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Disposition
Kinds of Disposition Terms modified by Disposition Selected AbstractsEFFECTS OF MORPHINE ON METHOTREXATE DISPOSITION IN MICECLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 4 2004Yuai Li SUMMARY 1.,Morphine has been shown to slow the renal excretion of other drugs. The present study in mice evaluated the effects of morphine on the disposition of methotrexate (MTX), an antimetabolite eliminated by the kidneys. 2.,Mice were injected with morphine (20 mg/kg) or saline s.c. After 30 min, 20,80 mg/kg MTX was injected i.v. Blood and urine samples were assayed for MTX by HPLC. 3.,Morphine reduced plasma clearance (CL) of MTX from 0.147 ± 0.015 to 0.061 ± 0.009 mL/min per g bodyweight (P < 0.01). The area under the plasma concentration,time curve (AUC0,,) was raised by morphine from 151 ± 18 to 369 ± 36 µg·mL per min (P < 0.01). Without morphine administration, 22,27% of an MTX dose was excreted into the urine in 30 min. The corresponding fractions excreted into the urine after morphine were reduced to 15,18% (P < 0.01). 4.,Plasma levels of MTX administered intravenously to mice are elevated by the concomitant administration of morphine, which reduces renal elimination of MTX. [source] Trauma Team Activation Criteria as Predictors of Patient Disposition from the Emergency DepartmentACADEMIC EMERGENCY MEDICINE, Issue 1 2004Michael A. Kohn MD Many trauma centers use mainly physiologic, first-tier criteria and mechanism-related, second-tier criteria to determine whether and at what level to activate a multidisciplinary trauma team in response to an out-of-hospital call. Some of these criteria result in a large number of unnecessary team activations while identifying only a few additional patients who require immediate operative intervention. Objectives: To separately evaluate the incremental predictive value of individual first-tier and second-tier trauma team activation criteria for severe injury as reflected by patient disposition from the emergency department (ED). Methods: This was a prospective cohort study in which activation criteria were collected prospectively on all adult patients for whom the trauma team was activated during a five-month period at an urban, Level 1 trauma center. Severe injury disposition ("appropriate" team activation) was defined as immediate operative intervention, admission to the intensive care unit (ICU), or death in the ED. Data analysis consisted of recursive partitioning and multiple logistic regression. Results: Of the 305 activations for the mainly physiologic first-tier criteria, 157 (51.5%) resulted in severe injury disposition. The first-tier criterion that caused the greatest increase in "inappropriate" activations for the lowest increase in "appropriate" activations was "age > 65." Of the 34 additional activations due to this criterion, seven (20.6%) resulted in severe injury disposition. Of the 700 activations for second-tier, mechanism-related criteria, 54 (7.7%) resulted in ICU or operating room admissions, and none resulted in ED death. The four least predictive second-tier criteria were "motorcycle crash with separation of rider,""pedestrian hit by motor vehicle,""motor vehicle crash with rollover," and "motor vehicle crash with death of occupant." Of the 452 activations for these four criteria, only 18 (4.0%) resulted in ICU or operating room admission. Conclusions: The four least predictive second-tier, mechanism-related criteria added little sensitivity to the trauma team activation rule at the cost of substantially decreased specificity, and they should be modified or eliminated. The first-tier, mainly physiologic criteria were all useful in predicting the need for an immediate multidisciplinary response. If increased specificity of the first-tier criteria is desired, the first criterion to eliminate is "age > 65." [source] Disposition of perfluorinated acid isomers in sprague-dawley rats; Part 1: Single doseENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2009Jonathan P. Benskin Abstract Perfluorinated acids (PFAs) and their precursors (PFA-precursors) exist in the environment as linear and multiple branched isomers. These isomers are hypothesized to have different biological properties, but no isomer-specific data are currently available. The present study is the first in a two-part project examining PFA isomer-specific uptake, tissue distribution, and elimination in a rodent model. Seven male Sprague-Dawley rats were administered a single gavage dose of approximately 500 ,g/kg body weight perfluorooctane sulfonate (C8F17SO3,, PFOS), perfluorooctanoic acid (C7F15CO2H, PFOA), and perfluorononanoic acid (C8F17CO2H, PFNA) and 30 ,g/kg body weight perfluorohexane sulfonate (C6F13SO3,, PFHxS). Over the subsequent 38 d, urine, feces, and tail-vein blood samples were collected intermittently, while larger blood volumes and tissues were collected on days 3 and 38 for isomer analysis by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). For all PFAs, branched isomers generally had lower blood depuration half-lives than the corresponding linear isomer. The most remarkable exception was for the PFOS isomer containing an alpha-perfluoromethyl branch (1m -PFOS), which was threefold more persistent than linear PFOS, possibly due to steric shielding of the hydrophilic sulfonate moiety. For perfluoromonomethyl-branched isomers of PFOS, a structure,property relationship was observed whereby branching toward the sulfonate end of the perfluoroalkyl chain resulted in increased half-lives. For PFHxS, PFOA, and PFOS, preferential elimination of branched isomers occurred primarily via urine, whereas for PFNA preferential elimination of the isopropyl isomer occurred via both urine and feces. Changes in the blood isomer profiles over time and their inverse correlation to isomer elimination patterns in