bluuebunny/crossref_metadata_2025 huggingface dataset:
All-optical polarization switch in a quadratic nonlinear photonic quasicrystal
Authors: Ganany-Padowicz Ayelet , Juwiler Irit , Gayer Ofer , Bahabad Alon , Arie Ady
Published: March 2009

We present an all-optical intensity-dependent polarization switch based on cascaded three-wave-mixing interactions in a quasiperiodic quadratic nonlinear photonic crystal. The polarization switching is realized by simultaneous quasiphase matching of upconversion and downconversion processes in LiNbO3 and achieves three orders of magnitude better efficiency than previous devices based on cascaded cubic nonlinearities. The switch allows extending mode-cleaning and mode-locking techniques to considerably lower input power. We demonstrate experimentally that a single linearly polarized 1550 nm fundamental wave generates a new fundamental wave of orthogonal polarization.
Depth-resolved subsurface defects in chemically etched SrTiO3
Authors: Zhang Jun , Doutt D. , Merz T. , Chakhalian J. , Kareev M. , Liu J. , Brillson L. J.
Published: March 2009

Depth-resolved cathodoluminescence spectroscopy of atomically flat TiO2-terminated SrTiO3 single crystal surfaces reveals dramatic differences in native point defects produced by conventional etching with buffered HF (BHF) and an alternative procedure using HCl–HNO3 acidic solution (HCLNO), which produces three times fewer oxygen vacancies before and nearly an order of magnitude fewer after pure oxygen annealing. BHF-produced defect densities extend hundreds of nanometers below the surface, whereas the lower HCLNO-treated densities extend less than 50 nm. This “Arkansas” HCLNO etch and anneal method avoids HF handling and provides high-quality SrTiO3 surfaces with low native defect density for complex oxide heterostructure growth.
Ferroelectric and piezoelectric properties of Na0.52K0.48NbO3 thin films prepared by radio frequency magnetron sputtering
Authors: Lee Hai Joon , Kim Ill Won , Kim Jin Soo , Ahn Chang Won , Park Bae Ho
Published: March 2009

Ferroelectric Na0.52K0.48NbO3 (NKN) thin film on Pt/Ti/SiO2/Si substrate was prepared using the radio frequency magnetron sputtering method. The single phase and grain morphologies of NKN were confirmed by x-ray diffraction and atomic force microscopy analysis, respectively. The remnant polarization Pr and coercive electric field Ec of NKN film were 22.5 μC/cm2 and 90 kV/cm, respectively. The NKN film displayed low frequency dielectric dispersion in the temperature range 25–500 °C. The leakage current density of the film was 3.0×10−7 A/cm2 at 100 kV/cm. The piezoelectric constant d33 was estimated to be 45 pm/V using the piezoelectric force microscopy.
The O
2
sensitivity of the transcription factor FNR is controlled by Ser24 modulating the kinetics of [4Fe-4S] to [2Fe-2S] conversion
Authors: Jervis Adrian J. , Crack Jason C. , White Gaye , Artymiuk Peter J. , Cheesman Myles R. , Thomson Andrew J. , Le Brun Nick E. , Green Jeffrey
Published: March 2009

Fumarate and nitrate reduction regulatory (FNR) proteins are bacterial transcription factors that coordinate the switch between aerobic and anaerobic metabolism. In the absence of O
2
, FNR binds a [4Fe-4S]
2+
cluster (ligated by Cys-20, 23, 29, 122) promoting the formation of a transcriptionally active dimer. In the presence of O
2
, FNR is converted into a monomeric, non-DNA-binding form containing a [2Fe-2S]
2+
cluster. The reaction of the [4Fe-4S]
2+
cluster with O
2
has been shown to proceed via a 2-step process, an O
2
-dependent 1-electron oxidation to yield a [3Fe-4S]
+
intermediate with release of 1 Fe
2+
ion, followed by spontaneous rearrangement to the [2Fe-2S]
2+
form with release of 1 Fe
3+
and 2 S
2−
ions. Here, we show that replacement of Ser-24 by Arg, His, Phe, Trp, or Tyr enhances aerobic activity of FNR in vivo. The FNR-S24F protein incorporates a [4Fe-4S]
2+
cluster with spectroscopic properties similar to those of FNR. However, the substitution enhances the stability of the [4Fe-4S]
2+
cluster in the presence of O
2
. Kinetic analysis shows that both steps 1 and 2 are slower for FNR-S24F than for FNR. A molecular model suggests that step 1 of the FNR-S24F iron–sulfur cluster reaction with O
2
is inhibited by shielding of the iron ligand Cys-23, suggesting that Cys-23 or the cluster iron bound to it is a primary site of O
2
interaction. These data lead to a simple model of the FNR switch with physiological implications for the ability of FNR proteins to operate over different ranges of in vivo O
2
concentrations.
Transforming Growth Factor β1-mediated Activation of the Smooth Muscle α-Actin Gene in Human Pulmonary Myofibroblasts Is Inhibited by Tumor Necrosis Factor-α via Mitogen-activated Protein Kinase Kinase 1-dependent Induction of the Egr-1 Transcriptional Repressor
Authors: Liu Xiaoying , Kelm Robert J. , Strauch Arthur R.
Published: March 2009

