bluuebunny/crossref_metadata_2025 huggingface dataset:
Rheb controls misfolded protein metabolism by inhibiting aggresome formation and autophagy
Authors: Zhou Xiaoming , Ikenoue Tsuneo , Chen Xiaowei , Li Li , Inoki Ken , Guan Kun-Liang
Published: May 2009

Perinuclear aggresome formation is a key mechanism to dispose of misfolded proteins that exceed the degradative capacity of ubiquitin–proteasome and autophagy–lysosome systems. Functional blockade of either degradative system leads to an enhanced aggresome formation. The tuberous sclerosis complex–Ras homologue enriched in brain–mammalian target of rapamycin (TSC–Rheb–mTOR) pathway is known to play a central role in modulating protein synthesis and autophagy. However, in spite of the constitutive activation of mTOR and the abrogated autophagy activity in TSC1- or TSC2-deficient cells, the TSC mutant cells are defective in aggresome formation and undergo apoptosis upon misfolded protein accumulation both in vitro and in vivo. High Rheb activity in TSC mutant cells inhibits aggresome formation and sensitizes cell death in response to misfolded proteins. Surprisingly, this previously unrecognized function of Rheb is independent of TOR complex 1. Active Rheb disrupts the interaction between dynein and misfolded protein cargos, and therefore blocks aggresome formation by inhibiting dynein-dependent transportation of misfolded proteins. This study reveals a function of Rheb in controlling misfolded protein metabolism by modulating aggresome formation.
Neural codes for perceptual discrimination of acoustic flutter in the primate auditory cortex
Authors: Lemus Luis , Hernández Adrián , Romo Ranulfo
Published: May 2009

We recorded from single neurons of the primary auditory cortex (A1), while trained monkeys reported a decision based on the comparison of 2 acoustic flutter stimuli. Crucially, to form the decision, monkeys had to compare the second stimulus rate to the memory trace of the first stimulus rate. We found that the responses of A1 neurons encode stimulus rates both through their periodicity and through their firing rates during the stimulation periods, but not during the working memory and decision components of this task. Neurometric thresholds based on firing rate were very similar to the monkey's discrimination thresholds, whereas neurometric thresholds based on periodicity were lower than the experimental thresholds. Thus, an observer could solve this task with a precision similar to that of the monkey based only on the firing rates evoked by the stimuli. These results suggest that the A1 is exclusively associated with the sensory and not with the cognitive components of this task.
The Development of Gaze Following in a Third‐Party Context
Authors: Collicott Cherie , Collins Stephanie , Moore Chris
Published: May 2009

Infants follow the gaze of an individual with whom they are directly interacting by the end of the first year. By 18 months infants are capable of learning novel words in observational (or third‐party) contexts (Floor & Akhtar, 2006). To examine third‐party gaze following in 12‐ and 18‐month‐olds, the parent and experimenter engaged in a conversation while the infant was present. For 8 trials approximately every 30 sec the experimenter would turn her head to the right or left to fixate on a toy placed on either side of the room with the parent following suit. In the first experiment, the parent was seated next to the infant and the experimenter opposite, whereas in the second experiment the positions of the adults were switched. In Experiment 1, 18‐month‐olds but not 12‐month‐olds followed gaze. In Experiment 2, 12‐month‐olds acquired a tendency to follow gaze during the experimental session. These results suggest that an incipient ability to follow third‐party gaze is present by 12 months and that infants acquire a more reliable and general ability to follow the gaze of noninteractive others between 12 and 18 months.
Categorical Representation of Facial Expressions in the Infant Brain
Authors: Leppänen Jukka M. , Richmond Jenny , Vogel‐Farley Vanessa K. , Moulson Margaret C. , Nelson Charles A.
Published: May 2009

Categorical perception, demonstrated as reduced discrimination of within‐category relative to between‐category differences in stimuli, has been found in a variety of perceptual domains in adults. To examine the development of categorical perception in the domain of facial expression processing, we used behavioral and event‐related potential (ERP) methods to assess discrimination of within‐category (happy‐happy) and between‐category (happy‐sad) differences in facial expressions in 7‐month‐old infants. Data from a visual paired‐comparison test and recordings of attention‐sensitive ERPs showed no discrimination of facial expressions in the within‐category condition, whereas reliable discrimination was observed in the between‐category condition. The results also showed that face‐sensitive ERPs over occipital‐temporal scalp (P400) were attenuated in the within‐category condition relative to the between‐category condition, suggesting a potential neural basis for the reduced within‐category sensitivity. Together, these results suggest that the neural systems underlying categorical representation of facial expressions emerge during the early stages of postnatal development, before acquisition of language.
12‐Month‐Olds Produce Others' Intended but Unfulfilled Acts
Authors: Nielsen Mark
Published: May 2009

Following Meltzoff's (1995) behavioral reenactment paradigm, this study investigated the ability of 12‐month‐olds (N = 44) to reproduce a model's attempted‐but‐failed actions on objects. Testing was conducted using a novel set of objects designed to enable young infants to readily identify the potential outcome of the model's actions. Infants who saw an adult's attempted‐but‐failed actions now produced her intended outcomes at an equivalent rate to infants who saw the model's completed acts, and significantly more so than infants who either observed an adult manipulating the test apparatus using nontarget actions or who did not see any actions demonstrated on the test apparatus. This result shows that, contrary to previous studies, 12‐month‐olds can produce the intended but unconsummated acts of others.
Methods for improving characteristics of laser source of ions
Authors: Khaydarov R.T. , Biesinbaeva H.B. , Sabitov M.M. , Terentev V.B. , Tojinazarov F.M.
Published: May 2009

