bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitivity characteristics in nanosized coated long period gratings
Authors: Cusano Andrea , Iadicicco Agostino , Pilla Pierluigi , Cutolo Antonello , Giordano Michele , Campopiano Stefania
Published: November 2006

This work presents an experimental analysis of the sensitivity characteristics to the surrounding refractive index (SRI) in long period gratings coated with polymeric overlay with high refractive index and thickness values ranging in hundreds of nanometers. The presence of the coating induces the cladding to overlay mode transition depending on the overlay features and the SRI. The immediate consequence is a drastic modification of the sensitivity characteristics from the sublinear monotone behavior to a resonantlike shape. Here, the sensitivity characteristics of coated long period gratings have been investigated to outline their dependence on the overlay thickness and order mode.
High performance InP-based quantum cascade distributed feedback lasers with deeply etched lateral gratings
Authors: Kennedy K. , Krysa A. B. , Roberts J. S. , Groom K. M. , Hogg R. A. , Revin D. G. , Wilson L. R. , Cockburn J. W.
Published: November 2006

The fabrication and operating characteristics of lateral grating distributed feedback InP-based quantum cascade lasers emitting at λ∼10μm are reported. High performance, room temperature single mode lasers, utilizing double-sided lateral gratings, are achieved in InP-based material grown by metal organic phase epitaxy. These deeply etched gratings are made possible by the development of a high aspect ratio, multistage, inductively coupled plasma etch process. A threshold current density of ∼5.5kA∕cm2 is measured at room temperature and side mode suppression ratio >20dB with a tuning coefficient of −0.067cm−1K−1 is observed over a temperature range of 190–330K.
Photoluminescence oscillations in porous alumina films
Authors: Huang K. , Pu L. , Shi Y. , Han P. , Zhang R. , Zheng Y. D.
Published: November 2006

The dominant oscillation shown in the laser-excited photoluminescence spectrum of the porous alumina film can be ascribed to the interference within a Fabry-Pérot optical cavity where the separation between two neighboring oscillations is highly sensitive to the film’s thickness and refractive index. The method, designated as photoluminescence oscillation, endows photoluminescence spectrum with another dimension and results in a nondestructive method for the measurement of the thickness and refractive index with a high resolution.
Geometrical cluster ensemble analysis of random sphere packings
Authors: Wouterse A. , Philipse A. P.
Published: November 2006

We introduce a geometric analysis of random sphere packings based on the ensemble averaging of hard-sphere clusters generated via local rules including a nonoverlap constraint for hard spheres. Our cluster ensemble analysis matches well with computer simulations and experimental data on random hard-sphere packing with respect to volume fractions and radial distribution functions. To model loose as well as dense sphere packings various ensemble averages are investigated, obtained by varying the generation rules for clusters. Essential findings are a lower bound on volume fraction for random loose packing that is surprisingly close to the freezing volume fraction for hard spheres and, for random close packing, the observation of an unexpected split peak in the distribution of volume fractions for the local configurations. Our ensemble analysis highlights the importance of collective and global effects in random sphere packings by comparing clusters generated via local rules to random sphere packings and clusters that include collective effects.
Glass transition in fullerenes: Mode-coupling theory predictions
Authors: Greenall M. J. , Voigtmann Th.
Published: November 2006

We report idealized mode-coupling theory results for the glass transition of ensembles of model fullerenes interacting via phenomenological two-body potentials. Transition lines are found for C60, C70, and C96 in the temperature-density plane. We argue that the observed glass transition behavior is indicative of kinetic arrest that is strongly driven by the interparticle attraction in addition to excluded-volume repulsion. In this respect, these systems differ from most standard glass-forming liquids. They feature arrest that occurs at lower densities and that is stronger than would be expected for repulsion-dominated hard-sphere-like or Lennard-Jones-type systems. The influence of attraction increases with increasing the number of carbon atoms per molecule. However, unrealistically large fullerenes would be needed to yield behavior reminiscent of recently investigated model colloids with strong short-ranged attraction (glass-glass transitions and logarithmic decay of time-correlation functions).
Fourier decompositions and pulse sequence design algorithms for nuclear magnetic resonance in inhomogeneous fields
Authors: Pryor Brent , Khaneja Navin
Published: November 2006

In this paper, we introduce algorithms based on Fourier synthesis for designing phase compensating rf pulse sequences for high-resolution nuclear magnetic resonance (NMR) spectroscopy in an inhomogeneous B0 field. We show that using radio frequency pulses and time varying linear gradients in three dimensions, it is possible to impart the transverse magnetization of spins phase, which is a desired function of the spatial (x,y,z) location. Such a sequence can be used to precompensate the phase that will be acquired by spins at different spatial locations due to inhomogeneous magnetic fields. With this precompensation, the chemical shift information of the spins can be reliably extracted and high resolution NMR spectrum can be obtained.
C
4
Cl
: Bent or linear?
Authors: Arulmozhiraja Sundaram , Ehara Masahiro , Nakatsuji Hiroshi
Published: November 2006

The ground state structure for the CCCCCl radical was computed by using symmetry-adapted cluster configuration-interaction (SAC-CI) theory along with density functional theory to overcome the differences raised in the recently published paper [Y. Sumiyoshi et al., Chem. Phys. Lett. 414, 82 (2005)] between the theory and the experiment. SAC-CI results clearly support the earlier experimental conclusion that the radical has the bent ground state structure corresponding to Π2 symmetry. Contrarily, probably due to spin contamination, mixing of a bent doublet ground state with the quartet components of a linear structure, coupled-cluster singles and doubles (CCSD) calculations were unable to provide reliable results. Results obtained using density functional theory also show that the radical has a bent structure. Some low-lying doublet excited states were also studied using the SAC-CI theory. The energy difference between the ground Π state and the nearby Σ state is around 0.2eV. The excitation energy for the transition with the largest oscillator strength agrees with the strongest absorption peak.
Polarizabilities of the alkali anions: Li− to Fr−
Authors: Lupinetti Concetta , Thakkar Ajit J.
Published: November 2006

