bluuebunny/crossref_metadata_2025_split huggingface dataset:
Desloratadine dose selection in children aged 6 months to 2 years: comparison of population pharmacokinetics between children and adults
Authors: Gupta Samir K. , Kantesaria Bhavna , Banfield Christopher , Wang Zaiqi 
Published: February 2007

What is already known about this subject • According to recent literature, the pathophysiologies of allergic rhinitis and chronic idiopathic urticaria are thought to be similar in adults and children. In addition, the response to antihistamine treatment is similar in adults and children, suggesting a similar concentration‐response relationship.• However, an appropriate dose selection and the pharmacokinetics of desloratadine in children of ≥6 months−≤2 years old have never been addressed in the literature. What this study adds • This study demonstrated that desloratadine syrup offers a safe treatment option for allergic conditions in young children.• A suitable dose for children aged ≥6 months−<1 year is 1.0 mg, while the corresponding predicted dose for children aged ≥1 year−≤2 years is 1.25 mg. These paediatric doses yielded similar systemic desloratadine exposures (AUC) to those seen with a typical adult dose of 5.0 mg.AimsThe aim of this study was to identify the dose of desloratadine in children aged ≥6 months−≤2 years that would yield a single‐dose target exposure (AUC) comparable with that in adults taking 5 mg desloratadine as syrup.MethodsIn a phase 1, single‐dose, open‐label, pharmacokinetic study in 58 children aged ≥6 months−<1 year and ≥1 year−≤2 years were randomly assigned to desloratadine syrup 0.625 mg (1.25 ml) and 1.25 mg (2.5 ml), respectively. Because the volume of blood that could be collected from individual subjects was limited, a population pharmacokinetic approach was used to estimate the pharmacokinetics of desloratadine. Safety was assessed based on results of screening and postdose physical examinations, laboratory safety tests, vital signs, and adverse events.ResultsThe apparent clearance (CL/F) of desloratadine, population estimate (%CV), in children aged ≥6 months−<1 year was 27.8 l h−1 (35) and corresponding values in children ≥1 year−≤2 years was 35.5 l h−1 (51), compared with 137 l h−1 (58) for adults. The CL/F ratios (children to adults) indicated that doses of 1 mg for ≥6 months−<1 year and 1.25 mg for ≥1 year−≤2 years would result in similar systemic exposure to that observed in adults receiving the recommended 5 mg dose. Desloratadine was well tolerated with no safety issues.ConclusionsDoses of 1.0 and 1.25 mg in children aged ≥6 months−≤2 years should result in an exposure to desloratadine similar to that of adults receiving doses of 5 mg.
Evidence of zolpidem abuse and dependence: results of the French Centre for Evaluation and Information on Pharmacodependence (CEIP) network survey
Authors: Victorri‐Vigneau Caroline , Dailly Eric , Veyrac Gwenaëlle , Jolliet Pascale 
Published: February 2007

AimTo show that the nonbenzodiazepine hypnotic zolpidem has a higher abuse potential than previously documented.MethodAn official enquiry was carried out by the Nantes Centre for Evaluation and Information on Pharmacodependence (CEIP). The authors made a review of literature and analysed French data corresponding to the drug's postmarketing period collected by the CEIP network from 1993 to 2002.ResultsThe literature review yielded mixed results concerning the behavioural effects of zolpidem. Data from the CEIP and the 53 literature case reports highlight significant dependence and abuse potential of zolpidem.ConclusionsThis study adds to the growing evidence that zolpidem has the potential for abuse and dependence. As a consequence, the French drug monograph has been modified by the French Health Authorities.
Population pharmacokinetics of melphalan in paediatric blood or marrow transplant recipients
Authors: Nath Christa E. , Shaw Peter J. , Montgomery Kay , Earl John W. 
Published: February 2007