urine, feces, or both provided unequivocal evidence of significant isomer-specific biological handling. Source assignment based on PFA isomer profiles in biota must therefore be conducted with caution, because isomer profiles are unlikely to be conserved in biological samples. [source] Disposition of perfluorinated acid isomers in sprague-dawley rats; Part 2: Subchronic doseENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2009Amila O. De Silva Abstract Two major industrial synthetic pathways have been used to produce perfluorinated acids (PFAs) or their precursors: Telomerization and electrochemical fluorination (ECF). Products of telomer and ECF origin can be distinguished by structural isomer profiles. A mixture of linear and branched perfluoroalkyl isomers is associated with ECF. Telomer products characteristically consist of a single perfluoroalkyl geometry, typically linear. In biota, it is unclear if the isomer profile is conserved relative to the exposure medium and hence whether PFA isomer profiles in organisms are useful for distinguishing environmental PFA sources. A companion study suggested isomer-specific disposition following a single oral gavage exposure to rats. To confirm these findings under a more realistic subchronic feeding scenario, male and female rats were administered PFA isomers by diet for 12 weeks, followed by a 12-week depuration period. The diet contained 500 ng/g each of ECF perfluorooctanoate (PFOA, ,80% n -PFOA), ECF perfluorooctane sulfonate (PFOS, ,70% n -PFOS), and linear and isopropyl perfluorononanoate (n - and iso -PFNA). Blood sampling during the exposure phase revealed preferential accumulation of n -PFOA and n -PFNA compared to most branched isomers. Female rats depurated all isomers faster than males. Both sexes eliminated most branched perfluorocarboxylate isomers more rapidly than the n -isomer. Elimination rates of the major branched PFOS isomers were not statistically different from n -PFOS. Two minor isomers of ECF PFOA and one branched PFOS isomer had longer elimination half-lives than the n-isomers. Although extrapolation of these pharmacokinetics trends in rats to humans and wildlife requires careful consideration of dosage level and species-specific physiology, cumulative evidence suggests that perfluorocarboxylate isomer profiles in biota may not be suitable for quantifying the relative contributions of telomer and ECF sources. [source] Changes in the Disposition of Oxcarbazepine and Its Metabolites during Pregnancy and the PuerperiumEPILEPSIA, Issue 3 2006Iolanda Mazzucchelli Summary:,Purpose: To determine potential changes in the plasma concentrations of oxcarbazepine (OXC) and its metabolites during pregnancy and puerperium. Methods: Five women receiving OXC monotherapy were followed prospectively during pregnancy and the puerperium. Four women were enrolled in the first trimester, and one woman, 2 weeks before delivery. Steady-state concentrations of OXC, its active R -(-)- and S -(+)-monohydroxy derivatives (MHD), and the additional metabolite carbamazepine-10,11- trans -dihydrodiol (DHD) were measured at regular intervals by an enantioselective HPLC assay. Results. In all samples, S -(+)-MHD was the most abundant compound in plasma and accounted almost entirely for the amount of active moiety (defined as the molar sum of OXC, R -(-)-MHD, and S -(+)-MHD) found in the circulation. The dose-normalized concentrations of active moiety decreased markedly during gestation and, in four of the five patients, increased strikingly after delivery. Plasma concentrations of S -(+)-MHD mirrored closely the levels of the active moiety. Plasma concentrations of the parent drug and other metabolites also tended to decrease during pregnancy and to increase after delivery. Conclusions: During treatment with OXC, S -(+)-MHD is by far the most abundant active compound in plasma. The concentration of this metabolite as well as the active moiety may decrease markedly during pregnancy and may increase severalfold after delivery. Because of these striking pharmacokinetic changes, the clinical response should be monitored closely in OXC-treated women throughout pregnancy and the puerperium. [source] The Effect of Seatbelt Use on Injury Patterns, Disposition, and Hospital Charges for EldersACADEMIC EMERGENCY MEDICINE, Issue 12 2002Andrew Coley MD Objective: To study the relationships between seatbelt use and injury patterns, hospital charges, morbidity, and mortality in elder motor vehicle crash victims. Methods: A retrospective review of individuals at least 65 years old presenting to an urban emergency department (ED) after a motor vehicle crash. Results: Over a two-year period, 339 patients had documentation of seatbelt use or non-use at the time of the crash. Of these, 241 (71%) patients had been wearing a seatbelt and 98 (29%) had not. Elders not using seatbelts were more likely to require hospitalization (29% unbelted vs. 17% belted) and had a higher mortality rate. Injury patterns were different in the two groups. Emergency department charges were significantly different between belted and unbelted elders ($351 vs. $451, p = 0.01) and head computed tomography (CT) utilization was higher in the unbelted group (25.6% vs 12.7%, p = 0.005). Conclusions: Improved seatbelt compliance in elders can reduce injuries, hospitalization rates, ED charges, and mortality resulting from motor vehicle crashes. [source] PRECLINICAL STUDY: Disposition of ,9 tetrahydrocannabinol in CF1 mice deficient in mdr1a P-glycoproteinADDICTION BIOLOGY, Issue 3-4 2008Laurence Bonhomme-Faivre ABSTRACT P-glycoprotein (P-gp) plays a major role in drug efflux. All the transported substrates are more or less hydrophobic and amphiphatic in nature. Being lipophilic, ,9 tetrahydrocannabinol (THC), the main cannabis component, could be a potential P-gp substrate. The aim of this project was to determine the contribution