Static dipole polarizabilities are calculated for the ground states of the alkali anions from Li− to Fr−. The polarizabilities include scalar relativistic effects at the second-order Douglas-Kroll level and were computed using the finite-field, coupled-cluster CCSD(T) method with large, carefully optimized basis sets. The relativistic polarizabilities increase with Z, reach a maximum at Cs−, and then decrease again unlike their nonrelativistic counterparts which increase monotonically with Z.
Abatement of SF6 and CF4 using an enhanced kerosene microwave plasma burner
Authors: Hun Shin Dong , Cheol Hong Yong , Cheon Cho Soon , Sup Uhm Han
Published: November 2006

A kerosene microwave plasma burner was presented as a tool for abatement of SF6 and CF4 gases, which cause global warming. The plasma burner operates by injecting kerosene as a liquid hydrocarbon fuel into a microwave plasma torch and by mixing the resultant gaseous hydrogen and carbon compounds with air or oxygen (O2) gas. The abatement of SF6 and CF4, by making use of the kerosene plasma burner, was conducted in terms of nitrogen (N2) flow rates. The destruction and removal efficiency of the burner were achieved up to 99.9999% for 0.1 liters per minute (lpm) SF6 in 120lpm N2 and 99.3% for 0.05lpm CF4 in 60lpm N2, revealing that the microwave plasma burner can effectively eliminate perfluorocompounds emitted from the semiconductor industries.
Interproton allylic spin-spin coupling involving exocyclic groups
Authors: Newsoroff GP , Sternhell S
Published: November 2006

N.m.r. parameters for 55
compounds incorporating exocyclic groups were obtained. In unstrained
structures the relative (as well as the absolute) magnitudes of transoid and cisoid allylic
coupling constants depend on the magnitudes of the dihedral angles but
additional effects were also identified. The magnitudes of geminal coupling
constants between the protons of exocyclic methylene groups and of homoallylic coupling constants involving exocyclic ethylidene and isopropylidene
groups vary systematically with ring size.
Participation of mouse DNA polymerase ι in strand-biased mutagenic bypass of UV photoproducts and suppression of skin cancer
Authors: Dumstorf Chad A. , Clark Alan B. , Lin Qingcong , Kissling Grace E. , Yuan Tao , Kucherlapati Raju , McGregor W. Glenn , Kunkel Thomas A.
Published: November 2006

DNA polymerase ι (pol ι) is a conserved Y family enzyme that is implicated in translesion DNA synthesis (TLS) but whose cellular functions remain uncertain. To test the hypothesis that pol ι performs TLS in cells, we compared UV-induced mutagenesis in primary fibroblasts derived from wild-type mice to mice lacking functional pol η, pol ι, or both. A deficiency in mouse DNA polymerase η (pol η) enhanced UV-induced
Hprt
mutant frequencies. This enhanced UV-induced mutagenesis and UV-induced mutagenesis in wild-type cells were strongly diminished in cells deficient in pol ι, indicating that pol ι participates in the bypass of UV photoproducts in cells. Moreover, a clear strand bias among UV-induced base substitutions was observed in wild-type cells that was diminished in pol η- and pol ι-deficient mouse cells and abolished in cells deficient in both enzymes. These data suggest that these enzymes bypass UV photoproducts in an asymmetric manner. To determine whether pol ι status affects cancer susceptibility, we compared the UV-induced skin cancer susceptibility of wild-type mice to mice lacking functional pol η, pol ι, or both. Although pol ι deficiency alone had no effect, UV-induced skin tumors in pol η-deficient mice developed 4 weeks earlier in mice concomitantly deficient in pol ι. Collectively, these data reveal functions for pol ι in bypassing UV photoproducts and in delaying the onset of UV-induced skin cancer.
NOTCH1 directly regulates
c-MYC
and activates a feed-forward-loop transcriptional network promoting leukemic cell growth
Authors: Palomero Teresa , Lim Wei Keat , Odom Duncan T. , Sulis Maria Luisa , Real Pedro J. , Margolin Adam , Barnes Kelly C. , O'Neil Jennifer , Neuberg Donna , Weng Andrew P. , Aster Jon C. , Sigaux Francois , Soulier Jean , Look A. Thomas , Young Richard A. , Califano Andrea , Ferrando Adolfo A.
Published: November 2006

The NOTCH1 signaling pathway directly links extracellular signals with transcriptional responses in the cell nucleus and plays a critical role during T cell development and in the pathogenesis over 50% of human T cell lymphoblastic leukemia (T-ALL) cases. However, little is known about the transcriptional programs activated by NOTCH1. Using an integrative systems biology approach we show that NOTCH1 controls a feed-forward-loop transcriptional network that promotes cell growth. Inhibition of NOTCH1 signaling in T-ALL cells led to a reduction in cell size and elicited a gene expression signature dominated by down-regulated biosynthetic pathway genes. By integrating gene expression array and ChIP-on-chip data, we show that NOTCH1 directly activates multiple biosynthetic routes and induces
c-MYC
gene expression. Reverse engineering of regulatory networks from expression profiles showed that NOTCH1 and c-MYC govern two directly interconnected transcriptional programs containing common target genes that together regulate the growth of primary T-ALL cells. These results identify c-MYC as an essential mediator of NOTCH1 signaling and integrate NOTCH1 activation with oncogenic signaling pathways upstream of c-MYC.
Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men
Authors: Petersen Kitt Falk , Dufour Sylvie , Feng Jing , Befroy Douglas , Dziura James , Man Chiara Dalla , Cobelli Claudio , Shulman Gerald I.
Published: November 2006

