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Target Concentration (target + concentration)
Selected AbstractsHigh-dose ribavirin in combination with standard dose peginterferon for treatment of patients with chronic hepatitis C,HEPATOLOGY, Issue 2 2005Karin Lindahl Improved treatment regimens for patients with chronic hepatitis C, genotype 1 and high viral load are needed. Increasing the dose of ribavirin has increased the response rate, but experience with doses of more than 1,200 mg/day is limited. The aim of this study was to investigate the safety and tolerance to treatment with a high and individualized dose of ribavirin in combination with peginterferon. Ten patients with chronic hepatitis C, genotype 1 and high viral load were treated with peginterferon alfa-2a and ribavirin for 48 weeks in a prospective trial. The initial ribavirin dose was individualized and calculated from a pharmacokinetic formula based mainly on renal function. Ribavirin plasma concentrations were monitored, and the dose was adjusted to reach the target concentration. Hemoglobin was monitored, and patients were treated with erythropoietin and blood transfusions when indicated. After dose adjustments, the mean dose of ribavirin was 2,540 mg/day (range, 1,600-3,600) at week 24. The main side effect was anemia, which was controlled with erythropoietin. Two patients required blood transfusions. One patient was withdrawn at week 24 because of a lack of viral response, and one patient at week 39 because of side effects, primarily interferon associated. At follow-up (,24 weeks posttreatment), nine of ten patients had undetectable HCV RNA and thus were cured by standard definitions. In conclusion, a high dose of ribavirin according to an individualized schedule is feasible but associated with more frequent and serious side effects such as anemia. The viral response merits further evaluation. (HEPATOLOGY 2005;41:275,279.) [source] Testing and improving experimental parameters for the use of low molecular weight targets in array-CGH experiments,HUMAN MUTATION, Issue 11 2006Marianne Stef Abstract Array,comparative genomic hybridization (CGH) has evolved as a useful technique for the detection and characterization of deletions, and, to a lesser extent, of duplications. The resolution of the technique is dictated by the genomic distance between targets spotted on the microarray, and by the targets' sizes. The use of region-specific, high-resolution microarrays is a specific goal when studying regions that are prone to rearrangements, such as those involved in deletion syndromes. The aim of the present study was to evaluate the best experimental conditions to be used for array-CGH analysis using low molecular weight (LMW) targets. The parameters tested were: the target concentration, the way LMW targets are prepared (either as linearized plasmids or as purified PCR products), and the way the targets are attached to the array-CGH slide (in a random fashion on amino-silane coated slides, or by one amino-modified end on epoxysilane-coated slides). As a test case, we constructed a microarray harboring LMW targets located in the CREBBP gene, mutations of which cause the Rubinstein-Taybi syndrome (RTS). From 10 to 15% of RTS patients have a CREBBP deletion. We showed that aminosilane- and epoxysilane-coated slides were equally efficient with targets above 1,000,bp in size. On the other hand, with the smallest targets, especially those below 500,bp, epoxysilane-coated slides were superior to aminosilane-coated slides, which did not allow deletion detection. Use of the high resolution array allowed us to map intragenic breakpoints with precision and to identify a very small deletion and a duplication that were not detected by the currently available techniques for finding CREBBP deletions. Hum Mutat 27(11), 1143,1150, 2006. © 2006 Wiley-Liss, Inc. [source] Effects of elevated carbon dioxide and increased nitrogen deposition on bog vegetation in the NetherlandsJOURNAL OF ECOLOGY, Issue 2 2001Monique M. P. D. Heijmans Summary 1,We studied the effects of elevated atmospheric CO2 and increased N deposition on the plant species composition of a Sphagnum -dominated bog ecosystem in the Netherlands. Large peat monoliths (surface area 1 m2, depth 0.6 m) with intact bog vegetation were kept outdoors in large containers and were exposed to elevated CO2 or increased N deposition for three growing seasons. Elevated CO2 conditions (target concentration 560 µmol CO2 mol,1) were created using MiniFACE technology. In a separate experiment, N deposition was increased by 5 g N m,2 year,1 by adding dissolved NH4NO3 at 3 week intervals during the growing season. 