In this work we discuss four methods to improve the characteristics of laser source of ions, namely: (i) the effect of the angle of interaction of laser radiation with targets on the plasma ions characteristics, (ii) the use of targets of different densities to improve the parameters of plasma ions, (iii) the influence of laser frequency on the plasma parameters and (iv) the effect of irradiation dose of the target on the emission of multi-charged ions. Our study will be based on the analysis of the mass-charge spectrum of laser-produced plasma ions for different intensities of laser radiation.
Dynamics of kinetic geodesic-acoustic modes and the radial electric field in tokamak neoclassical plasmas
Authors: Xu X.Q. , Belli E. , Bodi K. , Candy J. , Chang C.S. , Cohen R.H. , Colella P. , Dimits A.M. , Dorr M.R. , Gao Z. , Hittinger J.A. , Ko S. , Krasheninnikov S. , McKee G.R. , Nevins W.M. , Rognlien T.D. , Snyder P.B. , Suh J. , Umansky M.V.
Published: May 2009

We present edge gyrokinetic simulations of tokamak plasmas using the fully non-linear (full-f) continuum code TEMPEST. A non-linear Boltzmann model is used for the electrons. The electric field is obtained by solving the 2D gyrokinetic Poisson equation. We demonstrate the following. (1) High harmonic resonances (n > 2) significantly enhance geodesic-acoustic mode (GAM) damping at high q (tokamak safety factor), and are necessary to explain the damping observed in our TEMPEST q-scans and consistent with the experimental measurements of the scaling of the GAM amplitude with edge q
95 in the absence of obvious evidence that there is a strong q-dependence of the turbulent drive and damping of the GAM. (2) The kinetic GAM exists in the edge for steep density and temperature gradients in the form of outgoing waves, its radial scale is set by the ion temperature profile, and ion temperature inhomogeneity is necessary for GAM radial propagation. (3) The development of the neoclassical electric field evolves through different phases of relaxation, including GAMs, their radial propagation and their long-time collisional decay. (4) Natural consequences of orbits in the pedestal and scrape-off layer region in divertor geometry are substantial non-Maxwellian ion distributions and parallel flow characteristics qualitatively like those observed in experiments.
Achievements in the development of the Water Cooled Solid Breeder Test Blanket Module of Japan to the milestones for installation in ITER
Authors: Tsuru Daigo , Tanigawa Hisashi , Hirose Takanori , Mohri Kensuke , Seki Yohji , Enoeda Mikio , Ezato Koichiro , Suzuki Satoshi , Nishi Hiroshi , Akiba Masato
Published: May 2009

As the primary candidate of ITER Test Blanket Module (TBM) to be tested under the leadership of Japan, a water cooled solid breeder (WCSB) TBM is being developed. This paper shows the recent achievements towards the milestones of ITER TBMs prior to the installation, which consist of design integration in ITER, module qualification and safety assessment. With respect to the design integration, targeting the detailed design final report in 2012, structure designs of the WCSB TBM and the interfacing components (common frame and backside shielding) that are placed in a test port of ITER and the layout of the cooling system are presented. As for the module qualification, a real-scale first wall mock-up fabricated by using the hot isostatic pressing method by structural material of reduced activation martensitic ferritic steel, F82H, and flow and irradiation test of the mock-up are presented. As for safety milestones, the contents of the preliminary safety report in 2008 consisting of source term identification, failure mode and effect analysis (FMEA) and identification of postulated initiating events (PIEs) and safety analyses are presented.
Focal Adhesion Kinase Signaling Regulates the Expression of Caveolin 3 and β1 Integrin, Genes Essential for Normal Myoblast Fusion
Authors: Quach Navaline L. , Biressi Stefano , Reichardt Louis F. , Keller Charles , Rando Thomas A.
Published: May 2009

An essential phase of skeletal myogenesis is the fusion of mononucleated myoblasts to form multinucleated myotubes. Many cell adhesion proteins, including integrins, have been shown to be important for myoblast fusion in vertebrates, but the mechanisms by which these proteins regulate cell fusion remain mostly unknown. Here, we focused on the role of focal adhesion kinase (FAK), an important nonreceptor protein tyrosine kinase involved in integrin signaling, as a potential mediator by which integrins may regulate myoblast fusion. To test this hypothesis in vivo, we generated mice in which the Fak gene was disrupted specifically in muscle stem cells (“satellite cells”) and we found that this resulted in impaired myotube formation during muscle regeneration after injury. To examine the role of FAK in the fusion of myogenic cells, we examined the expression of FAK and the effects of FAK deletion on the differentiation of myoblasts in vitro. Differentiation of mouse primary myoblasts was accompanied by a rapid and transient increase of phosphorylated FAK. To investigate the requirement of FAK in myoblast fusion, we used two loss-of-function approaches (a dominant-negative inhibitor of FAK and FAK small interfering RNA [siRNA]). Inhibition of FAK resulted in markedly impaired fusion but did not inhibit other biochemical measures of myogenic differentiation, suggesting a specific role of FAK in the morphological changes of cell fusion as part of the differentiation program. To examine the mechanisms by which FAK may be regulating fusion, we used microarray analysis to identify the genes that failed to be normally regulated in cells that were fusion defective due to FAK inhibition. Several genes that have been implicated in myoblast fusion were aberrantly regulated during differentiation when FAK was inhibited. Intriguingly, the normal increases in the transcript of caveolin 3 as well as an integrin subunit, the β1D isoform, were suppressed by FAK inhibition. We confirmed this also at the protein level and show that direct inhibition of β1D subunit expression by siRNA inhibited myotube formation with a prominent effect on secondary fusion. These data suggest that FAK regulation of profusion genes, including caveolin 3 and the β1D integrin subunit, is essential for morphological muscle differentiation.
Dephosphorylation of Major Sperm Protein (MSP) Fiber Protein 3 by Protein Phosphatase 2A during Cell Body Retraction in the MSP-based Amoeboid Motility ofAscarisSperm
Authors: Yi Kexi , Wang Xu , Emmett Mark R. , Marshall Alan G. , Stewart Murray , Roberts Thomas M.
Published: May 2009