Type 2 diabetes mellitus (T2DM) is strongly associated with obesity in most, but not all, ethnic groups, suggesting important ethnic differences in disease susceptibility. Although it is clear that insulin resistance plays a major role in the pathogenesis of T2DM and that insulin resistance is strongly associated with increases in hepatic (HTG) and/or intramyocellular lipid content, little is known about the prevalence of insulin resistance and potential differences in intracellular lipid distribution among healthy, young, lean individuals of different ethnic groups. To examine this question, 482 young, lean, healthy, sedentary, nonsmoking Eastern Asians (
n
= 49), Asian-Indians (
n
= 59), Blacks (
n
= 48), Caucasians (
n
= 292), and Hispanics (
n
= 34) underwent an oral glucose tolerance test to assess whole-body insulin sensitivity by an insulin sensitivity index. In addition, intramyocellular lipid and HTG contents were measured by using proton magnetic resonance spectroscopy. The prevalence of insulin resistance, defined as the lower quartile of insulin sensitivity index, was ≈2- to 3-fold higher in the Asian-Indians compared with all other ethnic groups, and this could entirely be attributed to a 3- to 4-fold increased prevalence of insulin resistance in Asian-Indian men. This increased prevalence of insulin resistance in the Asian-Indian men was associated with an ≈2-fold increase in HTG content and plasma IL-6 concentrations compared with Caucasian men. These data demonstrate important ethnic and gender differences in the pathogenesis of insulin resistance in Asian-Indian men and have important therapeutic implications for treatment of T2DM and for the development of steatosis-related liver disease in this ethnic group.
Genomic analysis of the uncultivated marine crenarchaeote
Cenarchaeum symbiosum
Authors: Hallam Steven J. , Konstantinidis Konstantinos T. , Putnam Nik , Schleper Christa , Watanabe Yoh-ichi , Sugahara Junichi , Preston Christina , de la Torre José , Richardson Paul M. , DeLong Edward F.
Published: November 2006

Crenarchaeota
are ubiquitous and abundant microbial constituents of soils, sediments, lakes, and ocean waters. To further describe the cosmopolitan nonthermophilic
Crenarchaeota
, we analyzed the genome sequence of one representative, the uncultivated sponge symbiont
Cenarchaeum symbiosum
.
C. symbiosum
genotypes coinhabiting the same host partitioned into two dominant populations, corresponding to previously described a- and b-type ribosomal RNA variants. Although they were syntenic, overlapping a- and b-type ribotype genomes harbored significant variability. A single tiling path comprising the dominant a-type genotype was assembled and used to explore the genomic properties of
C. symbiosum
and its planktonic relatives. Of 2,066 ORFs, 55.6% matched genes with predicted function from previously sequenced genomes. The remaining genes partitioned between functional RNAs (2.4%) and hypotheticals (42%) with limited homology to known functional genes. The latter category included some genes likely involved in the archaeal–sponge symbiotic association. Conversely, 525
C. symbiosum
ORFs were most highly similar to sequences from marine environmental genomic surveys, and they apparently represent orthologous genes from free-living planktonic
Crenarchaeota
. In total, the
C. symbiosum
genome was remarkably distinct from those of other known Archaea and shared many core metabolic features in common with its free-living planktonic relatives.
Suppression of spontaneous genome rearrangements in yeast DNA helicase mutants
Authors: Schmidt Kristina H. , Kolodner Richard D.
Published: November 2006

Saccharomyces cerevisiaemutants lacking two of the three DNA helicases Sgs1, Srs2, and Rrm3 exhibit slow growth that is suppressed by disrupting homologous recombination. Cells lacking Sgs1 and Rrm3 accumulate gross-chromosomal rearrangements (GCRs) that are suppressed by the DNA damage checkpoint and by homologous recombination-defective mutations. In contrast,rrm3,srs2, andsrs2 rrm3mutants have wild-type GCR rates. GCR types in helicase double mutants include telomere additions, translocations, and broken DNAs healed by a complex process of hairpin-mediated inversion. Spontaneous activation of the Rad53 checkpoint kinase in therrm3mutant depends on the Mec3/Rad24 DNA damage sensors and results from activation of the Mec1/Rad9-dependent DNA damage response rather than the Mrc1-dependent replication stress response. Moreover, helicase double mutants accumulate Rad51-dependent Ddc2 foci, indicating the presence of recombination intermediates that are sensed by checkpoints. These findings demonstrate that different nonreplicative helicases function at the interface between replication and repair to maintain genome integrity.
Bone marrow-derived fibroblast precursors mediate ischemic cardiomyopathy in mice
Authors: Haudek Sandra B. , Xia Ying , Huebener Peter , Lee John M. , Carlson Signe , Crawford Jeff R. , Pilling Darrell , Gomer Richard H. , Trial JoAnn , Frangogiannis Nikolaos G. , Entman Mark L.
Published: November 2006