Transforming growth factor (TGF) β1 is a mediator of myofibroblast differentiation in healing wounds in which it activates transcription of the smooth muscle α-actin (SMαA) gene via dynamic interplay of nuclear activators and repressors. Targeting components of TGFβ1 signaling may be an effective strategy for controlling myofibroblasts in chronic fibrotic diseases. We examined the ability of proinflammatory tumor necrosis factor (TNF)-α to antagonize TGFβ1-mediated human pulmonary myofibroblast differentiation. TNF-α abrogated TGFβ1-induced SMαA gene expression at the level of transcription without disrupting phosphorylation of regulatory Smads. Intact mitogen-activated protein kinase kinase (Mek)–extracellular signal-regulated kinase (Erk) kinase signaling was required for myofibroblast repression by TNF-α via induction of the early growth response factor-1 (Egr-1) DNA-binding protein. Egr-1 bound to the GC-rich SPUR activation element in the SMαA promoter and potently suppressed Smad3- and TGFβ1-mediated transcription. Reduction in Smad binding to the SMαA promoter in TNF-α–treated myofibroblasts was accompanied by an increase in Egr-1 and YB-1 repressor binding, suggesting that the molecular mechanism underlying repression may involve competitive interplay between Egr-1, YB-1, and Smads. The ability of TNF-α to attenuate myofibroblast differentiation via modulation of a Mek1/Erk/Egr-1 regulatory axis may be useful in designing new therapeutic targets to offset destructive tissue remodeling in chronic fibrotic disease.
SpliceAid: a database of experimental RNA target motifs bound by splicing proteins in humans
Authors: Piva Francesco , Giulietti Matteo , Nocchi Linda , Principato Giovanni
Published: March 2009

Summary: The correct post-transcriptional RNA processing is finely regulated by RNA-binding proteins. Unfortunately, there is little experimental information on target RNA sequences of RNA-binding proteins and moreover such experimentally derived target sequences are annotated in a compact form by the score matrices that overestimate the number of possible recognized sequences. We carried out an exhaustive hand curated literature search to create a database, SpliceAid, collecting all the experimentally assessed target RNA sequences that are bound by splicing proteins in humans. We built a web resource, database driven, to easy query SpliceAid and give back the results by an accurate and dynamic graphic representation.

Availability: SpliceAid database is freely accessible at http://www.introni.it/splicing.html

Contact:  f.piva@univpm.it
LOCP—locating pilus operons in Gram-positive bacteria
Authors: Plyusnin Ilya , Holm Liisa , Kankainen Matti
Published: March 2009

Summary: Pilus operons encode a pivotal host–microbe interaction structure that is vital for pathogenicity, colonization and adhesion. LOCP is a computational tool to quickly test whether or not the genome of a Gram-positive bacterium of interest or some DNA-contig in a metagenomic sample hold pilus operons. Predictions are made based on distinctive motifs of pilus-related protein sequences and on the tendency of these protein sequences to occur in dense clusters. The tool showed a phenomenal accuracy and revealed that various novel, and even unexpected, Gram-positive bacteria do possess pilus operons. Thus, the tool helps us to focus the laboratory research on genes behind this important and indicative feature, and to screen for strains containing them.

Availability: Software is available at http://ekhidna.biocenter.helsinki.fi/locp/

Contact:  matti.kankainen@helsinki.fi

Supplementary information:  Supplementary data are available at Bioinformatics online.
Bacterial Colonization of Epidural Catheters Used for Short-term Postoperative Analgesia
Authors: Yuan Hui-Bih , Zuo Zhiyi , Yu Kwok-Woon , Lin Wan-May , Lee Hui-Chen , Chan Kwok-Han
Published: March 2009

Background

The authors conducted this prospective study to determine the incidence, potential routes, and risk factors of microbial colonization of epidural catheter used for postoperative pain control.

Methods

Two-hundred five patients with epidural analgesia for postoperative pain were studied. On removal of the catheter, five samples were sent for culture: the infusate, a swab from inside the hub of the epidural catheter connector, a swab from the skin around the catheter insertion site, the subcutaneous segment, and the tip of the catheter. Clinical data related to the catheter insertion, management, and general patient conditions were collected.

Results

The positive culture rates for the subcutaneous and tip segments of the catheter were 10.5% and 12.2%, respectively. The most common organism in the culture was coagulase-negative staphylococcus. There was a strong linear relationship between bacterial colonization in the skin around the catheter insertion site and growth from the subcutaneous and tip segments of catheter (P = 0.000). Catheter-related events at ward, blood transfusion, and positive culture from the skin at the insertion site were risk factors for bacterial colonization of epidural catheters. Inflammation at catheter insertion site, catheter indwelling time, and level of catheter insertion were not predicators for epidural catheter colonization.

Conclusions

The authors' results suggest that bacterial migration along the epidural catheter track is the most common route of epidural catheter colonization. Maintaining sterile skin around the catheter insertion site will reduce colonization of the epidural catheter tip.
Mechanical Ventilation with Lower Tidal Volumes and Positive End-expiratory Pressure Prevents Pulmonary Inflammation in Patients without Preexisting Lung Injury
Authors: Wolthuis Esther K. , Choi Goda , Dessing Mark C. , Bresser Paul , Lutter Rene , Dzoljic Misa , van der Poll Tom , Vroom Margreeth B. , Hollmann Markus , Schultz Marcus J.
Published: March 2009

Background

Mechanical ventilation with high tidal volumes aggravates lung injury in patients with acute lung injury or acute respiratory distress syndrome. The authors sought to determine the effects of short-term mechanical ventilation on local inflammatory responses in patients without preexisting lung injury.

