bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lack of Effect of Nizatidine‐Induced Elevation of Gastric pH on the Oral Bioavailability of Dapsone in Healthy Volunteers
Authors: Itokazu Gail S. , Fischer James H. , Manitpisitkul Prasarn , Hariharan Radhika , Danziger Larry H. 
Published: June 2004

Study Objective. To investigate the effect of histamine2 (H2)‐receptor antagonist‐induced elevation of gastric pH on oral bioavailability of a single dose of dapsone 100 mg.Design. Prospective, randomized, crossover, open‐label, single‐dose pharmacokinetic study.Setting. Teaching hospital.Patients. Sixteen men were enrolled in the study; data from 11 subjects were evaluable.Interventions. Participants received two treatments separated by at least 14 days. Treatment A consisted of a single dose of dapsone 100 mg. Treatment B consisted of a single dose of dapsone 100 mg plus two doses of oral nizatidine 300 mg administered 3–4 hours apart to maintain gastric pH above 6.0. Plasma samples collected before and up to 120 hours after dapsone administration were analyzed for dapsone and monoacetyldapsone (MADDS) by high‐performance liquid chromatography. Pharmacokinetic parameters were determined by noncompartmental analysis.Measurements and Main Results. Gastric pH in the first 6 hours after dapsone administration was above 6.0 for a mean ± SD of 1.1% ± 2.9% of the time in the absence of nizatidine and 69.5% ± 18.0% of the time during nizatidine therapy. The geometric mean dapsone maximum plasma concentration (Cmax) declined by 13% (p<0.01), and median time to Cmaxoccurred 2 hours later (p<0.01) with nizatidine coadministration compared with dapsone alone. Inclusion of the 90% confidence interval for the mean Cmax ratio within the equivalence interval of 0.8–1.25 demonstrated the lack of clinical significance for this modest decrease in Cmax. Neither the area under the dapsone plasma concentration‐time curve from zero to infinity nor the elimination half‐life of dapsone were significantly altered by nizatidine. No clinically significant changes were observed in the pharmacokinetics of MADDS with regard to coadministration of nizatidine.Conclusion. Elevation of gastric pH by H2‐receptor antagonists, such as nizatidine, does not result in clinically important changes in the rate or extent of oral dapsone absorption.
Changes in Pharmacy Practice Faculty 1995–2001: Implications for Junior Faculty Development
Authors: Raehl Cynthia L. 
Published: June 2004

Objective.To compare changes in United States pharmacy practice faculty demographics from 1995–2001 and to discuss the implications for junior faculty development.Methods.Demographic data were extracted from the American Association of Colleges of Pharmacy institutional research system for academic years 1995–1996 and 2000–2001.Results.In 2000–2001, pharmacy practice was the largest faculty discipline, 3.8 times larger than the next three disciplines. Junior pharmacy practice faculty occupied 65% of all junior full‐time pharmacy faculty positions. Tenure track assistant professors decreased 4% from 283 to 271, and nontenure track assistant professors increased 58% from 427 to 677 (χ2= 20.0, p<0.05). In 2000–2001, 72% of all pharmacy practice assistant professors were nontenure track, up from 59% in 1995–1996. Women assistant professors in pharmacy practice outnumbered men by 2:1. Challenges faced by new faculty include balancing teaching, practice, and research demands; selecting a nontenure or tenure track and understanding its expectations; limiting teaching preparation time; developing productive writing habits; setting performance goals; managing time; and handling the mental and physical stress of academic life. Senior faculty must actively help new members appreciate the many positive aspects of academic life by sharing their strategies and success stories.Conclusion.Schools and colleges of pharmacy relied heavily on increasing the number of nontenure track junior pharmacy practice faculty to meet increased clinical education demands.
Evaluation of Survival and Pharmacodynamic Relationships for Five Fluoroquinolones in a Neutropenic Murine Model of Pneumococcal Lung Infection
Authors: Ernst Erika J. , Klepser Michael E. , Petzold C. Rosemarie , Doern Gary V. 
Published: June 2004

