia , Brockmöller Jürgen , Meineke Ingolf , Bauer Steffen , Rohde Wolfgang , Meisel Christian , Roots Ivar 
Published: August 2002

BackgroundGlyburide (INN, glibenclamide) is a second‐generation sulfonylurea antidiabetic agent with high potency. We hypothesized that glyburide may be a substrate of cytochrome P450 2C9 (CYP2C9), an enzyme that has two low‐activity amino acid variants‐Arg144Cys (CYP2C9*2) and Ile359Leu (CYP2C9*3). We explored the impact of these polymorphisms on glyburide pharmacokinetics and the effects on insulin and glucose concentrations.MethodsTwenty‐one healthy volunteers who represented all possible combinations of the two variant alleles were studied (genotypes CYP2C9*1/*1, *1/*2, *2/*2, *1/*3, *2/*3, and *3/*3). They received a single oral dose of 3.5 mg glyburide followed by 75 g glucose at 1, 4.5, and 8 hours after administration of glyburide. Glyburide was quantified in plasma by reversed‐phase HPLC. Venous blood concentrations of glyburide, insulin, and glucose were analyzed with a population pharmacokinetic‐pharmacodynamic model by use of NONMEM statistical software.ResultsPharmacokinetics of glyburide depended significantly on CYP2C9 genotypes. In homozygous carriers of the genotype *3/*3, total oral clearance was less than half of that of the wild‐type genotype *1/*1 (P < .001). Correspondingly, insulin secretion measured within 12 hours after glyburide ingestion was higher in carriers of the genotype *3/*3 compared with the other genotypes (P = .028), whereas the differences in glucose concentrations were not significant.ConclusionsCarriers of the CYP2C9 variant *3 had decreased oral clearances of glyburide. This confirms that glyburide is metabolized by CYP2C9. Corresponding differences in insulin plasma levels indicated that dose adjustment based on CYP2C9 genotype may improve antidiabetic treatment.Clinical Pharmacology & Therapeutics (2002) 71, 286–296; doi: 10.1067/mcp.2002.122476
Optical Metrology of Adaptive Membrane Mirrors
Authors: Wagner John W. , Agnes Gregory S. , Magee Eric 
Published: August 2002

Current space-based imaging platforms are significantly constrained in both size and weight by the launch vehicle. Increased payload size and weight increases the cost and decreases the selection of launch vehicles. The challenge of membrane optics in space is implementing adaptive optics technology via a membrane surface that provides at least rough order of magnitude imaging—enabling a large lightweight imaging system where small can be eliminated by processes such as real time holography. A system was developed which categorizes surface properties of optical quality membrane material with the ability to interpret membrane mirror deformation. Membrane mirrors with adaptive control were constructed and analyzed using this system which provided sub-micron deformation data with associated optical aberrations, proving the ability of PVDF film to provide adaptive control to regions of interest on membrane mirrors. Remaining technical challenges include bonding methods and eventual multi-layer laminate bonding of the PVDF control surfaces to the membrane.
TOWARDS EXPERIMENTAL REALIZATION OF THE SUPERCONDUCTOR–SEMICONDUCTOR INTERFACE IN THE YBCO–Si COMPOSITE SYSTEM
Authors: ABO-ARAIS A. 
Published: August 2002

To study the solid state and chemical interactions between Y1Ba2Cu3O7-δ and Si, resistivity and X-ray diffraction measurements were carried out on Y1Ba2Cu3O7-δ–Si x compounds with 0<x>0.12. The transition temperature Tc was found to be slightly decreased by Si addition up to x=0.08 and sharply decreased at x=0.10. The superconducting phase incompletely disappeared at x=0.12. The resistivity was increased by Si doping and its behavior was changed from a metallic to an insulator and semiconductor-like nature. All peaks of the orthorhombic phase were still present by increasing the Si ratio and new phases were produced which were indexed as mainly barium silicates. At x=0.12 the orthorhombic phase was greatly decreased and the barium silicate phases were very clearly destroying the superconducting phase. The obtained results are discussed according to the superconductor–semiconductor composite model and with the idea of Bose–Einstein condensation. The superconductor–semiconductor composite as the YBCO–Si system seems to be a key to unlocking some secrets about the mechanisms of high Tc superconductors.
Relationship of Less Restrictive Interventions with Seclusion/Restraints Usage, Average Years of Psychiatric Experience, and Staff Mix
Authors: Williams J. Earle , Myers Rachel E. 
Published: August 2002

