bluuebunny/crossref_metadata_2025_split huggingface dataset:
Raman spectroscopy of phosphates of the variscite mineral group
Authors: Frost Ray L. , Weier Matt L. , Erickson Kristy L. , Carmody Onuma , Mills Stuart J. 
Published: December 2004

AbstractRaman spectra of phosphates of the variscite mineral group, namely strengite, variscite, metavariscite and phosphosiderite, were obtained at 298 and 77 K using a thermal stage and complemented with selected infrared data using a diamond attenuated total reflection cell. Multiple phosphate stretching bands are observed. Bands for strengite at 1006, 1012 and 1026 cm−1 at 298 K and at 997, 1006, 1014 and 1027 cm−1 at 77 K are observed. Variscite is characterized by PO stretching vibrations at 1023, 1005 and 938 cm−1 and phosphosiderite by bands at 1009 and 993 cm−1. These minerals are readily identified by their Raman spectrum both in the PO stretching region and in the low‐wavenumber region. Multiple bands attributed to the bending modes of PO4 are identified for each of the minerals. A model is proposed involving non‐hydrogen‐bonded PO4 and strongly hydrogen‐bonded PO4 units together with [Al or Fe(OH)2]+ ·(H2PO4)2−‐type species. Raman spectroscopy shows that at the molecular level multiple species of phosphate anions exist for the variscite phosphate minerals. Copyright © 2004 John Wiley & Sons, Ltd.
Transformational leadership, organizational culture, and innovativeness in nonprofit organizations
Authors: Jaskyte Kristina 
Published: December 2004

AbstractThis is an exploratory study of leadership, organizational culture, and organizational innovativeness in a sample of nonprofit human service organizations: Associations of Retarded Citizens. Although leadership has been held out as one of the most important predictors of innovation, this study found it was not correlated with organizational innovativeness. Examination of the relationships between leadership and cultural variables provided some alternative explanations for this finding. Positive relationships among transformational leadership, organizational values, and cultural consensus (degree of agreement among employees on those values) indicate that leadership practices employed in this sample created strong cultural consensus around values that may inhibit innovation. These findings suggest that examining the link between leadership and organizational culture is important for understanding how leadership and innovation are related. This article sets out practical implications, based on the results of the study, that may help nonprofit managers create workplaces supportive of innovation.
Commitment and performance of nonprofit board members
Authors: Preston Jennifer Bright , Brown William A. 
Published: December 2004

AbstractBoards of nonprofit organizations are entrusted to oversee and ensure that the organization remains true to its mission, functions within the confines of state and federal laws, and operates in a financially responsible manner. This critically important oversight is carried out by volunteers. This study examined the relationships between board member commitment and individual performance. Commitment was assessed using Meyer and Allen's Three‐Component Model of Commitment: Affective, Continuance, and Normative (1991). The population in this study was volunteer board members of midsized, social service nonprofit organizations in the Orange County, California, area. The strongest findings were between affective commitment and performance in board roles. Committed board members reported more involvement and are perceived by the executive to be more engaged and valuable. Analysis revealed that executive judgments of participation are based on both board member behavior and Affective commitment expressed by the board member.
Stereoselective pharmacokinetics of ketamine: R(−)‐Ketamine inhibits the elimination of S(+)‐ketamine
Authors: Ihmsen Harald , Geisslinger Gerd , Schüttler Jürgen 
Published: December 2004