Methods

Patients scheduled to undergo an elective surgical procedure (lasting > or = 5 h) were randomly assigned to mechanical ventilation with either higher tidal volumes of 12 ml/kg ideal body weight and no positive end-expiratory pressure (PEEP) or lower tidal volumes of 6 ml/kg and 10 cm H2O PEEP. After induction of anesthesia and 5 h thereafter, bronchoalveolar lavage fluid and/or blood was investigated for polymorphonuclear cell influx, changes in levels of inflammatory markers, and nucleosomes.

Results

Mechanical ventilation with lower tidal volumes and PEEP (n = 21) attenuated the increase of pulmonary levels of interleukin (IL)-8, myeloperoxidase, and elastase as seen with higher tidal volumes and no PEEP (n = 19). Only for myeloperoxidase, a difference was found between the two ventilation strategies after 5 h of mechanical ventilation (P < 0.01). Levels of tumor necrosis factor alpha, IL-1alpha, IL-1beta, IL-6, macrophage inflammatory protein 1alpha, and macrophage inflammatory protein 1beta in the bronchoalveolar lavage fluid were not affected by mechanical ventilation. Plasma levels of IL-6 and IL-8 increased with mechanical ventilation, but there were no differences between the two ventilation groups.

Conclusion

The use of lower tidal volumes and PEEP may limit pulmonary inflammation in mechanically ventilated patients without preexisting lung injury. The specific contribution of both lower tidal volumes and PEEP on the protective effects of the lung should be further investigated.
Are Blood Transfusions Associated with Greater Mortality Rates?
Authors: Vincent Jean-Louis , Sakr Yasser , Sprung Charles , Harboe Svein , Damas Pierre
Published: March 2009

Background

Studies have suggested worse outcomes in transfused patients and improved outcomes in patients managed with restricted blood transfusion strategies. The authors investigated the relation of blood transfusion to mortality in European intensive care units (ICUs).

Methods

The Sepsis Occurrence in Acutely Ill Patients study was a multicenter, observational study that included all adult patients admitted to 198 European ICUs between May 1 and May 15, 2002 and followed them until death, until hospital discharge, or for 60 days. Patients were classified depending on whether they had received a blood transfusion at any time during their ICU stay.

Results

Of 3,147 patients, 1,040 (33.0%) received a blood transfusion. These patients were older (mean age, 62 vs. 60 yr; P = 0.035) and were more likely to have liver cirrhosis or hematologic cancer, to be a surgical admission, and to have sepsis. They had a longer duration of ICU stay (5.9 vs. 2.5 days; P < 0.001) and a higher ICU mortality rate (23.0 vs. 16.3%; P < 0.001) but were also more severely ill on admission (Simplified Acute Physiology Score II, 40.2 vs. 34.7; P < 0.001; Sequential Organ Failure Assessment score, 6.5 vs. 4.5; P < 0.001). There was a direct relation between the number of blood transfusions and the mortality rate, but in multivariate analysis, blood transfusion was not significantly associated with a worse mortality rate. Moreover, in 821 pairs matched according to a propensity score, there was a higher 30-day survival rate in the transfusion group than in the other patients (P = 0.004).

Conclusion

This observational study does not support the view that blood transfusions are associated with increased mortality rates in acutely ill patients.
Predictors of Cognitive Dysfunction after Major Noncardiac Surgery
Authors: Monk Terri G. , Weldon B Craig , Garvan Cyndi W. , Dede Duane E. , van der Aa Maria T. , Heilman Kenneth M. , Gravenstein Joachim S.
Published: March 2009

Background

The authors designed a prospective longitudinal study to investigate the hypothesis that advancing age is a risk factor for postoperative cognitive dysfunction (POCD) after major noncardiac surgery and the impact of POCD on mortality in the first year after surgery.

Methods

One thousand sixty-four patients aged 18 yr or older completed neuropsychological tests before surgery, at hospital discharge, and 3 months after surgery. Patients were categorized as young (18-39 yr), middle-aged (40-59 yr), or elderly (60 yr or older). At 1 yr after surgery, patients were contacted to determine their survival status.

Results

At hospital discharge, POCD was present in 117 (36.6%) young, 112 (30.4%) middle-aged, and 138 (41.4%) elderly patients. There was a significant difference between all age groups and the age-matched control subjects (P < 0.001). At 3 months after surgery, POCD was present in 16 (5.7%) young, 19 (5.6%) middle-aged, and 39 (12.7%) elderly patients. At this time point, the prevalence of cognitive dysfunction was similar between age-matched controls and young and middle-aged patients but significantly higher in elderly patients compared to elderly control subjects (P < 0.001). The independent risk factors for POCD at 3 months after surgery were increasing age, lower educational level, a history of previous cerebral vascular accident with no residual impairment, and POCD at hospital discharge. Patients with POCD at hospital discharge were more likely to die in the first 3 months after surgery (P = 0.02). Likewise, patients who had POCD at both hospital discharge and 3 months after surgery were more likely to die in the first year after surgery (P = 0.02).

Conclusions

Cognitive dysfunction is common in adult patients of all ages at hospital discharge after major noncardiac surgery, but only the elderly (aged 60 yr or older) are at significant risk for long-term cognitive problems. Patients with POCD are at an increased risk of death in the first year after surgery.
Persistent Depression of Contractility and Vasodilation with Propofol but Not with Sevoflurane or Desflurane in Rabbits
Authors: Royse Colin Forbes , Liew David F. L. , Wright Christine E. , Royse Alistair G. , Angus James A.
Published: March 2009

Background

Propofol, sevoflurane, and desflurane may cause hemodynamic compromise during anesthesia and critical care management. The aim of the study was to compare these anesthetics during increased dose and recovery to maintenance level.

