bluuebunny/crossref_metadata_2025 huggingface dataset:
Bayesian rule learning for biomedical data mining
Authors: Gopalakrishnan Vanathi , Lustgarten Jonathan L. , Visweswaran Shyam , Cooper Gregory F.
Published: January 2010

Motivation: Disease state prediction from biomarker profiling studies is an important problem because more accurate classification models will potentially lead to the discovery of better, more discriminative markers. Data mining methods are routinely applied to such analyses of biomedical datasets generated from high-throughput ‘omic’ technologies applied to clinical samples from tissues or bodily fluids. Past work has demonstrated that rule models can be successfully applied to this problem, since they can produce understandable models that facilitate review of discriminative biomarkers by biomedical scientists. While many rule-based methods produce rules that make predictions under uncertainty, they typically do not quantify the uncertainty in the validity of the rule itself. This article describes an approach that uses a Bayesian score to evaluate rule models.

Results: We have combined the expressiveness of rules with the mathematical rigor of Bayesian networks (BNs) to develop and evaluate a Bayesian rule learning (BRL) system. This system utilizes a novel variant of the K2 algorithm for building BNs from the training data to provide probabilistic scores for IF-antecedent-THEN-consequent rules using heuristic best-first search. We then apply rule-based inference to evaluate the learned models during 10-fold cross-validation performed two times. The BRL system is evaluated on 24 published ‘omic’ datasets, and on average it performs on par or better than other readily available rule learning methods. Moreover, BRL produces models that contain on average 70% fewer variables, which means that the biomarker panels for disease prediction contain fewer markers for further verification and validation by bench scientists.

Contact:  vanathi@pitt.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
PSiFR: an integrated resource for prediction of protein structure and function
Authors: Pandit Shashi B. , Brylinski Michal , Zhou Hongyi , Gao Mu , Arakaki Adrian K. , Skolnick Jeffrey
Published: January 2010

Summary: In the post-genomic era, the annotation of protein function facilitates the understanding of various biological processes. To extend the range of function annotation methods to the twilight zone of sequence identity, we have developed approaches that exploit both protein tertiary structure and/or protein sequence evolutionary relationships. To serve the scientific community, we have integrated the structure prediction tools, TASSER, TASSER-Lite and METATASSER, and the functional inference tools, FINDSITE, a structure-based algorithm for binding site prediction, Gene Ontology molecular function inference and ligand screening, EFICAz2, a sequence-based approach to enzyme function inference and DBD-hunter, an algorithm for predicting DNA-binding proteins and associated DNA-binding residues, into a unified web resource, Protein Structure and Function prediction Resource (PSiFR).

Availability and implementation: PSiFR is freely available for use on the web at http://psifr.cssb.biology.gatech.edu/

Contact:  skolnick@gatech.edu
Active site prediction using evolutionary and structural information
Authors: Sankararaman Sriram , Sha Fei , Kirsch Jack F. , Jordan Michael I. , Sjölander Kimmen
Published: January 2010

Motivation: The identification of catalytic residues is a key step in understanding the function of enzymes. While a variety of computational methods have been developed for this task, accuracies have remained fairly low. The best existing method exploits information from sequence and structure to achieve a precision (the fraction of predicted catalytic residues that are catalytic) of 18.5% at a corresponding recall (the fraction of catalytic residues identified) of 57% on a standard benchmark. Here we present a new method, Discern, which provides a significant improvement over the state-of-the-art through the use of statistical techniques to derive a model with a small set of features that are jointly predictive of enzyme active sites.

Results: In cross-validation experiments on two benchmark datasets from the Catalytic Site Atlas and CATRES resources containing a total of 437 manually curated enzymes spanning 487 SCOP families, Discern increases catalytic site recall between 12% and 20% over methods that combine information from both sequence and structure, and by ≥50% over methods that make use of sequence conservation signal only. Controlled experiments show that Discern's improvement in catalytic residue prediction is derived from the combination of three ingredients: the use of the INTREPID phylogenomic method to extract conservation information; the use of 3D structure data, including features computed for residues that are proximal in the structure; and a statistical regularization procedure to prevent overfitting.

Contact:  kimmen@berkeley.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Faster computation of exact RNA shape probabilities
Authors: Janssen Stefan , Giegerich Robert
Published: January 2010

Motivation: Abstract shape analysis allows efficient computation of a representative sample of low-energy foldings of an RNA molecule. More comprehensive information is obtained by computing shape probabilities, accumulating the Boltzmann probabilities of all structures within each abstract shape. Such information is superior to free energies because it is independent of sequence length and base composition. However, up to this point, computation of shape probabilities evaluates all shapes simultaneously and comes with a computation cost which is exponential in the length of the sequence.

Results: We device an approach called RapidShapes that computes the shapes above a specified probability threshold T by generating a list of promising shapes and constructing specialized folding programs for each shape to compute its share of Boltzmann probability. This aims at a heuristic improvement of runtime, while still computing exact probability values.

Conclusion: Evaluating this approach and several substrategies, we find that only a small proportion of shapes have to be actually computed. For an RNA sequence of length 400, this leads, depending on the threshold, to a 10–138 fold speed-up compared with the previous complete method. Thus, probabilistic shape analysis has become feasible in medium-scale applications, such as the screening of RNA transcripts in a bacterial genome.