ObjectiveWe investigated the pharmacokinetics of ketamine with special regard to enantiomer‐specific differences.MethodsTen healthy young male volunteers (mean age, 28 ± 4 years; mean weight, 79 ± 11 kg) received racemic ketamine and S(+)‐ketamine in a randomized double‐blind crossover study. Drugs were administered by a computer‐controlled device. Two infusion cycles with linearly increasing targets [slope, 0.1 μg · ml−1 · min−1 for S(+)‐ketamine and 0.2 μg · ml−1 · min−1 for racemic ketamine] were administered. Concentrations of the ketamine enantiomers were determined from arterial blood, and pharmacokinetic parameters were estimated with a 2‐ and 3‐compartment model.ResultsThe total doses needed to reach defined end points were 271 ± 80 mg and 409 ± 75 mg for S(+)‐ketamine and racemic ketamine, respectively (P < .05). S(+)‐ketamine showed a significantly higher clearance (26.3 ± 3.5 ml · kg−1 · min−1) compared with racemic ketamine (14.8 ±1.7 ml · kg−1 · min−1; P < .05) and R(−)‐ketamine (13.8 ±1.3 ml · kg−1 · min−1; P < .05). Furthermore, the clearance of the S(+)‐ketamine was smaller in the racemate (18.5 ±0.7 ml · kg−1 · min−1; P < .05) than for the pure isomer.ConclusionsThese results demonstrate that R(−)‐ketamine inhibits the elimination of S(+)‐ketamine.Clinical Pharmacology & Therapeutics (2001) 70, 431–438; doi: 10.1016/S0009‐9236(01)06321‐4
Impaired cognitive function and compliance with antihypertensive drugs in elderly: The Rotterdam Study
Authors: Salas Maribel , In't Veld Bas A. , van der Linden Paul D. , Hofman Albert , Breteler Monique , Stricker Bruno H. 
Published: December 2004

BackgroundTo our knowledge, there are no epidemiologic studies on the association between cognitive impairment and noncompliance with antihypertensive therapy. We studied compliance with antihypertensive treatment in elderly patients with cognitive impairment.MethodsThe Rotterdam Study is a prospective community‐based cohort study of 7983 residents ≥55 years old. We studied 1979 participants in the study who had 2 consecutive Mini Mental State Examination (MMSE) assessments in the period from 1991 to 1996, who did not have dementia at baseline, and who had received 3 or more consecutive antihypertensive prescriptions for at least 6 months. We compared persons with MMSE scores ≤25 on both assessments to persons with MMSE scores >25 on both occasions. Compliance was estimated by dividing the number of days the subjects took antihypertensive drugs by the follow‐up period in days, and it was expressed as a ratio between 0 and 1. We defined patients as compliant if they had a compliance ratio ≥0.80 and as noncompliant if they had a compliance ratio ≤0.50 during the study period.ResultsWe followed‐up on 1573 patients (mean age, 68 years) during an average period of 1609 days. The risk of noncompliance in cognitively impaired elderly subjects was 2.0 (95% confidence interval, 1.4 to 2.8) after adjustment for age, sex, education, income, living situation, and smoking. Stratification by living situation showed that the risk increase predominantly occurred in those who lived alone (odds ratio, 2.9; 95% confidence interval, 1.2 to 7.5).ConclusionsCognitive function is an independent predictor of compliance with antihypertensive drugs in elderly patients who are living alone.Clinical Pharmacology & Therapeutics (2001) 70, 561–566; doi: 10.1016/S0009‐9236(01)14469‐3
Losartan attenuates symptomatic and hormonal responses to hypoglycemia in humans
Authors: Deininger Eva , Oltmanns Kerstin M. , Wellhoener Peter , Fruehwald‐Schultes Bernd , Kern Werner , Heuer Bettina , Dominiak Peter , Born Jan , Fehm Horst L. , Peters Achim 
Published: December 2004