Methods

Anesthetized, open-chest New Zealand White rabbits were used to acquire dose-response curves with sevoflurane, desflurane, and propofol, followed by reduction to baseline infusion. Simultaneous high-fidelity left ventricular pressure and volume data were acquired during caval occlusion with a dual-field conductance catheter inserted via an apical stab. The preload recruitable stroke work and the end-diastolic pressure-volume relationship were used as the primary measures of contractility and diastolic function.

Results

The time-matched controls were stable over time. Propofol and desflurane but not sevoflurane caused dose-dependent reductions in myocardial contractility, although sevoflurane reduced contractility more at 1 minimal alveolar concentration. All anesthetics reduced mean arterial pressure, and significant recovery occurred for sevoflurane and desflurane but not for propofol. The end-diastolic pressure-volume relationship was increased by sevoflurane. Ejection fraction decreased with sevoflurane only. All anesthetics caused dose-dependent vasodilation, with recovery for desflurane and sevoflurane but not propofol. Heart rate was decreased with propofol without significant recovery. Propofol plasma concentrations remained elevated after dose return to baseline infusion rate, suggestive of distribution compartment saturation.

Conclusion

All three anesthetics caused dose-dependent decreases in cardiovascular function. Recovery of cardiovascular function occurred rapidly with sevoflurane and desflurane, but persistent depression of contractility, vasodilation, mean arterial pressure, and heart rate occurred with propofol during a 30-min recovery period.
Bispectral Index, Entropy, and Quantitative Electroencephalogram during Single-agent Xenon Anesthesia
Authors: Laitio Ruut M. , Kaskinoro Kimmo , Särkelä Mika O. K. , Kaisti Kaike K. , Salmi Elina , Maksimow Anu , Långsjö Jaakko W. , Aantaa Riku , Kangas Katja , Jääskeläinen Satu , Scheinin Harry
Published: March 2009

Background

The aim was to evaluate the performance of anesthesia depth monitors, Bispectral Index (BIS) and Entropy, during single-agent xenon anesthesia in 17 healthy subjects.

Methods

After mask induction with xenon and intubation, anesthesia was continued with xenon only. BIS, State Entropy and Response Entropy, and electroencephalogram were monitored throughout induction, steady-state anesthesia, and emergence. The performance of BIS, State Entropy, and Response Entropy were evaluated with prediction probability, sensitivity, and specificity analyses. The power spectrum of the raw electroencephalogram signal was calculated.

Results

The mean (SD) xenon concentration during anesthesia was 66.4% (2.4%). BIS, State Entropy, and Response Entropy demonstrated low prediction probability values at loss of response (0.455, 0.656, and 0.619) but 1 min after that the values were high (0.804, 0.941, and 0.929). Thereafter, equally good performance was demonstrated for all indices. At emergence, the prediction probability values to distinguish between steady-state anesthesia and return of response for BIS, State Entropy, and Response Entropy were 0.988, 0.892, and 0.992. No statistical differences between the performances of the monitors were observed. Quantitative electroencephalogram analyses showed generalized increase in total power (P < 0.001), delta (P < 0.001) and theta activity (P < 0.001), and increased alpha activity (P = 0.003) in the frontal brain regions.

Conclusions

Electroencephalogram-derived depth of sedation indices BIS and Entropy showed a delay to detect loss of response during induction of xenon anesthesia. Both monitors performed well in distinguishing between conscious and unconscious states during steady-state anesthesia. Xenon-induced changes in electroencephalogram closely resemble those induced by propofol.
Effects of Aprotinin Dosage on Renal Function
Authors: Dietrich Wulf , Busley Raimund , Boulesteix Anne-Laure
Published: March 2009

Background

The nonspecific serine protease inhibitor aprotinin is widely used in cardiac surgery to limit bleeding. Recently, concerns about the safety of this drug were raised, especially regarding impaired renal outcome. This event rate was supposed to be dose dependent.

Methods

In this observational study, the authors analyzed prospectively collected data of a single-center cardiac-anesthetic database. Adult patients treated with various dosages of aprotinin were evaluated. Logistic regression analysis identified independent predictors of renal outcome. The primary endpoint was a composite of novel postoperative renal failure requiring hemodialysis, an increased postoperative creatinine plasma concentration of 2 mg/dl or greater, or a difference between maximal postoperative and preoperative plasma creatinine of 0.7 mg/dl or greater.

Results

The study analyzed 8,548 patients. Multiple logistic regression (c index = 0.861) did not show a significant association between aprotinin dosage and renal outcome, as did the bootstrap procedure (odds ratio, 0.98; confidence interval, 0.90-1.07). The most relevant predictor was a preoperatively elevated creatinine concentration (odds ratio, 11.4; confidence interval, 9.05-14.3). Patients with postoperative renal impairment or failure were at higher preoperative risk and/or underwent more complex procedures. In subgroups of patients with preoperatively impaired renal function (creatinine > or =1.5 mg/dl) (n = 1,075), complex procedures (n = 1,920), or insulin-dependent diabetes (n = 650) or patients undergoing isolated myocardial revascularization (n = 4,901), no association between aprotinin dosage and adverse renal outcome was observed.