Availability:  RapidShapes is available via http://bibiserv.cebitec.uni-bielefeld.de/rnashapes

Contact:  robert@techfak.uni-bielefeld.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
“This Astounding Car for $1,500”: The Year Automobile Advertising Came of Age
Authors: Schorman Rob
Published: January 2010

In 1906, a writer declared that it remained an “unsolved problem whether the automobile is to prove a fad like the bicycle, or a lasting factor in the industry of the country.” A few years later, concerned with the possibility of overproduction and market saturation, auto executives and other commentators were writing articles for the advertising trade press with titles like “Why Auto Production Must Be Curtailed” and “The Fading of the Automobile Rainbow.” Considering that by the early twenty-first century, the United States had a population of nearly 300 million people and an average of 2.1 registered motor vehicles per household, it is difficult to appreciate how uncertain the industry’s status seemed in its early years. Yet although contemporary observers may not have known it, in many ways by the end of 1908 the foundation stoneswere already in place for a hundred years of automotive economic and cultural preeminence in the United States. Two events from that year are well known as harbingers of the industry’s future. In September, General Motors was established, and in October, Ford introduced its Model T to the nation's auto dealers. In time, these developments had a profound impact on American automobile manufacture and management.
The dynamic assessment of right‐ventricular function and its relation to exercise capacity in heart failure
Authors: Rubiś Paweł , Podolec Piotr , Kopeć Grzegorz , Olszowska Maria , Tracz Wiesława
Published: January 2010

Aims

To evaluate right‐ventricular (RV) function during stress echocardiography (SE) and to assess its relationship with exercise capacity in heart failure (HF) patients.

Methods and results

We included 88 patients aged 60.9 ± 11.2 years with a mean LVEF of 27.2 ± 9.5%. The following RV parameters were measured at baseline and peak exercise during semi‐supine SE: velocity (IVV) and acceleration during isovolumic contraction (IVA), S′, E′, A′, and ratio of early diastolic tricuspid velocity to E′ (E/E′) and longitudinal strain and strain rate. Patients were stratified into two groups according to their VO2peak values: group 1 (n = 35) with VO2peak <14 mL/kg/min and group 2 (n = 53) with VO2peak ≥14 mL/kg/min. At rest, all analysed variables were similar in the two groups, but during stress IVV, S′, and E′ were significantly higher and the E/E′ ratio significantly lower in group 2. In broad terms, parameters measured at stress correlated much better with VO2peak than parameters assessed at baseline. However, results of multivariable analysis determined that the independent predictors of VO2peak were solely the left‐ventricular (LV) parameters: E/E′ and S′.

Conclusions

Right‐ventricular function (whether at rest or during stress tests) was not significantly associated with exercise capacity in our patients with HF. In contrast, systolic and, to a greater extent, diastolic LV parameters during the stress tests emerged as the most important indicators linked to exercise capacity in HF.
Menorrhagia
Authors: Bond Ruth
Published: January 2010

Menstrual problems are a common experience for most women and the majority of women suffering with menorrhagia can be managed in primary care. The GP curriculum requires GP trainees to have a solid knowledge base on common menstrual disorders. It is essential to be able to differentiate a history consistent with benign menstrual disorders, like fibroids or dysfunctional uterine bleeding, and symptoms which may suggest more significant pathology such as malignancy. GPs should know how to examine and investigate patients with menorrhagia and treat appropriately. This article summarizes examination, investigation and management.
Polycystic Ovarian Syndrome
Authors: Harding Emma
Published: January 2010

Polycystic ovarian syndrome (PCOS) was first recognized by Drs Stein and Leventhal in 1935. It is a common but poorly understood complex endocrine disorder clinically associated with infertility, hyperandrogenism and oligomenorrhoea. The UK prevalence is around 6–7%. 20% of women in the UK have polycystic ovaries on ultrasound without clinical features of PCOS and of those attending infertility clinics with anovulation, 90% have features of PCOS. It is therefore important for a GP to be able to recognize PCOS and approach treatment holistically as the condition has implications for a woman's menstrual and reproductive life, physical appearance and long-term health.
A Practice Audit of Diabetic Retinal Screening
Authors: Khan Bilal
Published: January 2010

Ongoing monitoring by a practice of its standard of care and willingness to make changes is a fundamental part of good practice. One method of doing this is through audit.
Crying Babies
Authors: Batchat Lara
Published: January 2010

Persistent crying at the start of life is a common problem and has been reported by approximately 20% of parents. In most cases, no organic cause is found, and crying improves by around 3–4 months. This article will describe the causes and management of persistent crying, or ‘colic’, in the first 3 months of life.
Enuresis
Authors: Watson Laura
Published: January 2010

Enuresis is defined as the uncontrolled or involuntary passage of urine by day, by night or both, in a child aged 5 years or older, in the absence of physical disease. The most common form is nocturnal enuresis or bedwetting. This is a lack of night-time bladder control and accounts for 85% of people with enuresis. Daytime enuresis is rarer but is important to identify as the causes and management can differ. This article aims to provide an overview of enuresis and its management in primary care.
Head Lice Infestation
Authors: Mirza Aslan , Shamsi Aamir
Published: January 2010