The crawling movement of nematode sperm requires coordination of leading edge protrusion with cell body retraction, both of which are powered by modulation of a cytoskeleton based on major sperm protein (MSP) filaments. We used a cell-free in vitro motility system in which both protrusion and retraction can be reconstituted, to identify two proteins involved in cell body retraction. Pharmacological and depletion-add back assays showed that retraction was triggered by a putative protein phosphatase 2A (PP2A, a Ser/Thr phosphatase activated by tyrosine dephosphorylation). Immunofluorescence showed that PP2A was present in the cell body and was concentrated at the base of the lamellipod where the force for retraction is generated. PP2A targeted MSP fiber protein 3 (MFP3), a protein unique to nematode sperm that binds to the MSP filaments in the motility apparatus. Dephosphorylation of MFP3 caused its release from the cytoskeleton and generated filament disassembly. Our results suggest that interaction between PP2A and MFP3 leads to local disassembly of the MSP cytoskeleton at the base of the lamellipod in sperm that in turn pulls the trailing cell body forward.
Influence of Auditory Stimulation Rates on Evoked Potentials during General Anesthesia
Authors: McNeer Richard R. , Bohórquez Jorge , Özdamar Özcan
Published: May 2009

Background

The auditory middle-latency response (transient) and the 40-Hz auditory steady state response (ASSR) are modulated by anesthetics. However, the quantitative relation between these evoked responses is difficult to obtain because of technical limitations of the recording methods used to obtain transients at high stimulation rates. This study uses continuous-loop averaging deconvolution to fill this technical gap and to study the relation between the transient and ASSR waveform during general anesthesia.

Methods

The authors recorded 5- and 40-Hz transients and 40-Hz ASSRs in 13 subjects during general anesthesia. The 5- and 40-Hz transients were used to predict the 40-Hz ASSR by linearly superimposing the transient waveforms. The predicted and recorded ASSRs were analyzed and compared using phasor and Hotelling T(2) analyses.

Results

Grand-averaged recordings revealed differences in the early middle-latency peaks between 5- and 40-Hz transients, e.g., the peak P(x) was present only in 5-Hz transient. Only the predicted 40-Hz ASSR derived from the 40-Hz transient matched the actual ASSR. Phasor analysis showed that the early peaks contribute significantly to the steady state waveform, and this explains why 5-Hz transient does not predict the 40-Hz ASSR. Oscillations in both the 5- and 40-Hz transients were observed during anesthesia.

Discussion

The 40-Hz ASSR represents a composite waveform and arises when transient waveforms elicited with a 40-Hz stimulation rate are overlapped and superimposed. During general anesthesia, the morphology of the transient is dependent on the rate of stimulus presentation. The composite nature of the ASSR may explain nonmonotonic anesthetic dose-response relations observed by others.
Systematic Review of Questionnaires Measuring Patient Satisfaction in Ambulatory Anesthesia
Authors: Chanthong Pratamaporn , Abrishami Amir , Wong Jean , Herrera Francisco , Chung Frances
Published: May 2009

Background

Patient satisfaction has become an important component of quality improvement in ambulatory anesthesia services. However, it is difficult to measure due to its subjective and complex psychological construct. Psychometric methodology has been successfully used to evaluate this outcome. The authors conducted a systematic review to evaluate questionnaires to measure patient satisfaction with ambulatory anesthesia.

Methods

A systematic literature search of The Cochrane Library, MEDLINE, EMBASE, CINAHL, HAPI, PsycINFO, and Dissertation Abstracts was performed to identify studies on questionnaires evaluating patient satisfaction after ambulatory anesthesia. The authors included the articles that used multiple-item questionnaires, and the questionnaires were assessed with the strategy of psychometric questionnaire construction, validity, reliability, and acceptability.

Results

The authors scanned 131 articles yielded by our search strategy. Eleven articles were included in the study. Two questionnaires, IOWA Satisfaction with Anesthesia Scale and Evaluation du Vecu de I'Anesthesie Generale, fulfilled the criteria, but the latter was not developed specifically for ambulatory anesthesia, whereas Iowa Satisfaction with Anesthesia Scale was designed only for monitored anesthesia patients.

Conclusions

In a large number of trials, patient satisfaction has been evaluated using overall satisfaction or nonvalidated questionnaires. Only a few studies have developed questionnaires with rigorous psychometric methods to measure patient satisfaction with anesthesia care. At this time, there is still no valid or reliable questionnaire for measuring patient satisfaction in ambulatory anesthesia. Further study should be conducted to develop standardized instruments to measure this outcome.
Postoperative Urinary Retention
Authors: Baldini Gabriele , Bagry Hema , Aprikian Armen , Carli Franco , Warner David S. , Warner Mark A.
Published: May 2009