Study Objective. To compare the antistreptococcal activity of five fluoroquinolone antibiotics, using a neutropenic murine model of pneumococcal pulmonary infection.Design. Animal experiment.Setting. University‐affiliated research center.Animals. Neutropenic and control mice weighing 24–29 g.Intervention. After induction of neutropenia, renal failure, and infection with Streptococcus pneumoniae, the mice received one of five fluoroquinolones twice/day for 72 hours beginning 12 hours after infection. Dosages were selected to approximate 0.1 × AUC0–24 (area under the concentration‐time curve from 0–24 hours) and AUC0–24 achieved in humans. Control mice received normal saline. Survival was assessed at regular intervals for up to 10 days. At least 10 mice were included in each cohort (range 10–34).Measurements and Main Results. Ciprofloxacin, clinafloxacin, grepafloxacin, levofloxacin, and moxifloxacin were studied at subtherapeutic and therapeutic dosages against three quinolone‐susceptible isolates of S. pneumoniae that lacked mutations in parC, parE, and gyrA. Pharmacokinetic profile of each agent and dosing regimen was determined. A composite survival curve for all fluoroquinolones and isolates was constructed. Relationships between survival rate at 72 hours and AUC: MIC (minimum inhibitory concentration), peak: MIC, time above the MIC (percentage of dosing interval) for total and free drug concentrations were fit by using a sigmoid maximal effect (Emax) model. Survival was significantly better in the higher dosage group than in the lower dosage group. Time above MIC did not display a correlation with outcome. The AUC: MIC showed a greater correlation with outcome (R2 = 0.56 total, 0.54 free) than did peak: MIC (R2 = 0.52 total, 0.51 free). With use of composite data, total AUC: MIC ratios associated with 50%, 90%, and 99% of Emax were 34:1, 56:1, and 95:1, respectively.Conclusions. In this model, efficacy was achieved with the fluoroquinolone antibiotics at dosages yielding AUC0–24 comparable to those obtained in humans. One pharmacodynamic parameter (i.e., AUC: MIC) may be applied to various fluoroquinolones and isolates of S. pneumoniae. The AUC: MIC was more predictive of outcome than was time above the MIC or peak: MIC.
Clinical Efficacy and Pharmacoeconomics of a Continuous‐Infusion Piperacillin‐Tazobactam Program in a Large Community Teaching Hospital
Authors: Grant Edward M. , Kuti Joseph L. , Nicolau David P. , Nightingale Charles , Quintiliani Richard 
Published: June 2004

Study Objective. To compare continuous versus intermittent administration of piperacillin‐tazobactam with regard to clinical, microbiologic, and economic outcomes.Design. Prospective, open‐label controlled study.Setting. Community teaching hospital.Patients. Ninety‐eight hospitalized patients prescribed piperacillintazobactam.Intervention. Substitutions were implemented so that 47 patients initially prescribed intermittent infusion of piperacillin‐tazobactam were switched to continuous infusion of this drug combination. Dosages varied in accordance with the type of infection and each patient's renal function. Fifty‐one other patients with similar demographics and types of infection received intermittent infusion with piperacillin‐tazobactam.Measurements and Main Results. Clinical success rates were 94% for the continuous‐infusion group and 82% for the intermittent‐infusion group (p=0.081). Microbiologic success rates were 89% for the continuous‐infusion group and 73% for the intermittent‐infusion group (p=0.092). Days to normalization of fever were significantly lower (p=0.012) in the continuous‐infusion group (1.2 ± 0.8 days) than in the intermittent‐infusion group (2.4 ± 1.5 days). Level 1 and level 2 costs/patient were both reduced by continuous infusion, although the difference was statistically significant only for level 2 costs ($399.38 ± 407.22 for continuous infusion vs $523.49 ± 526.85 for intermittent infusion, p=0.028).Conclusion. Continuous infusion of piperacillin‐tazobactam provided clinical and microbiologic outcomes equivalent to those for intermittent infusion. Compared with intermittent infusion, continuous infusion significantly shortened the time to temperature normalization, while also offering a significant reduction in level 2 expenditures.
Patient Perceptions of a Proton Pump Inhibitor Therapeutic Interchange Program Across the Continuum of Care
Authors: Sodorff Michelle M. , Galt Kimberly A. , Galt Michael A. , Turner Paul D. , Lambrecht Jason E. 
Published: June 2004