of the mdr1a gene product to THC disposition. Therefore, oral THC and digoxin (substrate test for P-gp) pharmacokinetics have been investigated in the intestinal epithelium and in the brain capillary endothelium of CF1 mdr1a (,/,) mice (mice naturally deficient in P-gp). These pharmacokinetics were compared to THC and digoxin oral pharmacokinetics in wild type mice mdr1a (+/+) (not P-gp deficient). The application of Bailer's method showed that THC total exposure measured by the area under the plasma concentration time curve was 2.17-fold higher in CF1 mice naturally deficient in P-gp than in wild type mice after oral administration of 25 mg/kg of THC, and 2.4-fold higher after oral administration of 33 µg/kg of digoxin. As a consequence, the oral bioavailability of THC and digoxin was higher in naturally P-gp-deficient mice. We concluded that P-gp limits THC oral uptake and mediates direct drug excretion from the systemic circulation into the intestinal lumen. [source] Stereoselective Disposition of the Geminal Dimethyl Group in the Cyclization of Geranyl Acetate under Zeolite Confinement ConditionsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 19 2006Constantinos Tsangarakis Abstract The stereochemistry in the acid-catalysed biomimetic cyclization of [8,8,8-D3]geranyl acetate was examined in solution and under conditions of zeolite Y confinement. In the intrazeolite reaction the gem -allylic methyl group adopts a diastereoselective disposition in the cyclization product (64,% dr). In contrast, the gem -dimethyl disposition in a homogeneous medium (ClSO3H/2-nitropropane) proceeds with negligible diastereoselectivity (dr < 5,%). The enhanced diastereoselection within the zeolite is attributed to the proximity of the nucleophilic double bond to the intermediate carbocation, as a result of confinement (entropy effect). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Disposition of rainwater under creosotebushHYDROLOGICAL PROCESSES, Issue 13 2003Athol D. Abrahams Abstract In desert shrubland ecosystems water and nutrients are concentrated beneath shrub canopies in ,resource islands'. Rain falling on to these islands reaches the ground as either stemflow or throughfall and then either infiltrates into the soil or runs off as overland flow. This study investigates the partitioning of rainwater between stemflow and throughfall in the first instance and between infiltration and runoff in the second. Two series of 40 rainfall simulation experiments were performed on 16 creosotebush shrubs in the Jornada Basin, New Mexico. The first series of experiments was designed to measure the surface runoff and was performed with each shrub in its growth position. The second series was designed to measure stemflow reaching the shrub base and was conducted with the shrub suspended above the ground. The experimental data show that once equilibrium is achieved, 16% of the rainfall intercepted by the canopy or 6·7% of the rain falling inside the shrub area (i.e. the area inside the shrub's circumscribing ellipse) is funnelled to the shrub base as stemflow. This redistribution of the rainfall by stemflow is a function of the ratio of canopy area (i.e. the area covered by the shrub canopy) to collar area (i.e. a circular area centred on the shrub base), with stemflow rate being positively correlated and throughfall rate being negatively correlated with this ratio. The surface runoff rate expressed as a proportion of the rate at which rainwater arrives at a point (i.e. stemflow rate plus throughfall rate) is the runoff coefficient. A multiple regression reveals that 75% of the variance in the runoff coefficient can be explained by three independent variables: the rainfall rate, the ratio of the canopy area to the collar area, and the presence or absence of subcanopy vegetation. Although the last variable is a dummy variable, it accounts for 66·4% of the variance in the runoff coefficient. This suggests that the density and extent of the subcanopy vegetation is the single most important control of the partitioning of rainwater between runoff and infiltration beneath creosotebush. Although these findings pertain to creosotebush, similar findings might be expected for other desert shrubs that generate significant stemflow and have subcanopy vegetation. Copyright © 2003 John Wiley & Sons, Ltd. [source] The Voting Propensity of Hong Kong Christians: Individual Disposition, Church Influence, and the China FactorJOURNAL FOR THE SCIENTIFIC STUDY OF RELIGION, Issue 3 2000Che-po Chan Considering China's history of unfavorable treatment of mainland Chinese Christians, the authors hypothesize that Christians in Hong Kong reflected their concern over the future protection of religious freedom during the 1995 Legislative Council election, the last election before the handover of the British colony to Chinese sovereignty. We have looked at the relative contributions of individual disposition, the China factor and church influence on the presence of Hong Kong Christians at the polling booth on election day. Our analysis found that Hong Kong Christians are subjected more to the influenceof the latter two factors. The influence of socio-economic status is relatively unimportant in determining the voting propensity of Hong Kong Christians. While both Catholics and Protestants are influenced by general church teachings, this research found that Catholic voters, are more subject to their church's organizational mobilization than Protestant voters. [source] Disposition and pharmacokinetics of a lubricant contaminant, 2,6-di- tert -butyl 4-nitrophenol, in grafted human skinJOURNAL OF APPLIED TOXICOLOGY, Issue 5 2006Lynn K. Pershing Abstract Disposition and uptake/elimination profiles of topical 2,6-di- t -butyl, 4-nitrophenol (DBNP), the nitrated metabolite of an antioxidant additive of lubricant and hydraulic fluids was quantified in human