bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applying Modern Error Theory to the Problem of Missed Injuries in Trauma
Authors: Clarke D. L. , Gouveia J. , Thomson S. R. , Muckart D. J. J. 
Published: March 2008

AbstractBackgroundModern theory of human error has helped reduce the incidence of adverse events in commercial aviation. It remains unclear whether these lessons are applicable to adverse events in trauma surgery. Missed injuries in a large metropolitan surgical service were prospectively audited and analyzed using a modern error taxonomy to define its applicability to trauma.MethodsA prospective database of all patients who experienced a missed injury during a 6‐month period in a busy surgical service was maintained from July 2006. A missed injury was defined as one that escaped detection from primary assessment to operative exploration. Each missed injury was recorded and categorized. The clinical significance of the error and the level of physician responsible was documented. Errors were divided into planning or execution errors, acts of omission or commission, or violations, slips, and lapses.ResultsA total of 1,024 trauma patients were treated by the surgical services over the 6‐month period from July to December 2006 in Pietermaritzburg. Thirty‐four patients (2.5%) with missed injuries were identified during this period. There were 29 men and 5 women with an average age of 29 years (range: 21–67 years). In 14 patients, errors were related to inadequate clinical assessment. In 11 patients errors involved the misinterpretation of, or failure to respond to radiological imaging. There were 9 cases in which an injury was missed during surgical exploration. Overall mortality was 27% (9 patients). In 5 cases death was directly attributable to the missed injury. The level of the physicians making the error was consultant surgeon (4 cases), resident in training (15 cases), career medical officer (2 cases), referring doctor (6 cases).ConclusionsMissed injuries are uncommon and are made by all grades of staff. They are associated with increased morbidity and mortality. Understanding the pattern of these errors may help develop error‐reduction strategies. Current taxonomies help in understanding the error process, but efforts must be made to develop innovative mechanisms that reduce the potential for error.
Sexually dimorphic effects of maternal separation stress on corticotrophin‐releasing factor and vasopressin systems in the adult rat brain
Authors: Desbonnet Lieve , Garrett Lillian , Daly Emma , McDermott Kieran W. , Dinan Timothy G. 
Published: March 2008

AbstractNeonatal maternal separation has been widely used to model the well‐established causal relationship between stress in early life and the later development of depression. As corticotrophin‐releasing factor (CRF) and vasopressin (AVP) have been implicated in depression, we aimed to determine the long‐term effects of maternal separation stress on these neuropeptide systems, and also to explore whether these effects are gender‐dependent. Immunohistochemical staining of CRF, AVP and c‐Fos was used to assess whether these neuropeptide systems were affected following an acute swim stress in male and female maternally separated rats.There was an increase in CRF‐immunoreactivity (IR) (p < 0.05), and an increased co‐localisation of c‐Fos and CRF (p < 0.05) following stress, in the paraventricular nucleus of the hypothalamus (PVN) of maternally separated female rats only. We found no differences in CRF in the hypothalamus of maternally separated and control male rats. However, male maternally separated rats exhibited decreases in AVP‐IR in both the non‐stressed and stressed groups relative to controls (p < 0.001). These data provide further evidence of the involvement of the neuropeptides CRF and AVP in the long‐term maladaptive effects of maternal separation stress in early life. The enhanced CRF response to stress in MS females relative to males suggests that maternal separation stress results in a more reactive neuroendocrinological stress system in females, than in males. Furthermore, the sexually dimorphic effects of maternal separation on these neuropeptides indicate that gender is an important factor influencing the trajectory of early life stress effects on CRF and AVP systems in the brain.
Force Microscopy: Applications in Biology and Medicine. Edited by Bhanu P. Jena and J.K. Heinrich Hörber
Authors: Anderson Lloyd L. 
Published: March 2008