Conclusion

In the current analysis, aprotinin dosage was not associated with increased adverse renal outcome. In regard to renal outcome, this analysis did not demonstrate an essential detrimental influence of aprotinin dosage on renal function.
Desflurane but Not Sevoflurane Impairs Airway and Respiratory Tissue Mechanics in Children with Susceptible Airways
Authors: von Ungern-Sternberg Britta S. , Saudan Sonja , Petak Ferenc , Hantos Zoltan , Habre Walid
Published: March 2009

Background

Although sevoflurane and desflurane exert bronchoactive effects, their impact on the airway and respiratory tissue mechanics have not been systematically compared in children, especially in those with airway susceptibility (AS). The aim of this study was to assess airway and respiratory tissue mechanics in children with and without AS during sevoflurane and desflurane anesthesia.

Methods

Respiratory system impedance was measured in healthy control children (group C, n = 20) and in those with AS (group AS, n = 20). Respiratory system impedance was determined during propofol anesthesia and during inhalation of sevoflurane and desflurane 1 minimum alveolar concentration in random order. Airway resistance, tissue damping, and elastance were determined from the respiratory system impedance spectra by model fitting.

Results

Children in group AS exhibited significantly higher respiratory impedance parameters compared with those in group C. Sevoflurane slightly decreased airway resistance (-7.0 +/- 1.5% vs. -4.8 +/- 2.4% in groups C and AS, respectively) in both groups. In contrast, desflurane caused elevations in airway resistance and tissue mechanical parameters, with markedly enhanced airway narrowing in children with AS (18.2 +/- 2.8% vs. 53.9 +/- 5%; P < 0.001 for airway resistance in groups C and AS, respectively). Neither the order of drug administration nor the time after the establishment of their steady state concentrations affected these findings.

Conclusions

These results emphasized the deleterious effects of desflurane on the airways, particularly in children with susceptible airways in contrast with the consistent beneficial effects of sevoflurane, questioning the use of desflurane in children with AS.
Identification and Biochemical Characterization of a Novel Ryanodine Receptor Gene Mutation Associated with Malignant Hyperthermia
Authors: Anderson Ayuk A. , Brown Rosemary L. , Polster Brenda , Pollock Neil , Stowell Kathryn M.
Published: March 2009

Background

Mutations in the skeletal muscle ryanodine receptor gene may result in altered calcium release from sarcoplasmic reticulum stores, giving rise to malignant hyperthermia (MH). MH is a pharmacogenetic skeletal muscle disorder triggered by volatile anesthetics and depolarizing muscle relaxants. Diagnosis of MH is by in vitro contracture testing of quadriceps muscle. DNA analysis of causative mutations is limited by the large number of mutations that cosegregate with MH and the relatively few that have been biochemically characterized.

Methods

DNA sequence analysis was used to screen the skeletal muscle ryanodine receptor gene in MH-susceptible individuals. A diagnostic test using real-time polymerase chain reaction was developed to detect the mutation in individuals diagnosed as MH susceptible by in vitro contracture testing. The functional relevance of this mutation was examined in Epstein-Barr virus-immortalized B-lymphoblastoid cells.

Results

A novel ryanodine receptor mutation (cytosine 14997 thymine resulting in a histidine 4833 tyrosine substitution) was identified in pathology specimens from two patients with fatal MH reactions. B lymphocytes from patients with this mutation were approximately twofold more sensitive than MH-negative cells to activation with 4-chloro-m-cresol. The amount of Ca released from B lymphocytes of MH-susceptible patients was significantly greater than that released from cells of family members without this mutation. Haplotype analysis suggests that both families had a common ancestor.

Conclusions

DNA analysis to detect mutations which cosegregate with MH as well as biochemical assays on cultured lymphocytes obtained from blood can serve as useful diagnostic tools for MH susceptibility and genotype-phenotype correlations.
Inhibition of Poly(Adenosine Diphosphate–Ribose) Polymerase Attenuates Ventilator-induced Lung Injury
Authors: Vaschetto Rosanna , Kuiper Jan W. , Chiang Shyh Ren , Haitsma Jack J. , Juco Jonathan W. , Uhlig Stefan , Plötz Frans B. , Corte Francesco Della , Zhang Haibo , Slutsky Arthur S.
Published: March 2009

Background

Mechanical ventilation can induce organ injury associated with overwhelming inflammatory responses. Excessive activation of poly(adenosine diphosphate-ribose) polymerase enzyme after massive DNA damage may aggravate inflammatory responses. Therefore, the authors hypothesized that the pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase by PJ-34 would attenuate ventilator-induced lung injury.

Methods

Anesthetized rats were subjected to intratracheal instillation of lipopolysaccharide at a dose of 6 mg/kg. The animals were then randomly assigned to receive mechanical ventilation at either low tidal volume (6 ml/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (15 ml/kg) with zero positive end-expiratory pressure, in the presence and absence of intravenous administration of PJ-34.

Results

The high-tidal-volume ventilation resulted in an increase in poly(adenosine diphosphate-ribose) polymerase activity in the lung. The treatment with PJ-34 maintained a greater oxygenation and a lower airway plateau pressure than the vehicle control group. This was associated with a decreased level of interleukin 6, active plasminogen activator inhibitor 1 in the lung, attenuated leukocyte lung transmigration, and reduced pulmonary edema and apoptosis. The administration of PJ-34 also decreased the systemic levels of tumor necrosis factor alpha and interleukin 6, and attenuated the degree of apoptosis in the kidney.