What is already known about this subject • In one of the largest studies in children to date, we have already published a paper that has described the pharmacokinetics of melphalan using a two‐stage approach. What this study adds • The current paper is a follow‐up study in which a population pharmacokinetic model for melphalan is developed and validated in children.• There have been no other population pharmacokinetic analyses published on melphalan given as a short infusion.• Additionally, a nomogram is produced to guide melphalan dosing.AimTo develop a population pharmacokinetic model for melphalan in children with malignant diseases and to evaluate limited sampling strategies for melphalan.MethodsMelphalan concentration data following a single intravenous dose were collected from 59 children with malignant diseases aged between 0.3 and 18 years. The data were split into two sets: the model development dataset (39 children, 571 concentration observations) and the model validation dataset (20 children, 277 concentration observations). Population pharmacokinetic modelling was performed with the NONMEM software. Stepwise multiple linear regression was used to develop a limited sampling model for melphalan.ResultsA two‐compartment model was fitted to the concentration‐vs.‐time data. The following covariate population pharmacokinetic models were obtained: (i) Clearance (l h−1) = 0.34.WT − 3.17.CPT + 0.0377.GFR, where WT = weight (kg), CPT = prior carboplatin therapy (0 = no, 1 = yes), and GFR = glomerular filtration rate (ml min−1 1.73 m−2); (ii) Volume of distribution (l) = 1.12 + 0.178.WT. Interpatient variability (coefficient of variation) was 27.3% for clearance and 33.8% for volume of distribution. There was insignificant bias and imprecision between observed and model‐predicted melphalan concentrations in the validation dataset. A three‐sample limited sampling model was developed which adequately predicted the area under the concentration–time curve (AUC) in the development and validation datasets.ConclusionsA population pharmacokinetic model for melphalan has been developed and validated and may now be used in conjunction with pharmacodynamic data to develop safe and effective dosing guidelines in children with malignant diseases.
Nitroglycerin protects the endothelium from ischaemia and reperfusion: human mechanistic insight
Authors: Gori Tommaso , Di Stolfo Giuseppe , Sicuro Silvia , Dragoni Saverio , Lisi Monica , Forconi Sandro , Parker John D. 
Published: February 2007

What is already known about this subject • The production of oxygen free radicals upon administration of nitroglycerin (GTN) and other organic nitrates has been advocated as one of the causes of nitrate‐induce tolerance and endothelial dysfunction.• It has been shown that nitrates also cause a protective phenomenon that is similar to ischaemic preconditioning, but the mechanisms of this effect have never been investigated in humans. What this study adds • We show, in vivo in humans, that GTN causes endothelial protection against ischaemic damage.• Furthermore, we show that this effect is mediated by release of oxygen free radicals and by opening of the mitochondrial permeability transition pore.AimsNitroglycerin (GTN) modulates tissue damage induced by ischaemia and reperfusion (IR) in a mechanism that is similar to ischaemic preconditioning. We set out to study, using a human model of endothelial IR injury, whether GTN‐induced endothelial preconditioning is mediated by reactive oxygen species (ROS) formation and/or opening of mitochondrial permeability transition pores (mPTP).MethodsIn two double‐blind, randomized, parallel studies, a total of 66 volunteers underwent measurement of radial artery endothelium‐dependent, flow‐mediated dilation (FMD) before and after local IR. Subjects were treated, 24 h before IR, with different drugs in order to test the mechanism of GTN‐induced endothelial protection.ResultsTransdermal GTN (0.6 mg h−1 for 2 h, administered 24 h before IR) significantly reduced the impairment of FMD caused by IR (placebo group: FMD after IR, 1.3 ± 0.8%; GTN group: FMD after IR, 5.3 ± 0.9%, P < 0.01 compared with placebo). This protective effect was lost when vitamin C (2 g i.v. at the time of GTN administration) or ciclosporin (an inhibitor of mPTP, 100 mg 2 h prior to GTN administration) were coadministered (FMD after IR: vit C + GTN group, 2.1 ± 1.0%; ciclosporin + GTN group, 1.7 ± 0.8%; both P < 0.05 compared with GTN alone).ConclusionsWe demonstrate that GTN protects the endothelium against IR‐induced endothelial dysfunction, in an effect similar to delayed ischaemic preconditioning. Using a human model, we provide evidence supporting the concept that this protective effect is mediated by ROS release and mPTP opening upon GTN administration.
Attitudes and experiences of community pharmacists towards paediatric off‐label prescribing: a prospective survey
Authors: Stewart Derek , Rouf Abdul , Snaith Ailsa , Elliott Kathleen , Helms Peter J. , McLay James S. 
Published: February 2007

