bluuebunny/crossref_metadata_2025_split huggingface dataset:
Corneal shape of Hong Kong‐Chinese⋆
Authors: Cheung Sin‐wan , Cho Pauline , Douthwaite William 
Published: October 2002

SummaryCorneal asphericity (the p‐value, p) and apical corneal radius (r0) were calculated for 63 Hong Kong‐Chinese (39 male and 24 female), using the Topographic Modeling System (TMS‐1). The values of p and r0 in, and between, the two principal meridians were compared, and the effects of refractive error and gender were also investigated. The mean±SD r0 and p along the flattest meridian of the right eye were 7.82±0.26 mm and 0.78±0.12 respectively. The mean±SD r0 and p along the steepest meridian of the right eye were 7.64±0.26 mm and 0.83±0.15 respectively. Meridional variations were found in r0 and in p. There was no correlation between p and r0 along the two principal meridians. p was not significantly correlated to the refractive error but r0 was. Our results agree with previous findings that while males have longer r0 than females, their p are not significantly different.
A prospective, randomized clinical trial of universal WBC reduction
Authors: Dzik W.H. , Anderson J.K. , O'Neill E.M. , Assmann S.F. , Kalish L.A. , Stowell C.P. 
Published: October 2002

BACKGROUND : Recipient exposure to allogeneic donor WBCs results in transfusion complications for selected populations of recipients. Whether or not WBC reduction should be universally applied is highly controversial. STUDY DESIGN AND METHODS : In a general hospital, a randomized, controlled clinical trial of conversion to universal WBC reduction was conducted. Patients (11%) with established medical indications for WBC‐reduced blood were not eligible. All other patients who required transfusion were assigned at random to receive either unmodified blood components or stored WBC‐reduced RBCs and platelets. Analysis for each patient was restricted to the first hospitalization. RESULTS : All eligible patients (n = 2780) were enrolled. Three specified primary outcome measures were not different between the two groups: 1) in‐hospital mortality (8.5% control; 9.0% WBC‐reduced; OR, 0.94 [95% CI, 0.72‐1.22]; p = 0.64); 2) hospital length of stay (LOS) after transfusion (median number of days, 6.4 for control and 6.3 for WBC‐reduced; p = 0.21); and 3) total hospital costs (median, $19,500 for control and $19,200 for WBC‐reduced, p = 0.24). Secondary outcomes (intensive care LOS, postoperative LOS, antibiotic usage, and readmission rate) were not different between the two groups. Subgroup analysis based on patient age, sex, amount of blood transfused, or category of surgical procedure showed no effect of WBC reduction. Patients who received WBC‐reduced blood had a lower incidence of febrile reactions (p = 0.06). CONCLUSION : A beneficial effect of conversion from selective to universal WBC reduction was not demonstrated.
Circulation and hemostatic function of autologous fresh, liquid‐preserved, and cryopreserved baboon platelets transfused to correct an aspirin‐induced thrombocytopathy
Authors: Valeri C. Robert , MacGregor Hollace , Giorgio Albert , Ragno Gina 
Published: October 2002

BACKGROUND : The survival of fresh and preserved platelets has been used primarily to determine their therapeutic effectiveness. The function of the fresh and preserved platelets has been difficult to assess. In stable thrombocytopenic patients, platelet function of fresh and preserved allogeneic platelets is evaluated by the reduction in bleeding time. In this study of healthy male baboons, both the survival and function of autologous fresh, liquid‐preserved, and cryopreserved platelets in the correction of an aspirin‐induced thrombocytopathy was evaluated. STUDY DESIGN AND METHODS
: Five healthy male baboons were studied on eight occasions over a 4‐year period. To produce a prolonged bleeding time, the baboon was administered 325 mg of aspirin 18 hours before receiving autologous transfusion. The fresh, liquid‐preserved, and previously frozen washed platelets were labeled with
111
In‐oxine before autologous transfusion. The autologous, nonaspirinated platelets' ability to reduce the aspirin‐induced prolonged bleeding time and increase the shed blood thromboxane B
2 level at the template bleeding time site was studied. RESULTS
: Platelets stored at 22°C for 48 hours had in vivo recovery values similar to those platelets stored for 18 hours, and they significantly reduced the bleeding time and increased the shed blood thromboxane level after transfusion. Platelets stored at 22°C for 72 hours had in vivo recovery values similar to those platelets stored for 18 hours, but the bleeding time was not corrected after transfusion, although there was a significant increase in the shed blood thromboxane B
2 level. The cryopreserved platelets significantly reduced the bleeding time and significantly increased the shed blood thromboxane level after transfusion. Cryopreserved platelets had better in vivo survival and function than the 5‐day liquid‐stored platelets. CONCLUSIONS : The survival of autologous fresh, liquid‐preserved, or cryopreserved platelets did not correlate with their function to reduce an increased bleeding time in baboons treated with aspirin.
Lessons learned from a phase III population pharmacokinetic study of cariporide in coronary artery bypass graft surgery
Authors: Weber Willi , Harnisch Lutz , Jessel Andreas 
Published: October 2002