skin grafted on athymic mice after a single topical 75 µg dose in corn oil. DBNP was quantified throughout the stratum corneum (SC), epidermis (E) and dermis (D) in punch biopsies collected from treated skin 0.5, 1, 2, 4, 8 and 24 h after application. SC samples were harvested from the treated skin with 20 adhesive discs. E and D were generated from the biopsy using a manual sectioning method. Detectable DBNP concentrations were measured in all skin compartments at all time points investigated. The Cmax of DBNP in SC was 1663 ± 602 µg cm,3, and ,30 and ,300 fold greater than the Cmax for E and D, respectively. Tmax occurred at 1.0, 0.5 and 1.0 in the SC, E and D, respectively. Over a 24 h interval (AUC0,24 h) there was 52 and 520 fold more DBNP in the SC than E and D, respectively. The elimination half-life of DBNP was 11 h from the SC and 9 h from both E and D. Thus, DBNP was quickly absorbed into the outermost layer of skin and established a steep concentration profile through human skin. The data are consistent with the vast majority of DBNP remaining on the surface (77%) or within human skin (15%) in vivo with only 0.2% of the DBNP dose quantified in the systemic blood circulation. Copyright © 2006 John Wiley & Sons, Ltd. [source] Reconstructing the Sequence of Events Surrounding Body Disposition Based on Color Staining of Bone,JOURNAL OF FORENSIC SCIENCES, Issue 5 2009Meaghan A. Huculak H.B.Sc. Abstract:, Literature regarding bone color is limited to determining location of primary and secondary dispositions. This research is the first to use bone color to interpret the sequence of events surrounding body disposition. Two scenarios were compared,bones buried and then exposed on the ground surface and bones exposed then buried. Forty juvenile pig humeri with minimal tissue were used in each scenario with an additional 20 controls to determine if decomposing tissue affects bone color. Munsell Color Charts were used to record bone color of surface and 2.5 cm cross-sections. Results reveal five main surface colors attributed to soil, sun, hemolysis, decomposition, and fungi. Fungi on buried bones suggests prior surface exposure. Cross-sections of strictly buried bones are identical to buried then exposed bone, stressing the importance of bone surface analysis. Cross-sectioning may help verify remains have been exposed then buried. Decomposition of excess tissue creates minimal color staining. [source] Disposition of axonal caspr with respect to glial cell membranes: Implications for the process of myelinationJOURNAL OF NEUROSCIENCE RESEARCH, Issue 15 2009Liliana Pedraza Abstract Neurofascin-155 (NF155) and caspr are transmembrane proteins found at discrete locations early during development of the nervous system. NF155 is present in the oligodendrocyte cell body and processes, whereas caspr is on the axonal surface. In mature nerves, these proteins are clustered at paranodes, flanking the node of Ranvier. To understand how NF155 and caspr become localized to the paranodal regions of myelinated nerves, we have studied their distribution over time in myelinating cultures. Our observations indicate that these two proteins are recruited to the cell surface at the contact zone between axons and oligodendrocytes, where they trans-interact. This association explains the early pattern of caspr distribution, a helical coil that winds around the axon, resembling the turns of the myelin sheath. Caspr, an axonal membrane protein, therefore seems to move in register with the overlying myelinating cell via its interactions with myelin proteins. We suggest that NF155 is the glial cell membrane protein responsible for caspr distribution. The pair act as interacting partners on either side of the axoglial contact area. Most likely, there are other proteins on the axonal surface whose distribution is equally influenced by interaction with the nascent myelin sheath. The fact that caspr follows the movement of the spiraling membrane has a direct affect on the interpretation of the way in which myelin is formed. © 2009 Wiley-Liss, Inc. [source] Disposition and pharmacokinetics of L-N6-(1-iminoethyl)lysine-5-tetrazole-amide, a selective iNOS inhibitor, in ratsJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2004Ji Y. Zhang Abstract The metabolism, pharmacokinetics, tissue distribution, and excretion of L-N6-(1-iminoethyl)lysine-5-tetrazole-amide (L-NIL-TA), a selective inducible NO synthase (iNOS) inhibitor, were investigated in rats. [14C]L-NIL-TA is extensively metabolized after either oral or IV administration with a minor amount (<1%) excreted as the prodrug. L-NIL-TA is metabolized via a single hydrolysis pathway to form the active drug, L-N6-(1-iminoethyl)lysine (L-NIL). The oxidative deamination of 2-amino group of L-NIL forms a 2-keto metabolite (M5), which further loses carbon dioxide to yield a carboxylic acid metabolite (M6). Acetylation of L-NIL and M5 resulted in the formations of metabolites M7 and M4, respectively. Complete recovery of the radioactive dose was achieved after either oral (91.2% in urine and 4.66% in feces) and IV (99.3% in urine and 5.11% in feces) administration. L-NIL-TA-related material was extensively distributed to the tissues, with the highest concentration of radioactivity being found in muscle. Maximal concentration of radioactivity was reached between 0.5 and 1 h post-dose in the majority of tissues, with the exception of muscle and skin where the maximal concentrations were achieved at 8 h post-dose. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1229,1240, 2004 [source] Life in the Mindful Classroom: Nurturing the Disposition of MindfulnessJOURNAL OF SOCIAL ISSUES, Issue 1 2000Ron Ritchhart In this article, we review the appropriateness of ,mindfulness' as an educational goal and explore what it means to cultivate mindfulness as a disposition, that is, as an enduring trait, rather than a temporary state. We identify three high-leverage instructional practices for enculturatingmindfulness: looking closely, exploring possibilities and perspectives, and introducing ambiguity. We conclude by exploring what it might look like to cultivate the trait of mindfulness within individual classrooms. This report includes a review of an experimental study of ,conditional instruction,' which explores mindfulness as a state, and then drawson a series of qualitative case studies of ,thoughtful' classrooms to provide an example of conditional instruction as it might serve to develop a disposition of mindfulness. [source] Disposition of oral telithromycin in foals and in vitro activity of the drug against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolatesJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2010L. H. JAVSICAS Javsicas, LH., Gigučre, S., Womble, AY. Disposition of oral telithromycin in foals and in vitro activity of the drug against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolates. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365-2885.2009.01151.x. The objectives of this study were to determine the serum and pulmonary disposition of telithromycin in foals and to determine the minimum inhibitory concentration (MIC) of telithromycin against macrolide-susceptible and macrolide-resistant Rhodococcus equi isolates. A single dose of telithromycin (15 mg/kg of body weight) was administered to six healthy 6,10-week-old foals by the intragastric route. Activity of telithromycin was measured in serum, pulmonary epithelial lining fluid (PELF), and bronchoalveolar lavage (BAL) cells using a microbiological assay. The broth macrodilution method was used to determine the MIC of telithromycin, azithromycin, clarithromycin and erythromycin against R. equi. Following intragastric administration, mean ± SD time to peak serum telithromycin activity (Tmax) was 1.75 ± 0.76 h, maximum serum activity (Cmax) was 1.43 ± 0.37 ,g/mL, and terminal half-life (t˝) was 3.81 ± 0.40 h. Telithromycin activity, 4 h postadministration was significantly higher in BAL cells (50.9 ± 14.5 ,g/mL) than in PELF (5.07 ± 2.64 ,g/mL), and plasma (0.84 ± 0.25 ,g/mL). The MIC90 of telithromycin for macrolide-resistant R. equi isolates (8 ,g/mL) was significantly higher than that of macrolide-susceptible isolates (0.25 ,g/mL). The MIC of telithromycin for macrolide-resistant isolates (MIC50 = 4.0 ,g/mL) was significantly lower than that of clarithromycin (MIC50 = 24.0 ,g/mL), azithromycin (MIC50 =256 ,g/mL) and erythromycin (MIC50 = 24 ,g/mL). [source] Confessions and Criminal Case Disposition in ChinaLAW & SOCIETY REVIEW, Issue 3 2003Hong Lu This research examines confessions and criminal case disposition in China. It describes how wider economic reforms in China and subsequent changes in its legal system may have affected the nature and consequence of criminal confessions. Bivariate and multivariate analyses of a sample of 1,009 criminal court cases reveal that the majority of offenders confessed to their crime and that confession is associated with less severe punishments (e.g., lower risks for imprisonment, shorter sentences). Changes in the nature of confession and its impact on criminal court practices are also examined before and after legal reforms in the mid-1990s. These context-specific findings are then discussed in terms of their implications for understanding the interrelationships between legal structure, legal culture, and case disposition in communitarian-based societies. [source] Soft Tissue Infections and Emergency Department Disposition: Predicting the Need for Inpatient AdmissionACADEMIC EMERGENCY MEDICINE, Issue 12 2009Alfredo Sabbaj MD Abstract Objectives:, Little empiric evidence exists to guide emergency department (ED) disposition of patients presenting with soft tissue infections. This study's objective was to generate a clinical decision rule to predict the need for greater than 24-hour hospital admission for patients presenting to the ED with soft tissue infection. Methods:, This was a retrospective cohort study of consecutive patients presenting to a tertiary care hospital ED with diagnosis of nonfacial soft tissue infection. Standardized chart review was used to collect 29 clinical variables. The primary outcome was >24-hour hospital admission (either general admission or ED observation unit), regardless of initial disposition. Patients initially discharged home and later admitted for more than 24 hours were included in the outcome. Data were analyzed using classification and regression tree (CART) analysis and multivariable logistic regression. Results:, A total of 846 patients presented to the ED with nonfacial soft tissue infection. After merging duplicate records, 674 patients remained, of which 81 (12%) required longer than 24-hour admission. Using CART, the strongest predictors of >24-hour admission were patient temperature at ED presentation and mechanism of infection. In the multivariable logistic regression model, initial patient temperature (odds ratio [OR] for each degree over 37°C = 2.91, 95% confidence interval [CI] = 1.65 to 5.12) and history of fever (OR = 3.02, 95% CI = 1.41 to 6.43) remained the strongest predictors of hospital admission. Despite these findings, there was no combination of factors that reliably identified more than 90% of target patients. Conclusions:, Although we were unable to generate a high-sensitivity decision rule to identify ED patients with soft tissue infection requiring >24-hour admission, the presence of a fever (either by initial ED vital signs or by history) was the strongest predictor of need for >24-hour hospital stay. These findings may help guide disposition of patients presenting to the ED with nonfacial soft tissue infections. [source] Effect of Opioid Dependence Pharmacotherapies on Zidovudine DispositionTHE AMERICAN JOURNAL ON