2,Elevated atmospheric CO2 increased height growth of Sphagnum magellanicum, the dominant Sphagnum species, in the second and third growing seasons. Vascular plant biomass was not significantly affected by elevated CO2, but growth of species growing close to the moss surface was influenced negatively by the increased Sphagnum height growth. Elevated CO2 did not change allocation to below-ground plant parts. 3,Adding N increased above-ground vascular plant biomass. The shallow-rooted species Vaccinium oxycoccus responded most to the increased N deposition. Sphagnum growth was significantly reduced in the third growing season. This reduction was likely the result of the increased vascular plant cover, given the observed negative relation between vascular plant cover and Sphagnum growth. 4,The observed shifts in species composition as a result of species-specific responses to treatments, and interactions between peat mosses and vascular plants will have important consequences for the sequestration of carbon in the bog ecosystem. [source] Recurrence of hepatic artery thrombosis following acute tacrolimus overdose in pediatric liver transplant recipientPEDIATRIC TRANSPLANTATION, Issue 6 2005Soshi Takahashi Abstract:, Acute overdose of tacrolimus appears to cause no or minimal adverse clinical consequences. We encountered a pediatric case who underwent liver transplantation associated with hepatic artery thrombosis (HAT), which recurred following acute tacrolimus overdose. A 10-month-old girl underwent living-related liver transplantation because of biliary atresia. To reconstruct the hepatic artery, the right gastroepiploic artery of the donor was interposed between the right hepatic artery of the recipient (2.5 mm in diameter) and the left hepatic graft artery (1 mm in diameter) under microscopy. On postoperative day 4, Doppler ultrasonography showed a remarkable reduction in hepatic arterial flow, which was consistent with HAT. The patient underwent immediate hepatic arteriography and balloon angioplasty. The stenotic sites were dilated by the procedure. Tacrolimus was infused intravenously after transplantation and the infusion rate was adjusted to achieve a target concentration of 18,22 ng/mL, which remained stable until the morning of day 6. An unexpectedly high blood concentration of tacrolimus (57.4 ng/mL) was detected at 6:00 pm on day 6, and tacrolimus was discontinued at 9:00 pm; however, the tacrolimus level reached 119.5 ng/mL at 0:00 h on day 7. While the concentration decreased to 55.2 ng/mL on the morning of day 7, the hepatic arterial flow could not be observed by Doppler ultrasonography. Emergent hepatic arteriography showed stenosis of the artery at the proximal site of the anastomosis. Balloon angioplasty was again performed and the stenotic site was successfully dilated. High level of tacrolimus exposure to the hepatic artery with injured endothelium by preceding angioplasty may have been related to the recurrence of HAT in the present case. [source] Closing the mass balance at chlorinated solvent sites: Sources and attenuation processesREMEDIATION, Issue 2 2010Roopa Kamath Using detailed mass balance and simple analytical models, a spreadsheet-based application (BioBalance) was developed to equip decision makers with a predictive tool that can provide a semiquantitative projection of source-zone concentrations and provide insight into the long-term behavior of the associated chlorinated solvent plume. The various models were linked in a toolkit in order to predict the composite impacts of alternative source-zone remediation technologies and downgradient attenuation processes. Key outputs of BioBalance include estimates of maximum plume size, the time frame for plume stabilization, and an assessment of the sustainability of anaerobic natural attenuation processes. The toolkit also provides spatial and temporal projections of integrated contaminant flux and plume centerline concentrations. Results from model runs of the toolkit indicate that, for sites trying to meet traditional, "final" remedial objectives (e.g., two to three orders of magnitude reduction in concentration with restoration to potable limits), "dispersive" mechanisms (e.g., heterogeneous flow and matrix diffusion) can extend remedial time frames and limit the benefits of source remediation in reducing plume sizes. In these cases, the removal of source mass does not result in a corresponding reduction