We previously described a mouse model of fibrotic ischemia/reperfusion cardiomyopathy (I/RC) arising from daily, brief coronary occlusion. One characteristic of I/RC was the prolonged elevation of monocyte chemoattractant protein 1 (MCP-1), which was obligate to its phenotype and may contribute to the uptake of bloodborne cells. Here we describe in I/RC hearts a population of small spindle-shaped fibroblasts that were highly proliferative and expressed collagen I and α-smooth muscle actin (myofibroblast markers), CD34 (a precursor marker), and CD45 (a hematopoietic marker). These cells represented 3% of all nonmyocyte live cells. To confirm the cells' bone marrow origin, chimeric mice were created by the rescue of irradiated C57BL/6 mice with marrow from ROSA26, a congenic line expressing lacZ. I/RC resulted in a large population of spindle-shaped fibroblasts containing lacZ. We postulated that the fibroblast precursors represented a developmental path for a subset of monocytes, whose phenotype we have shown to be influenced by serum amyloid P (SAP). Thus, we administered SAP
in vivo
, which markedly reduced the number of proliferative spindle-shaped fibroblasts and completely prevented I/RC-induced fibrosis and global ventricular dysfunction. By contrast, SAP did not suppress the inflammation or chemokine expression seen in I/RC. SAP, a member of the pentraxin family, binds to Fcγ receptors and modifies the pathophysiological function of monocytes. Our data suggest that SAP interferes with assumption of a fibroblast phenotype in a subset of monocytes and that SAP may be an important regulator in the linkage between inflammation and nonadaptive fibrosis in the heart.
Bone morphogenetic protein signaling regulates the size of hair follicles and modulates the expression of cell cycle-associated genes
Authors: Sharov Andrey A. , Sharova Tatyana Y. , Mardaryev Andrei N. , di Vignano Alice Tommasi , Atoyan Ruzanna , Weiner Lorin , Yang Shi , Brissette Janice L. , Dotto G. Paolo , Botchkarev Vladimir A.
Published: November 2006

Bone morphogenetic protein (BMP) signaling is involved in the regulation of a large variety of developmental programs, including those controlling organ sizes. Here, we show that transgenic (TG) mice overexpressing the BMP antagonist noggin (promoter, K5) are characterized by a marked increase in size of anagen hair follicles (HFs) and by the replacement of zig-zag and auchen hairs by awl-like hairs, compared with the age-matched WT controls. Markedly enlarged anagen HFs of TG mice show increased proliferation in the matrix and an increased number of hair cortex and medulla cells compared with WT HFs. Microarray and real-time PCR analyses of the laser-captured hair matrix cells show a strong decrease in expression of Cdk inhibitor p27
Kip1
and increased expression of selected cyclins in TG vs. WT mice. Similar to TG mice, p27
Kip1
knockout mice also show an increased size of anagen HFs associated with increased cell proliferation in the hair bulb. Primary epidermal keratinocytes (KC) from TG mice exhibit significantly increased proliferation and decreased p27
Kip1
expression, compared with WT KC. Alternatively, activation of BMP signaling in HaCaT KC induces growth arrest, stimulates p27
Kip1
expression, and positively regulates p27
Kip1
promoter activity, thus further supporting a role of p27
Kip1
in mediating the effects of BMP signaling on HF size. These data suggest that BMP signaling plays an important role in regulating cell proliferation and controls the size of anagen HFs by modulating the expression of cell-cycle-associated genes in hair matrix KC.
Trends in Anesthesia-related Death and Brain Damage
Authors: Cheney Frederick W. , Posner Karen L. , Lee Lorri A. , Caplan Robert A. , Domino Karen B.
Published: November 2006

Background

The authors used the American Society of Anesthesiologists Closed Claims Project database to determine changes in the proportion of claims for death or permanent brain damage over a 26-yr period and to identify factors associated with the observed changes.

Methods

The Closed Claims Project is a structured evaluation of adverse outcomes from 6,894 closed anesthesia malpractice claims. Trends in the proportion of claims for death or permanent brain damage between 1975 and 2000 were analyzed.

Results

Claims for death or brain damage decreased between 1975 and 2000 (odds ratio, 0.95 per year; 95% confidence interval, 0.94-0.96; P < 0.01). The overall downward trend did not seem to be affected by the use of pulse oximetry and end-tidal carbon dioxide monitoring, which began in 1986. The use of these monitors increased from 6% in 1985 to 70% in 1989, and thereafter varied from 63% to 83% through the year 2000. During 1986-2000, respiratory damaging events decreased while cardiovascular damaging events increased, so that by 1992, respiratory and cardiovascular damaging events occurred in approximately the same proportion (28%), a trend that continued through 2000.

Conclusion

The significant decrease in the proportion of claims for death or permanent brain damage from 1975 through 2000 seems to be unrelated to a marked increase in the proportion of claims where pulse oximetry and end-tidal carbon dioxide monitoring were used. After the introduction and use of these monitors, there was a significant reduction in the proportion of respiratory and an increase in the proportion of cardiovascular damaging events responsible for death or permanent brain damage.
Survey of Anesthesia-related Mortality in France
Authors: Lienhart André , Auroy Yves , Péquignot Françoise , Benhamou Dan , Warszawski Josiane , Bovet Martine , Jougla Eric
Published: November 2006

Background

This study describes a nationwide survey that estimates the number and characteristics of anesthesia-related deaths for the year 1999.

Methods

Death certificates from the French national mortality database were selected from the International Classification of Diseases, Ninth Revision codes using a variable sampling fraction. Medical certifiers were sent a questionnaire (response rate, 97%), and the anesthesiologist in charge was offered a peer review (acceptance rate, 97%). Files were reviewed to determine the mechanism of each perioperative death and its relation to anesthesia. Mortality rates were calculated using the number of anesthetic procedures estimated from a national 1996 survey and compared with a previous (1978-1982) nationwide study.