Conclusion

The pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase reduces ventilator-induced lung injury and protects kidney function.
Severe Brachial Plexopathy after an Ultrasound-guided Single-injection Nerve Block for Total Shoulder Arthroplasty in a Patient with Multiple Sclerosis
Authors: Koff Matthew D. , Cohen Jeffrey A. , McIntyre John J. , Carr Charles F. , Sites Brian D.
Published: March 2009

DESPITE the known benefits of regional anesthesia for patients undergoing joint arthroplasty, the performance of peripheral nerve blocks in patients with multiple sclerosis (MS) remains controversial. MS has traditionally been described as an isolated disease of the central nervous system, without involvement of the peripheral nerves, and peripheral nerve blockade has been suggested to be safe. However, careful review of the literature suggests that MS may also be associated with involvement of the peripheral nervous system, challenging traditional teachings. There is a paucity of evidence with regard to safety in using peripheral nerve regional anesthesia in these patients. This makes it difficult to provide adequate "informed consent" to these patients. This case report describes a patient with MS who sustained a severe brachial plexopathy after a total shoulder arthroplasty during combined general anesthesia and interscalene nerve block.
Enhanced Peripheral Analgesia Using Virally Mediated Gene Transfer of the μ-Opioid Receptor in Mice
Authors: Zhang Guohua , Mohammad Husam , Peper Brad D. , Raja Srinivasa , Wilson Steven P. , Sweitzer Sarah M.
Published: March 2009

Background

The use of opioids to treat pain is often limited by side effects mediated through the central nervous system. The current study used a recombinant herpes simplex virus type 1 to increase expression of the mu-opioid receptor (muOR) in primary afferent neurons. The goal of this strategy was to enhance peripheral opioid analgesia.

Methods

Cutaneous inoculation with herpes simplex virus containing muOR complementary DNA (cDNA) in antisense (SGAMOR) or sense (SGMOR) orientation relative to a constitutive promoter, or complementary DNA for Escherichia coli lac Z gene as a control virus (SGZ) was used to modify the levels of muOR in primary afferents. The effects of altered muOR levels on peripheral analgesia were then examined.

Results

At 4 weeks after SGAMOR and SGMOR infection, decreased and increased muOR immunoreactivity was observed in ipsilateral dorsal hind paw skin, lumbar dorsal root ganglion cells, and superficial dorsal horns, respectively, compared with SGZ. This change in muOR expression in mice by SGAMOR and SGMOR was accompanied at the behavioral level with a rightward and leftward shift in the loperamide dose-response curve, respectively, compared with SGZ.

Conclusions

This gene therapy approach may provide an innovative strategy to enhance peripheral opioid analgesia for the treatment of pain in humans, thereby minimizing centrally mediated opioid side effects such as sedation and addiction.
Attenuation of the 40-Hertz Auditory Steady State Response by Propofol Involves the Cortical and Subcortical Generators
Authors: Plourde Gilles , Garcia-Asensi Alfonso , Backman Steven , Deschamps Alain , Chartrand Daniel , Fiset Pierre , Picton Terence W.
Published: March 2009

Background

The 40-Hz auditory steady state response (40-Hz ASSR) provides a reliable marker of anesthetic-induced unconsciousness. Brain electric source analysis indicates that the 40-Hz ASSR arises from cortical and subcortical generators. The authors used source analysis to assess the effect of propofol anesthesia on the cerebral generators of the 40-Hz ASSR. They also examined the effect of propofol on two auditory evoked potentials of cortical origin: the N1 and the sustained potential.

Methods

Eleven healthy human volunteers were anesthetized with propofol given in target-concentration mode at the minimal concentration causing unconsciousness. The 40-Hz ASSR was recorded before, during, and after anesthesia. The source model consisted of five concurrently active generator dipoles: two in the contralateral auditory cortex (one tangentially oriented, one radially oriented), two in the ipsilateral auditory cortex (same orientations), and one in the midline brainstem.

Results

During anesthesia, the strength of the cortical and brainstem dipoles was reduced to the same extent (to 54% of baseline for the four cortical dipoles pooled vs. 53% for the brainstem dipole). Dipole strength during anesthesia was significantly less (P < 0.01) than during baseline and recovery for both cortical and brainstem dipoles. The N1 and sustained potential were no longer recordable during anesthesia.

Conclusions

The attenuation of the 40-Hz ASSR during propofol anesthesia results from a reduction of similar magnitude of the activity of the cortical and brainstem generators. The N1 and sustained potential are so profoundly attenuated during propofol anesthesia that they are no longer recordable from the scalp.
The Neonatologist's Dilemma: Catch‐up Growth or Beneficial Undernutrition in Very Low Birth Weight Infants—What Are Optimal Growth Rates?
Authors: Thureen Patti J
Published: March 2009

As the threshold of viability decreases, clinicians who care for preterm neonates increasingly are faced with making decisions regarding feeding in a population for which there are no clear guidelines and minimal scientific data to inform optimal nutritional strategies. It is becoming more apparent that the amount of nutrition, as well as the timing of nutrient delivery, may affect long‐term growth and metabolic outcomes. Both overnutrition and undernutrition at critical growth periods may have adverse effects. The risks and benefits of nutrient delivery designed to achieve “catch‐up” growth need to be further identified. This article reviews both established concepts and more recently identified issues that need to be considered by the neonatologist when making feeding decisions in the very preterm neonate.
Use of Lactobacillus casei Subspecies Rhamnosus GG and Gastrointestinal Colonization by Candida Species in Preterm Neonates
Authors: Manzoni Paolo
Published: March 2009