Head lice infestation results from colonization of hairy skin by Pediculus capitis, a wingless blood-feeding parasite of the order Phthiraptera. Head lice remain a significant problem as they may cause intense pruritus, and infestation is socially and psychologically stigmatizing. The prevalence of infestations has been increasing and is higher in children aged 4–11 years, in parents of young children and in urban areas. This possibly results from an increase in social mixing and movement around the country. Over a third of children in the United Kingdom will host head lice during any year and surveys show that one to two of every 10 children have head lice at any one point in time. This article aims to provide an overview of head lice infestation and its management in primary care.
Infertility
Authors: Seepana Sreekala , Allamsetty Sudhakar
Published: January 2010

Infertility affects one in seven couples in the western world and this figure may rise as more women are delaying parenthood. It is a major cause of psychological and marital stress and, hence, deserves to be managed as a disease entity along with more traditionally recognized diseases. This article deals with the causes of both male and female infertility, initial assessment and investigations for the couple along with general advice to help them conceive in the primary care. Further assessment and investigations should be undertaken in a dedicated infertility clinic either at secondary or tertiary level.
Redox Balance and Cellular Inflammation in the Diaphragm, Limb Muscles, and Lungs of Mechanically Ventilated Rats
Authors: Marín-Corral Judith , Martínez-Caro Leticia , Lorente José A. , de Paula Marta , Pijuan Lara , Nin Nicolas , Gea Joaquim , Esteban Andrés , Barreiro Esther
Published: January 2010

Background

High tidal volume (VT) mechanical ventilation was shown to induce organ injury other than lung injury and systemic inflammation in animal models of ventilator-induced lung injury. The authors aimed to explore whether high VT mechanical ventilation per se induces early oxidative stress and inflammation in the diaphragm, limb muscles, and lungs of healthy rats exposed to ventilator-induced lung injury.

Methods

Protein carbonylation and nitration, antioxidants (immunoblotting), and inflammation (immunohistochemistry) were evaluated in the diaphragm, gastrocnemius, soleus, tibialis anterior, and lungs of mechanically ventilated healthy rats and in nonventilated control animals (n = 8/group) for 1 h, using two different strategies (moderate VT [VT = 9 ml/kg] and high VT [VT = 35 ml/kg]).

Results

The main findings are summarized as follows: compared with controls, (1) the diaphragms and gastrocnemius of high-VT rats exhibited a decrease in reactive carbonyls, (2) the soleus and tibialis of high- and moderate-VT rodents showed a reduction in reactive carbonyls and malondialdehyde-protein adducts, (3) the lungs of high-VT rats exhibited a significant rise in malondialdehyde-protein adducts, (4) the soleus and tibialis of both high- and moderate-VT rats showed a reduction in protein nitration, (5) the lungs of high- and moderate-VT rats showed a reduction in antioxidant enzyme levels, but not in the muscles, and (6) the diaphragms and gastrocnemius of all groups exhibited very low inflammatory cell counts, whereas the lungs of high-VT rats exhibited a significant increase in inflammatory infiltrates.

Conclusions

Although oxidative stress and inflammation increased in the lungs of rats exposed to high VT, the diaphragm and limb muscles exhibited a decline in oxidative stress markers and very low levels of cellular inflammation.
Persistent Cortical Blindness after a Thoracic Epidural Test Dose of Bupivacaine
Authors: Visser W Anton , Kolling Joy Bach , Groen Gerbrand J. , Tetteroo Eric , van Dijl Ron , Rosseel Peter M. J. , van der Meer Nardo J. M.
Published: January 2010

Thoracic epidural anesthesia is considered as an essential component of the perioperative care for patients undergoing lung resection. Although neurologic adverse events have been associated with this technique, permanent injury is rare. These events primarily involve the peripheral nervous system; for example, nerve root injury. We present a case of persistent cortical blindness after a test dose of bupivacaine was administered into an uneventfully placed thoracic epidural catheter.
Ultrasound Imaging for Regional Anesthesia in Infants, Children, and Adolescents
Authors: Tsui Ban C. H. , Suresh Santhanam , Warner David S.
Published: January 2010

The use of ultrasound guidance has provided an opportunity to perform many peripheral nerve blocks that would have been difficult to perform in children based on pure landmark techniques due to the potential for injection into contiguous sensitive vascular areas. This review article provides the readers with techniques on ultrasound-guided peripheral nerve blocks of the extremities and trunk with currently available literature to substantiate the available evidence for the use of these techniques. Ultrasound images of the blocks with corresponding line diagrams to demonstrate the placement of the ultrasound probe have been provided for all the relevant nerve blocks in children. The authors hope that this review will stimulate further research into ultrasound-guided regional anesthesia in infants, children, and adolescents and stimulate more randomized controlled trials to provide a greater understanding of the anatomy and physiology of regional anesthesia in pediatrics.
Brainstem Regions Affecting Minimum Alveolar Concentration and Movement Pattern during Isoflurane Anesthesia
Authors: Jinks Steven L. , Bravo Milo , Satter Omar , Chan Yuet-Ming
Published: January 2010

Background

Spinal transection or selective delivery of volatile anesthetics to the spinal cord reduces minimum alveolar concentration (MAC), whereas precollicular decerebration does not. The authors sought to determine which brainstem regions influence anesthetic requirements and movement responses with isoflurane.

Methods

Movement (biceps femoris electromyogram) and MAC were measured in adult rats before and after decerebration at the precollicular, mid-collicular, pontine or medullary level, or decerebellation. Additional experiments assessed the effects of lidocaine inactivation of the mesencephalic locomotor region on MAC and the effects of isoflurane on nociceptive neuronal responses in this region.