ObjectiveReduced awareness of hypoglycemic symptoms and compromised hormonal counterregulation increase the risk of severe hypoglycemia in people with diabetes mellitus. Up to the present, angiotensin 1 receptor blockers, which play an important role in controlling diabetic complications, have not been known to increase the risk of hypoglycemia. Nevertheless, we observed 3 cases of diabetic patients complaining of reduced awareness of hypoglycemic symptoms while they were under treatment with losartan in our outpatients clinic. We therefore investigated the effects of losartan on symptomatic and hormonal responses to hypoglycemia in humans.Research design and methodsWe carried out a randomized, double‐blind, crossover study including 16 healthy men. The subjects received losartan 50 mg/d versus placebo. Treatment periods lasted for 7 days and were followed by a stepwise hypoglycemic clamp session (4.5 to 3.8 to 3.1 to 2.4 mmol/L) with measurement of counterregulatory hormones (epinephrine, norepinephrine, adrenocorticotropin, cortisol, glucagon), symptoms, and hemodynamic parameters (blood pressure, heart rate).ResultsLosartan attenuated the hypoglycemia‐induced rise in plasma epinephrine (6480 ± 490 pmol/L versus placebo 8970 ± 790 pmol/L; P < .001) and the rise in plasma adrenocorticotropin (21 ± 2 pmol/L versus 26 ± 3 pmol/L; P < .01). Losartan also reduced symptom scores during hypoglycemia (P < .05).ConclusionWe conclude that short‐term treatment with losartan slightly attenuates symptomatic and hormonal responses to hypoglycemia. At present, for patients who are unaware of hypoglycemia and who require antihypertensive or nephroprotective treatment, we would recommend caution concerning treatment with losartan.Clinical Pharmacology & Therapeutics (2001) 70, 362–369; doi: 10.1016/S0009‐9236(01)26448‐0
Effect of high‐dose lansoprazole on intragastic pH in subjects who are homozygous extensive metabolizers of cytochrome P4502C19
Authors: Furuta Takahisa , Shirai Naohito , Xiao Fang , Ohashi Kyoichi , Ishizaki Takashi 
Published: December 2004

Backgrounds and AimLansoprazole is mainly metabolized by cytochrome P4502C19 (CYP2C19) in the liver. The effect of lansoprazole is assumed to be insufficient in subjects who are homozygous extensive metabolizers of CYP2C19. This study aimed to examine whether the CYP2C19 genotype status affected the acid‐inhibitory effects of lansoprazole and to develop a strategy to overcome this pharmacogenetic problem.MethodsEighteen Helicobacter pylori3‐negative healthy volunteers, whose CYP2C19 genotypic status had been assessed, participated in the study. They consisted of 7 subjects who were homozygous extensive metabolizers, 7 subjects who were heterozygous extensive metabolizers, and 4 subjects who were poor metabolizers of CYP2C19, who took a placebo or lansoprazole 30 mg once daily in the morning for 8 days. On day 8 of dosing, 24‐hour intragastric pH values were recorded. Five of the homozygous extensive metabolizer subjects underwent the 24‐hour intragastric pH monitoring on day 8 of dosing of lansoprazole 30 mg 4 times daily.ResultsWhen lansoprazole 30 mg was given once daily, the mean 24‐hour intragastric pH values in the subjects who were homozygous extensive metabolizers, heterozygous extensive metabolizers, and poor metabolizers were 4.5, 4.9, and 5.5, respectively (P < .005). On day 8 of dosing of lansoprazole 30 mg 4 times daily in subjects who were homozygous extensive metabolizers, the mean 24‐hour intragastric pH value was 7.4.ConclusionThe effect of lansoprazole on intragastric pH depended significantly on CYP2C19 genotype status. Complete acid inhibition could be achieved by the frequent administration of lansoprazole (eg, 30 mg 4 times daily) in subjects who were homozygous extensive metabolizers. A genotyping test of CYP2C19 status appears useful for prescribing an optimal dosing scheme of lansoprazole.Clinical Pharmacology & Therapeutics (2001) 70, 484–492; doi: 10.1016/S0009‐9236(01)28055‐2
Early postoperative erythromycin breath test correlates with hepatic cytochrome P4503A activity in liver transplant recipients
Authors: Schmidt Lars E. , Olsen Anette Kristensen , Stentoft Karen , Rasmussen Allan , Kirkegaard Preben , Dalhoff Kim 
Published: December 2004