Results

Among the 4,200 certificates analyzed, 256 led to a detailed evaluation. The death rates totally or partially related to anesthesia for 1999 were 0.69 in 100,000 (95% confidence interval, 0.22-1.2 in 100,000) and 4.7 in 100,000 (3.1-6.3 in 100,000), respectively. The death rate increased from 0.4 to 55 in 100,000 for American Society of Anesthesiologists physical status I and IV patients, respectively. Rates increased with increasing age. Although concerns regarding aspiration of gastric contents remain, intraoperative hypotension and anemia associated with postoperative ischemic complications were the associated factors most often encountered. Deviations from standard practice and organizational failure were often found to be associated with death.

Conclusion

In comparison with data from a previous nationwide study (1978-1982), the anesthesia-related mortality rate in France seems to be reduced 10-fold in 1999. Much remains to be done to improve compliance of physicians to standard practice and to improve the anesthetic system process.
A Phase I, Two-center Study of the Pharmacokinetics and Pharmacodynamics of Dexmedetomidine in Children
Authors: Petroz Guy C. , Sikich Nancy , James Michael , van Dyk Hanlie , Shafer Steven L. , Schily Markus , Lerman Jerrold
Published: November 2006

Background

To investigate dexmedetomidine in children, the authors performed an open-label study of the pharmacokinetics and pharmacodynamics of dexmedetomidine.

Methods

Thirty-six children were assigned to three groups; 24 received dexmedetomidine and 12 received no drug. Three doses of dexmedetomidine, 2, 4, and 6 microg x kg x h, were infused for 10 min. Cardiorespiratory responses and sedation were recorded for 24 h. Plasma concentrations of dexmedetomidine were collected for 24 h and analyzed. Pharmacokinetic variables were determined using nonlinear mixed effects modeling (NONMEM program). Cardiorespiratory responses were analyzed.

Results

Thirty-six children completed the study. There was an apparent difference in the pharmacokinetics between Canadian and South African children. The derived volumes and clearances in the Canadian children were V1 = 0.81 l/kg, V2 = 1.0 l/kg, Cl1 (systemic clearance) = 0.013 l x kg x min, Cl2 = 0.030 l x kg x min. The intersubject variabilities for V1, V2, and Cl1 were 45%, 38%, and 22%, respectively. Plasma concentrations in South African children were 29% less than in Canadian children. The volumes and clearances in the South African children were 29% larger. The terminal half-life was 110 min (1.8 h). Median absolute prediction error for the two-compartment mammillary model was 18%. Heart rate and systolic blood pressure decreased with time and with increasing doses of dexmedetomidine. Respiratory rate and oxygen saturation (in air) were maintained. Sedation was transient.

Conclusion

The pharmacokinetics of dexmedetomidine in children are predictable with a terminal half-life of 1.8 h. Hemodynamic responses decreased with increasing doses of dexmedetomidine. Respiratory responses were maintained, whereas sedation was transient.
Forehead Pulse Oximetry
Authors: Agashe Geeta S. , Coakley Joseph , Mannheimer Paul D.
Published: November 2006

Background

This study investigated whether a tensioning headband that applies up to 20 mmHg pressure over a forehead pulse oximetry sensor could improve arterial hemoglobin oxygen saturation reading accuracy in presence of venous pooling and pulsations at the forehead site.

Methods

Healthy volunteers were studied breathing room air in supine and various levels of negative incline (Trendelenburg position) using the forehead sensor with the headband adjusted to its maximum and minimum recommended pressure limits. Saturation readings obtained from the forehead sensor with the subjects supine and the headband in place were used as a baseline to compare the effects of negative incline on reading accuracy when using and not using the headband. Occurrences of false low-saturation readings detected by forehead sensors were compared with those from digit sensors.

Results

No difference was observed between saturation readings obtained from the forehead sensor in supine and negative incline positions when the headband was applied. Forehead sensor readings obtained while subjects were inclined and the headband was not used were significantly lower (P < 0.05) than the supine readings. There was no statistically significant difference between the digit and forehead sensor in reporting false low-saturation readings when the headband was applied, regardless of body incline.

Conclusions

Application of up to 20 mmHg pressure on the forehead pulse oximetry sensor using an elastic tensioning headband significantly reduced reading errors and provided consistent performance when subjects were placed between supine and up to 15 degrees head-down incline (Trendelenburg position).
The Effects of Ketamine and Rocuronium on the A-Line® Auditory Evoked Potential Index, Bispectral Index, and Spectral Entropy Monitor during Steady State Propofol and Remifentanil Anesthesia
Authors: Vereecke Hugo E. M. , Vanluchene Ann L. , Mortier Eric P. , Everaert Karel , Struys Michel M. R. F.
Published: November 2006

Background

The authors studied the effects of ketamine and rocuronium on the Bispectral Index, A-Line auditory evoked potential index, state entropy, and response entropy during a calculated steady state anesthesia with propofol and remifentanil.

Methods

After ethics committee approval, 42 patients were allocated to four groups. Baseline measurements were performed after implementing a calculated steady state anesthesia with propofol and remifentanil. The control group received no additional medication. The ketamine group received a bolus and continuous infusion of ketamine. The rocuronium group received a bolus of rocuronium. The rocuronium-ketamine group received both. All data were stored during 15 min after baseline. After inspection of the raw data, the authors conducted an explorative statistical analysis.

Results

No significant changes were found in the control group for any of the monitors. Mean values decreased in the rocuronium group for the A-Line auditory evoked potential index, Bispectral Index, and response entropy, but not for state entropy. In the ketamine group, the A-Line auditory evoked potential index and Bispectral Index did not change significantly, but state and response entropy increased. In the rocuronium-ketamine group, the A-Line auditory evoked potential index and Bispectral Index did not decrease as found in the rocuronium group. Response and state entropy increased significantly.