Results

Transections placed at the level of the mid-colliculus, rostral pons, and pontomedullary junction significantly reduced MAC by approximately 10, 40, and 45%, respectively. MAC was decreased 9% after mid-medullary transections that were placed caudal to the nucleus raphe magnus but rostral to the dorsal reticular nucleus; however, only weak, single movements occurred. Caudal medullary transections at the obex decreased MAC by 60%. Bilateral inactivation of the mesencephalic locomotor region with lidocaine caused a reversible, 32% decrease in MAC and reduced the number and amplitude of movements at sub-MAC isoflurane concentrations. Neuronal responses of mesencephalic locomotor region neurons to supramaximal noxious tail clamp were reduced by 87% by 1.2 MAC isoflurane.

Conclusions

The authors conclude that the mesencephalic locomotor region influences anesthetic requirements and promotes repetitive movement with sub-MAC isoflurane by facilitating ventral spinal locomotor circuits, where anesthetics seem to exert their key immobilizing effects. However, net brainstem influences on MAC seem to result from interaction among descending nociceptive and locomotor modulatory pathways.
Perioperative Tobacco Interventions by Chinese Anesthesiologists
Authors: Shi Yu , Yu Chunhua , Luo Ailun , Huang Yuguang , Warner David O.
Published: January 2010

Background

The prevalence of cigarette smoking in China is high. Surgery provides an excellent opportunity for patients to quit smoking, and anesthesiologists can play an important role in tobacco control. However, little is known about the practices, knowledge, and attitudes of Chinese anesthesiologists regarding perioperative tobacco interventions.

Methods

Chinese anesthesiologists were surveyed at a national meeting in 2009, with written questionnaires distributed to 800 practicing anesthesiologists.

Results

The survey response rate was 60.3%, and 10% of respondents themselves smoked cigarettes. Most (73%) of them frequently or almost always asked about smoking status; 51% advised about the health risk of tobacco use; and 60% advised patients to quit. Compared with nonsmokers, smokers were significantly less likely to advise about the health risks of smoking and quitting. A high proportion of respondents had accurate perceptions of perioperative and long-term health risks of smoking. Although most respondents agreed that advising patients to quit is the responsibility of anesthesiologists and the perioperative period is a good time to help patients quit smoking, few knew how to counsel about smoking or help patients get the help they needed to quit. Nonetheless, most of the respondents were willing to learn about perioperative interventions and spend an extra 5 min to help patients quit smoking.

Conclusions

Given their adequate knowledge of health risks of smoking, strong perception of responsibilities, and willingness to participate in tobacco control, Chinese anesthesiologists are poised to play a significant role in tobacco control in China that could improve perioperative outcomes and promote long-term health.
Propofol Anesthesia Significantly Alters Plasma Blood Levels of Melatonin in Rats
Authors: Dispersyn Garance , Pain Laure , Touitou Yvan
Published: January 2010

Background

General anesthesia combined with surgery has been shown to decrease the nocturnal peak of melatonin in patients. However, the role of anesthesia itself on melatonin secretion remains unknown. We previously showed that anesthesia induced by propofol modifies the circadian time structure in both rats and humans and phase advances the circadian rest-activity rhythm in rats. In this study, we examined the secretion of melatonin during 24 h after a 30-min propofol anesthesia in rats.

Methods

Rats were exposed to 12-h light/12-h dark alteration conditions and anesthetized with propofol (120 mg/kg intraperitoneally) around their peak of melatonin secretion (Zeitgeber time 16). Trunk blood samples were collected at seven subsequent Zeitgeber times to assess the effects of propofol on circadian melatonin secretion.

Results

Propofol modifies the peripheral melatonin by significantly decreasing its concentration ( approximately 22-28%) during the immediate 3 h after the wake up from anesthesia and then significantly increasing melatonin secretion 20 h after anesthesia ( approximately 38%). Cosinor analysis suggests that propofol induces a phase advance of the circadian secretion of peripheral melatonin.

Conclusions

The results demonstrate the disturbing effects of propofol anesthesia on the circadian rhythm of plasma melatonin in rats under normal light conditions. These results parallel the desynchronization of the circadian rhythms of locomotor activity and temperature previously observed after propofol anesthesia.
Comparison of Single-use and Reusable Metal Laryngoscope Blades for Orotracheal Intubation during Rapid Sequence Induction of Anesthesia
Authors: Amour Julien , Manach Yannick Le , Borel Marie , Lenfant François , Nicolas-Robin Armelle , Carillion Aude , Ripart Jacques , Riou Bruno , Langeron Olivier
Published: January 2010

Background

Single-use metal laryngoscope blades are cheaper and carry a lower risk of infection than reusable metal blades. The authors compared single-use and reusable metal blades during rapid sequence induction of anesthesia in a multicenter cluster randomized trial.

Methods

One thousand seventy-two adult patients undergoing general anesthesia under emergency conditions and requiring rapid sequence induction were randomly assigned on a weekly basis to either single-use or reusable metal blades (cluster randomization). After induction, a 60-s period was allowed to complete intubation. In the case of failed intubation, a second attempt was performed using the opposite type of blade. The primary endpoint was the rate of failed intubation, and the secondary endpoints were the incidence of complications (oxygen desaturation, lung aspiration, and/or oropharynx trauma) and the Cormack and Lehane score.