BackgroundInterindividual variation in the pharmacokinetics of the immunosuppressive agents cyclosporine (INN, ciclosporin) and tacrolimus may result from differences in the activity of cytochrome P4503A (CYP3A). The erythromycin breath test is an in vivo assay of hepatic CYP3A activity, but the method has never been directly validated. The aim of the study was to investigate whether an early post‐operative erythromycin breath test correlated with the hepatic CYP3A protein level and catalytic activity in liver transplant recipients.MethodsIn 18 liver transplant recipients, the erythromycin breath test was performed within 2 hours after transplantation. A graft biopsy was obtained during surgery and analyzed for the CYP3A protein level by Western blotting and for CYP3A activity with erythromycin demethylation and testosterone 6β‐hydroxylation assays.ResultsThe erythromycin breath test values ranged from 0.14% to 1.65% of carbon 14 per hour, and the CYP3A protein level ranged from 732 to 7822 as measured by optical density. The in vitro catalytic activity determined by the erythromycin demethylation assay ranged from 94 to 902 disintegrations per minute per 5 minutes per milligram of protein, and the activity determined by testosterone 6β‐hydroxylation ranged from 0.030 to 0.627 nmol per minute per milligram of protein. Significant correlation was demonstrated between the erythromycin breath test and both the erythromycin demethylation (Spearman correlation coefficient: R = 0.76, R2 = 0.57; P = .0004) and the testosterone 6β‐hydroxylation (Spearman correlation coefficient: R = 0.79, R2 = 0.63; P = .0001) assays. The erythromycin breath test also correlated with the CYP3A protein level (Spearman correlation coefficient: R = 0.60, R2 = 0.36; P = .01).ConclusionOur data support the erythromycin breath test as a specific in vivo assay of CYP3A activity in humans. The test is applicable in liver transplant recipients in the early postoperative phase. Future studies should evaluate the clinical usefulness of an early postoperative erythromycin breath test as a predictor of cyclosporine‐tacrolimus pharmacokinetics in liver transplantation.Clinical Pharmacology & Therapeutics (2001) 70, 446–454; doi: 10.1016/S0009‐9236(01)36203‐3
Fluvoxamine‐theophylline interaction: Gap between in vitro and in vivo inhibition constants toward cytochrome P4501A2
Authors: Yao Caiping , Kunze Kent L. , Kharasch Evan D. , Wang Yi , Trager William F. , Ragueneau Isabelle , Levy René H. 
Published: December 2004

ObjectiveSeveral reports indicate that fluvoxamine decreases the clearance of cytochrome P4501A2 (CYP1A2) substrates. This study compared in vitro and in vivo inhibition potencies of fluvoxamine toward CYP1A2 with an approach based on inhibition constants (Ki) determined in vitro and in vivo.MethodsIn vitro inhibition constant values were determined with human liver microsomes and complementary deoxyribonucleic acid‐expressed CYP1A2 (supersomes). Fluvoxamine in vivo inhibition constants (Kiiv) for CYP1A2 were obtained from an investigation of single‐dose theophylline (250 mg) disposition in 9 healthy volunteers receiving steady‐state (9 days) fluvoxamine at 3 doses (0, 25, or 75 mg/d) in a randomized crossover design.ResultsIn vitro Ki values based on total inhibitor concentrations were 177 ±56 nmol/L, 121 ±21 nmol/L, and 52 ±13 nmol/L in human liver microsomes with 1 mg/ml protein and 0.5 mg/ml protein and in supersomes with 0.3 mg/ml protein, respectively. The corresponding in vitro Ki values based on unbound fluvoxamine concentrations were 35 nmol/L, 36 nmol/L, and 36 nmol/L. The ratio of 1‐methyluric acid formation clearances (control/inhibited) in 8 subjects was positively correlated with fluvoxamine concentration (r2 = 0.87; P < .001) with an intercept near 1. Mean values for Kiiv based on total and unbound plasma concentrations at steady state were 25.3 nmol/L (range, 14–39 nmol/L) and 3.6 nmol/L (range, 2.4–5.9 nmol/L), respectively.ConclusionComparison of in vitro and in vivo Ki values based on unbound fluvoxamine concentrations suggests that fluvoxamine inhibition potency is approximately 10 times greater in vivo than in vitro.Clinical Pharmacology & Therapeutics (2001) 70, 415–424; doi: 10.1016/S0009‐9236(01)62844‐3
Red wine decreases cyclosporine bioavailability
Authors: Tsunoda Shirley M. , Harris Robert Z. , Christians Uwe , Velez Rebecca L. , Freeman Richard B. , Benet Leslie Z. , Warshaw Abigail 
Published: December 2004