Force Microscopy: Applications in Biology and Medicine. Edited by Bhanu P. Jena and J.K. Heinrich Hörber. John Wiley & Sons, Inc., Hoboken, NJ; 2006, 300 pages. ISBN 978-0-471-39628-4The excitement of man's imagination and discovery by the scope of imaging tools, whether tele- or micro-, from 1015 to 10−15 m, ranges from the limits of the known universe to the atomic level. Light and electron microscopy opened vistas of biology and medicine with discovery of the unit of life, the cell and viruses. In the mid-1980s development of scanning probe microscopy allowed studies on live cells at the near-nanometer level. Thus, results from studies using the atomic force microscope (AFM) have given birth to a new field, “NanoCellBiology”, by providing investigators a three-dimensional view of the structure and dynamics of live cells and biomolecules at near-angstrom resolution. Applications of force microscopy to the study of physiological processes of living cells combined with biochemical and molecular biology are yielding rapid advances on how normal and diseased cells function. This exciting book contains 15 chapters by invited experts that examine cell secretory machinery and the discovery of a new cellular structure—the porosome—involved in cell secretion, properties of microbial and cell plant surfaces, cellular interactions of nanodrug delivery systems, intermolecular forces and avidity modulation of leukocyte adhesion molecules, micromechanical properties of lipid bilayers and vesicles, imaging of soft surfaces, high-speed action of biomolecules in motion, cytogenetic applications, and the study of macromolecular interactions in hemostasis and thrombosis.
Assessment of genetic diversity ofGuizotia abyssinica(L.f.) Cass. (Asteraceae) from Ethiopia using amplified fragment length polymorphism
Authors: Geleta Mulatu , Bryngelsson Tomas , Bekele Endashaw , Dagne Kifle 
Published: March 2008

Seventeen populations of niger (Guizotia abyssinica), representing all regions in Ethiopia where this crop is grown, were investigated using the amplified fragment length polymorphism (AFLP) technique, in order to determine the extent and distribution of its genetic diversity. A total of 539 AFLP loci were scored using seven primer combinations applied to 170 individual plants. Of these, 90% were polymorphic and all the individuals investigated were genetically unique. Despite the fact that most of the variation was within populations, populations were differentiated at a significant level (analysis of molecular variance;P < 0.001). There were no significant differences between populations in relation to the extent and altitude of cultivation. A significant positive correlation was revealed between Nei's standard genetic distance and geographic distance. Cluster analysis and principal coordinate analysis revealed that populations from the same regions were clustered together in most cases. Further collection of niger germplasm from areas underrepresented in gene bank collections is recommended.
‘Governance of’ and ‘Governance by’: Implementing a Clinical Governance Framework in an Area Mental Health Service
Authors: O'Connor Nick , Paton Michael 
Published: March 2008

Objective: A framework developed to promote the understanding and application of clinical governance principles in an area mental health service is described. The framework is operationalized through systems, processes, roles and responsibilities. Methods: The development of an explicit and operationalizable framework for clinical governance arose from the authors' experiences in leading and managing mental health services. There is a particular emphasis on improvement of quality of care and patient safety. The framework is informed by recent developments in thinking about clinical governance, including key documents from Australia and the United Kingdom. Results: The operational nature of the framework allows for key components of clinical governance to be described explicitly, communicated effectively, and continually tested and improved. Further consideration and assessment of the value of differing approaches to this task are required. For example, a general, illustrative approach to raise clinician awareness can be contrasted with prescriptive and specified approaches which progressively encompass the many functions and processes of a mental health service. Conclusions: Mental health clinicians and managers can be guided by a framework that will ensure safe, high quality and continually improving processes of care.
Phylogenetic analysis of the endemic New Caledonian cockroach Lauraesilpha. Testing competing hypotheses of diversification
Authors: Murienne J. , Pellens R. , Budinoff R. B. , Wheeler W. C. , Grandcolas P. 
Published: March 2008

AbstractNew Caledonia is a tropical hotspot of biodiversity with high rates of regional and local endemism. Despite offering an ideal setting to study the evolution of endemism, New Caledonia has received little attention compared with the other nearby hotspots, particularly New Zealand. Most studies of the Neocaledonian endemism have been carried out at the regional level, comparing the various groups and species present in New Caledonia but absent in neighboring territories. In addition, remarkably high short‐range endemism has been documented among plants, lizard and invertebrates, although these have usually been done, lacking a phylogenetic perspective. Most studies of Neocaledonian endemism have referred to the geological Gondwanan antiquity of the island and its metalliferous soils derived from ultramafic rocks. Very old clades are thought to have been maintained in refugia and diversified on the metalliferous soils. The present study documents the pattern of diversification and establishment of short‐range endemism in a phylogenetic context using the Neocaledonian cockroach genus Lauraesilpha. Mitochondrial and nuclear genes were sequenced to reconstruct phylogenetic relationships among the species of this genus. These relationships, in the light of the species distribution, do not support the hypothesis that species diversified via an adaptive radiation on metalliferous soils and are not consistent with areas of highest rainfall. Species of Lauraesilpha have similar altitudinal ranges and ecological habits and are short‐range endemics on mountains. What our analysis did reveal was that closely related species are found on nearby or contiguous mountains, and thus these formations probably played the key role establishing short‐range endemism (in association with recent climatic changes).© The Willi Hennig Society 2008.
Unanticipated difficult airway management in anaesthetised patients: a prospective study of the effect of mannequin training on management strategies and skill retention
Authors: Kuduvalli P. M. , Jervis A. , Tighe S. Q. M. , Robin N. M. 
Published: March 2008