What is already known about this subject • There are increasing concerns about the safety and efficacy of paediatric off‐label medicines.• In the UK, each year 26% of children receive an off‐label prescription from their general practitioner.• The community pharmacist is the final and key professional in the chain, with the responsibility to ensure that medicines are both prescribed and dispensed appropriately. What this study adds • The majority of community pharmacists are aware of off‐label prescribing, but through work experience rather than undergraduate or postgraduate training or professional development.• Community pharmacists, like UK general practitioners, underestimate the levels of paediatric off‐label prescribing, and appear unclear as to the most common reasons for a prescription being off label.• Most community pharmacists stated that they should inform the prescriber that a medicine was off label; however, when given specific practical examples, less than half would actually appear to do so.• The majority of community pharmacists have been asked by the public to sell over‐the‐counter medicines for paediatric off‐label use.AimTo identify community pharmacist experiences of, and attitudes towards paediatric off‐label prescribing.MethodsA prospective questionnaire‐based study, with a 21‐item questionnaire issued to 1500 randomly selected community pharmacies throughout the UK during 2005 on three separate occasions.ResultsFour hundred and eighty‐two (32.1%) completed questionnaires were returned. Over 70% of respondents were familiar with the concept of off‐label prescribing, primarily through dispensing experience rather than education, although only 40% were aware of having dispensed a paediatric off‐label prescription within the previous month. The reasons given for a prescription being off label were younger age than recommended (84.6%, 297/351), primarily for antihistamines, analgesics and β2‐agonists, and higher (73.9%, 229/310) or lower than (41%, 103/258) recommended dose, primarily antibiotics and analgesics. Over 60% of respondents had been asked by the public to sell paediatric over‐the‐counter medicines, such as antihistamines, analgesics and steroid preparations for off‐label use. The majority of respondents used the British National Formulary or the Pack Insert rather than specialist formularies or guidelines as a source of specialist paediatric information. Although 78% of respondents believed they had a responsibility to inform the prescriber that a medicine was off label, only 66% believed that they had a similar responsibility to inform parents.ConclusionThe community pharmacists who responded to this questionnaire appear to be aware of and concerned by the issues which surround paediatric off‐label prescribing. Despite this, most gained relevant knowledge through work experience rather than undergraduate or postgraduate training or professional development.
Relationships between life‐history strategies of European freshwater fish species and their habitat preferences
Authors: BLANCK AURELIE , TEDESCO PABLO A. , LAMOUROUX NICOLAS 
Published: February 2007

Summary1. Focusing on the current environmental characteristics, the ‘habitat template’ theory proposes that life‐history strategies summarise how evolution has shaped species to cope with the temporal and spatial variability of their present environment. The hierarchical ‘landscape filters’ concept predicts that the distribution of species reflects their specific traits that allow them to pass through multiple habitat filters. Together, these theories showed the importance of identifying the functional relationships of species to selective habitat forces in order to predict the organisation and response of communities to the environment.2. We test the relationships between life‐history traits of European freshwater fish species’ and their habitat preferences, to detect the strategies adopted by fish to cope with their current habitat. For this purpose, we use published data on species traits and habitat preferences (microhabitat hydraulics, temperature and oxygen level). We use multivariate analyses to classify fish species’ strategies and test the relationships between strategies and habitat preferences.3. We identified a continuum of life‐history patterns between two extremes, with opportunistic and periodic species. Our study supports the idea that microhabitat hydraulics plays a more important role as a template for these species ecological strategies than temperature and oxygen level. Indeed, riffle habitats may select opportunistic species whereas weak relationships are found between species strategies and both their temperature and oxygen level preferences. In addition, the ratio between mortality and growth rate (dimensionless trait), reflecting a trade‐off between growth and survival, varied among species according to the use of their hydraulic habitat, with species using deep habitats exhibiting the highest values.4. These general relationships between hydraulics and traits may be of importance in community ecology to develop predictive models to understand how fish communities change with the hydraulic environment.
Undesirable side‐effects of water hyacinth control in a shallow tropical reservoir
Authors: BICUDO DENISE DE C. , FONSECA BÁRBARA M. , BINI LUIS M. , CROSSETTI LUCIANE O. , BICUDO CARLOS E. DE M. , ARAÚJO‐JESUS TATIANE 
Published: February 2007