Results

Both groups were similar in their main characteristics, including the risk factors for difficult intubation. The rate of failed intubation was significantly decreased with single-use metal blades at the first attempt compared with reusable blades (2.8 vs. 5.4%, P < 0.05). In addition, the proportion of grades III and IV in Cormack and Lehane score were also significantly decreased with single-use metal blades (6 vs. 10%, P < 0.05). The global complication rate did not reach statistical significance, although the same trend was noted (6.8% vs. 11.5%, P = not significant). An investigator survey and a measure of illumination pointed that illumination might have been responsible for this result.

Conclusions

The single-use metal blade was more efficient than a reusable metal blade in rapid sequence induction of anesthesia.
Estrogen Is Renoprotective via a Nonreceptor-dependent Mechanism after Cardiac Arrest In Vivo
Authors: Hutchens Michael P. , Nakano Takaaki , Kosaka Yasuharu , Dunlap Jennifer , Zhang Wenri , Herson Paco S. , Murphy Stephanie J. , Anderson Sharon , Hurn Patricia D.
Published: January 2010

Background

Severe ischemia induces renal injury less frequently in women than men. In this study, cardiac arrest and cardiopulmonary resuscitation were used to assess whether estradiol is renoprotective via an estrogen receptor (ER)-dependent mechanism.

Materials and Methods

Male and female C57BL/6 and ER gene-deleted mice underwent 10 min of cardiac arrest followed by cardiopulmonary resuscitation. Serum chemistries and renal stereology were measured 24 h after arrest.

Results

Estrogen did not affect mean arterial pressure, regional renal cortical blood flow, and arterial blood gases. Hence, female kidneys were protected (mean +/- SEM: blood urea nitrogen, 65+/- 21 vs.149+/- 27 mg/dl, P = 0.04; creatinine, 0.14 +/- 0.05 vs. 0.73 +/- 0.16 mg/dl, P = 0.01; volume of necrotic tubules, 7 +/- 1% vs. 10 +/- 0%, P = 0.04). Estrogen also reduced renal injury. In intact females (n = 5), ovariectomized/vehicle-treated (n = 8), and ovariectomized/estrogen-treated (n = 8) animals, blood urea nitrogen was 65 +/- 21, 166 +/- 28, and 50 +/- 14 mg/dl (P = 0.002); creatinine was 0.14 +/- 0.05, 0.74 +/- 0.26, and 0.23 +/- 0.27 mg/dl (P = 0.014); necrotic tubules were 2.5 +/- 0.25%, 12.0 +/- 1.9%, and 5.0 +/- 1.6% (P = 0.004), respectively. In ER-[alpha] and ER-[beta] gene-deleted mice and controls estradiol-reduced functional injury (blood urea nitrogen: estradiol 117 +/- 71, vehicle 167 +/- 56, P = 0.007; creatinine: estradiol 0.5 +/- 0.5, vehicle 1.0 +/- 0.4, P = 0.013), but the effect of estradiol was not different between ER-[alpha] or ER-[beta] gene-deleted mice. Adding ICI 182,780 to estradiol did not alter injury.

Conclusions

In women, kidneys were protected from cardiac arrest through estrogen. Estradiol-mediated renoprotection was not affected by ER deletion or blockade. Estradiol is renoprotective after cardiac arrest. The results indicate that estradiol renoprotection is ER-[alpha] and ER-[beta] independent.
Adverse Events with Medical Devices in Anesthesia and Intensive Care Unit Patients Recorded in the French Safety Database in 2005–2006
Authors: Beydon Laurent , Ledenmat Pierre Yves , Soltner Christophe , Lebreton Frédéric , Hardin Vincent , Benhamou Dan , Clergue François , Laguenie Gérard
Published: January 2010

Background

French regulations require that adverse events involving medical devices be reported to the national healthcare safety agency. The authors evaluated reports made in 2005-2006 for patients in anesthesiology and critical care.

Methods

For each type of device, the authors recorded the severity and cause of the event and the manufacturer's response where relevant. The authors compared the results with those obtained previously from the reports (n = 1,004) sent in 1998 to the same database.

Results

The authors identified 4,188 events, of which 91% were minor, 7% severe, and 2% fatal. The cause was available for 1,935 events (46%). Faulty manufacturing was the main cause of minor events. Inappropriate use was the cause in a significantly larger proportion of severe events than minor events (P < 0.001) and was usually considered preventable via improved knowledge or device verification before use. Compared to with that in 1998, the annual number of reported events doubled and the rate of severe events decreased slightly (12-10%, P = 0.03). The rate of events related to manufacturing problems remained stable (59-60%, P = nonsignificant), and the rate of events caused by human errors was 32-42% (P = 0.01). There were no changes in the mortality rate (2% in both studies).

Conclusions

The number of adverse events related to medical devices indicates a need for greater attention to these complex pieces of equipment that can suffer from faulty design and manufacturing and from inappropriate use. Improvements in clinician knowledge of medical devices, and to a lesser extent improvement in manufacturing practices, should improve safety.
Comparison of Anesthetic Depth Indexes Based on Thalamocortical Local Field Potentials in Rats
Authors: Silva Aura , Cardoso-Cruz Hélder , Silva Francisco , Galhardo Vasco , Antunes Luís
Published: January 2010

Background

Local field potentials may allow a more precise analysis of the brain electrical activity than the electroencephalogram. In this study, local field potentials were recorded in the thalamocortical axis of rats to (i) compare the performance of several indexes of anesthetic depth and (ii) investigate the existence of thalamocortical correlated or disrupted activity during isoflurane steady-state anesthesia.