SummaryThis prospective study on a medium‐fidelity simulator (SimMan®, Laerdal Medical Corporation, Wappingers Falls, NY, USA) examined the management of unanticipated difficult airway by 21 anaesthetists and the effect of training in this context. There were two scenarios investigated: ‘cannot intubate, can ventilate’(CI) and ‘cannot intubate, cannot ventilate’(CICV). Following initial evaluation, volunteers underwent training in the ‘Difficult Airway Society’ (DAS) algorithms and associated technical skills. At 6–8 weeks and 6–8 months, performance was compared with the initial evaluation. There was a more structured approach following training (p < 0.05), which was sustained at 6–8 months, but only for the CICV scenario (p < 0.01). In CI, use of standard and intubating laryngeal mask airway increased following training (p = 0.021). This was sustained over time (p = 0.01). In both scenarios there was a reduced incidence of equipment misuse (p < 0.0005), which was sustained over time (p < 0.0001). We conclude that simulation‐based training significantly improves performance for at least 6–8 weeks. Training should be repeated at intervals of 6 months or less.
Effects of methylene blue on propofol requirement during anaesthesia induction and surgery
Authors: Licker M. , Diaper J. , Robert J. , Ellenberger C. 
Published: March 2008

SummaryDelayed emergence from anaesthesia and neurological disturbances have been reported in patients undergoing parathyroidectomy who received methylene blue (MB) pre‐operatively. We hypothesised that MB would decrease propofol requirements. The Bispectral index (BIS) and a target‐controlled infusion of propofol were used in two groups of 11 matched patients. Patients in one group were pretreated with MB. During induction, clinical sedation scores and BIS values were significantly lower at the predicted effect‐site propofol concentration of 2 μg.ml−1 in the MB compared with the control group. Intra‐operatively, although similar BIS values were achieved in the two groups, patients pretreated with MB required a mean 50% lower dose of propofol compared with controls. In view of these findings, care should be taken to ensure an adequate depth of anaesthesia by titrating the administration of anaesthetic agents whenever MB is infused peri‐operatively.
The effect of bolus administration of remifentanil on QTc interval during induction of sevoflurane anaesthesia
Authors: Kweon T. D. , Nam S. B. , Chang C. H. , Kim M. S. , Lee J. S. , Shin C. S. , June D. B. , Han D. W. 
Published: March 2008

SummaryStimulation of the sympathetic nervous system associated with tracheal intubation causes corrected QT (QTc) interval prolongation. We postulated that the use of remifentanil during induction of anaesthesia might prevent this. Sixty unpremedicated, ASA grade 1 patients were selected and randomly allocated to receive either saline (group S), remifentanil 0.5 μg.kg−1 (group R 0.5) or remifentanil 1.0 μg.kg−1 (group R1.0) 1 min before laryngoscopy. The QTc interval was significantly prolonged immediately following intubation in group S and group R0.5, but it remained stable in group R1.0, compared with the QTc interval just before laryngoscopy. It is concluded that the administration of remifentanil 1.0 μg.kg−1 before intubation can prevent the prolongation of the QTc interval associated with tracheal intubation during induction of anaesthesia with sevoflurane.
In vivo visualization of donepezil binding in the brain of patients with Alzheimer's disease
Authors: Okamura Nobuyuki , Funaki Yoshihito , Tashiro Manabu , Kato Motohisa , Ishikawa Yoichi , Maruyama Masahiro , Ishikawa Hiroyasu , Meguro Kenichi , Iwata Ren , Yanai Kazuhiko 
Published: March 2008