Urinary retention is common after anesthesia and surgery, reported incidence of between 5% and 70%. Comorbidities, type of surgery, and type of anesthesia influence the development of postoperative urinary retention (POUR). The authors review the overall incidence and mechanisms of POUR associated with surgery, anesthesia and analgesia. Ultrasound has been shown to provide an accurate assessment of urinary bladder volume and a guide to the management of POUR. Recommendations for urinary catheterization in the perioperative setting vary widely, influenced by many factors, including surgical factors, type of anesthesia, comorbidities, local policies, and personal preferences. Inappropriate management of POUR may be responsible for bladder overdistension, urinary tract infection, and catheter-related complications. An evidence-based approach to prevention and management of POUR during the perioperative period is proposed.
Resistance to d-Tubocurarine of the Rat Diaphragm as Compared to a Limb Muscle
Authors: Nguyen-Huu Tu , Molgó Jordi , Servent Denis , Duvaldestin Philippe
Published: May 2009

Background

The diaphragm is resistant to competitive neuromuscular blocking agents, as compared to peripheral muscles. The basis of this difference may be a higher concentration of acetylcholine released or higher number of postsynaptic nicotinic acetylcholine receptors in diaphragmatic neuromuscular junctions.

Methods

Nerve-evoked twitch-tension was measured in rat hemidiaphragm as was Extensor digitorum longus (EDL) nerve-muscle preparation to determine the effective D-tubocurarine concentration that decreased twitch responses by 50%. The mean quantal content of endplate potentials was determined in single junctions in a low-Ca(2+), high-Mg(2+) Krebs-Ringer medium. Strips of hemidiaphragm and EDL muscle, containing the endplate regions, were used to determine the number of nAChR nicotinic acetylcholine receptor binding sites with the aid of radiolabeled [(125)I]alpha-bungarotoxin.

Results

The effective D-tubocurarine concentration that decreased twitch responses by 50% (median [interquartile range]) was seven-fold higher in the hemidiaphragm than in the EDL (1.82 microm [1.43-2.20] vs. 0.26 microm [0.23-0.29], P < 0.01). The median of the mean quantal content was higher in the hemidiaphragm than in the EDL (0.57 [0.44-0.84] vs. (0.14 [0.11-0.19], P < 0.01). The number of specific [(125)I]alpha-bungarotoxin binding sites to junctional nicotinic acetylcholine receptors was higher in the diaphragm than in the EDL (1.15 fmol/mg [0.48-1.70] vs. 0.55 fmol/mg [0.23-0.70 ], P < 0.05).

Conclusion

The current study indicates that the resistance of the diaphragm to neuromuscular blocking agents can be explained by both a higher mean quantal content of endplate potentials and a higher number of nicotinic acetylcholine receptor binding sites than in the peripheral EDL muscle.
Preoperative Electrocardiograms
Authors: Correll Darin J. , Hepner David L. , Chang Candace , Tsen Lawrence , Hevelone Nathanael D. , Bader Angela M.
Published: May 2009

Background

Age is often the sole criterion for determining the need for preoperative electrocardiograms. However, screening electrocardiograms have not been shown to add value above clinical information. This study was designed to determine whether it is possible to target electrocardiograms ordering to patients most likely to have an abnormality that would affect management and if age alone is predictive of significant electrocardiograms abnormalities.

Methods

A list was developed of electrocardiograms abnormalities considered significant enough to impact management, as well as a list of patient factors believed to increase cardiovascular risk. electrocardiograms in all patients over 50 yr of age presenting for preoperative evaluation during a 2-month period were reviewed.

Results

A total of 1,149 electrocardiograms were reviewed, with 89 patients (7.8%) having at least one significant abnormality. These patients were compared with a group of 195 patients who had electrocardiograms that did not contain significant abnormalities. Patients at higher risk of having a significantly abnormal electrocardiograms that would potentially affect management were those older than 65 yr of age or who had a history of heart failure, high cholesterol, angina, myocardial infarction, or severe valvular disease. Five patients (0.44%) had an abnormal electrocardiograms in the absence of risk factors. The sensitivity of the model is 87.6%.

Conclusion

Age greater than 65 yr remains an independent predictor for significant preoperative electrocardiograms abnormalities. The specific clinical risk factors that were found have a high sensitivity and identified all but 0.44% of patients with electrocardiograms abnormalities that may affect preoperative management.
Amitriptyline Suppresses Neuroinflammation-dependent Interleukin-10-p38 Mitogen-activated Protein Kinase-Heme Oxygenase-1 Signaling Pathway in Chronic Morphine-infused Rats
Authors: Tai Yueh-Hua , Tsai Ru-Yin , Lin Shinn-Long , Yeh Chun-Chang , Wang Jhi-Joung , Tao Pao-Luh , Wong Chih-Shung
Published: May 2009

Background

This study explores the underlying mechanism of the antiinflammatory effect of amitriptyline in chronic morphine-infused rats.

Methods

Male Wistar rats were implanted with two intrathecal catheters. One catheter was for the continuous infusion of saline, amitriptyline (15 microg/h), morphine (15 microg/h), p38 mitogen-activated protein kinase inhibitor SB203580 (0.5 microg/h), morphine plus amitriptyline, or morphine plus amitriptyline plus SB203580 for 5 days. The other catheter was used for daily intrathecal injection of anti-interleukin-10 (IL-10) antibody or heme oxygenase-1 inhibitor zinc protoporphyrin for 5 days.

Results

Amitriptyline/morphine coinfusion upregulated IL-10 protein expression in microglia; this was not observed in morphine-infused rats. Anti-IL-10 antibody effectively neutralized the amitriptyline-induced IL-10 expression in chronic morphine-infused rats. In addition, coinfusion of amitriptyline restored the antinociceptive effect of morphine (a 4.8-fold right-shift of the morphine dose-response curve compared to a 77.8-fold right-shift in its absence), and the injection of anti-IL-10 antibody or coinfusion of SB203580 partially reversed the effect of amitriptyline on the antinociceptive effect of morphine in morphine-infused rats (a 17.9-fold and 15.1-fold right-shift in morphine dose-response curves). Anti-IL-10 antibody and SB203580 significantly inhibited the amitriptyline-induced p38 mitogen-activated protein kinase and heme oxygenase-1 expression and the associated antiinflammatory effect of amitriptyline. Daily injection of zinc protoporphyrin also demonstrated that it reverses the effect of amitriptyline in morphine's antinociception and antiinflammation in chronic morphine-infused rats.