BackgroundCariporide (HOE642) is a recently developed inhibitor of the myocardial sodium‐hydrogen exchange system. The clinical effects of sodium‐hydrogen exchange inhibition in patients at high risk for myocardial cell necrosis were investigated in the GUARDIAN trial (n = 11,590 patients). Although the trial did not show a significant benefit of cariporide over placebo in the overall population, a 25% relative risk reduction in the primary end point of death or myocardial infarction (12.1% for the highest tested cariporide dose of 120 mg 3 times a day versus 16.2% for placebo; P = .03) was observed in the subpopulation of patients who underwent bypass surgery.ObjectiveOur objective was to identify an optimal dosing regimen that might offer increased protection during the period of highest risk.MethodsA population pharmacokinetic model of cariporide was developed with use of data from phase I studies. After adequate predictability was shown for the patients in the pharmacokinetic substudy of the GUARDIAN trial (n = 269 patients), the model was used to predict the individual pharmacokinetic profile in the remaining patients. These predicted concentrations were used to calculate the mean concentration during the period of coronary artery bypass graft surgery (the acute risk period in patients who receive coronary artery bypass grafts), and this mean concentration was used as predictor variable in a time‐to‐event analysis.ResultsA mixture of two Weibull functions adequately described the time course of the observed sum of the acute and chronic hazard rate. The calculated mean concentration during the period of surgery was an adequate predictor for the probability of an event in the acute risk period. The estimated minimal effective mean concentration was 0.5 mg/L.ConclusionsA dosing regimen with a loading dose of an infusion of 120 mg/h for 1 hour followed by an infusion of 20 mg/h for 47 hours should achieve stable exposure above the estimated minimal effective concentration in more than 95% of patients during and after coronary artery bypass graft surgery.Clinical Pharmacology & Therapeutics (2002) 71, 457–467; doi: 10.1067/mcp.2002.124078
Pharmacokinetics and electrocardiographic effects of a new controlled‐release form of flecainide acetate: Comparison with the standard form and influence of the CYP2D6 polymorphism
Authors: Tennezé Laurent , Tarral Eliane , Ducloux Nicole , Funck‐Brentano Christian 
Published: October 2002

ObjectivesOur objectives were study the single‐ and repeated‐dose pharmacokinetics and electrocardiographic effects (QRS duration) of a new controlled‐release form offlecainide acetate compared with the immediate‐release form and to examine the influence of CYP2D6 activity.MethodsTwenty‐four healthy subjects (6 men and 6 women at both dosages) received single and repeated doses of 100 or 200 mg immediate‐release and controlled‐release flecainide in a randomized crossover design. Electrocardiograms were recorded and flecainide plasma concentrations were measured before administration and up to 96 hours after administration.ResultsThe controlled‐release formulation had sustained‐release properties, with a significantly lower maximum concentration (Cmax) and delayed time to reach Cmax. Compared with the immediate‐release formulation, the relative bioavailability of the controlled‐release formulation at steady state was 0.85 ± 0.17 and0.89 ± 0.17 for the 100‐mg/day and 200‐mg/day doses, respectively. Trough flecainide plasma concentration at steady state was bioequivalent for both formulations. Maximumand minimum QRS increases were not significantly different for either the immediate‐release or the controlled‐release form of flecainide after administration of both single and repeated doses. Mean QRS duration during a dosing interval at steady state correlated withmean plasma concentration for both forms (pooled data; P < .001). The 95% confidence interval for this regression was 26% narrower for the controlled‐release form thanfor the immediate‐release form. Flecainide‐induced QRS prolongation and pharmacokinetics were not significantly influenced by CYP2D6 activity.ConclusionsFlecainide‐induced QRS prolongation did not differ between the newcontrolled‐release form and the immediate‐release form. Flecainide plasma concentrations associated with the new controlled‐release form predicted QRS prolongation with less variability compared with the immediate‐release form. The CYP2D6 polymorphism did not appear to influence flecainide disposition kinetics or electrocardiographic effects at steady state.Clinical Pharmacology & Therapeutics (2002) 72, 112–122; doi: 10.1067/mcp.2002.125946
Risk factors for antituberculous chemotherapy‐induced hepatotoxicity in Japanese pediatric patients
Authors: Ohkawa Katsushito , Hashiguchi Masayuki , Ohno Keiko , Kiuchi Chikako , Takahashi Setsuko , Kondo Shinya , Echizen Hirotoshi , Ogata Hiroyasu 
Published: October 2002