BackgroundMany commonly ingested substances such as grapefruit juice and Hypericum perforatum (St John's wort) have been found to interact with important therapeutic agents such as cyclosporine (INN, ciclosporin). The mechanism for these interactions is thought to involve modulation of the activity of the drug‐metabolizing enzyme cytochrome P4503A4 (CYP3A4) and/or the drug transport protein P‐glycoprotein. In vitro data suggest that red wine may interact with CYP3A4 substrates such as cyclosporine.MethodsWe conducted a randomized, 2‐way crossover study of 12 healthy individuals. Subjects received a single 8‐mg/kg dose of oral cyclosporine with water (control) and with 12 oz of red wine (Blackstone Merlot 1996; Blackstone Winery, Graton, Calif). Whole blood was analyzed for cyclosporine and 6 metabolites by specific fluorescence polarization immunoassay and tandem liquid chromatography‐mass spectrometry. Blood levels of cyclosporine were compared between the 2 arms.ResultsRed wine caused a 50% increase in the oral clearance of cyclosporine. Systemic exposure as measured by the area under the concentration‐versus‐time curve (AUC) and peak concentration (Cmax) were significantly decreased by red wine. However, half‐life was not affected, suggesting that red wine decreased cyclosporine absorption. In vitro, the solubility of cyclosporine in red wine appeared to be lower than in water.ConclusionsAdministration of cyclosporine with red wine causes a significant decrease in cyclosporine exposure. Because cyclosporine is a narrow therapeutic range compound, caution may be warranted with concomitant intake of red wine and cyclosporine.Clinical Pharmacology & Therapeutics (2001) 70, 462–467; doi: 10.1016/S0009‐9236(01)70992‐7
Effect of gemfibrozil on the pharmacokinetics and pharmacodynamics of glimepiride
Authors: Niemi Mikko , Neuvonen Pertti J. , Kivistö Kari T. 
Published: December 2004

ObjectiveOur objective was to study the effects of gemfibrozil on the pharmacokinetics and pharmacodynamics of glimepiride, a new sulfonylurea antidiabetic drug and a substrate of cytochrome P4502C9 (CYP2C9).MethodsIn a randomized, 2‐phase crossover study, 10 healthy volunteers were treated for 2 days with 600 mg oral gemfibrozil or placebo twice daily. On day 3, they received a single dose of 600 mg gemfibrozil or placebo and 1 hour later a single dose of 0.5 mg glimepiride orally. Plasma glimepiride, serum insulin, and blood glucose concentrations were measured up to 12 hours.ResultsGemfibrozil increased the mean total area under the plasma concentration‐time curve of glimepiride by 23% (range, 6%–56%; P < .005). The mean elimination half‐life of glimepiride was prolonged from 2.1 to 2.3 hours (P < .05) by gemfibrozil. No statistically significant differences were found in the serum insulin or blood glucose variables between the two phases.ConclusionsGemfibrozil modestly increases the plasma concentrations of glimepiride. This may be caused by inhibition of CYP2C9.Clinical Pharmacology & Therapeutics (2001) 70, 439–445; doi: 10.1016/S0009‐9236(01)84578‐1
QT interval lengthening in premature infants treated with doxapram
Authors: Maillard Christine , Boutroy Marie‐Jeanne , Fresson Jeanne , Barbé Françoise , Hascoët Jean‐Michel 
Published: December 2004