ADDICTIONS, Issue 4 2001Elinore F. McCance-Katz M.D., Ph.D. Injection drug users are frequently infected with human immunodeficiency virus (HIV) and receive opioid dependence pharmacotherapies and zidovudine (ZDV), the latter as a component of highly active antiretroviral therapy. We previously reported that methadone substantially increases ZDV concentrations. We now report on oral ZDV pharmacokinetics in 52 subjects receiving the opioid dependence pharmacotherapies l-a-acetylmethadol LAAM, buprenorphine, or naltrexone, and 17 non-opioid-treated controls. Relative to the area under the time-concentration curve (AUC) of ZDV in control subjects, no statistically significant differences in ZDV AUC were observed in participants treated with LAAM (p = .75), buprenorphine (p = .37), or naltrexone (p = .34). While methadone maintenance may result in ZDV toxicity and possibly require dose adjustments, other opioid pharmacotherapies should not produce ZDV toxicity. [source] Viral Nucleic Acid Testing (NAT) and OPO-Level Disposition of High-Risk Donor OrgansAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009L. M. Kucirka The use of Public Health Service/Centers for Disease Control and Prevention (PHS/CDC) high-risk donor (HRD) organs remains controversial, especially in light of a recent high-profile case of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) transmission. Nucleic acid testing (NAT), while more expensive and time consuming, reduces infectious risk by shortening the period between infection and detectability. The purpose of this study was to characterize HRDs and disposition of their organs by organ procurement organization (OPO), to measure NAT practices by OPO and to examine associations between NAT practices and use of HRD organs. We analyzed 29 950 deceased donors (2574 HRDs) reported to UNOS since July 1, 2004 and May 8, 2008. We then surveyed all OPO clinical directors about their use of NAT, average time to receive NAT results, locations where NAT is performed and percentage of the time NAT results are available for allocation decisions. In total, 51.7% of OPOs always perform HIV NAT, while 24.1% never do. A similar pattern is seen for HCV NAT performance, while the majority (65.6%) never perform HBV NAT. AIDS prevalence in an OPO service area is not associated with NAT practice. OPOs that perform HIV NAT are less likely to export organs outside of their region. The wide variation of current practice and the possibility that NAT would improve organ utilization support consideration for a national policy. [source] Airway Selectivity: An Update of Pharmacokinetic Factors Affecting Local and Systemic Disposition of Inhaled SteroidsBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 6 2006Staffan Edsbäcker The antiinflammatory properties of these products, combined with the targeting of formulations and optimization of the intrinsic pharmacokinetic features of the newer corticosteroid molecules has resulted in substantially improved airway selectivity. This review sets out to summarize the pharmacokinetic properties of inhaled corticosteroids that are important for the achievement of high levels of airway selectivity, with additional focus on the use of prodrugs/softdrugs relative to those of conventional corticosteroid molecules, mechanisms (such as esterification) by which retention at the target site is achieved while minimizing systemic exposure, and the role of plasma protein binding. [source] Disposition of WR-1065 in the liver of tumor-bearing rats following regional vs systemic administration of amifostineBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2004Micha Levi Abstract Purpose,Amifostine is a prodrug in which selectivity is largely determined by the preferential formation and uptake of its cytoprotective metabolite, WR-1065, in normal tissues as a result of differences in membrane-bound alkaline phosphatase activity. It was hypothesized that amifostine may be a good candidate for regional drug delivery to the liver because of its large hepatic extraction and total body clearance. Methods,Rat livers were implanted with Walker-256 tumors. The tumor-bearing rats received 15 min infusions of amifostine (200 mg/kg) via the portal vein or the femoral vein. WR-1065 concentrations in the blood, liver and tumor were measured at various times. Results,The WR-1065 tumor portal dosing AUC15,60 was 40% of systemic dosing, and tumor concentrations following portal dosing were one-fifth of that following systemic dosing. The portal dosing WR-1065 liver AUC15,60 was 60% higher than the values for systemic dosing. The liver/tumor concentration ratios of WR-1065 following portal dosing were up to 8-fold higher than the ratio following systemic administration. Unfortunately, systemic exposure to WR-1065 was greater following portal vs systemic amifostine. Conclusions,Amifostine may provide increased liver protection and decreased tumor protection from radio- or chemotherapy when administered by the portal vein. However, portal dosing also increases systemic exposure to WR-1065, which is associated with hypotension. Copyright © 2004 John Wiley & Sons, Ltd. [source] Disposition of acamprosate in the rat: Influence of probenecidBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 7 2002Teodoro Zornoza Abstract The purpose of the present study was to investigate the disposition of acamprosate (calcium bis acetyl-homotaurine) in the rat. Initially, we studied the linearity of acamprosate disposition and the fraction of acamprosate excreted unchanged in the urine of the animals. Rats received 9.3, 36.6 or 73.3 mg/kg of the drug as an intravenous bolus. The statistical analysis of the pharmacokinetic parameters did not reveal any significant difference, indicating that acamprosate disposition was linear within the range of the doses assayed. On average, 95% of the administered dose was