BACKGROUND: Seclusion and/or restraints (S/R) usage is a legal, moral, and ethical issue of patient rights and safety. Current emphasis is on using lesser restrictive interventions (LRI) in crisis management. OBJECTIVE: This descriptive/correlational study examined the relationship of LRI with S/R usage, average years of psychiatric experience of nursing staff, and staff mix. STUDY DESIGN: The sample included 82 events requiring crisis intervention. Data were collected at a state mental health facility using a crisis cycle intervention tool and staff questionnaire. RESULTS: Data revealed a significant relationship between LRI and S/R usage and a significant positive relationship between percentage of licensed nurses and LRI. However, the relationship between average years of psychiatric experience and LRI was not significant. Fourteen percent of LRI could be predicted by percentage of licensed staff. CONCLUSION: The findings supported using LRI in crisis management. Using LRI individualized to the crisis event promotes a safer, more therapeutic environment for both parties and staff. The findings revealed the need to evaluate the impact of a change in staff mix on quality of care and desired outcomes. Further research is needed to explore the multiple variables that influence LRI.
Inpatient Group Therapies for People with Bipolar Disorder: Comparison of a Self-Management and an Interactional Model
Authors: Pollack Linda E. , Harvin Sheila , Cramer Roxy D. 
Published: August 2002

BACKGROUND: Although diagnostically homogeneous group therapy is a generally accepted component of the outpatient treatment of persons with bipolar disorder, investigations into the use of this modality in the inpatient setting are preliminary. OBJECTIVES: The purpose of this study was to compare the effectiveness of the Self-Management Group Model with that of the Interactional Group Model in improving the ability of patients hospitalized with bipolar disorder to care for themselves when discharged. DESIGN: This study used a quasi-experimental, nonequivalent comparison group design with repeated measures that were administered before the intervention, after the intervention, and 3 months after discharge from the hospital. Instruments elicited data on self-reported mood states, behavior and symptom identification, coping resources, and satisfaction with the group services. RESULTS: One hundred twenty-two people participated at the first measurement period. No significant total score differences were found between the two groups on any of the four measurements. However, 3 months after hospitalization, Interactional Group Model participants reported significantly less difficulty with behaviors and symptoms at the 3-month measurement period when compared with their admission scores but less satisfaction with the groups than they had at discharge. CONCLUSIONS: Results suggest that each method has advantages; the optimal model may be one that combines elements of both methods within a self-management focus.
Crisis Child Care: Implications for Family Interventions
Authors: Cowen Perle Slavik 
Published: August 2002

BACKGROUND: Crisis child care programs provide caregiving respite on an emergency basis and counseling and referral services to stressed parents who are at risk for maltreating their children. OBJECTIVES: The objectives of this study were to describe the sociodemographic and stress characteristics of rural parents who accessed crisis child care services and to determine if the utilization of these services would reduce the reported incidence of child maltreatment. STUDY DESIGN: Parents completed a basic sociodemographic questionnaire and the Parenting Stress Inventory (PSI). Child maltreatment reporting statistics were used to determine if there was a significant decrease in the reported incidence of child maltreatment. RESULTS: The demographic data painted a portrait of economic disadvantage. The data indicated that parents perceived external stressors, those outside of the parent-child relationship, as the major contributor to their current life crisis. Comparison of child maltreatment rates between rural communities that did and did not receive crisis child care preventive interventions indicated that the programs were effective in preventing child maltreatment. CONCLUSION: The findings of this study provide support for the ecological model of child maltreatment which posits that availability of social support for families who experience high stress or crisis can decrease the incidence of child maltreatment.
Depression and Behavioral Manifestations of Depression in Female Survivors of the Suicide of their Significant Other and Female Survivors of Abuse
Authors: Constantino Rose E. , Sekula L. Kathleen , Lebish Jeanne , Buehner Elizabeth 
Published: August 2002

BACKGROUND: Depression is one of the most commonly diagnosed and persistent psychiatric disorders among women. Women survivors of the suicide of their significant other and women survivors of abuse appear to be two groups who might likely experience depression. However, little research has been done to identify the psychological implications of both situations. OBJECTIVE: The study sought to compare psychological implications, specifically depression and behavioral manifestations of depression, among female survivors of the suicide of their significant other and female survivors of abuse. STUDY DESIGN: A descriptive cohort design was used. The Beck Depression Inventory (BDI) was used to measure the presence and behavioral manifestations of depression. RESULTS: The two groups of women did not differ in their overall level of depression. Both groups were moderately to severely depressed. Differences on three BDI items were found: sadness, irritability, and social withdrawal. CONCLUSIONS: Researchers have only just begun to explore and report information with respect to women’s health in relation to abuse and bereavement. The presence of depression and behavioral manifestations of depression in these two groups of women (survivors of the suicide of their significant other and survivors of abuse) needs to be examined further. Subsequently, psychiatric mental-health interventions may be developed that will impact the outcomes for both groups.
MODULAR THEORY AND GEOMETRY
Authors: SCHROER B. , WIESBROCK H.-W. 
Published: August 2002