Methods

Five rats chronically implanted with microelectrodes were used to record local field potentials in the primary somatosensory cortex and ventroposterolateral thalamic nuclei at six periods: before induction of anesthesia; in the last 5 min of randomized 20-min steady-state end-tidal 0.8, 1.1, 1.4, and 1.7% isoflurane concentrations; and after recovery. The approximate entropy, the index of consciousness, the spectral edge frequency, and the permutation entropy were estimated using epochs of 8 s. A correction factor for burst suppression was applied to the spectral edge frequency and to the permutation entropy. The correlation between the derived indexes and the end-tidal isoflurane was calculated and compared for the two studied brain regions indexes. Coherence analysis was also performed.

Results

The burst suppression-corrected permutation entropy showed the highest correlation with the end-tidal isoflurane concentration, and a high coherence was obtained between the two studied areas.

Conclusions

The permutation entropy corrected with the classic burst suppression ratio is a promising alternative to other indexes of anesthetic depth. Furthermore, high coherence level of activity exists between the somatosensory cortical and thalamic regions, even at deep isoflurane stages.
Phenyl N -tert-butylnitrone, a Free Radical Scavenger, Reduces Mechanical Allodynia in Chemotherapy-induced Neuropathic Pain in Rats
Authors: Kim Hee Kee , Zhang Yan Ping , Gwak Young Seob , Abdi Salahadin
Published: January 2010

Background

Paclitaxel is a widely used chemotherapeutic drug for breast and ovarian cancer. Unfortunately, it induces neuropathic pain, which is a dose-limiting side effect. Free radicals have been implicated in many neurodegenerative diseases. The current study tests the hypothesis that a free radical scavenger plays an important role in reducing chemotherapy-induced neuropathic pain.

Methods

Neuropathic pain was induced by intraperitoneal injection of paclitaxel (2 mg/kg) on four alternate days (days 0, 2, 4, and 6) in male Sprague-Dawley rats. Phenyl N-tert-butylnitrone (PBN), a free radical scavenger, was administered intraperitoneally as a single dose or multiple doses before or after injury. Mechanical allodynia was measured by using von Frey filaments.

Results

The administration of paclitaxel induced mechanical allodynia, which began to manifest on days 7-10, peaked within 2 weeks, and plateaued for at least 2 months after the first paclitaxel injection. A single injection or multiple intraperitoneal injections of PBN ameliorated paclitaxel-induced pain behaviors in a dose-dependent manner. Further, multiple administrations of PBN starting on day 7 through day 15 after the first injection of paclitaxel completely prevented the development of mechanical allodynia. However, an intraperitoneal administration of pbn for 8 days starting with the first paclitaxel injection did not prevent the development of pain behavior.

Conclusions

This study clearly shows that PBN alleviated mechanical allodynia induced by paclitaxel in rats. Furthermore, our data show that PBN given on days 7 through 15 after the first paclitaxel injection prevented the development of chemotherapy-induced neuropathic pain. This clearly has a clinical implication.
Direct Evidence for the Ongoing Brain Activation by Enhanced Dynorphinergic System in the Spinal Cord under Inflammatory Noxious Stimuli
Authors: Taketa Yasuko , Niikura Keiichi , Kobayashi Yasuhisa , Furuya Masaharu , Shimizu Toshikazu , Narita Michiko , Imai Satoshi , Kuzumaki Naoko , Maitani Yoshie , Yamazaki Mitsuaki , Inada Eiichi , Iseki Masako , Suzuki Tsutomu , Narita Minoru
Published: January 2010

Background

Dynorphin A in the spinal cord is considered to contribute to nociceptive stimuli. However, it has not yet been determined whether activation of the spinal dynorphinergic system under nociceptive stimuli plays a role in direct acceleration of the ascending nociceptive pathway. In this study, the authors investigated the role of spinal dynorphinergic transmission in ongoing brain activation under noxious stimuli in mice.

Methods

The changes in prodynorphin messenger RNA expression and dynorphin A (1-17)-like immunoreactivity in the mouse spinal cord were determined after the intraplantar injection of complete Freund's adjuvant in mice. The signal intensity in different brain regions after the intraplantar injection of complete Freund's adjuvant or intrathecal injection of dynorphin A (1-17) was measured by a pharmacological functional magnetic resonance imaging analysis.

Results

Complete Freund's adjuvant injection produced pain-associated behaviors and induced a dramatic increase in signal intensity in the mouse cingulate cortex, somatosensory cortex, insular cortex, and thalamic nuclei. These effects were not seen in prodynorphin knockout mice. Prodynorphin messenger RNA expression and dynorphin A (1-17)-like immunoreactivity on the ipsilateral side of the spinal cord were markedly increased in complete Freund's adjuvant-injected mice. Furthermore, intrathecal injection of dynorphin A (1-17) at relatively high doses caused pain-associated behaviors and a remarkable increase in the activities of the cingulate cortex, somatosensory cortex, insular cortex, and medial and lateral thalamic nuclei in mice.