ObjectiveOur objective was to clarify risk factors associated with the development of severe hepatotoxicity during antituberculosis chemotherapy in Japanese children.MethodsIn a retrospective analysis in a 350‐bed referral children's hospital in a metropolitan area, the medical charts of all pediatric patients who received antituberculosis chemotherapy between January 1995 and November 1999 were surveyed. Univariate and multivariate analyses were performed to find any demographic parameters (ie, sex, age, height, and body weight), clinical characteristics (ie, nutritional or developmental status, co‐infection with hepatitis viruses [B or C] or human immunodeficiency virus, presence of extrapulmonary tuberculosis, or medical history of liver disease), or individual antituberculosis agents used that would be associated with the likelihood of development of severe hepatotoxicity during antituberculous chemotherapy. Severe hepatotoxicity (definedas an elevation of ALT and AST levels that were greater than 5 times the respective reference values) was attributed to the chemotherapy when it developed in children with normalpretreatment values for these parameters and no other potential causes were identified. Those who had abnormal ALT or AST values before treatment were excluded from analysis.ResultsAmong the 117 patients surveyed (58 males and 59 females; age range, 0to 16 years), 18 were excluded from the analysis because of abnormal baseline ALT and ASTvalues. Severe hepatotoxicity developed in 8 of the 99 eligible children, and all 8 of those children were younger than 5 years old. The univariate analysis revealed that the children in whom hepatotoxicity developed were significantly (P < .05) younger, were predominantly male, had extrapulmonary tuberculosis, and were given pyrazinamide more often than those who had no hepatotoxicity. However, the multivariate logistic regression analysis revealed that only age and the administration of pyrazinamide would have a significant contribution (P < .05) to the development of severe hepatotoxicity, with odds ratios of 143 (95% confidence interval, 4.2 to 4934.9) and 0.60 (95% confidenceinterval, 0.39 to 0.90), respectively: the estimated probability of development of hepatotoxicity in a typical pediatric patient at 1, 5, and 10 years receiving pyrazinamide withrifampin (INN, rifampicin) and isoniazid would be 0.95, 0.72, and 0.16, respectively.ConclusionsThis study indicated that intensive monitoring of hepatotoxicity should be performed for younger children (<5 years) receiving pyrazinamide for antituberculosis chemotherapy.Clinical Pharmacology & Therapeutics (2002) 72, 220–226; doi: 10.1067/mcp.2002.126175
Enantioselective disposition of lansoprazole in extensive and poor metabolizers of CYP2C19
Authors: Kim Kyoung‐Ah , Shon Ji‐Hong , Park Ji‐Young , Yoon Young‐Ran , Kim Min‐Jung , Yun Doo‐Hee , Kim Moon‐Kyung , Cha In‐June , Hyun Myung‐Ho , Shin Jae‐Gook 
Published: October 2002