in the time frame for source remediation or plume stabilization. However, this should not discourage practitioners from implementing source-depletion technologies, since results from the toolkit demonstrate a variety of measurable benefits of source remediation. Model runs suggest that alternative, "intermediate" performance metrics can improve and clarify source remediation objectives and better monitor and evaluate effectiveness. Suggested intermediate performance metrics include reduction in overall concentrations or mass within the plume, reduction of flux moving within a plume, and reduction in the potential for risk to a receptor or migration of a target concentration of contaminant beyond a site boundary. This article describes the development of two key modules of the toolkit as well as illustrates the value of using intermediate performance metrics to evaluate the performance of a source-remediation technology. © 2010 Wiley Periodicals, Inc. [source] Effects of different doses of remifentanil on the end-tidal concentration of sevoflurane required for tracheal intubation in childrenANAESTHESIA, Issue 8 2009L. He Summary We investigated the effects of different doses of remifentanil on the end-tidal concentration of sevoflurane required for tracheal intubation in children without the use of neuromuscular blocking drugs. One hundred and thirty paediatric patients, aged 3,8 years, were randomly allocated to receive no remifentanil (group control) or remifentanil 0.1 ,g.kg,1.min,1 (group remi0.1), 0.2 ,g.kg,1.min,1 (group remi0.2), 0.3 ,g.kg,1.min,1 (group remi0.3). All patients were anaesthetised using 5% sevoflurane. After loss of eyelash reflex, remifentanil 1 ,g.kg,1 was injected over 1 min followed by an appropriate group-dependent infusion and the end-tidal sevoflurane concentration was changed. Predetermined end-tidal sevoflurane concentrations for each group were determined using the Dixon up-and-down method. After the target concentration of sevoflurane was maintained for 5 min, the child's trachea was intubated. Successful intubation was defined as excellent or good intubating conditions. The end-tidal concentration (SD) of sevoflurane for successful tracheal intubation in 50% of children (ED50) were 5.16 (0.22)% in control, 3.27 (0.18)%, 1.81 (0.20)% and 1.01 (0.11)%, in remi0.1, remi0.2, and remi0.3 groups, respectively. Using probit analysis, the 95% effective dose (ED95) of sevoflurane were 5.60% (95% CI 5.35,7.66), 3.77% (95% CI 3.45,7.74), 2.18% (95% CI 1.96,3.86), 1.19% (95% CI 1.06,1.82) in control, remi0.1, remi0.2, and remi0.3 groups, respectively. [source] Patient-maintained propofol sedation: a follow-up safety study using a modified system in volunteersANAESTHESIA, Issue 4 2002F. Henderson Summary Patient-maintained sedation is a mode of patient-controlled sedation during which propofol is administered using a target-controlled infusion, with patient demand increasing the target concentration. A system tested previously for safety in our institution resulted in oversedation. Aiming to improve safety, we modified the system by increasing the lockout period to 4 min, reducing the starting concentration to 0.5 µg.ml,1 and the increments on demand to 0.1 µg.ml,1. As in the previous study, healthy volunteers attempted to render themselves unconscious by frequently pressing the demand button. To assess effects on memory, volunteers were given keywords to remember every 15 min. The maximum target concentration reached varied between 1.0 and 2.5 µg.ml,1. No volunteers lost consciousness, however, one volunteer had a brief period of apnoea and oxygen desaturation. The Cp50 for loss of memory for words was 1.26 µg.ml,1. Although this version represents an improvement, we conclude that the system is not yet completely suitable for use without anaesthetic supervision. [source] Stocking strategies for production of Litopenaeus vannamei (Boone) in amended freshwater in inland pondsAQUACULTURE RESEARCH, Issue 1 2008Bartholomew W Green Abstract The performance of the Pacific white shrimp Litopenaeus vannamei (Boone) under various stocking strategies was evaluated in earthen ponds filled with freshwater amended with major ions. Six 0.1-ha earthen ponds located in Pine Bluff, AR, USA, were filled with freshwater in 2003 and 2004, and potassium magnesium sulphate added to provide 50 mg K+ L,1 and stock salt added to provide 0.5 g L,1 salinity. In 2003, three ponds either were stocked with PL15 shrimp (39 PL m,2) for 125 days of grow out or with PL25 shrimp for 55 days (23 PL m,2) followed