Conclusions

The response of all monitors after ketamine administration is not affected by simultaneous administration of rocuronium. Interpretation of all studied indices must be done cautiously while taking into account the clinical setting during measurement.
Pharmacokinetics and Pharmacodynamics of Midazolam and Metabolites in Nonventilated Infants after Craniofacial Surgery
Authors: Peeters Mariska Y. M. , Prins Sandra A. , Knibbe Catherijne A. J. , DeJongh Joost , Mathôt Ron A. A. , Warris Celesta , van Schaik Ron H. N. , Tibboel Dick , Danhof Meindert
Published: November 2006

Background

Because information on the optimal dose of midazolam for sedation of nonventilated infants after major surgery is scant, a population pharmacokinetic and pharmacodynamic model is developed for this specific group.

Methods

Twenty-four of the 53 evaluated infants (aged 3-24 months) admitted to the Pediatric Surgery Intensive Care Unit, who required sedation judged necessary on the basis of the COMFORT-Behavior score and were randomly assigned to receive midazolam, were included in the analysis. Bispectral Index values were recorded concordantly. Population pharmacokinetic and pharmacodynamic modeling was performed using NONMEM V (GloboMax LLC, Hanover, MD).

Results

For midazolam, total clearance was 0.157 l/min, central volume was 3.8 l, peripheral volume was 30.2 l, and intercompartmental clearance was 0.30 l/min. Assuming 60% conversion of midazolam to 1-OH-midazolam, the volume of distribution for 1-OH-midazolam and 1-OH-midazolamglucuronide was 6.7 and 1.7 l, and clearance was 0.21 and 0.047 l/min, respectively. Depth of sedation using COMFORT-Behavior could adequately be described by a baseline, postanesthesia effect (Emax model) and midazolam effect (Emax model).The midazolam concentration at half maximum effect was 0.58 mum with a high interindividual variability of 89%. Using the Bispectral Index, in 57% of the infants the effect of midazolam could not be characterized.

Conclusion

In nonventilated infants after major surgery, midazolam clearance is two to five times higher than in ventilated children. From the model presented, the recommended initial dosage is a loading dose of 1 mg followed by a continuous infusion of 0.5 mg/h during the night for a COMFORT-Behavior of 12-14 in infants aged 1 yr. Large interindividual variability warrants individual titration of midazolam in these children.
A Multicenter Clinical Study of the Safety and Activity of Maleimide-Polyethylene Glycol–modified Hemoglobin (Hemospan®) in Patients Undergoing Major Orthopedic Surgery
Authors: Olofsson Christina , Ahl Torbjörn , Johansson Torsten , Larsson Sune , Nellgård Per , Ponzer Sari , Fagrell Bengt , Przybelski Robert , Keipert Peter , Winslow Nancy , Winslow Robert M.
Published: November 2006

Background

Hemospan (Sangart Inc., San Diego, CA), a polyethylene glycol-modified hemoglobin with unique oxygen transport properties, has successfully completed a phase I trial in healthy volunteers. Because adverse events are expected to increase with age, the authors conducted a phase II safety study of Hemospan in elderly patients undergoing elective hip arthroplasty during spinal anesthesia.

Methods

Ninety male and female patients, American Society of Anesthesiologists physical status I-III, aged 50-89 yr, in six Swedish academic hospitals were randomly assigned to receive either 250 or 500 ml Hemospan or Ringer's acetate (30 patients/group) before induction of spinal anesthesia. Safety assessment included vital signs and Holter monitoring from infusion to 24 h, evaluation of laboratory values, and fluid balance. The hypothesis to be tested was that the incidence of adverse events would be no more frequent in patients who received Hemospan compared with standard of care (Ringer's acetate).

Results

Three serious adverse events were noted, none of which was deemed related to study treatment. Liver enzymes, amylase, and lipase increased transiently in patients in all three groups. There were no significant differences in electrocardiogram or Holter parameters, but there was a suggestion of more bradycardic events in the treated groups. Hypotension was less frequent in the treated patients compared with controls.

Conclusions

In comparison with Ringer's acetate, Hemospan mildly elevates hepatic enzymes and lipase and is associated with less hypotension and more bradycardic events. The absence of a high frequency of serious adverse events suggests that further clinical trials should be undertaken.
Pharmacologic and Functional Characterization of Malignant Hyperthermia in the R163C RyR1 Knock-in Mouse
Authors: Yang Tianzhong , Riehl Joyce , Esteve Eric , Matthaei Klaus I. , Goth Samuel , Allen Paul D. , Pessah Isaac N. , Lopez José R.
Published: November 2006

Background

Malignant hyperthermia is a pharmacogenetic disorder affecting humans, dogs, pigs, and horses. In the majority of human cases and all cases in animals, malignant hyperthermia has been associated with missense mutations in the skeletal ryanodine receptor (RyR1).

Methods

The authors used a "knock-in" targeting vector to create mice carrying the RyR1 R163C malignant hyperthermia mutation.

Results

Validation of this new mouse model of human malignant hyperthermia susceptibility includes (1) proof of transcription of the R163C allele and expression of ryanodine receptor protein in R163C heterozygous and R163C homozygous animals; (2) fulminant malignant hyperthermia episodes in R163C heterozygous mice after exposure to 1.25-1.75% halothane or an ambient temperature of 42 degrees C characterized by increased rectal temperature, respiratory rate, and inspiratory effort, with significant blood biochemical changes indicating metabolic acidosis, ending in death and hyperacute rigor mortis; (3) intraperitoneal pretreatment with dantrolene provided 100% protection from the halothane-triggered fulminant malignant hyperthermia episode; (4) significantly increased sensitivity (decreased effective concentration causing 50% of the maximal response) of R163C heterozygous and homozygous myotubes to caffeine, 4-chloro-m-cresol, and K-induced depolarization; (5) R163C heterozygous and homozygous myotubes have a significantly increased resting intracellular Ca concentration compared with wild type; (6) R163C heterozygous sarcoplasmic reticulum membranes have a twofold higher affinity (Kd = 35.4 nm) for [H]ryanodine binding compared with wild type (Kd = 80.1 nm) and a diminished inhibitory regulation by Mg.