Conclusions

These findings indicate that spinally released dynorphin A (1-17) by noxious stimuli leads to the direct activation of ascending pain transmission.
Isoflurane Does Not Affect Brain Cell Death, Hippocampal Neurogenesis, or Long-term Neurocognitive Outcome in Aged Rats
Authors: Stratmann Greg , Sall Jeffrey W. , Bell Joseph S. , Alvi Rehan S. , May Laura d. V. , Ku Ban , Dowlatshahi Mitra , Dai Ran , Bickler Philip E. , Russell Isobel , Lee Michael T. , Hrubos Margit W. , Chiu Cheryl
Published: January 2010

Background

Roughly, 10% of elderly patients develop postoperative cognitive dysfunction. General anesthesia impairs spatial memory in aged rats, but the mechanism is not known. Hippocampal neurogenesis affects spatial learning and memory in rats, and isoflurane affects neurogenesis in neonatal and young adult rats. We tested the hypothesis that isoflurane impairs neurogenesis and hippocampal function in aged rats.

Methods

Isoflurane was administered to 16-month-old rats at one minimum alveolar concentration for 4 h. FluoroJade staining was performed to assess brain cell death 16 h after isoflurane administration. Dentate gyrus progenitor proliferation was assessed by bromodeoxyuridine injection 4 days after anesthesia and quantification of bromodeoxyuridine+ cells 12 h later. Neuronal differentiation was studied by determining colocalization of bromodeoxyuridine with the immature neuronal marker NeuroD 5 days after anesthesia. New neuronal survival was assessed by quantifying cells coexpressing bromodeoxyuridine and the mature neuronal marker NeuN 5 weeks after anesthesia. Four months after anesthesia, associative learning was assessed by fear conditioning. Spatial reference memory acquisition and retention was tested in the Morris Water Maze.

Results

Cell death was sporadic and not different between groups. We did not detect any differences in hippocampal progenitor proliferation, neuronal differentiation, new neuronal survival, or in any of the tests of long-term hippocampal function.

Conclusion

In aged rats, isoflurane does not affect brain cell death, hippocampal neurogenesis, or long-term neurocognitive outcome.
Hypercapnia and Acidosis in Sepsis
Authors: Curley Gerard , Contreras Maya , Nichol Alistair D. , Higgins Brendan D. , Laffey John G. , Warner David S.
Published: January 2010

Acute respiratory distress syndrome is a devastating disease that causes substantial morbidity and mortality. Mechanical ventilation can worsen lung injury, whereas ventilatory strategies that reduce lung stretch, resulting in a "permissive" hypercapnic acidosis (HCA), improve outcome. HCA directly reduces nonsepsis-induced lung injury in preclinical models and, therefore, has therapeutic potential in these patients. These beneficial effects are mediated via inhibition of the host immune response, particularly cytokine signaling, phagocyte function, and the adaptive immune response. Of concern, these immunosuppressive effects of HCA may hinder the host response to microbial infection. Recent studies suggest that HCA is protective in the earlier phases of bacterial pneumonia-induced sepsis but may worsen injury in the setting of prolonged lung sepsis. In contrast, HCA is protective in preclinical models of early and prolonged systemic sepsis. Buffering of the HCA is not beneficial and may worsen pneumonia-induced injury.
Coding of Incisional Pain in the Brain
Authors: Pogatzki-Zahn Esther M. , Wagner Christian , Meinhardt-Renner Anne , Burgmer Markus , Beste Christian , Zahn Peter K. , Pfleiderer Bettina
Published: January 2010

Introduction

In this study, the activation of different brain areas after an experimental surgical incision was assessed by functional magnetic resonance imaging, and the pathophysiological role of distinct brain activation patterns for pain perception after incision was analyzed.

Methods

Thirty male volunteers (mean age +/-SD, 25+/- 5 yr) received an experimental incision (4 mm) within the volar aspect of the right forearm using a ceramic scalper blade, and 14 volunteers (mean age +/- SD, 25 +/- 4 yr) received a sham procedure. Magnetic resonance images were taken before, during (0-2 min), and after incision or sham procedure (2-4.5, 4.5-10, 24-29, and 44-49 min) at a 3T scanner using a block design. Subjective pain ratings by a numerical pain scale were performed between the scans.

Results

Functional magnetic resonance imaging analysis showed a distinct temporal profile of activity within specific brain regions during and after the injury. Lateralization (predominantly contralateral to the incision) and increased brain activity of the somatosensory cortex, frontal cortex, and limbic system were observed in subjects after incision, when compared with individuals receiving sham procedure. Peak brain activation occurred about 2 min after incision and decreased subsequently. A distinct correlation between evoked pain ratings and brain activity was observed for the anterior cingulate cortex, insular cortex, thalamus, frontal cortex, and somatosensory cortex.

Conclusion

These findings show different and distinct cortical and subcortical activation patterns over a relevant time period after incision. Pain sensitivity hereby has an influence on the activity profile. This may have important implications for encoding ongoing pain after a tissue injury, for example, resting pain in postoperative patients.
Continuous Peripheral Nerve Blocks
Authors: Ilfeld Brian M. , Moeller Lisa K. , Mariano Edward R. , Loland Vanessa J. , Stevens-Lapsley Jennifer E. , Fleisher Adam S. , Girard Paul J. , Donohue Michael C. , Ferguson Eliza J. , Ball Scott T.
Published: January 2010

Background

The main determinant of continuous peripheral nerve block effects--local anesthetic concentration and volume or simply total drug dose--remains unknown.