by a 65-day (28 PL m,2) grow-out period. In 2004, ponds were stocked with 7, 13 or 30 PL15 m,2 for 134 days of grow out. Salinity averaged 0.7 g L,1 during both years, and concentration of SO4,2, K+, Ca2+ and Mg2+ was higher, and Na+ and Cl, was lower in amended pond water than in seawater at 0.7 g L,1 salinity. Potassium concentration in amended water was 52,61% of the target concentration. Shrimp yields ranged from 3449 kg ha,1 in 2003 to 4966 kg ha,1 in 2004 in ponds stocked with 30,39 PL15 m,2 for a 125,134-day culture period. At harvest, mean individual weight ranged from 17.1 to 19.3 g shrimp,1. In ponds stocked with PL25 shrimp, yields averaged 988 and 2462 kg ha,1 for the 1st and 2nd grow-out periods respectively. Gross shrimp yield in 2004 increased linearly from 1379,4966 kg ha,1 with increased stocking rate. These experiments demonstrated that L. vannamei can be grown successfully in freshwater supplemented with major ions to a final salinity of 0.7 g L,1. [source] Reduced valproate plasma levels possible after introduction of efavirenz in a bipolar patientBIPOLAR DISORDERS, Issue 4 2006Michael Saraga The case of a bipolar patient with concomitant multidrug addiction is described who presented a decrease in valproate plasma level of more than 50% shortly after antiretroviral therapy was initiated. Despite important dose augmentations of up to 4 g/day, plasma levels were difficult to raise to the target concentration of 50 mg/dL. The possible mechanisms underlying the observed pharmacokinetic changes are discussed: (i) a uridine diphosphate-glucuronosyl transferase induction by efavirenz; and (ii) a plasma protein displacement of valproate by efavirenz with subsequent increased elimination of the free fraction. [source] Ultrahighly Sensitive Homogeneous Detection of DNA and MicroRNA by Using Single-Silver-Nanoparticle CountingCHEMISTRY - A EUROPEAN JOURNAL, Issue 3 2010Fagong Xu Dr. Abstract DNA and RNA analysis is of high importance for clinical diagnoses, forensic analysis, and basic studies in the biological and biomedical fields. In this paper, we report the ultrahighly sensitive homogeneous detection of DNA and microRNA by using a novel single-silver-nanoparticle counting (SSNPC) technique. The principle of SSNPC is based on the photon-burst counting of single silver nanoparticles (Ag NPs) in a highly focused laser beam (about 0.5,fL detection volume) due to Brownian motion and the strong resonance Rayleigh scattering of single Ag NPs. We first investigated the performance of the SSNPC system and then developed an ultrasensitive homogeneous detection method for DNA and microRNA based on this single-nanoparticle technique. Sandwich nucleic acid hybridization models were utilized in the assays. In the hybridization process, when two Ag-NP,oligonucleotide conjugates were mixed in a sample containing DNA (or microRNA) targets, the binding of the targets caused the Ag NPs to form dimers (or oligomers), which led to a reduction in the photon-burst counts. The SSNPC method was used to measure the change in the photon-burst counts. The relationship between the change of the photon-burst counts and the target concentration showed a good linearity. This method was used for the assay of sequence-specific DNA fragments and microRNAs. The detection limits were at about the 1,fM level, which is 2,5 orders of magnitude more sensitive than current homogeneous methods. [source] Creating metal-spiked bed sediments: A case study from Orewa estuary, New Zealand,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2008Xueqiang Lu Abstract Spiking sediments to achieve target concentrations of heavy metal pollutants is a key step in sediment toxicity tests. It is difficult, however, to ensure that metals in an artificially spiked sediment will behave naturally. A method has been developed in the present study to create Cu-, Pb-, and Zn-spiked sediments in which naturally occurring adsorption onto sediment surfaces is the dominant process binding the metals and in which precipitation of readily redissolved minerals and other metal-bearing phases (artifacts of the spiking procedure) are avoided. Uncontaminated bed sediment from an intertidal mudflat in the Orewa estuary, New Zealand, was characterized in terms of existing metal content, optimal adsorption pH, and adsorption capacity. Competitive adsorption between Cu and Pb as well as complexation by seawater anions only slightly affected metal adsorption from seawater. Surface complexation modeling indicated that iron oxide surfaces in the sediment