Candida species increasingly cause morbidity and mortality in the premature infant in neonatal intensive care units, and the gut reservoir is the site from which dissemination most frequently starts in such patients. Specific antifungal prophylaxis is the most suitable strategy with which to limit the severity and the frequent neurodevelopmental impairment in survivors that is associated with neonatal invasive fungal infections. Recent interest has focused on the use of probiotics for the treatment of several diseases in neonatal patients. Pilot studies have implicated these organisms in necrotizing enterocolitis, sepsis, and urinary tract infections. Other applications of probiotic therapy in preterm neonates may also include the prevention of fungal colonization and of Candida‐related disorders. Probiotics could provide an innovative and less invasive approach because they modify the bowel flora by colonizing the gastrointestinal tract. Basic research has shown that in mice models, the Lactobacillus casei subsp Rhamnosus GG (LGG) is effective in preventing Candida gut colonization and systemic dissemination. A pilot, randomized, double‐blind, placebo‐controlled trial in human preterm neonates has demonstrated that LGG administered in the first month of life significantly reduces enteric Candida colonization. The present article summarizes the state of the art about probiotics and Candida‐related diseases in the preterm neonate and emphasizes the need for further investigations to determine unequivocally the possible role of LGG in the prevention and management of the fungal diseases in preterm neonates.
Wireless Capsule Endoscopy: Indications, Limitations, and Future Challenges
Authors: El‐Matary Wael
Published: March 2009

Wireless capsule endoscopy is one of the recent inventions that has made an impact in the diagnostic work‐up of gastrointestinal diseases, mainly in small intestinal pathology, the part of the gut that cannot be totally visualized by upper and lower gastrointestinal endoscopy. Since the first report documenting the use of capsule endoscopy, many adult clinical trials have taken place. Although the Food and Drug Administration approved the use of the capsule in children (ages 10–18 years) in October 2003, few small clinical trials exploring the diagnostic yield of capsule endoscopy in pediatric populations have been published.
GLP‐2 Administration Results in Increased Proliferation but Paradoxically an Adverse Outcome in a Juvenile Piglet Model of Short Bowel Syndrome
Authors: Pereira‐Fantini Prue M , Nagy Eva S , Thomas Sarah L , Taylor Russell G , Sourial Magdy , Paris Monique CJ , Holst Jens J , Fuller Peter J , Bines Julie E
Published: March 2009

Objective:

The objective of the present study was to examine the effect of glucagon‐like peptide‐2 (GLP‐2) administration in a piglet, juvenile model of short bowel syndrome.

Materials and Methods:

Four‐week‐old piglets underwent either a sham operation or 75% small bowel resection. Postoperatively, piglets received either polymeric infant formula diet or the diet and subcutaneous human recombinant GLP‐2 (1600 μg/day for 7 days, 800 μg/day thereafter). Food intake was monitored throughout the experiment, and stool and serum samples obtained fortnightly. After the piglets were killed, tissues were obtained from the duodenum, jejunum, ileum, and terminal ileum, and used for morphological and functional analysis.

Results:

Treatment with GLP‐2 resulted in significantly increased numbers of proliferating and apoptotic cells in the ileum of sham and small bowel resection piglets (P < 0.05). GLP‐2 administration resulted in decreased weight gain, serum albumin, and disaccharidases in both sham and small bowel resection piglets (P < 0.001 compared with polymeric infant formula diet alone).

Conclusions:

This is the first study to our knowledge to examine the effect of GLP‐2 administration in a juvenile short bowel syndrome model. Contrary to adult rodent studies, administration of GLP‐2 resulted in adverse outcomes including reduced ability to gain weight; decreased serum albumin, tissue maltase, and sucrase; and villous atrophy. We anticipate this information will have important implications for future paediatric clinical trials.
Na+‐dependent Neutral Amino Acid Transporter ASCT2 Is Downregulated in Seriously Traumatized Human Intestinal Epithelial Cells
Authors: Huang Qian , Li Ning , Zhang Wei , Zhu Weiming , Li Qiurong , Wang Bin , Li Jieshou
Published: March 2009

Objective:

Serious trauma to the body often is associated with changes in protein metabolism in multiple organs and tissues. Clinically, the catabolic response results in a generalized negative nitrogen balance. Nutrition support has been an important component of the care of seriously traumatized patients. However, during states of severe trauma, enterocyte transport function remains unclear. This study aims to quantitate the Na+‐dependent neutral amino acid transport and expression of its transporter in traumatically injured Caco‐2 cell lines.

Materials and Methods:

Transport and transporter of Na+‐dependent neutral amino acid in Caco‐2 cell lines were characterized. Then the cell lines were cultured under hypoxic, nutrient‐deprived, and ischemic conditions for 1, 2, 4, and 6 hours. After severe trauma was performed, we investigated the transport of Na+‐dependent neutral amino acids and the expression of transporter protein and mRNA in apical membrane vesicles.

Results:

Among the neutral amino acid transporters, only ASCT2 mRNA was amplified successfully. Under nutrient‐deprived and ischemic conditions, transport of L‐alanine and L‐glutamine decreased significantly compared with control (P < 0.01), whereas hypoxia had no significant effect. The changes were associated with a decrease in maximum transport velocity without an influence on transport affinity. Expression of relative transporter proteins and mRNA decreased significantly compared with control (P < 0.01).