Objective. To determine if participation in a hospital‐based proton pump inhibitor (PPI) therapeutic interchange program resulted in differences in patient perceptions related to clinical and humanistic outcomes.Methods. A quasiexperimental repeated‐measures study compared patients' perceptions in two groups (111 patients) at hospital admission, discharge, 3–4 days after discharge, and 2–3 weeks after discharge to detect differences across the continuum of care. Patient awareness of the hospital‐based interchange also was examined. Clinical and quality‐of‐life outcomes were measured by using a condition‐specific instrument modified for use with patients. Satisfaction and expectations were measured by using extent‐of‐agreement measures. Group 1 (60 patients) was prescribed omeprazole before admission, switched to lansoprazole during hospitalization, and discharged taking omeprazole. Group 2 (51 patients) was prescribed lansoprazole before admission and continued taking lansoprazole throughout hospitalization and after discharge. Patients who were unable to communicate or who had a substantial change in severity of illness (not attributable to gastrointestinal disorders) during the study were excluded.Results. No significant differences were found between groups 1 and 2 for clinical outcomes, quality of life, extent to which expectations were met, or satisfaction at the four time periods. Nineteen (36%) of 53 surveyed patients in group 1 were not aware that their therapy had been interchanged while in the hospital.Conclusion. Patient‐perceived outcomes and expectations of therapy across the continuum of care were not affected by a hospital‐based PPI therapeutic interchange program.
Dynamic patterns of expression of BMP isoforms 2, 4, 5, 6, and 7 during chicken heart development
Authors: Somi Semir , Buffing Anita A.M. , Moorman Antoon F.M. , Van Den Hoff Maurice J.B. 
Published: June 2004

AbstractBone morphogentic proteins (BMPs) play an important role in cardiac development. Using an in vitro explant analysis, we show that BMPs are crucial for myocardium formation. As a first approach to identify which BMP may be involved in myocardium formation in intra‐ and extracardiac mesenchyme in vivo, a survey of the expression patterns of BMP2, ‐4, ‐5, ‐6, and ‐7 mRNA is prepared by in situ hybridization in chicken embryonic hearts from HH5 to 44. During recruitment of mesodermal cells to the outflow tract myocardium (HH10–23), BMP2, ‐4, ‐5, and ‐7 mRNA are expressed in the distal myocardial border and the flanking mesenchyme. After completion, BMP2 and ‐4 mRNA become restricted to the mesenchyme and BMP5 and ‐7 mRNA to the myocardium. At the venous pole, BMP2, ‐5, and ‐7 mRNA are expressed in the distal myocardial border of the caval vein, while BMP2, ‐5, ‐6, and ‐7 mRNA are expressed in the distal myocardium around the pulmonary vein. BMP4 mRNA is expressed in the adjacent mesenchyme at both sides. During muscularization of the atrioventricular cushions and the tricuspid valve, the cardiomyocytes that protrude into the mesenchyme express BMP2, ‐4, ‐5, and ‐7 mRNA, whereas BMP6 mRNA is expressed in the cushion mesenchyme. The myocardial protrusions formed in the mesenchymal proximal outlet septum express BMP4, ‐5, and ‐7 mRNA, while BMP2 and ‐6 mRNA are expressed in the mesenchyme. The spatiotemporal expression patterns of these BMPs in relation to myocardium formation at the distal ends and within the heart suggest a role for BMPs in myocardium formation. During delamination of the valves, BMP4 and ‐6 mRNA are expressed at the ventricular side of the forming mitral valve, BMP4 mRNA at the ventricular side of the forming tricuspid valve, and BMP2, ‐4, and ‐6 mRNA at the vascular side of the forming semilunar valves. © 2004 Wiley‐Liss, Inc.
Membrane‐transport systems in the fenestrated capillaries of the area postrema in rat and calf
Authors: Bombardi Cristiano , Grandis Annamaria , Chiocchetti Roberto , Lucchi Maria Luisa , Callegari Emilio , Bortolami Ruggero 
Published: June 2004

AbstractThe capillaries of the area postrema (AP) lack the morphological peculiarity of the blood‐brain barrier (BBB), and the AP neurons are considered located outside the BBB. Using the immunofluorescent method, we have investigated the expression of membrane transport systems that are instrumental to the BBB function, such as caveolin‐1, ‐2, P‐glycoprotein, and glut‐4, in the capillary endothelium of the rat and calf AP. The expression of these molecules was verified after fibronectin immunostaining of the microvessels. Both in the rat and calf, caveolin‐1, ‐2, and P‐glycoprotein were expressed in the AP capillaries. A quantitative analysis revealed that the proportion of the capillary profiles expressing these transport systems was very close to 100% of the fibronectin immunolabelled profiles. On the contrary, none of the AP capillaries showed glut‐4 immunoreactivity. The present investigation demonstrates that the endothelial layer of the AP capillaries, in spite of the paracellular passage of polar molecules through the leaky tight junctions and fenestrations, could be an active interface which is able to control the entry of a wide range of blood‐borne compounds into the brain by means of specific mechanisms, including an efflux pump. © 2004 Wiley‐Liss, Inc.
Development of the synovial membrane in the rat temporomandibular joint as demonstrated by immunocytochemistry for heat shock protein 25
Authors: Ikeda Nobuyuki , Nozawa‐Inoue Kayoko , Takagi Ritsuo , Maeda Takeyasu 
Published: June 2004