Conclusions

Heterozygous R163C mice represent a valid model for studying the mechanisms that cause the human malignant hyperthermia syndrome.
Influence of Mannitol and Furosemide, Alone and in Combination, on Brain Water Content after Fluid Percussion Injury
Authors: Todd Michael M. , Cutkomp Johann , Brian Johnny E.
Published: November 2006

Background

Furosemide and mannitol are used to reduce intracranial pressure, but the impact of furosemide on edema of injured brain is unclear. The authors examined the effects of furosemide and mannitol, alone and in combination, on brain water content in brain-injured rats.

Methods

Anesthetized rats were subjected to a 2.2-atm left hemispheric fluid percussion injury. Two and three-quarters hours later, animals received 0.5, 1, 4, or 8 g/kg mannitol; 8 mg/kg furosemide; a combination of 4 g/kg mannitol plus 4 mg/kg furosemide; or 8 g/kg mannitol plus 8 mg/kg furosemide. One hour later (4 h after injury), plasma osmolality was measured, and hemispheric water content was determined by drying. Other animals were subjected to injury without drug treatment (impact only) or did not undergo injury (control). Pairwise group comparisons regarding the effects of mannitol and furosemide were restricted to only four groups: impact only, 8 g/kg mannitol, 8 mg/kg furosemide, and 8 g/kg mannitol plus 8 mg/kg furosemide.

Results

The water content of both hemispheres in the impact-only group was greater than in the control group (left greater than right). Mannitol, 8 g/kg, increased osmolality from 306 +/- 4 to 351 +/- 6 mOsm/kg (mean +/- SD) and reduced water content in the left hemisphere from 80.06 +/- 0.84% (impact only) to 78.24 +/- 0.73%. Furosemide, 8 mg/kg, had no effect on osmolality or water content. Brain water in animals treated with 8 g/kg mannitol plus 8 mg/kg furosemide did not differ from that seen with 8 g/kg mannitol alone.

Conclusions

Mannitol increased plasma osmolality and reduced water content of the injured and contralateral hemispheres, whereas the authors observed no effect of furosemide when given either alone or in combination with mannitol.
Inhibition of Glutamatergic Activation of Extracellular Signal–regulated Protein Kinases in Hippocampal Neurons by the Intravenous Anesthetic Propofol
Authors: Kozinn Jonathan , Mao Limin , Arora Anish , Yang Lu , Fibuch Eugene E. , Wang John Q.
Published: November 2006

Background

Intravenous anesthetics cause amnesia, but the underlying molecular mechanisms are poorly understood. Recent studies reveal a significant role of extracellular signal-regulated protein kinases (ERKs) in controlling synaptic plasticity and memory formation. As a major synapse-to-nucleus superhighway, ERK transmits N-methyl-D-aspartate (NMDA) receptor signals to inducible transcriptional events essential for NMDA receptor-dependent forms of synaptic plasticity and memory. This study investigated the role of the widely used intravenous anesthetic propofol in regulating NMDA receptor-dependent ERK phosphorylation.

Methods

The possible effect of propofol on NMDA receptor-mediated ERK phosphorylation was detected in cultured rat hippocampal neurons with Western blot analysis.

Results

The authors found that propofol at clinical relevant concentrations (1-10 microm) reduced NMDA receptor-mediated ERK phosphorylation. This reduction was independent of gamma-aminobutyric acid transmission. The inhibition of the NMDA receptor seems to contribute to the effect of propofol on NMDA-stimulated ERK phosphorylation, because propofol reduced constitutive NMDA receptor NR1 subunit phosphorylation and impaired NMDA receptor-mediated Ca influx. Furthermore, by inhibiting the ERK pathway, propofol blocked NMDA receptor-dependent activation of two key transcription factors, Elk-1 and cyclic adenosine monophosphate response element-binding protein (CREB), and, as a result, attenuated Elk-1/CREB-dependent reporter gene (c-Fos) expression.

Conclusions

These results suggest that propofol possesses the ability to inhibit NMDA receptor activation of the ERK pathway and subsequent transcriptional activities in hippocampal neurons. These findings indicate a new avenue to explore a transcription-dependent mechanism that may underlie anesthetic interference with synaptic plasticity related to amnesic properties of intravenous anesthetics.
Pulmonary Responses to Overventilation in Late Multiple Organ Failure
Authors: Uhlig Ulrike , Drömann Daniel , Goldmann Torsten , Dombrowsky Heike , Vollmer Ekkehard , Zabel Peter , Uhlig Stefan
Published: November 2006

Background

Patients with multiple organ failure (MOF) require mechanical ventilation for several days. The enormous significance of the ventilation strategy for the outcome of these patients is well appreciated. However, most studies have focused on the onset and the early phase of MOF. It was the aim of the current study to investigate the effect of ventilation in the course of MOF.

Methods

Using a model where mice develop MOF 7-14 days after intraperitoneal injection of zymosan, the authors analyzed lung functions, signaling pathways, and mediator release in response to protective ventilation (end-expiratory pressure -3 cm H2O; end-inspiratory pressure -10 cm H2O) and overventilation (-22.5 cm H2O) in isolated lungs ex vivo.