Summary1. Based on a comprehensive data set collected monthly during 8 years (1997–2004), we evaluated the effects of mechanical removal ofEichhornia crassipeson the limnological characteristics and algal biomass of a polymictic shallow tropical reservoir.2. Interrupted time series analyses indicated that the limnological responses to macrophyte removal can be classified as an ‘abrupt permanent impact’ implying that the overall mean of the time‐series shifted promptly after intervention. These analyses indicated a significant increase for pH, total phosphorus, total phytoplankton and cyanobacterial biomass, and a decrease in water transparency and CO2concentrations in the surface water; also, the increase in water stability, increase of bottom soluble reactive phosphorus (SRP) and decrease in bottom oxygen levels.3. Cyclic anoxic periods previously observed during springs and summers were replaced by a persistent period of anoxic conditions in the sediment overlying water. Anoxic conditions were suitable for SRP release from sediments. Heavy cyanobacterial blooms became more persistent, maximum biomass (4229 mm3 L−1) was 30 times larger, the blooms frequently reached 2 m and sometimes the bottom of the reservoir, contrasting to the preremoval period in which it reached at most 1 m deep.4. The long‐term P dynamics in the system, initially driven by allochthonous nutrient loadings were replaced by internal ecological processes. Water hyacinth removal markedly accelerated the process of eutrophication due to internal feedback mechanisms, leading to a switch to a more turbid state. Biological feedback mechanisms were driven by cyanobacterial blooms by enhancing water stability, oxygen anoxia at the bottom and by increasing suitable conditions for P internal loading. These data support the hypothesis of the role of cyanobacterial blooms as an important factor impairing water quality and driving the ecosystem towards a stable degraded state.5. These findings have important implications for the restoration of shallow stratifying eutrophic lakes, as the alternative degraded state is most likely to occur when compared with their non‐stratifying counterparts. Moreover, feedback mechanisms in tropical and subtropical shallow lakes seem to be stronger than in temperate ones, as stratification events are more likely to occur over the year, intensifying system resilience to restorative strategies.
Semi‐arid grazing systems and climate change: a survey of present modelling potential and future needs
Authors: TIETJEN BRITTA , JELTSCH FLORIAN 
Published: February 2007

Summary

Sustainable land use under climate change requires detailed knowledge of the system dynamics. This applies particularly for the management of domestic livestock in semi‐arid and arid grazing systems, where the risk of degradation is high and likely climate change may have a strong impact. A suitable way to assess potential future trends of these complex systems is through the application of simulation models.
We reviewed 41 models published between 1995 and 2005 simulating semi‐arid and arid livestock grazing systems. The models were categorized according to the model aim and type, their temporal and spatial scale, and several indicators of model complexity. Additionally, we developed a list of model requirements for adequately simulating the effects of climate change. Based on these requirements, we evaluated the potential of current models to simulate impacts of climate change and determine important shortcomings.
Three general model types could be distinguished, namely state and transition, difference and differential equation, and rule‐based models. Over time, we found that the number of models aiming to improve management strategies increased, while there were fewer models that aimed to understand system dynamics. This was accompanied by a trend to simplify model descriptions of hydrological relationships.
Important shortcomings of current models included the impact of increased CO2 levels on plant productivity and the ability to resolve changes in intra‐annual precipitation patterns. The consideration of both external drivers is crucial under climate change, hence sustainable long‐term decision making is currently lacking important information.
Synthesis and applications. Sustainable livestock management in semi‐arid and arid systems requires knowledge about effects of future climate change to adjust livestock density adequately. Producers’ experiences from current weather conditions are not necessarily transferable to future conditions, thus models could help to support management. However, an analysis of current models has shown that few existing models are able to assess the impacts of the predicted climate change. Therefore, we call for the development of new dynamic grazing models that provide land managers with the necessary tools to face the threat of future climate changes.
Broad‐ to fine‐scale population genetic patterning in the smallmouth bassMicropterus dolomieuacross the Laurentian Great Lakes and beyond: an interplay of behaviour and geography
Authors: STEPIEN CAROL A. , MURPHY DOUGLAS J. , STRANGE REX MEADE 
Published: February 2007