ObjectiveTo evaluate the enantioselective disposition of lansoprazole in relation to the genetic polymorphism of CYP2C19.MethodsA single oral dose of racemic lansoprazole (30 mg) was administered to6 extensive metabolizers and 6 poor metabolizers whose genotypes were determined by use of polymerase chain reaction‐restriction fragment length polymorphism. The pharmacokineticparameters were estimated from the plasma concentrations of lansoprazole racemate, its enantiomers, and metabolites, which were measured for 24 hours after drug administration. The unbound fraction of lansoprazole enantiomers was determined by means of ultrafiltrationof fresh human serum spiked with racemic lansoprazole.ResultsThe plasma concentrations of R(+)‐lansoprazole were consistently higher than those of the S(−)‐enantiomer in both extensive and poor metabolizers of CYP2C19, and the meanarea under the plasma concentration‐time curve of the (+)‐ and (−)‐enantiomersshowed 4.3‐ and 5.8‐fold differences between poor and extensive metabolizers, respectively. The (+)/(−) ratios of lansoprazole clearance were not significantly different betweenpoor and extensive metabolizers (0.19 ± 0.07 and 0.05 ± 0.08, respectively). The values for volume of distribution of the (−)‐enantiomer were 3‐ and 10‐fold greater, respectively, than those of the (+)‐enantiomer in poor and extensive metabolizers, which was related to a 2‐fold higher unbound fraction of the (−)‐enantiomer.ConclusionsThe effect of CYP2C19 genetic polymorphism on the enantioselectivedisposition of lansoprazole seems to be less significant than the effect on omeprazole and pantoprazole. The disposition of lansoprazole enantiomers appears to be influenced by enantioselective protein binding and by enantioselective metabolism of lansoprazole.Clinical Pharmacology & Therapeutics (2002) 72, 90–99; doi: 10.1067/mcp.2002.126176
A target‐mediated model to describe the pharmacokinetics and hemodynamic effects of recombinant human vascular endothelial growth factor in humans
Authors: Eppler Stephen M. , Combs Daniel L. , Henry Timothy D. , Lopez John J. , Ellis Stephen G. , Yi Joo‐Hee , Annex Brian H. , McCluskey Edward R. , Zioncheck Thomas F. 
Published: October 2002

BackgroundThe Vascular Endothelial Growth Factor (VEGF) in Ischemiafor Vascular Angiogenesis (VIVA) trial was a double‐blind, placebo‐controlled, phase II clinical trial designed to evaluate the safety, efficacy, and pharmacokinetics of combinedintracoronary and intravenous infusions of recombinant human vascular endothelial growth factor (rhVEGF165) for therapeutic angiogenesis. This study describes the use of a mechanism‐based model to characterize the nonlinear kinetics observed after intravenous administration of rhVEGF165. The model predicts that rhVEGF165 distribution occurs through both saturable binding to high‐affinity receptors and reversible interactions with low‐affinity binding sites.MethodsIn this trial, rhVEGF165 was administered to patients with coronary artery disease at a dose rate of 17 or 50 ng/kg/min by means of intracoronary infusion for 20 minutes, followed by three 4‐hour intravenous infusions on days 3, 6, and 9. Pharmacokinetic samples and blood pressure measurements were collected at baseline, during infusion, and for 6 hours after infusion.ResultsThe plasma clearance, steady‐state volume of distribution, and terminal half‐life after a 4‐hour intravenous infusion of rhVEGF165 at the high dose were 19.1 ± 5.7 mL/min/kg, 960 ± 260 mL/kg, and 33.7 ± 13 minutes, respectively. The duration of hypotension that occurred after rhVEGF165 administration appeared to be related to the model‐predicted VEGF165 concentration associated with the high‐affinity receptor compartment.ConclusionsThis mechanism‐based model accurately predicted VEGF concentrations and allowed for the simulation of various rhVEGF165 dose regimens that may aid in optimization of drug delivery for future clinical trials.Clinical Pharmacology & Therapeutics (2002) 72, 20–32; doi: 10.1067/mcp.2002.126179
Pharmacokinetics of valganciclovir and ganciclovir in renal impairment
Authors: Czock David , Scholle Cornelia , Rasche Franz Maximilian , Schaarschmidt Dieter , Keller Frieder 
Published: October 2002