What is already known about this subject • Deficit in central cholinergic neurotransmission is a consistent change associated with Alzheimer's disease (AD).• Donepezil hydrochloride exhibits selective inhibition of acetylcholinesterase (AChE) and is widely used for the treatment of AD.• The biodistribution of donepezil in the brain after administration is not precisely understood in vivo.• There is no method to measure the amount of binding of orally administered donepezil to AChE. What this study adds • This study clearly visualizes the distribution of donepezil in human brain using [11C]‐donepezil and positron emission tomography.• This study demonstrates prominent reduction of the donepezil binding site in the AD brain.• This study provides methodology to measure the AChE binding occupancy of orally administered donepezil and provides a new surrogate marker for evaluation and prediction of response to donepezil treatment.AimsThe aims of this study were to visualize in vivo binding of donepezil to acetylcholinesterase (AChE) in the brain and to establish a method for measuring the amount of binding of orally administered donepezil.Methods[5‐11C‐methoxy]‐donepezil ([11C]‐donepezil) was radiolabelled as a positron emission tomography (PET) tracer. The biodistribution of [11C]‐donepezil was measured by PET in 10 AD patients and six elderly normal subjects. Two AD patients underwent additional PET measurements after oral administration of donepezil for 6 months.Results[11C]‐donepezil‐PET images demonstrated high densities of tracer distribution in AChE‐rich brain regions such as the striatum, thalamus, and cerebellum. Compared with elderly normal subjects, patients with mild AD exhibited about 18–20% reduction of donepezil binding in the neocortex and hippocampus, while patients with moderate AD exhibited about 24–30% reduction of donepezil binding throughout the brain. Orally administered donepezil (5 mg day−1) induced 61.6–63.3% reduction of donepezil binding in AD brains. The distribution volume of [11C]‐donepezil in the hippocampus was significantly correlated with MMSE scores in AD patients.Conclusions[11C]‐donepezil‐PET enables quantitative measurement of donepezil binding in the brain. AD patients exhibited reduction of donepezil binding in the brain, even in the early stage of disease. Longitudinal evaluation by this technique enables determination of AChE binding occupancy of orally administered donepezil.
Assessment of the pharmacokinetics, safety and tolerability of maraviroc, a novel CCR5 antagonist, in healthy volunteers
Authors: Abel Samantha , Van Der Ryst Elna , Rosario Maria C. , Ridgway Caroline E. , Medhurst Christine G. , Taylor‐Worth Richard J. , Muirhead Gary J. 
Published: March 2008

AIMSTo evaluate the pharmacokinetics, safety and tolerability of single and multiple oral doses of maraviroc in healthy volunteers.METHODSThree double‐blind, placebo‐controlled, dose‐escalation studies with either single or multiple doses of maraviroc were conducted in healthy volunteers. Plasma and urine samples were collected to investigate the pharmacokinetics of maraviroc and evaluate any changes with respect to dose and duration/frequency of dosing. Safety and toleration of maraviroc were also assessed.RESULTSMaraviroc is rapidly absorbed following oral administration, and plasma Tmax is achieved within 0.5–4.0 h postdose. Steady‐state plasma concentrations are achieved after 7 consecutive days of dosing. Although the pharmacokinetics of maraviroc is nonproportional over the dose range studied (3–1200 mg), the degree of nonproportionality is small at clinically relevant doses. Renal clearance is approximately 10–12 l h−1 and appears unaffected by increasing maraviroc doses. Maraviroc does not significantly modulate the activity of CYP2D6 or CYP3A4 at clinically relevant doses. There were no serious adverse events in any of these studies, and doses up to 900 mg were generally well tolerated, with postural hypotension being the dose‐limiting event. There was no pattern or dose relationship observed with maraviroc with regard to laboratory abnormalities, including hepatic transaminases. No clinically significant increases in QTc were noted at clinically relevant doses.CONCLUSIONSMaraviroc is absorbed into the systemic circulation and reaches steady state by day 7 of multiple dosing. It does not significantly influence the activity of major drug‐metabolizing enzymes and is well tolerated at clinically relevant doses, with most adverse events being mild or moderate.
The effects of cotrimoxazole or tenofovir co‐administration on the pharmacokinetics of maraviroc in healthy volunteers
Authors: Abel Samantha , Russell Deborah , Whitlock Lyndsey A. , Ridgway Caroline E. , Muirhead Gary J. 
Published: March 2008