In this communication we present some new results on modular theory in the context of quantum field theory. In doing this we develop some new proposals how to generalize concepts of finite dimensional geometrical actions to infinite dimensional "hidden" symmetries. The latter are of a purely modular origin and remain hidden in any quantization approach. The spirit of this work is more on a programmatic side, with many details remaining to be elaborated.
SUPPORTING DISTRIBUTED AUTONOMOUS INFORMATION SERVICES USING COORDINATION
Authors: GAL AVIGDOR , MYLOPOULOS JOHN 
Published: August 2002

The large quantity and often questionable quality of available information in the information age provides a shaky foundation for decision making by individuals and organizations alike. This has created a tremendous demand for information services which can access, filter, process and present information on an as-needed basis. However, two factors complicate the design of such information services, namely the distributed and the autonomous nature of data sources. This paper reports on the design and implementation of a generic architecture for supporting information services, which meets the above challenge. The architecture adopts concepts from conceptual modeling to offer a transparent description of the information sources' setting and uses active databases techniques to offer a declarative, event-based language for defining coordination rules for integrating distributed information services. Accordingly, the proposed architecture supports two of the most prominent utilities of information services, namely the pre-designed flow of operations and the reactive provision of information. In addition to describing the architecture and illustrating its features with an example, the paper presents a prototype implementation and reports on some experimental performance results.
Pharmacokinetics and pharmacodynamics of methadone enantiomers after a single oral dose of racemate
Authors: Boulton David W. , Arnaud Philippe , DeVane C. Lindsay 
Published: August 2002

BackgroundThe pharmacokinetics and dynamics of methadone are characterized by high interindividual variability. This study aimed to examine a number of factors that may contribute to this variability.MethodsEight healthy drug‐free women were administered 0.2 mg/kg of R,S‐methadone orally. The concentrations of methadone's enantiomers in plasma and urine were monitored for 96 hours. Vital signs, blood biochemical parameters, and pupillary diameter were monitored frequently during this period. Cytochrome P450 3A (CYP3A) activity and α1‐acid glycoprotein (α1‐AGP) concentrations and phenotypes were determined. Pharmacokinetic and pharmacodynamic modeling was used to assess the influence of the above‐mentioned covariables on methadone enantiomer disposition and actions.ResultsThe pharmacokinetic profile of the active enantiomer of methadone, R‐methadone, showed a relatively normal distribution with 38% to 90% of the interindividual variability in modeled pharmacokinetic parameters being explained by their individual variability in CYP3A activity, the cumulative amount of the main CYP3A4 metabolite, 2‐ethylidene‐1,5‐dimethyl‐3,3‐diphenylpyrolidine, excreted in the urine, the fraction unbound in plasma, and the α1‐AGP orosomucoid 2 (ORM2) variant plasma concentration. S‐Methadone showed an idiosyncratic distribution with largely unpredictable pharmacokinetics. Pupillary constriction response was highly variable between individuals.ConclusionsThe disposition of the active enantiomer, R‐methadone, can be predicted in part by CYP3A activity and protein binding to α1‐AGP (ORM2), whereas S‐methadone disposition is not well explained by the factors examined in this study. Central nervous system effects were difficult to interpret on the basis of plasma R‐methadone pharmacokinetics.Clinical Pharmacology & Therapeutics (2001) 70, 48–57; doi: 10.1067/mcp.2001.116793
Effect of growth hormone on hepatic cytochrome P450 activity in healthy elderly men
Authors: Jürgens Gesche , Lange Kai Henrik Wiborg , Reuther Lene Ørskov , Rasmussen Birgitte Buur , Brøsen Kim , Christensen Hanne Rolighed 
Published: August 2002