BackgroundValganciclovir is the oral prodrug of ganciclovir. The pharmacokinetics of valganciclovir in patients with renal impairment is not known. Furthermore, it is not known whether there are any pharmacokinetic differences between patients who are positive for human immunodeficiency virus (HIV) and cytomegalovirus (CMV) and healthy subjects.MethodsA total of 44 patients were included—18 with mild, medium, or severe renal impairment; 6 with end‐stage renal disease who were on long‐term hemodialysis;8 HIV/CMV‐positive patients with normal renal function; and 12 healthy subjects serving as controls. Valganciclovir and ganciclovir serum concentrations were measured after oral administration of 900 mg of valganciclovir. Pharmacokinetic parameters were estimated by means of noncompartmental and compartmental methods.ResultsAfter oral administration of the prodrug valganciclovir, ganciclovir bioavailability was 60% and ganciclovir concentrations were higher (maximum concentration [Cmax], 8.5 μg/mL versus 5.8 μg/mL) and appeared later (time to maximum concentration [Tmax], 4.3 versus 2.0 hours) in patients with severe renal impairment compared with healthy subjects. The elimination half‐life (t1/2)of ganciclovir was longer in patients with renal failure (t1/2 of 68.1 hours in patients with end‐stage renal disease compared with 3.5 hours in healthy subjects). Ganciclovir clearance was correlated with creatinine clearance (r = 0.975). Hemodialysis removed 50% of ganciclovir. We observed no differences in pharmacokinetics between HIV/CMV‐positive patients and healthy subjects. A 2‐compartment model with zero‐order input and first‐order elimination proved to be the most appropriate model for ganciclovir after oral administration of valganciclovir.ConclusionsThe dosage of valganciclovir has to be adjusted to the degree of renal impairment. Dosage adjustment is not necessary for HIV/CMV‐positive patients.Clinical Pharmacology & Therapeutics (2002) 72, 142–150; doi: 10.1067/mcp.2002.126306
Peripheral prostanoid levels and nonsteroidal anti‐inflammatory drug analgesia: Replicate clinical trials in a tissue injury model
Authors: Gordon Sharon M. , Brahim Jaime S. , Rowan Janet , Kent Allison , Dionne Raymond A. 
Published: October 2002

BackgroundNonsteroidal anti‐inflammatory drug (NSAID) analgesia is generally attributed to peripheral suppression of cyclooxygenase (COX) enzymes, leading to decreased products of the arachidonic acid cascade. This study evaluated the in vivo relationship between levels of prostanoids at the site of tissue injury and analgesia aftersystemic or local NSAID administration in a clinical model of tissue injury.MethodsSubjects in two replicate clinical trials had one or two mandibular third molars removed and a microdialysis probe implanted at the surgical site for measurement of immunoreactive prostaglandin E2 (PGE2) or immunoreactive thromboxane B2 (TxB2) and pain measured concurrently. In the first study, ketorolac tromethamine (INN, ketorolac) was administered at pain onset in a 30‐mg intramuscular dose, a 1‐mg intramuscular dose, or a 1‐mg submucosal dose at the extraction site in comparison with placebo. In the second study, subjects received either ketorolac tromethamine 30 mg by the intravenous route or placebo at pain onset.ResultsPGE2 was detectable in the first postoperative sample, decreased over the next hour, and then increased significantly coincident with the onset of postoperative pain. Administration of 30 mg ketorolac tromethamine produced parallel decreases in pain, PGE2 levels, and TxB2 levels at the surgical site. Administration of 1 mg ketorolac tromethamine intramuscularly or directly at the surgical site was analgesic but without measurable effects on PGE2 levels.ConclusionThe temporal profile of PGE2 and TxB2 in the immediate postoperative period is consistent with constitutive COX‐1 initially, followed by an increase in PGE2 resulting from expression of COX‐2. The temporal association between NSAID analgesia and decreased prostanoids at the site of injury is consistent with a dual COX‐1/COX‐2 peripheral site of action. The analgesic effects of 1 mg ketorolac tromethamine without a reduction in PGE2 at the site of injury suggests an additional central site for NSAID analgesia.Clinical Pharmacology & Therapeutics (2002) 72, 175–183; doi: 10.1067/mcp.2002.126501
Sense of Belonging as a Buffer Against Depressive Symptoms
Authors: Sargent Judy , Williams Reg Arthur , Hagerty Bonnie , Lynch-Sauer Judith , Hoyle Kenneth 
Published: October 2002

BACKGROUND: Lack of a sense of belonging has been shown to be associated with loneliness, emotional distress, psychosocial disturbance, and mental illness. Conversely, sense of belonging was found to correspond with psychosocial health. OBJECTIVE: The purpose of this study was to determine the buffering effect of sense of belonging against the development of depression. STUDY DESIGN: This study used a comparative design. The sample consisted of 443 Navy recruits in basic training who were divided into depressed and control groups based on depressive symptoms. The groups were then further stratified based on risk factors: a personal history of abuse and family histories of mental illness, alcohol, and drug abuse. RESULTS: The results refuted a significant buffering effect of sense of belonging against the development of depressive symptoms in several of the subgroups. However, sense of belonging significantly buffered those with a family history of alcohol abuse against developing depressive symptoms. CONCLUSION: Sense of belonging is a concept that has important implications for psychosocial well being. Interventions that enhance sense of belonging will be useful in the treatment and primary prevention of depression.