excreted unchanged in the urine of the animals in the 0,6 h post-administration period indicating that renal excretion is the main elimination route for this drug. Acamprosate was also administered by the intravenous route at three different constant infusion rates (2.65, 132.5 and 530 ,g/min) in order to quantify total (Clt) and renal (Clr) plasma clearances at steady-state conditions. The mean Clr values were, respectively, 4.60±0.42, 4.28±0.52 and 4.08±0.67 ml/min, practically equivalent to the Clt values (4.78±0.38, 4.51±0.36 and 4.21±0.56 ml/min), confirming that the drug is mainly eliminated via renal excretion. Moreover, Clr values were clearly higher than the glomerular filtration rate (2.61±0.26 ml/min), suggesting the existence of a highly efficient tubular secretion mechanism in the renal excretion of the drug. To confirm this hypothesis, two groups of rats were intravenously treated with probenecid (33.3 or 66.6 mg/kg) prior to acamprosate administration (9.3 mg/kg). Probenecid provoked a statistically significant dose-dependent reduction in the total clearance of acamprosate (from 5.8±0.7 ml/min in the control group to 2.6±0.1 ml/min in the animals treated with 66 mg/kg of probenecid) demonstrating the existence of a tubular secretion process on the renal excretion of acamprosate in the rat. Copyright © 2002 John Wiley & Sons, Ltd. [source] Drug Transporters: Molecular Characterization and Role in Drug Disposition.BIOTECHNOLOGY JOURNAL, Issue 8 2008By Guofeng You, Marilyn E. Morris (Eds.) No abstract is available for this article. [source] 9 A Communication Tool for Emergency Medicine Residents to Improve Patient Care and Professional DevelopmentACADEMIC EMERGENCY MEDICINE, Issue 2008Jacqueline Mahal For every patient in the ED, a web of communication is created. A resident is at the center of this web , connecting team members in and outside the ED. Careful communication, a required ACGME competency, helps the team provide safe, high-quality care and master their respective specialties. We designed a three module curriculum that supports ACGME core competencies by providing training in professional communication and a framework with which to organize patient data. In the first module, residents are introduced to the concept that there is more to communication than content alone. Other elements include context, audience and forum. Together, these components comprise relevant communication. The second module introduces the Disposition, Situation, Background, Assessment, Recommendation, Safety (D-SBARS) Framework, an ED modification of The Joint Commission's communication tool. This framework will enable the resident to focus on communicating the relevant data for a particular audience in an appropriate manner. In the last module, residents participate in a case-based role-play. After presentation of a complicated patient, residents are each assigned a communication task. They communicate with attendings, ED staff and consultants. Each role is played by senior residents. Finally, participants deliver presentations to the on-coming team on "rounds" under time constraints, declining from two minutes to 30 seconds. Residents experience how the D-SBARS tool helps them communicate critical clinical and safety. [source] Comparison of Nebulized Epinephrine to Albuterol in BronchiolitisACADEMIC EMERGENCY MEDICINE, Issue 4 2008Paul Walsh MB Abstract Objectives:, To compare the effect of nebulized racemic epinephrine to nebulized racemic albuterol on successful discharge from the emergency department (ED). Methods:, Children up to their 18th month of life presenting to two teaching hospital EDs with a clinical diagnosis of bronchiolitis who were ill enough to warrant treatment but did not need immediate intubation were eligible for this double-blind randomized controlled trial (RCT). Patients received either three doses of racemic albuterol or one dose of racemic epinephrine plus two saline nebulizers. Disposition was decided 2 hours after the first nebulizer. Successful discharge was defined as not requiring additional bronchodilators in the ED after study drug administration and not subsequently admitted within 72 hours. Adjusted relative risks (aRR) were estimated using the modified Poisson regression with successful discharge as the dependent variable and study drug and severity of illness as exposures. Secondary analysis was performed for patients aged less than 12 months and first presentation. Results:, The authors analyzed 703 patients; 352 patients were given albuterol and 351 epinephrine. A total of 173 in the albuterol group and 160 in the epinephrine group were successfully discharged (crude RR = 1.08, 95% confidence interval [CI] = 0.92 to 1.26). When adjusted for severity of illness, patients who received albuterol were significantly more likely than patients receiving epinephrine to be successfully discharged (aRR = 1.18, 95% CI = 1.02 to 1.36). This was also true among those with first presentation and in those less than 12 months of age. Conclusions:, In children up to the 18th month of life, ED treatment of bronchiolitis with nebulized racemic albuterol led to more successful discharges than nebulized epinephrine. [source] Hospital and Demographic Influences on the Disposition of Transient Ischemic AttackACADEMIC EMERGENCY MEDICINE, Issue 2 2008Jeffrey H. Coben MD Abstract Objectives:, There is substantial variation in the emergency department (ED) disposition of patients with transient ischemic attack (TIA), and the factors responsible for this variation have not been determined. In this study, the authors examined the influence of clinical, sociodemographic, and hospital characteristics on ED disposition. Methods:, All ED-treated TIA cases from community hospitals in 11 states were identified from the 2002 Healthcare Cost and Utilization Project (HCUP). Using the aggregate data, descriptive