Conclusions

These results suggest that the antiinflammatory effect of amitriptyline on morphine tolerance, probably acting by increasing IL-10 expression, is mediated by p38 mitogen-activated protein kinase heme oxygenase-1 signal transduction cascade.
Continuous Perioperative Insulin Infusion Decreases Major Cardiovascular Events in Patients Undergoing Vascular Surgery
Authors: Subramaniam Balachundhar , Panzica Peter J. , Novack Victor , Mahmood Feroze , Matyal Robina , Mitchell John D. , Sundar Eswar , Bose Ruma , Pomposelli Frank , Kersten Judy R. , Talmor Daniel S.
Published: May 2009

Background

A growing body of evidence suggests that hyperglycemia is an independent predictor of increased cardiovascular risk. Aggressive glycemic control in the intensive care decreases mortality. The benefit of glycemic control in noncardiac surgery is unknown.

Methods

In a single-center, prospective, unblinded, active-control study, 236 patients were randomly assigned to continuous insulin infusion (target glucose 100-150 mg/dl) or to a standard intermittent insulin bolus (treat glucose > 150 mg/dl) in patients undergoing peripheral vascular bypass, abdominal aortic aneurysm repair, or below- or above-knee amputation. The treatments began at the start of surgery and continued for 48 h. The primary endpoint was a composite of all-cause death, myocardial infarction, and acute congestive heart failure. The secondary endpoints were blood glucose concentrations, rates of hypoglycemia (< 60 mg/dl) and hyperglycemia (> 150 mg/dl), graft failure or reintervention, wound infection, acute renal insufficiency, and duration of stay.

Results

The groups were well balanced for baseline characteristics, except for older age in the intervention group. There was a significant reduction in primary endpoint (3.5%) in the intervention group compared with the control group (12.3%) (relative risk, 0.29; 95% confidence interval, 0.10-0.83; P = 0.013). The secondary endpoints were similar. Hypoglycemia occurred in 8.8% of the intervention group compared with 4.1% of the control group (P = 0.14). Multivariate analysis demonstrated that continuous insulin infusion was a negative independent predictor (odds ratio, 0.28; 95% confidence interval, 0.09-0.87; P = 0.027), whereas previous coronary artery disease was a positive predictor of adverse events.

Conclusion

Continuous insulin infusion reduces perioperative myocardial infarction after vascular surgery.
Computer-based Finite Element Modeling of Insulated Tuohy Needles Used in Regional Anesthesia
Authors: Cantrell Meredith B. , Grill Warren M. , Klein Stephen M.
Published: May 2009

Background

Differences in needle design may impact nerve localization. This study evaluates the electrical properties of two insulated Tuohy needles using computational finite element modeling.

Methods

Three-dimensional geometric computer-based models were created representing two 18-gauge, insulated Tuohy needles: (1) with an exposed metal tip and (2) with an insulated tip. The models were projected in simulated human tissue. Using finite element methodology, distributions of current-density were calculated. Voltages in the modeled medium were calculated, and activation patterns of a model nerve fiber around the tip of each needle were estimated using the activating function.

Results

Maximum current density on the exposed-tip needle occurred along the edge of the distal tip; the distal edge was 1.7 times larger than the side edges and 3.5 times larger than the proximal edge. Conversely, maximum current density occurred along the proximal edge of the insulated-tip Tuohy opening; the proximal edge was 1.9 times larger than the side edges of the opening and 3.5 times larger than the distal edge of the opening. Voltages generated by the exposed-tip needle were larger and had a wider spatial distribution than that of the insulated-tip needle, which restricted to the area immediately adjacent to the opening. Different changes in threshold were predicted to excite a nerve fiber as the needles were rotated or advanced toward the modeled nerve.

Conclusions

The needles displayed different asymmetric distributions of current density and positional effects on threshold. If this analysis is validated clinically, it may prove useful in testing stimulating needles before clinical application.
Pentobarbital Dose-dependently Increases Respiratory Genioglossus Muscle Activity while Impairing Diaphragmatic Function in Anesthetized Rats
Authors: Eikermann Matthias , Fassbender Philipp , Zaremba Sebastian , Jordan Amy S. , Rosow Carl , Malhotra Atul , Chamberlin Nancy L.
Published: May 2009

Background

Anesthetics depress both ventilatory and upper airway dilator muscle activity and thus put the upper airway at risk for collapse. However, these effects are agent-dependent and may involve upper airway and diaphragm muscles to varying degrees. The authors assessed the effects of pentobarbital on upper airway dilator and respiratory pump muscle function in rats and compared these results with the effects of normal sleep.

Methods

Tracheostomized rats were given increasing doses of pentobarbital to produce deep sedation then light and deep anesthesia, and negative pressure airway stimuli were applied (n = 11). To compare the effects of pentobarbital with those of natural sleep, the authors chronically instrumented rats (n = 10) with genioglossus and neck electromyogram and electroencephalogram electrodes and compared genioglossus activity during wakefulness, sleep (rapid eye movement and non-rapid eye movement), and pentobarbital anesthesia.

