bluuebunny/crossref_metadata_2025 huggingface dataset:
Measurement of atmospheric O3 → O(1D) photolysis frequencies using filterradiometry
Authors: Bohn B. , Kraus A. , Müller M. , Hofzumahaus A.
Published: May 2004

In this work the instrumentation and characterization of a filterradiometer suitable for field measurements of O3 → O(1D) photolysis frequencies, j(O1D), is described. A nonlinear calibration function considering ozone column and solar zenith angle is derived as well as a procedure utilizing an irradiance standard as an absolute reference. The measurement concept is tested by a field comparison with a spectroradiometer. Based solely on laboratory characterizations and simulated solar actinic flux spectra, a systematic deviation of 4% is obtained with a standard deviation of 3% at solar zenith angles below 70°. The standard deviation rises to 8% at solar zenith angles in the range 70°–85°. The systematic difference is within the accuracy of the applied radiometric calibrations while the standard deviation is mainly caused by insufficient synchronization of the different measurement techniques under variable field conditions. In addition, the relative temperature dependence of j(O1D) as a function of solar zenith angle and ozone column is derived which is applicable to any ground‐based j(O1D) measurement.
Depth, distribution, and density of CO2 deposition on Mars
Authors: Aharonson Oded , Zuber Maria T. , Smith David E. , Neumann Gregory A. , Feldman William C. , Prettyman Thomas H.
Published: May 2004

Observations by the Mars Orbiter Laser Altimeter have been used to detect subtle changes of the polar surface height during the course of seasonal cycles that correlate with the expected pattern of CO2 deposition and sublimation. Using altimetric crossover residuals from the Mars Orbiter Laser Altimeter, we show that while zonally averaged data capture the global behavior of CO2 exchange, there is a dependence of the pattern on longitude. At the highest latitudes the surface height change is as high as 1.5–2 m peak to peak, and it decreases equatorward. Decomposition of the signal into harmonics in time allows inspection of the spatial pattern and shows that the annual component is strongly correlated with the residual south polar cap deposits and, to a lesser extent, with the north polar cap. In the north, the second harmonic (semiannual) component correlates with the location of the ice deposits. The phases of the annual cycles are in agreement with observations by the Thermal Emission Spectrometer of the timing of the annual disappearance of CO2 frost from the surface at the high latitudes. At lower latitudes, frost sublimation (“Crocus date”) predates the mean depositional minima, as expected. These global‐scale, volumetric measurements of the distribution of condensed CO2 can be combined with measurements of the deposited column mass density derived from the Neutron Spectrometer on board Mars Odyssey to yield an estimate of the density of the seasonally exchanging material of 0.5 ± 0.1 g/cm3. These constraints should be considered in models of the Martian climate system and volatile cycles.
On the low‐level circulation over the western north Pacific in relation with the duration of El Niño
Authors: Boo Kyung‐On , Lim Gyu‐Ho , Kim Kwang‐Yul
Published: May 2004

We investigate how the low‐level circulation centered at 10°N over the western north Pacific differs between the shorter (SHORT‐E) and longer (LONG‐E) El Niño events based on their duration time. One major difference is the intensity of this circulation. This difference is due to the greater contribution of the 2–3 year quasi‐biennial (QB) signal for the SHORT‐E; strength of the 3–6 year interannual signal is almost the same in a mean sense between the two event types. Further, the amplitude of the QB signal is in phase with that of the interannual signal during the SHORT‐E so that the circulation intensifies and evolves rapidly. The enhanced anticyclonic circulation during the mature stage of SHORT‐E results in shallower thermocline in the equatorial western Pacific, and exerts influence on the duration of the event. During the LONG‐E, the mentioned feature diminishes because of the weak QB. Our analysis further indicates a significant correlation between the zonal SSTA gradient over the Indian Ocean and the intensity of the western north Pacific circulation. A complete understanding of the related mechanism needs further study.
Rupture process and near‐source shaking of the 1965 Seattle‐Tacoma and 2001 Nisqually, intraslab earthquakes
Authors: Ichinose Gene A. , Thio Hong Kie , Somerville Paul G.
Published: May 2004

We inverted teleseismic data for the 1965 Seattle‐Tacoma earthquake slip and rake. The earthquake had 2 asperities of 12 and 16 km2 near the hypocenter with average slip of 2 and 2.8 m respectively (Mo = 9.4 × 1025 dyne‐cm; Mw = 6.6). We also inverted strong‐motion and teleseismic data for the 2001 Nisqually earthquake. This earthquake had 2 subevents with an asperity area of 45 km2 between 59 and 62 km depth with an average slip of 1.7 m (Mo = 1.7 × 1026 dyne‐cm; Mw = 6.8). Shake‐maps of peak ground acceleration (PGA) and spectral acceleration (Sa) were generated using a time‐domain approach including slip model, site, and basin‐depth corrections based on California geology. Corrections reduced the residuals between observed and predicted PGA and Sa. The simulated pattern of shaking from the 1965 earthquake was twice as high as in the 2001 earthquake due to the proximity of the 1965 epicenter to sedimentary basins.
Issues Raised by the Impact of Tax Reforms and Regional Devolution on Health-Care Financing in Spain, 1996–2002
Authors: Puig-Junoy Jaume , Rovira Joan
Published: May 2004