analyses compared admitted and discharged cases. Pearson's chi-square test was used to determine the statistical significance of these comparisons. Based on the results of the bivariate analyses, logistic regression models of the likelihood of hospital admission were derived, using a stepwise selection process. Adjusted risk ratios and 95% confidence intervals (CI) were calculated from the logistic regression models. Results:, A total of 34,843 cases were identified in the 11 states, with 53% of cases admitted to the hospital. In logistic regression models, differences in admission status were found to be strongly associated with clinical characteristics such as age and comorbidities. After controlling for comorbidities, differences in admission status were also found to be associated to hospital type and with sociodemographic characteristics, including county of residence and insurance status. Conclusions:, While clinical factors predictably and appropriately impact the ED disposition of patients diagnosed with TIA, several nonclinical factors are also associated with differences in disposition. Additional research is needed to better understand the basis for these disparities and their potential impact on patient outcomes. [source] The Biochemistry of Drug Metabolism , An IntroductionCHEMISTRY & BIODIVERSITY, Issue 10 2006Abstract This paper reviews the general principles and concepts underlying Drug and Xenobiotic Metabolism. Its five Chapters deal with: 1.1. Drugs and Xenobiotics, 1.2. What are Drug Disposition and Metabolism?, 1.3. Where does Drug Metabolism Occur?, 1.4. Consequences of Drug Metabolism -- An Overview, and 1.5. Drug Metabolism and Drug Discovery. This review is the first of seven Parts which will be published at intervals. The subsequent Parts will cover: 2. Redox Reactions and Their Enzymes, 3. Reactions of Hydrolysis and Their Enzymes, 4. Conjugation Reactions and Their Enzymes, 5. Metabolism and Bioactivity, 6. Inter-Individual Factors Affecting Drug Metabolism, and 7. Intra-Individual Factors Affecting Drug Metabolism. [source] Disposition of isosteviol in the rat isolated perfused liverCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2010Hongping Jin Summary 1. The aim of the present study was to investigate the mechanisms involved in the clearance of isosteviol using the rat isolated perfused liver. 2. Six livers from male Sprague-Dawley rats were perfused with 15.7 ,mol isosteviol in a recirculating system. Perfusate and bile samples were collected for 60 min and the liver was collected at the end of the perfusion. All samples collected were incubated with ,-glucuronidase. Isosteviol,glucuronide was determined as equivalent isosteviol. Isosteviol concentrations were determined using a previously developed liquid chromatography,tandem mass spectrometry method. The final isosteviol liver/perfusate (L/P), bile/liver (B/L) and isosteviol-glucuronide in bile/liver (BG/LG) ratios were determined. 3. Isosteviol has a high clearance (21.4 ± 4.8 mL/min) from the perfusate, with a short half-life (13 ± 4 min). ,-Glucuronidase incubation revealed that isosteviol is conjugated in the liver and excreted into the bile. There was no isosteviol-glucuronide detected in perfusate samples. The total recovery of the rat isolated perfused liver system is 74 ± 14% and glucuronidated isosteviol accounted for 23 ± 4% of the administered dose. 4. In conclusion, we are the first to characterize the metabolism of isosteviol using rat isolated liver perfusion. Our results strongly suggest that the liver is the main organ of isosteviol elimination and that isosteviol is glucuronidated in the liver before it is excreted into the bile. [source] Computed Tomography Coronary Angiography for Rapid Disposition of Low-risk Emergency Department Patients with Chest Pain SyndromesACADEMIC EMERGENCY MEDICINE, Issue 2 2007Judd E. Hollander MD Background Patients with recent normal cardiac catheterization are at low risk for complications of ischemic chest pain. Computed tomography (CT) coronary angiography has high correlation with cardiac catheterization for detection of coronary stenosis. Therefore, the investigators' emergency department (ED) incorporated CT coronary angiography into the evaluation of low-risk patients with chest pain. Objectives To report on the 30-day cardiovascular event rates of the first 54 patients evaluated by this strategy. Methods Low-risk chest pain patients (Thrombolysis In Myocardial Infarction [TIMI] score of 2 or less) without acute ischemia on an electrocardiogram had CT coronary angiography performed in the ED. If the CT coronary angiography was negative, the patient was discharged home. The main outcomes were death and myocardial infarction within 30 days of ED discharge, as determined by telephone follow up and record review. Data are presented as percentage frequency of occurrence with 95% confidence intervals (CIs). Results Of the 54 patients evaluated, after CT coronary angiography, 46 patients (85%) were immediately released from the ED, and none had cardiovascular complications within 30 days. Eight patients were admitted after CT coronary angiography: one had >70% stenosis, five patients had 50%,69% stenosis, and two had 0,49% stenosis. Three patients had further noninvasive testing; one had reversible ischemia, and catheterization confirmed the results of CT coronary angiography. All patients were followed for 30 days, and none (0; 95% CI = 0 to 6.6%) had an adverse event during index hospitalization or at 30-day follow up. Conclusions When used in the clinical setting for the evaluation of ED patients with low-risk chest pain, CT coronary angiography may safely allow rapid discharge of patients with negative studies. Further study to conclusively determine the safety and cost effectiveness of this approach is warranted. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||