Results

Pentobarbital caused a dose-dependent decrease in ventilation and in phasic diaphragmatic electromyogram by 11 +/- 0.1%, but it increased phasic genioglossus electromyogram by 23 +/- 0.2%. Natural non-rapid eye movement sleep and pentobarbital anesthesia (10 mg/kg intraperitoneally) decreased respiratory genioglossus electromyogram by 61 +/- 29% and 45 +/- 35%, respectively, and natural rapid eye movement sleep caused the greatest decrease in phasic genioglossus electromyogram (95 +/- 0.3%).

Conclusions

Pentobarbital in rats impairs respiratory genioglossus activity compared to the awake state, but the decrease is no greater than seen during natural sleep. During anesthesia, in the absence of pharyngeal airflow, phasic genioglossus activity is increased in a dose-dependent fashion.
A Model for Understanding the Impacts of Demand and Capacity on Waiting Time to Enter a Congested Recovery Room
Authors: Schoenmeyr Tor , Dunn Peter F. , Gamarnik David , Levi Retsef , Berger David L. , Daily Bethany J. , Levine Wilton C. , Sandberg Warren S.
Published: May 2009

Background

When a recovery room is fully occupied, patients frequently wait in the operating room after emerging from anesthesia. The frequency and duration of such delays depend on operating room case volume, average recovery time, and recovery room capacity.

Methods

The authors developed a simple yet nontrivial queueing model to predict the dynamics among the operating and recovery rooms as a function of the number of recovery beds, surgery case volume, recovery time, and other parameters. They hypothesized that the model could predict the observed distribution of patients in recovery and on waitlists, and they used statistical goodness-of-fit methods to test this hypothesis against data from their hospital. Numerical simulations and a survey were used to better understand the applicability of the model assumptions in other hospitals.

Results

Statistical tests cannot reject the prediction, and the model assumptions and predictions are in agreement with data. The survey and simulations suggest that the model is likely to be applicable at other hospitals. Small changes in capacity, such as addition of three beds (roughly 10% of capacity) are predicted to reduce waiting for recovery beds by approximately 60%. Conversely, even modest caseload increases could dramatically increase waiting.

Conclusions

A key managerial insight is that there is a sensitive relationship among caseload and number of recovery beds and the magnitude of recovery congestion. This is typical in highly utilized systems. The queueing approach is useful because it enables the investigation of future scenarios for which historical data are not directly applicable.
Changes in Functional Residual Capacity and Lung Mechanics during Surgical Repair of Congenital Heart Diseases
Authors: von Ungern-Sternberg Britta S. , Petak Ferenc , Hantos Zoltan , Habre Walid
Published: May 2009

Background

To characterize the impact of lung volume changes in the lung function impairment after the surgical repair of congenital heart diseases, combined measurements of functional residual capacity, lung clearance index, and respiratory mechanics were performed in children with hypoperfused lungs (tetralogy of Fallot [TOF]) or with pulmonary hyperperfusion (ventricular septal defect [VSD]).

Methods

Lung volume and clearance were assessed by using a sulfur hexafluoride washout technique, and the mechanical properties of the respiratory system were assessed using a low-frequency oscillation technique. Lung volume and oscillatory measurements were made preoperatively, before and after cardiopulmonary bypass and aortic clamping (AC), and after chest closure.

Results

Impairments in airway (36 +/- 2%) and tissue mechanics (22 +/- 3%) were observed in the children with TOF after bypass; AC and chest closure were associated with marked decreases in functional residual capacity (-24 +/- 3% and -13 +/- 2% for TOF and VSD after AC, respectively) and increases in lung clearance index (-60 +/- 6% and -24 +/- 3% for TOF and VSD after AC, respectively). Smaller impairments in lung mechanics were observed after bypass and AC in children with VSD.

Conclusions

These findings suggest that the lung volume loss and lung mechanical deteriorations are probably caused by a diminished tethering effect of the lung periphery through a reduced filling of the pulmonary capillaries. This effect seems to be more pronounced in children with hypoperfused lungs (TOF) than in those with pulmonary hyperperfusion (VSD). The beneficial postoperative changes in children with VSD are consequences of the reversal of the pulmonary vascular engorgement after surgical repair.
Heterotopic Ossification of Muscle and Nerve: An Unusual Cause of Painful Mononeuropathy
Authors: Young Nathan P , O'Driscoll Shawn W , Crum Brian A
Published: May 2009

We describe a case of painful radial mononeuropathy due to focal heterotopic ossification with diagnostic imaging, intraoperative illustration, and literature review.
Off-Pump Coronary Artery Bypass Grafting is Associated with Reduced Operative Mortality and In-Hospital Adverse Events in Patients with Left Main Coronary Artery Disease
Authors: Sarin Eric L. , Puskas John D. , Kilgo Patrick D. , Thourani Vinod H. , Guyton Robert A. , Lattouf Omar M.
Published: May 2009

Objective

Left main coronary artery disease (LMD) is a known risk factor for perioperative complications. This study compares off-pump coronary artery bypass (OPCAB) versus on-pump coronary artery bypass (ONCAB) grafting, CABG, with respect to in-hospital death, stroke, myocardial infarction, and major adverse cardiac events (MACE) in CABG patients with and without LMD.

Methods

Among 13,108 consecutive isolated patients with CABG treated from 1997 to 2007, 2891 patients (22.1%) were preoperatively found to have LMD. Of 5917 patients with OPCAB, 1276 (21.6%) had LMD, whereas among patients with ONCAB, 1615 of 7191 (22.5%) had LMD. Surgery type, LMD, and their interaction were examined for their impact on operative mortality, stroke, myocardial infarction, and MACE via multiple logistic regression models and adjusted odds ratios (AOR).