likely were dominating metal adsorption processes. Spiking experiments were designed using these established adsorption characteristics but with significantly higher (>100-fold) concentrations of sediments and dissolved metals and a liquid to solid (L:S) ratio of approximately 5.5. An equilibration time of at least 36 h was required to achieve a reproducible target metal concentration, which could be reliably predicted from the L:S ratio and the initial metal concentration in the spiking solution. Adsorption equilibrium remained the process governing metal binding to the sediment, and no indication was observed that the adsorption capacity of the sediment had been exceeded or that additional metal-bearing phases had been formed. [source] Comparative insecticidal power of three pyrethroids on nettingMEDICAL AND VETERINARY ENTOMOLOGY, Issue 1 2002K. J. Adams Abstract Adult mosquitoes, Anopheles gambiae Giles and Culex quinquefasciatus Say (Diptera: Culicidae), were exposed for 3 min to replicate samples of polyester netting cut from replicate bednets treated with pyrethroid insecticide formulations at the recommended concentration (alphacypermethrin SC at 40 mg ai/m2; cyfluthrin EW at 50 mg ai/m2; deltamethrin WT at 25 mg ai/m2), or treated with only a quarter of those dosages. After 4 months domestic use of the bednets in Malawi, chemical assays showed that pyrethroid deposits on the netting were somewhat less than the target concentrations. Comparing the pyrethroid bioassay results with Anopheles at both treatment concentrations, deltamethrin gave significantly higher mortality (99.7,100%) than the other compounds (alphacypermethrin 94,96%, cyfluthrin 80,89%). Culex bioassay mortality was lower (alphacypermethrin 56,74%; cyfluthrin 63,65%; deltamethrin 50,81%) and results with the three pyrethroid insecticides at their recommended doses did not differ significantly. [source] Effect-site concentration of propofol for reduction of remifentanil-induced coughANAESTHESIA, Issue 7 2010J. Y. Kim Summary This study examined the effectiveness of different propofol infusion target concentrations on cough suppression, during a target-controlled remifentanil infusion. Four hundred patients were randomly assigned to receive propofol target effect-site concentrations of 0, 3.0, 4.5, or 6.0 ,g.ml,1. When the propofol effect-site concentration reached the target, remifentanil was administered at a target effect-site concentration of 4.0 ng.ml,1. Episodes of cough were recorded over a 2-min period after remifentanil commencement, and graded as mild (1,2), moderate (3,4), or severe (5 or more). The overall incidence of cough was significantly decreased in by propofol 6.0 ,g.ml,1 compared with 0 or 3.0 ,g.ml,1 propofol (p < 0.001). The incidence of severe cough was significantly lower with propofol 6.0 ,g.ml,1 compared with 3.0 ,g.ml,1 (p = 0.03). A propofol target effect-site concentration of 6.0 ,g.ml,1 effectively suppressed remifentanil-induced cough when remifentanil was administrated at a target effect-site concentration of 4.0 ng.ml,1. [source] Age-related differences in the pharmacokinetics of stavudine in 272 children from birth to 16 years: a population analysisBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2007V. Jullien Aims To develop a population pharmacokinetic model for stavudine in children and to investigate the consistency of the currently recommended dose based on adult target concentrations. Methods The pharmacokinetics of stavudine were investigated using a population approach. Individual estimates of CL/F were used to calculate the stavudine dose required to achieve the area under the concentration-time curve reported in adults given recommended doses. Results Stavudine pharmacokinetics were well described by a one-compartment model with zero-order absorption. Typical population estimates (% interindividual variability) of the apparent distribution volume (V/F) and plasma clearance (CL/F) were 40.9 l (32%) and 16.5 l h,1 (38%), respectively. Stavudine V/F and CL/F were similarly related to age. Mean calculated doses (0.61 mg kg,1 for children less than 2 weeks, 1.23 mg kg,1 for children more than 2 weeks with bodyweight less than 30 kg, and 31.5 mg for children with a bodyweight between 30 and 60 kg) were in agreement with the current paediatric doses (0.5 mg kg,1, 1 mg kg,1, and 30 mg, respectively). Conclusions Our findings support the current recommended paediatric dosage regimens for stavudine, as they result in the same exposure to the drug as in adults. [source] | ||||||||||||||||