AbstractAnalysis of population genetic relationships reveals the signatures of current processes such as spawning behaviour and migration, as well as those of historical events including vicariance and climate change. This study examines these signatures through testing broad‐ to fine‐scale genetic patterns among smallmouth bassMicropterus dolomieuspawning populations across their native Great Lakes range and outgroup areas, with fine‐scale concentration in Lake Erie. Our primary hypotheses include whether genetic patterns result from behavioural and/or geographical isolation, specifically: (i) Are spawning groups in interconnected waterways genetically separable? (ii) What is the degree of isolation across and among lakes, basins, and tributaries? (iii) Do genetic divergences correspond to geographical distances? and (iv) Are historical colonization patterns from glacial refugia retained? Variation at eight nuclear microsatellite DNA loci are analysed for 666 smallmouth bass from 28 locations, including 425 individuals in Lake Erie; as well as Lakes Superior, Huron, and Ontario, and outgroups from the Mississippi, Ohio, St. Lawrence, and Hudson River drainages. Results reveal marked genetic differences among lake and river populations, as well as surprisingly high divergences among closely spaced riverine sites. Results do not fit an isolation‐by‐geographical‐distance prediction for fine‐scale genetic patterns, but show weak correspondence across large geographical scales. Genetic relationships thus are consistent with hypotheses regarding divergent origins through vicariance in glacial refugia, followed by colonization pathways establishing modern‐day Great Lakes populations, and maintenance through behavioural site fidelity. Conservation management practices thus should preserve genetic identity and unique characters among smallmouth bass populations.
Urological emergency in neonates with congenital hydronephrosis
Authors: Shimada Kenji , Matsumoto Fumi , Kawagoe Mari , Matsui Futoshi 
Published: February 2007

Objective:  It is well described that unilateral pelviureteric junction obstruction (PUJO) is a benign condition, because the dilatation resolves spontaneously and the function does not decrease in most of the kidneys. However, there is exceptional PUJO that requires emergent treatment in neonatal periods. The aim of this article is to report the urological emergency and management in neonates with PUJO.Materials and Methods:  Nine children (seven boys and two girls) with PUJO who underwent neonatal emergent treatment during the last 13 years were reviewed. Renal function was evaluated according to decay curve of serum creatinine (SCr) levels corresponding to gestational age (GA) at delivery. Physical examination, ultrasonographic monitoring, and chest and abdominal plain radiographs were repeated in each neonate.Results:  Eight patients were detected prenatally. In five patients, multicystic dysplastic kidney (MCDK) was demonstrated on the contralateral side. Three patients underwent percutaneous puncture of fetal hydronephrosis. Decrease of amniotic fluid was evident in three fetuses. Indications for emergent treatment included mass effect from hydronephrosis in three patients, renal dysfunction in five, and severe urinary tract infection in one. During neonatal periods, a percutaneous nephrostomy tube was placed in seven, and open nephrostomy in one with anorectal malformation. Repeated punctures of the dilated renal pelvis were done in one patient. Renal function after pyeloplasty was stable in eight patients, while it was moderately decreased in one who was associated with oligohydramnios in utero.Conclusion:  Indications for emergent treatment in neonates with PUJO included mass effect from giant hydronephrosis, renal dysfunction and severe urinary tract infection. At birth, respiratory and circulatory conditions must first be stabilized. In neonates with hydronephrosis of the solitary kidney or severe bilateral PUJO, serial SCr should be monitored to evaluate renal function. Decrease of amniotic fluid suggested renal functional compromise that would not recover after urological management.