Results

Utilization of OPCAB for coronary revascularization in patients with LMD disease gradually increased from an initial low of 1.3% of patients in 1997 to a peak of 80.8% in 2007. OPCAB was associated with reduced incidence of stroke (AOR = 0.51, P < 0.001) and MACE (AOR = 0.66, P = 0.002), whereas LMD was associated with an increased incidence of MACE (AOR = 1.24, P = 0.038). No interactions between surgery type and LMD existed, meaning that the 2 conditions did not combine in any way to modify outcomes.

Conclusions

Patients with LMD are more likely to suffer a MACE event than those without LMD. Off-pump coronary artery bypass grafting is marginally associated with lesser risk of operative mortality and significantly associated with less stroke and overall MACE when compared with ONCAB. This benefit of OPCAB is similar for patients with and without LMD.
Tissue Stabilizer Reverse Mounting in Minimally Invasive Direct Coronary Artery Bypass, a Simple Tool in Difficult Times
Authors: Mourad Faisal , Duncan Andrew J.
Published: May 2009

The simple reverse mounting of an Octopus arm over a rib retractor can give more arm length by up to 5 cm inside the chest cavity which could prove to be very useful in patients with huge chest cavities, i.e. chronic obstructive pulmonary disease, high body mass index, allowing more flexibility and better maneuverability of the stabilizer arm during MIDCAB.
Clinical Characteristics and VPS33B Mutations in Patients With ARC Syndrome
Authors: Jang Joo Young , Kim Kyung Mo , Kim Gu‐Hwan , Yu Eunsil , Lee Jin‐Joo , Park Young Seo , Yoo Han‐Wook
Published: May 2009

Objectives:

ARC (arthrogryposis, renal dysfunction, and cholestasis) syndrome is a rare, fatal cause of neonatal intrahepatic cholestasis without known treatment modalities and has recently been ascribed to a mutation in the VPS33B gene. We assessed the clinical characteristics and investigated the VPS33B mutations in Korean patients with ARC syndrome.

Patients and Methods:

We reviewed the medical records of 6 patients with ARC syndrome among 90 patients with neonatal cholestasis from 2000 to 2005 and assessed the relative incidence rate ratio, clinical symptoms, laboratory findings, and pathological findings. DNA samples from 5 patients, 4 parents, and 2 fetuses were analyzed for VPS33B mutations.

Results:

The relative incidence rate ratio was 1/7 that of biliary atresia (95% CI 0.33–0.06). All 6 patients presented with ichthyosis and recurrent infection, and failed to thrive with the 3 main symptoms. All of the patients died within the age of 12 months. They had various severities of cholestasis, metabolic acidosis, nephrogenic diabetes insipidus, chronic diarrhea, platelet abnormalities, and central nervous system anomalies. We identified 1 novel c.403+2T>A splice‐site mutation, 2 frame‐shift mutations (c.1509_1510insG, c.790_791del), 1 nonsense mutation (c.661C>A), and 1 known nonsense mutation (c.1518C>T) in the VPS33B gene. Prenatal diagnosis was performed in 2 different families.

Conclusions:

This study indicates that the incidence of ARC syndrome is not as rare as has been thought. We found 4 novel and 1 known mutations in ARC syndrome patients and performed prenatal diagnosis in 2 families, which will facilitate genetic diagnosis and counseling for affected families.
Follow‐up and Surgical Management of Peutz‐Jeghers Syndrome in Children
Authors: Vidal Isabelle , Podevin Guillaume , Piloquet Hugues , Le Rhun Marc , Frémond Benjamin , Aubert Didier , Leclair Marc‐David , Héloury Yves
Published: May 2009

Background:

Peutz‐Jeghers syndrome (PJS) is an autosomal dominant syndrome with an increased risk of polyposis complications and intestinal and extraintestinal tumours.

Methods:

During the last 15 years, we reviewed a series of 11 children with PJS, with special attention to evolution and follow‐up. Diagnosis was based on at least 1 hamartomatous polyp associated with 2 of the 3 following criteria: family record of PJS, polyposis localised on small bowel, and mucocutaneous pigmentation. Diagnosis of PJS also could be raised by a single genetic analysis of STK11 gene.

Results:

Median age at beginning of symptoms was 6 years old. Seven of the 11 children had genetic tests, which were positive for STK11 gene mutation. Among the 10 children presenting with gastrointestinal complications, 8 were operated on, 6 had at least 1 small bowel resection, and 4 had repeat surgery for recurrent intussusceptions. In case of complications leading to a surgical procedure, we performed intraoperative enteroscopy to remove all large polyps. To prevent any polyposis complications, we suggest a complete check‐up of polyposis topography with some of the new endoscopic tools, either double‐balloon endoscopy or videocapsule endoscopy.

Conclusions:

Children with PJS have a high risk of numerous laparotomies due to polyps' complications. Therefore, a screening of intestinal polyposis by videocapsule endoscopy is recommended, as well as a screening of the most frequent sites of cancers for the patient's whole life. During any abdominal procedure, they should have an intraoperative endoscopy, this management allowing an increased time interval between 2 laparotomies.
Gastrointestinal Norovirus Infection Associated With Exacerbation of Inflammatory Bowel Disease
Authors: Khan Raheel R , Lawson April D , Minnich Linda L , Martin Kathleen , Nasir Amana , Emmett Mary K , Welch Christine A , Udall John N
Published: May 2009

Objective:

In this study we aimed to determine, in pediatric patients, whether norovirus infection could be associated with exacerbations of inflammatory bowel disease (IBD) and ascertain whether the clinical expression of norovirus gastroenteritis was similar in patients with IBD compared with non‐IBD controls.