AbstractThe synovial lining layer of the temporomandibular joint (TMJ) consists of macrophage‐like type A cells and fibroblast‐like type B cells. Until now, little information has been available on the development of the synovial membrane in TMJ. In the present study we examined the development of the synovial lining layer in the rat TMJ by light‐ and electron‐microscopic immunocytochemistry for heat shock protein (Hsp) 25, which is a useful marker for type B cells. At embryonic day 19 (E19), a few Hsp25‐positive cells first appeared in the upper portion of the developing condyle. During the formation of the upper articular cavity (E21 to postnatal day 1 (P1)), a few positive cells were arranged on its surface. Immunoelectron microscopy demonstrated that these cells had ultrastructural features of fibroblast‐like type B cells. In addition, some Hsp25‐positive cells moved to the deep portion by extending their cytoplasmic processes toward the articular cavity at P3. At that time, the presence of typical macrophage‐like type A cells in the lining layer was confirmed by immunoelectron microscopy. The slender processes of Hsp25‐positive cells showed a continuous covering with the synovial surface at P7, followed by a drastic increase in the Hsp25‐positive cells at P15 and later, when active jaw movement occurred. These findings suggested that the arrangement and morphological maturation of type B cells are closely related to the formation of the articular cavity in the embryonic period and the commencement of active jaw movement after birth, respectively. © 2004 Wiley‐Liss, Inc.
Expression of bone morphogenetic protein‐10 mRNA during chicken heart development
Authors: Somi Semir , Buffing Anita A.M. , Moorman Antoon F.M. , Van Den Hoff Maurice J.B. 
Published: June 2004

AbstractIn this communication we describe the expression pattern of BMP10 mRNA during cardiac development in chickens. BMP10 is considered an important factor in the regulation of cardiac growth and trabeculation in the murine embryo. We identified chicken Ests, which are similar to mouse and human BMP10 in the UMIST database. The cDNA clone that contained most sequences was obtained, verified by sequence analysis, and used to determine the spatiotemporal pattern of gene expression. BMP10 mRNA is initially expressed at HH10 in the myocardium of the arterial pole of the heart tube, anterior to the interventricular groove. Between HH14 and HH22, BMP10 mRNA becomes broadly expressed in the outflow tract, the distal part of the inflow tract, and the trabeculated part of the developing ventricles and atria. From HH31 onward, BMP10 mRNA expression decreases in the ventricular myocardium by first disappearing from the compact myocardium and then from the tips of the trabecules. At HH44, BMP10 mRNA is expressed only in the trabeculated myocardium of the atria and the endocardium of the ventricles. The observed expression pattern of BMP10 mRNA suggests that it may play a role in regulating the formation of the ventricular wall and trabecules. © 2004 Wiley‐Liss, Inc.
Ultrastructural evidence for co‐localization of dopamine D2 and μ‐opioid receptors in the rat dorsolateral striatum
Authors: Ambrose L.M. , Unterwald E.M. , Van Bockstaele E.J. 
Published: June 2004