ObjectiveOur objective was to study the effect of recombinant human growth hormone (rhGH) on hepatic cytochrome P450 (CYP) activity in 30 healthy elderly men.MethodsThe study was carried out as a randomized, double‐blind, placebo‐controlled parallel‐group study. rhGH or placebo was administered for a period of 12 weeks. CYP activity was measured before, after 12 weeks of rhGH and placebo administration, and at 4 weeks after termination of rhGH and placebo administration with use of the biomarker reactions of CYP1A2 (caffeine), CYP2C19 (mephenytoin), CYP2D6 (sparteine), CYP3A4 (endogenous cortisol metabolism), and antipyrine clearance as common markers of CYP activity.ResultsThe metabolic ratio of caffeine increased significantly in the group that received growth hormone compared with placebo (median difference, 4.55; 95% confidence interval (CI), 1.64 to 8.60; versus −0.90; 95% CI, −5.70 to 1.36), indicating an induction of CYP1A2. Moreover, the S/R ratio of mephenytoin showed a small but significant increase (median difference, 0.02; 95% CI, 0 to 0.31; versus 0; 95% CI, −0.01 to 0.06), indicating an inhibition of CYP2C19. There were no significant changes of the metabolic ratios of cortisol and sparteine or the antipyrine clearance compared with placebo.ConclusionsThese results indicate that growth hormone induces CYP1A2 and, to a lesser extent, inhibits CYP2C19 in elderly men, but it exerts no effects on CYP2D6 and CYP3A4. Although the induction of CYP1A2 may be of some clinical relevance, the small inhibition of CYP2C19 is probably unimportant.Clinical Pharmacology & Therapeutics (2002) 71, 162–168; doi: 10.1067/mcp.2002.121373
Influence of the Selection of the Suture Material on the Mechanical Behavior of a Biomaterial to be Employed in the Construction of Implants. Part 2: Porcine Pericardium
Authors: Páez J. M. García , Carrera A. , Herrero E. Jorge , Millán I. , Rocha A. , Cordón A. , Sainz N. , Mendez J. , Castillo-Olivares J. L. 
Published: August 2002

Using a hydraulic stress simulator, the mechanical behavior of the porcine pericardium used in the construction of cardiac valve leaflets was characterized following the same procedure employed with calf pericardium in Part 1 of this study. One hundred fifty pairs of tissue samples were subjected to tensile testing to rupture. One of the two samples from each of 120 pairs (four series of 30 pairs each) was saturated with commercially available threads made of nylon, silk, Prolene or Gore-Tex, while the other sample in each of these pairs was left unsewn. The remaining 30 pairs were employed as controls in which neither of the two samples was subjected to suturing. The sutured tissue samples showed a significant decrease in tensile strength at rupture (range: 11.61 to 21.22 MPa) when compared with unsutured samples (range: 50.80 to 89.45 MPa; p < 0.01). When these results were compared with their equivalent in calf pericardium, no significant differences were observed (the mean values at rupture in calf pericardium ranged between 211.61 MPa and 26.04 MPa). Again, the application of morphological and mechanical selection criteria to ensure the homogeneity of the samples provided excellent fit with respect to the stress/strain curves. The interaction of the different suture materials with the pericardial tissue was also assessed by comparing the mechanical behavior of the sutured samples with that of the control samples. At the working stress of a cardiac valve leaflet, 0.250 MPa, samples sewn with Gore-Tex were found to show the least difference in behavior with respect to the controls, indicating that this material presented the lowest degree of interaction with the pericardium. In conclusion, the suture clearly has deleterious effects on the resistance of both calf and porcine pericardium, which showed no statistically significant differences in terms of resistance to rupture when their respective sutured or unsutured samples were compared, except in the case of porcine pericardium sewn with silk, which presented lower resistance to rupture in all the zones studied. These findings suggest that the hypothesis that porcine pericardium is less resistant is erroneous. The Gore-Tex suture also presented a lower degree of interaction with the porcine pericardium, with values similar to the working stress of a cardiac valve leaflet. This methodology and the results should be evaluated in dynamic studies, such as fatigue testing, that not only confirm the resistance of the material but establish the durability of the samples being assayed.
Comparison of the Instrumented Falling Weight Impact Response of Polypropylene Composites Reinforced by Continuous and Discontinuous Fiber Mats
Authors: Czigány T. , Karger-Kocsis J. 
Published: August 2002

The temperature dependent instrumented falling weight impact (IFWI) behavior of glass mat reinforced thermoplastic polypropylene (GMT-PP) composites with continuous (GM-C) and discontinuous (GM-D) fiber mats were studied at three different temperatures: −40°C, room temperature (RT) and +90°C. Apart from the mat type the matrix viscosity and the fiber/matrix adhesion were also varied in the GMT-PP samples. It was established that the mat type is that parameter which controls the fracture and failure behavior. The high perforation impact resistance of GM-C compared to GM-D is due to an efficient stress redistribution via the continuous fibers and rovings within the mat. Effects of the matrix and interface variations could not be detected during IFWI. The testing temperatures also affected the IFWI characteristics marginally, especially in case of GM-C reinforced PP.