ObjectiveDoxapram, routinely used in premature infants treated for apnea of prematurity unresponsive to methylxanthines, has been related to cardiac conduction disorders. This study was designed to evaluate doxapram cardiac and general tolerance and its relationship to drug plasma concentrations in very premature infants.MethodsForty infants (mean ±SEM, 28.9 ±0.3 weeks of gestation) who were given intravenous doxapram, 0.5 to 1 mg/kg per hour, at 15.9 ±2.4 days of life were evaluated prospectively. Electrocardiograms were monitored before and during the first 3 days of treatment. QT interval corrected for heart rate (QTc) longer than 440 ms was regarded as clinically pertinent, given that it is considered a significant risk of conduction disorder leading to torsades de pointes and sudden death. Other side effects were recorded. Toxic plasma concentration of doxapram and ketodoxapram was set at >4 mg/L.ResultsA statistically significant but moderate lengthening of QTc interval has been observed from 394 ±4 ms before doxapram to 409 ±4 ms at 48 and 72 hours of treatment (P = .0065). For 6 patients, QTc interval became longer than 440 ms without any other rhythm or conduction disorder. Digestive disorders were observed in 20 infants but 9 presented with concomitant septicemia. No relationship was found between presence or absence of adverse effects and drug plasma concentrations.ConclusionOur study enlightened the lengthening effect of doxapram on QTc interval in premature infants with a risk of exceeding the 440 ms threshold that is considered life‐threatening. This finding emphasizes the need for electrocardiogram follow‐up when using doxapram in neonates.Clinical Pharmacology & Therapeutics (2001) 70, 540–545; doi: 10.1016/S0009‐9236(01)95877‐1
How Smart Is my Dummy? Time Series Tests for the Influence of Politics
Authors: Caporale Tony , Grier Kevin 
Published: December 2004

Of necessity, many tests for political influence on policies or outcomes involve the use of dummy variables. However, it is often the case that the hypothesis against which the political dummies are tested is the null hypothesis that the intercept is otherwise constant throughout the sample. This simple null can cause inference problems if there are (nonpolitical) intercept shifts in the data and the political dummies are correlated with these unmodeled shifts. Here we present a method for more rigorously testing the significance of political dummy variables in single equation models estimated with time series data. Our method is based on recent work on detecting multiple regime shifts by Bai and Perron. The article illustrates the potential problem caused by an overly simple null hypothesis, exposits the Bai and Perron model, gives a proposed methodology for testing the significance of political dummy variables, and illustrates the method with two examples.Before the curse of statistics fell upon mankind we lived a happy, innocent life—Hilaire Belloc,On Statistics
Reorganization and in Vivo Dynamics of Microtubules during Arabidopsis Root Hair Development
Authors: Van Bruaene Nathalie , Joss Greg , Van Oostveldt Patrick 
Published: December 2004

Abstract
Root hairs emerge from epidermal root cells (trichoblasts) and differentiate by highly localized tip growth. Microtubules (MTs) are essential for establishing and maintaining the growth polarity of root hairs. The current knowledge about the configuration of the MT cytoskeleton during root hair development is largely based on experiments on fixed material, and reorganization and in vivo dynamics of MTs during root hair development is at present unclear. This in vivo study provides new insights into the mechanisms of MT (re)organization during root hair development in Arabidopsis (Arabidopsis thaliana). Expression of a binding site of the MT-associated protein-4 tagged with green fluorescent protein enabled imaging of MT nucleation, growth, and shortening and revealed distinct MT configurations. Depending on the dynamics of the different MT populations during root hair development, either repeated two-dimensional (x, y, t) or repeated three-dimensional (x, y, z, t) scanning was performed. Furthermore, a new image evaluation tool was developed to reveal important data on MT instability. The data show how MTs reorient after apparent contact with other MTs and support a model for MT alignment based on repeated reorientation of dynamic MT growth.