AbstractPrevious studies have shown significant changes in dopamine and opioid receptors in the basal ganglia following administration of cocaine. Cocaine administration results in a significant increase in the number of opioid receptors in dopamine‐enriched brain regions. The aim of this study was to determine if dopamine D2 receptors (D2r) and μ‐opioid receptors (μOr) are localized to the same neurons in the dorsolateral striatum. Immunoperoxidase and immunogold‐silver labeling combined with electron microscopy was used to examine the ultrastructural localization of both receptors in the dorsolateral striatum. Approximately half of the μOr‐labeled somatodendritic processes showed immunolabeling for the D2r. Similarly, about half of the D2r‐labeled dendrites and cell bodies showed immunolabeling for the μOr. In conclusion, our results indicate that individual neurons in the rat dorsolateral striatum may be directly modulated by both dopaminergic and opioid ligands. These data also suggest that the molecular mechanism responsible for the up‐regulation of μOrs in the caudate and putamen following cocaine exposure may depend, in part, on the co‐existence of D2rs and μ‐Ors in these cells. © 2004 Wiley‐Liss, Inc.
Efficacy and safety of leflunomide in the treatment of psoriatic arthritis and psoriasis: A multinational, double‐blind, randomized, placebo‐controlled clinical trial
Authors: Kaltwasser J. Peter , Nash Peter , Gladman Dafna , Rosen Cheryl F. , Behrens Frank , Jones Peter , Wollenhaupt Jürgen , Falk Franziska G. , Mease Philip 
Published: June 2004

AbstractObjectiveCurrent treatment options for psoriatic arthritis (PsA) are limited. Leflunomide, an oral pyrimidine synthesis inhibitor, is highly effective in the treatment of rheumatoid arthritis, and small studies have suggested similar efficacy in PsA. We undertook this double‐blind, randomized, placebo‐controlled trial to evaluate the efficacy and safety of leflunomide in patients with PsA and psoriasis.MethodsOne hundred ninety patients with active PsA and psoriasis (at least 3% skin involvement) were randomized to receive leflunomide (100 mg/day loading dose for 3 days followed by 20 mg/day orally) or placebo for 24 weeks. The primary efficacy end point was the proportion of patients classified as responders by the Psoriatic Arthritis Response Criteria (PsARC). Additional efficacy (joint and skin involvement), safety, and quality‐of‐life assessments were performed.ResultsAt 24 weeks, 56 of 95 leflunomide‐treated patients (58.9%; 95% confidence interval [95% CI] 48.4–68.9) and 27 of 91 placebo‐treated patients (29.7% [95% CI 20.6–40.2]) were classified as responders by the PsARC (P < 0.0001). Significant differences in favor of leflunomide were also observed in the proportions of patients achieving modified American College of Rheumatology 20% improvement criteria, improvement in the designated psoriasis target lesion, and mean changes from baseline in Psoriasis Area and Severity Index scores and quality‐of‐life assessments. Diarrhea and alanine aminotransferase increases occurred at higher rates in the leflunomide group. No cases of serious liver toxicity were observed.ConclusionLeflunomide is an effective treatment for PsA and psoriasis, providing a safe and convenient alternative to current therapies.
Induction of interferon‐α production in plasmacytoid dendritic cells by immune complexes containing nucleic acid released by necrotic or late apoptotic cells and lupus IgG
Authors: Lövgren Tanja , Eloranta Maija‐Leena , Båve Ullvi , Alm Gunnar V. , Rönnblom Lars 
Published: June 2004

AbstractObjectiveTo investigate the release of interferon‐α (IFNα)–inducing material by necrotic or apoptotic cells, its properties, and the necessity of autoantibodies from systemic lupus erythematosus (SLE) patients for the interferogenic activity.MethodsU937 monocytic leukemia cells or peripheral blood mononuclear cells (PBMCs) were rendered necrotic by freeze‐thawing or apoptotic by treatment with ultraviolet light. Cell culture supernatants from these cells and IgG from SLE patients (SLE IgG) were added to cultures of normal PBMCs or purified plasmacytoid dendritic cells (PDCs). The importance of nucleic acids for IFNα induction was investigated by RNase and DNase treatment. The IFNα levels were measured by immunoassay.ResultsBoth necrotic and apoptotic U937 cells released material that, combined with SLE IgG, induced IFNα production in PDCs. The release from apoptotic cells occurred with a 16‐hour delay, in late apoptosis. Also, normal PBMCs released IFNα‐inducing material, but only during necrosis. The interferogenic activity of the necrotic material required the presence of RNA, while both RNA and DNA were important in the apoptotic material. In both cases, the presence of SLE IgG was necessary, and its activity correlated with the presence of antibodies to RNA‐binding proteins, but not anti‐DNA antibodies.ConclusionNecrotic and late apoptotic cells release material that, combined with SLE IgG, induces production of IFNα in PDCs. The IFNα inducers probably consist of immune complexes (ICs) containing RNA and possibly DNA as essential interferogenic components. The presence of such interferogenic ICs could explain the ongoing production of IFNα in SLE and could be of etiopathogenic importance.