Conclusions:

Na+‐dependent neutral amino acid transport and its key transporter are differently regulated during state of traumatic injury. It may be of use to provide some strategies targeting the special nutrient requirements and transport capabilities of seriously traumatized patients.
Critical Analysis of Bariatric Procedures in Prader‐Willi Syndrome
Authors: Scheimann AO , Butler MG , Gourash L , Cuffari C , Klish W
Published: March 2009

Prader‐Willi syndrome (PWS) is a complex genetic disorder localized to chromosome 15 and is considered the most common genetic cause of the development of life‐threatening obesity. Although some morbidities associated with PWS, including respiratory disturbance/hypoventilation, diabetes, and stroke, are commonly seen in obesity, others such as osteoporosis, growth hormone deficiency, and hypogonadism, and also altered pain threshold and inability to vomit, pose unique issues. Various bariatric procedures have been used to cause gastric stasis, decrease gastric volume, and induce malabsorption, with poor results in PWS patients in comparison with normal obese individuals.
Complementary Feeding: A Commentary by the ESPGHAN Committee on Nutrition
Authors:   ESPGHAN Committee on Nutrition:, Agostoni Carlo , Decsi Tamas , Fewtrell Mary , Goulet Olivier , Kolacek Sanja , Koletzko Berthold , Michaelsen Kim Fleischer , Moreno Luis , Puntis John , Rigo Jacques , Shamir Raanan , Szajewska Hania , Turck Dominique , van Goudoever Johannes
Published: March 2009

This position paper on complementary feeding summarizes evidence for health effects of complementary foods. It focuses on healthy infants in Europe. After reviewing current knowledge and practices, we have formulated these conclusions: Exclusive or full breast‐feeding for about 6 months is a desirable goal. Complementary feeding (ie, solid foods and liquids other than breast milk or infant formula and follow‐on formula) should not be introduced before 17 weeks and not later than 26 weeks. There is no convincing scientific evidence that avoidance or delayed introduction of potentially allergenic foods, such as fish and eggs, reduces allergies, either in infants considered at increased risk for the development of allergy or in those not considered to be at increased risk. During the complementary feeding period, >90% of the iron requirements of a breast‐fed infant must be met by complementary foods, which should provide sufficient bioavailable iron. Cow's milk is a poor source of iron and should not be used as the main drink before 12 months, although small volumes may be added to complementary foods. It is prudent to avoid both early (<4 months) and late (≥7 months) introduction of gluten, and to introduce gluten gradually while the infant is still breast‐fed, inasmuch as this may reduce the risk of celiac disease, type 1 diabetes mellitus, and wheat allergy. Infants and young children receiving a vegetarian diet should receive a sufficient amount (∼500 mL) of breast milk or formula and dairy products. Infants and young children should not be fed a vegan diet.
A Conceptual Framework for the Use of Illness Narratives in Medical Education
Authors: Kumagai Arno K.
Published: March 2009

The use of narratives, including physicians’ and patients’ stories, literature, and film, is increasingly popular in medical education. There is, however, a need for an overarching conceptual framework to guide these efforts, which are often dismissed as “soft” and placed at the margins of medical school curricula. The purpose of this article is to describe the conceptual basis for an approach to patient-centered medical education and narrative medicine initiated at the University of Michigan Medical School in the fall of 2003. This approach, the Family Centered Experience, involves home visits and conversations between beginning medical students and patient volunteers and their families and is aimed at fostering humanism in medicine. The program incorporates developmental and learning theory, longitudinal interactions with individuals with chronic illness, reflective learning, and small-group discussions to explore the experience of illness and its care. The author describes a grounding of this approach in theories of empathy and moral development and clarifies the educational value that narratives bring to medical education. Specific pedagogical considerations, including use of activities to create “cognitive disequilibrium” and the concept of transformative learning, are also discussed and may be applied to narrative medicine, professionalism, multicultural education, medical ethics, and other subject areas in medical education that address individuals and their health care needs in society.
Organizational Models of Educational Technology in U.S. and Canadian Medical Schools
Authors: Souza Kevin H. , Kamin Carol , O’Sullivan Patricia , Moses Anna , Heestand Diane
Published: March 2009

Purpose

To examine the organizational structure of educational technology units within U.S. and Canadian medical schools in order to (1) identify organization models that support educational technology, (2) describe key attributes of these models, and (3) discuss the strengths and challenges associated with these models.

Method

The authors distributed a survey to 88 schools that had previously provided information on their educational technology services and infrastructure. The authors developed the survey through a series of pilots and, then, from the data for each respondent school, created concept maps, which were used to identify organizational models. The authors conducted analyses to determine differences among models. The authors coded the comments about organizational models and identified themes.

Results

The authors received adequate data for analysis from 61 schools (69%). Four models for educational technology organizations emerged: (1) centralized units located in the school of medicine, (2) centralized units located at the health science center, (3) centralized units at the comprehensive university, and (4) no centralized unit (Dispersed Model). The majority (75%) of schools relied on some type of centralized organization. Whereas few organization attributes proved to be statistically significant, the centralized models have more resources devoted to educational technology and a closer alignment with the academic mission than the Dispersed Model.

Conclusions

Medical schools primarily use central models. The authors recommend that schools structuring their educational technology resources consider exploration of a central model because of its focused use of resources to improve teaching and learning.