AIMSTo assess the potential of cotrimoxazole and tenofovir, drugs which are inhibitors and/or substrates of renal transporters, to alter the pharmacokinetic profile of maraviroc.METHODSTwo randomized, placebo‐controlled, two‐way crossover studies were conducted in healthy male and female subjects. In study 1, 16 subjects, aged 18–45 years, received maraviroc (300 mg b.i.d.) with and without cotrimoxazole (960 mg b.i.d.; 160 mg trimethoprim and 800 mg sulfamethoxazole). In study 2, 12 subjects, aged 21–45 years, received maraviroc (300 mg b.i.d.) with and without tenofovir (300 mg q.d.). For study 1, blood was collected predose and on days 1–7. In study 2, blood was collected predose, on day 1 and days 3–7. In both studies, blood was collected at intervals up to 12 h postdose on day 7. Urine was collected on day 7, 0–12 h post morning dose. Blood and urine were analysed for maraviroc using liquid chromatography/tandem mass spectrometry.RESULTSThe geometric mean ratios for Cmax and AUC12 were 119% and 111%, respectively, for maraviroc plus cotrimoxazole and 104% and 103%, respectively, for maraviroc plus tenofovir, compared with maraviroc plus placebo. Renal clearance of maraviroc plus placebo was 8.3 l h−1 and 8.5 l h−1 and was 7.8 l h−1 for maraviroc plus cotrimoxazole and maraviroc plus tenofovir. There were no serious or severe adverse events or any clinically significant changes in laboratory tests, blood pressure, or electrocardiograms.CONCLUSIONSNeither cotrimoxazole nor tenofovir caused a clinically significant effect on the pharmacokinetics of maraviroc. Maraviroc 300 mg b.i.d. was well tolerated when co‐administered with either cotrimoxazole or tenofovir.
Population pharmacokinetic/ pharmacodynamic analysis of CCR5 receptor occupancy by maraviroc in healthy subjects and HIV‐positive patients
Authors: Rosario Maria C. , Jacqmin Philippe , Dorr Pat , James Ian , Jenkins Timothy M. , Abel Samantha , Van Der Ryst Elna 
Published: March 2008

BACKGROUNDMaraviroc, a noncompetitive antagonist of the CCR5 coreceptor, was recently approved in the USA as a treatment of HIV infection. For antiretroviral agents that target the virus, antiviral effect can be related to some extent to plasma drug concentrations. For CCR5 antagonists that target the host cells, receptor occupancy in vivo might be a better predictor of efficacy.AIMSTo develop a population pharmacokinetic (PK)–pharmacodynamic (PD) model that describes CCR5 receptor occupancy by maraviroc after oral administration at different doses in healthy volunteers and HIV‐positive patients and to assess the relevance of receptor occupancy in predicting the decrease in viral load (HIV‐1 RNA copies ml−1) in HIV‐positive patients.METHODSReceptor occupancy data from 88 individuals enrolled in two multiple dose trials were included in the population PK–receptor binding model. Out of the 88 individuals, 25 were HIV‐1‐infected patients and had viral load measurements, whereas the remaining 63 were healthy volunteers. Doses ranged from 3 mg b.i.d. to 600 mg q.d. A previously published PK–PD disease model describing the effect of maraviroc on the viral load was updated by replacing its PD module by the receptor occupancy model. Simulated viral load–time profiles with the updated model were compared with the profiles observed in patients.RESULTSThe majority of measured plasma concentrations were associated with receptor occupancy ≥50% even at the lowest dose of 3 mg b.i.d. A simple direct Emax model appeared to describe satisfactorily the PK–receptor occupancy relationship. The estimated KD was around 0.0894 ng ml−1, far below the operational in vivo antiviral IC50 of 8 ng ml−1. Accordingly, simulations led to marked overprediction of the decrease in viral load–time profiles.CONCLUSIONSMaraviroc receptor occupancy close to the maximum is required to induce a significant decrease in viral load, indicating that in vivo CCR5 receptor occupancy by maraviroc is not a direct measure of drug inhibitory activity. Considering the imprecision of the measurement in the upper flat part of the maraviroc concentration vs. percent CCR5 occupancy curve, it can reasonably be concluded that routine monitoring of receptor occupancy as a biomarker for maraviroc efficacy will not be helpful. Based on this analysis, it was decided not to use receptor occupancy as a biomarker of viral load inhibition during the development of CCR5 antagonist compounds.