Materials and Methods:

We performed a case‐control retrospective chart review, over a 10‐month interval, of patients with IBD with an exacerbation of their disease. The presence of norovirus in stool and/or rectal swab samples, as determined by an enzyme‐linked immunoassay, was assessed. In addition, sex, age, type of IBD, presence or absence of diarrhea, hematochezia, and the need for hospitalization were determined. A similar number of control patients who did not have IBD were used as controls.

Results:

Nine patients with IBD (8 ulcerative colitis/1 Crohn disease) had exacerbations with diarrhea. Eight had norovirus antigen in at least 1 sample. All 9 patients with IBD presented with bloody diarrhea and 6 of the 8 norovirus‐positive patients with IBD required hospitalization. All of the control patients experienced diarrhea; however, no hematochezia was noted and no hospitalization was required. Several patients with IBD and controls remained positive for norovirus months after the initial positive stool and/or rectal swab sample. The virus appeared to be more common during winter months.

Conclusions:

We conclude that norovirus may be associated with exacerbations of IBD. When norovirus accompanies IBD it is more likely to be associated with hematochezia than when the infection occurs in the absence of IBD.
Randomized, Double‐blind, Placebo‐controlled Trial: Effect of Lactobacillus GG Supplementation on Helicobacter Pylori Eradication Rates and Side Effects During Treatment in Children
Authors: Szajewska Hania , Albrecht Piotr , Topczewska‐Cabanek Agnieszka
Published: May 2009

Objective:

To determine the effectiveness of Lactobacillus GG (LGG) in children with Helicobacter pylori infection undergoing eradication therapy.

Materials and Methods:

We conducted a double‐blind, placebo‐controlled, randomized trial comparing a 7‐day, triple eradication regimen consisting of 2 antibiotics (amoxicillin tablets, 25 mg/kg twice per day, and clarithromycin tablets, 10 mg/kg twice per day) plus a proton pump inhibitor (omeprazole capsules, 0.5 mg/kg twice per day) supplemented with LGG (109 colony‐forming units) or placebo in 83 children with H pylori infection confirmed by 2 of 3 tests (13C‐urea breath test, histopathology, rapid urease test). The primary outcome measure was the H pylori eradication rate. The secondary outcome measure was the proportion of patients who experienced therapy‐related adverse effects during anti–H pylori treatment.

Results:

The groups did not differ with respect to H pylori eradication rates. Of the 34 children in the LGG group, 23 (69%) experienced eradication, compared with 22 of 32 children (68%) in the placebo group (RR 0.98, 95% CI 0.7–1.4). The groups did not differ with respect to adverse effects.

Conclusions:

In children with H pylori infection, supplementation of standard triple therapy with LGG did not significantly alter the eradication rate or side effects.
AIRE Gene Analysis in Children With Autoimmune Hepatitis Type I or II
Authors: Lankisch Tim O , Mourier Olivia , Sokal Etienne M , Habes Dalila , Lacaille Florence , Bridoux‐Henno Laure , Hermeziu Bogdan , Lenaerts Catherine , Strassburg Christian P , Jacquemin Emmanuel
Published: May 2009

The present report describes AIRE gene analysis in 25 children with autoimmune hepatitis type I or II. The heterozygous transversion c.961C > G (p.Ser278Arg) located in exon 7 was identified in 4 patients with autoimmune hepatitis type I, and mostly in those presenting with a positive family history for autoimmune diseases. In this subgroup of patients, the allelic frequency of this polymorphic variant was at least 3‐fold higher than in healthy controls. These results suggest that heterozygous AIRE gene mutation may represent a genetic predisposition to childhood autoimmune hepatitis type I.
Factors Predictive of Crohn Disease Following Colectomy in Medically Refractory Pediatric Colitis
Authors: Evers Elisa A , Pfefferkorn Marian D , Steiner Steven J
Published: May 2009

Objectives:

Crohn disease (CD) has been diagnosed following colectomy for ulcerative colitis (UC). This study aims to determine the frequency of this occurrence, and to identify predictive factors leading to a CD diagnosis.

Materials and Methods:

A retrospective chart review was performed in patients who have undergone colectomy.

Results:

From 1996 to 2006, colectomy was performed in 212 patients, 37 of whom were diagnosed preoperatively with UC. The mean ages at diagnosis and at colectomy were 10.6 ± 4.3 years and 13.7 ± 3.7 years, respectively. Inflammatory bowel disease serology at diagnosis in 29 patients showed that 26 (90%) were pANCA+. Serology was negative in 3. Ten (27%) had nonspecific inflammation of the upper digestive tract. Radiographs in 25 patients indicated no abnormalities in the small intestine. Before colectomy, patients (n = 35) were treated with corticosteroid (97%), 5‐ASA (69%), immunomodulator (66%), infliximab (29%), and cyclosporin (11%). The mean postoperative follow‐up was 2.6 ± 2 years. Six patients (16%) were found to have CD. All 6 patients were pANCA+ with elevated anti‐OmpC (n = 4), ASCA immunoglobulin A (n = 2), and ASCA immunoglobulin G (n = 1). The CD group had higher mean anti‐OmpC compared with the UC group, 16.9 ± 5.2 and 6.2 ± 3.4, respectively (P < 0.005). Weight z score at time of surgery was lower in the CD group (−1.38 ± 0.79) than in the UC group (0.29 ± 0.24), P < 0.05.

Conclusions:

The possibility of CD remains in a small fraction of patients who undergo colectomy for medically refractory UC. A lower weight and a higher anti‐OmpC titer may be predictive of CD.