Methods

We compared two different concentrations and basal rates of ropivacaine--but at equivalent total doses--for continuous posterior lumbar plexus blocks after hip arthroplasty. Preoperatively, a psoas compartment perineural catheter was inserted. Postoperatively, patients were randomly assigned to receive perineural ropivacaine of either 0.1% (basal 12 ml/h, bolus 4 ml) or 0.4% (basal 3 ml/h, bolus 1 ml) for at least 48 h. Therefore, both groups received 12 mg of ropivacaine each hour with a possible addition of 4 mg every 30 min via a patient-controlled bolus dose. The primary endpoint was the difference in maximum voluntary isometric contraction (MVIC) of the ipsilateral quadriceps the morning after surgery, compared with the preoperative MVIC, expressed as a percentage of the preoperative MVIC. Secondary endpoints included hip adductor and hip flexor MVIC, sensory levels in the femoral nerve distribution, hip range-of-motion, ambulatory ability, pain scores, and ropivacaine consumption.

Results

Quadriceps MVIC for patients receiving 0.1% ropivacaine (n = 26) declined by a mean (SE) of 64.1% (6.4) versus 68.0% (5.4) for patients receiving 0.4% ropivacaine (n = 24) between the preoperative period and the day after surgery (95% CI for group difference: -8.0-14.4%; P = 0.70). Similarly, the groups were found to be equivalent with respect to secondary endpoints.

Conclusions

For continuous posterior lumbar plexus blocks, local anesthetic concentration and volume do not influence nerve block characteristics, suggesting that local anesthetic dose (mass) is the primary determinant of perineural infusion effects.
Characterization of the Postconditioning Effect of Dexmedetomidine in Mouse Organotypic Hippocampal Slice Cultures Exposed to Oxygen and Glucose Deprivation
Authors: Dahmani Souhayl , Rouelle Danielle , Gressens Pierre , Mantz Jean
Published: January 2010

Background

There is an increasing interest in the use of dexmedetomidine for anesthesia and sedation. Here, we used the mouse organotypic hippocampal slice culture to investigate whether dexmedetomidine exhibits postconditioning properties against oxygen and glucose deprivation (OGD). The role of the focal adhesion and extracellular-regulated kinases pathways in these effects were examined in both postconditioning and preconditioning.

Materials and Methods

Slices were obtained from P5 mouse. In postconditioning experiments, Dexmedetomidine (1 microm) was incubated 60 min after the end of OGD. In preconditioning experiments, dexmedetomidine was applied 3 h before OGD. Pharmacologic modulation of the studied pathways was achieved by using selective inhibitors of these cascades. Cell death was assessed 72 h after OGD using propidium iodide labeling and protein expression of activated caspase 3.

Results

Maximum cell death increased with the duration of OGD. Dexmedetomidine induced a postconditioning effect in the CA1 (but not dentate gyrus) subfield area, which was significantly reduced by modulators of the focal adhesion and the extracellular-regulated kinases pathways. The combination of the inhibitors of the two pathways completely abolished the postconditioning effect of dexmedetomidine. The preconditioning effect of dexmedetomidine against ischemia-induced injury was observed in all hippocampal subfield areas. Results obtained with the pharmacologic modulation used for postconditioning also applied to dexmedetomidine-induced preconditioning.

Discussion

Dexmedetomidine exhibits significant, but moderate, postconditioning properties against oxygen and glucose deprivation-induced injury. Activation of focal adhesion and the imidazoline 1 receptors-extracellular-regulated kinases pathways is involved in dexmedetomidine-induced postconditioning and preconditioning as well.
Factor VII Levels and International Normalized Ratios in the Early Phase of Warfarin Therapy
Authors: Benzon Honorio T. , Avram Michael J. , Benzon Hubert A. , Kirby-Nolan Misty , Nader Antoun
Published: January 2010

Background

Factor VII is the most affected clotting factor during the early phase of warfarin therapy. An international normalized ratio (INR) of more than 1.4 is considered unsafe for epidural catheter placement or removal, according to the American Society of Regional Anesthesia and Pain Medicine. The authors tested the hypothesis that factor VII activities would be consistent with safe removal of the epidural catheter on postoperative day (POD) 1 regardless of INR value.

Methods

Data from 121 patients who took warfarin after undergoing total joint surgery and had INRs and factor VII levels determined were reviewed. Patient characteristics and factor VII activities were compared between patients with INRs of more than 1.4 and those with INRs less than or equal to 1.4 on PODs 1, 2, and 3.

Results

Eleven patients had INRs of more than 1.4 on POD 1; their mean +/- SD factor VII activities were 60 +/- 28% (normal: 50-160%). On POD 2, 78 patients with INRs more than of 1.4 had factor VII activities of 32 +/- 15%, whereas on POD 3, 84 patients with INRs of more than 1.4 had factor VII activities of 44 +/- 19%. Variables included in the final multiple logistic regression model as predictors of an INR of more than 1.4 on POD 2 were warfarin dose on POD 1 and factor VII activity on POD 2.

Conclusions

The range of factor VII activities in the patients with INRs of more than 1.4 within 12 h of warfarin therapy was compatible with adequate hemostasis. The authors found no evidence that epidural catheters should not be removed even with INRs up to 1.9, the highest INR on POD 1 noted in their study.