Results

On day 7, pulmonary compliance, pulmonary resistance, and tidal volume were normal, but vascular resistance was elevated compared with untreated animals. During ex vivo ventilation, these lungs showed enhanced nuclear factor-kappaB activation, Akt kinase phosphorylation, and cytokine release, and this was further aggravated by overventilation. After 14 days, zymosan-treated animals were characterized by pulmonary hypertension, reduced tidal volume, elevated pulmonary resistance, and increased mediator production. However, in these lungs, neither nuclear factor-kappaB activation nor cytokine production where enhanced by overventilation.

Conclusions

The zymosan model is characterized by pulmonary inflammation, diminished lung functions, and chronic hypertension. Mechanical ventilation with high distending pressures further augmented cytokine production in this chronic model of MOF only if it significantly augmented tidal volume. The authors speculate that these findings may be explained on the basis of different degrees of lung stretch.
Heme Oxygenase 1, Nuclear Factor E2–related Factor 2, and Nuclear Factor κB Are Involved in Hemin Inhibition of Type 2 Cationic Amino Acid Transporter Expression and l-Arginine Transport in Stimulated Macrophages
Authors: Tsai Pei-Shan , Chen Chien-Chuan , Tsai Pei-Shan , Yang Lin-Cheng , Huang Wan-Yu , Huang Chun-Jen
Published: November 2006

Background

L-Arginine transport mediated by type 2 cationic amino acid transporter (CAT-2) is one crucial mechanism that regulates nitric oxide production mediated by inducible nitric oxide synthase. Heme oxygenase (HO)-1 induction has been reported to significantly attenuate inducible nitric oxide synthase expression and nitric oxide production. The authors sought to explore the effects of HO-1 induction on CAT-2 expression and L-arginine transport. The effects of HO-1 induction on nuclear factor E2-related factor 2 (Nrf2) and nuclear factor kappaB (NF-kappaB) were also investigated.

Methods

Murine macrophages (RAW264.7 cells) were randomized to receive lipopolysaccharide, lipopolysaccharide plus hemin (an HO-1 inducer; 5, 50, or 500 microm), lipopolysaccharide plus hemin (5, 50, or 500 microm) plus tin protoporphyrin (an HO-1 inhibitor), or lipopolysaccharide plus hemin (5, 50, or 500 microm) plus hemoglobin (a carbon monoxide scavenger). Then, cell cultures were harvested and analyzed.

Results

Lipopolysaccharide significantly induced Nrf2 activation and HO-1 expression. Lipopolysaccharide also significantly induced NF-kappaB activation, CAT-2 expression, and L-arginine transport. In a dose-dependent manner, hemin enhanced the lipopolysaccharide-induced Nrf2 activation and HO-1 expression. In contrast, hemin, also in a dose-dependent manner, significantly attenuated the lipopolysaccharide-induced NF-kappaB activation, CAT-2 expression, and L-arginine transport. Furthermore, the effects of hemin were significantly reversed by both tin protoporphyrin and hemoglobin.

Conclusions

HO-1 induction significantly inhibited CAT-2 expression and L-arginine transport in lipopolysaccharide-stimulated macrophages, possibly through mechanisms involved activation of Nrf2 and inhibition of NF-kappaB. In addition, carbon monoxide mediated, at least in part, the effects of HO-1 induction on CAT-2 expression and L-arginine transport.
Up-regulation of Hypoxia Inducible Factor 1α by Isoflurane in Hep3B Cells
Authors: Li Qi Fang , Wang Xiang Rui , Yang Yue Wu , Su Dian San
Published: November 2006

Background

The volatile anesthetic isoflurane induces hypoxia inducible factor (HIF)-1-responsive genes heme oxygenase 1, inducible nitric oxide synthase, and vascular endothelial growth factor (VEGF) expression. Little is known about the extent to which induction of HIF-1alpha is affected by isoflurane.

Methods

Hep3B cells were exposed to isoflurane at various concentrations (0.5-4%) or for different time periods (2-8 h) at 37 degrees C. HIF-1alpha gene expression and transcriptional activity, heme oxygenase 1, inducible nitric oxide synthase, and VEGF gene expression were quantified.

Results

Isoflurane induced a time- and concentration-dependent increase in HIF-1alpha protein but not for HIF-1alpha messenger RNA (mRNA) in Hep3B cells. The maximal increase was induced by 2% isoflurane, and the cells incubated with 2% isoflurane for 4-8 h expressed the highest protein. Similarly, HIF-1alpha transcriptional activity was higher in Hep3B cells exposed to 2% isoflurane for 16 h than that in control cells. The combination of 2% isoflurane and desferrioxamine, a hypoxia mimetic, caused a higher level of HIF-1alpha protein than that induced by 2% isoflurane alone. Reoxygenation and inhibitor of proteasome pathway MG132 did not affect the isoflurane-induced HIF-1alpha protein accumulation. Cycloheximide, an inhibitor for protein synthesis, completely abrogated the induction of HIF-1alpha protein by isoflurane. Isoflurane stimulated heme oxygenase 1, inducible nitric oxide synthase, and VEGF mRNA expression in a concentration-dependent manner, and inactivation of HIF-1alpha attenuated the induction of VEGF mRNA by isoflurane.

Conclusion

Isoflurane can up-regulate HIF-1alpha and enhance HIF-1-responsive genes heme oxygenase 1, inducible nitric oxide synthase, and VEGF mRNA expression in Hep3B cells. The induction of HIF-1alpha by isoflurane does not involve protein degradation but depends on translation pathway.