The authors aim to describe and discuss the likely effects of three recent policy measures related to the financing of the Spanish National Health System which have been introduced over the period 1996–2002 under the conservative Popular Party government. First, tax incentives for private health insurance were introduced with the 1999 income tax reform. Second, in 2002 the devolution of health-services management to regional governments was completed along with reform of the regional mechanism of allocation of public funds (intergovernmental grants, tax revenues, and fiscal accountability). Third, earmarked indirect taxes were introduced in 2002 as a source of additional revenues devoted to public-health financing.
Locating and Explaining Area-Based Urban Initiatives: New Deal for Communities in England
Authors: Lawless Paul
Published: May 2004

It is now more than thirty years since the first area-based initiative (ABI) was launched in England. New Deal for Communities announced in 1998 is one of the most ambitious of English ABIs in that it aims over a period of ten years to close gaps between these thirty-nine areas and national standards in five outcome areas of crime, education, health, worklessness, and housing. Evidence gleaned from the national evaluation of 2002/03 helps illuminate trends and tensions within three themes which have proved central to the wider urban debate: community engagement, partnership working, and the complexity of ABIs. On the broad canvas, evidence from the evaluation suggests that institutional factors continue to impinge strongly on the programme, that the original assumption that partnerships should be given a strong degree of local flexibility and freedoms has been steadily eroded, and that the initiative as a whole sits within that raft of essentially reformist policy interventions effected by the Labour government since 1997.
A Flyvbjergian Perspective on Public Elementary School Closures in Toronto: A Question of ‘Rationality’ or ‘Power’?
Authors: Basu Ranu
Published: May 2004

The notion of social capital in contemporary societies is viewed as being necessary for the rejuvenation of civil society. However, such assumptions are based on inclusionary democratic practices; the heterogeneity of societal needs and the underlying power structures are often not taken into account. The author explores the possibility of examining neighbourhood-based social capital along the lines of ‘intrinsic’ (within neighbourhood) and ‘extrinsic’ (neighbourhood–city) relations. A spatial comparison of such preexisting, dense, dynamic networks of everyday mundane activities often leads to a better understanding of how power is created, maintained, and eventually used in times of neighbourhood crises. More specifically, by using a Flyvbjergian perspective of rationality and power, the author combines the notion of social capital as proposed by Putnam with Epstein's framework of participation within schools, to identify variations in civic activities within Public Elementary School Districts in Toronto (TDSB). Drawing from a unique descriptive dataset on parental and community participation available from the TDSB, and by combining it with enumeration-area data aggregated at the school-district level, this framework is empirically tested to gain an understanding of how such links relate to school-closure decisions. Within the context of education reform in Ontario, the results reveal the paradoxical nature of social capital in promoting and subjugating notions of democracy and civil society.
Expression Influences the Recognition of Familiar Faces
Authors: Kaufmann Jürgen M , Schweinberger Stefan R
Published: May 2004

Face recognition has been assumed to be independent of facial expression. We used familiar and unfamiliar faces that were morphed from a happy to an angry expression within a given identity. Participants performed speeded two-choice decisions according to whether or not a face was familiar. Consistent with earlier findings, reaction times for classifications of unfamiliar faces were independent of facial expressions. In contrast, expression clearly influenced the recognition of familiar faces, with fastest recognition for moderately happy expressions. This suggests that representations of familiar faces for recognition preserve some information about typical emotional expressions.
Eye Movements in a Simple Spatial Reasoning Task
Authors: Körner Christof , Gilchrist Iain D
Published: May 2004

We report two experiments in which participants read a question about the spatial relationship between two letters, then viewed a visual display containing the letters and were required to respond to the question. The format of the question influenced the nature of the eye movements generated to the visual display. Participants also had a tendency to make additional eye movements in order to generate a fixation sequence that corresponded to the order of the letters in the question. This demonstrates an influence of stored information on eye movement generation, and suggests that the scanpath plays a role in structuring the visual information to facilitate reasoning.
Judgments of Exocentric Direction in Large-Scale Space
Authors: Kelly Jonathan W , Loomis Jack M , Beall Andrew C
Published: May 2004

Judgments of exocentric direction are quite common, especially when judging where others are looking or pointing. To investigate these judgments in large-scale space, observers were shown two targets in a large open field and were asked to judge the exocentric direction specified by the targets. The targets ranged in egocentric distance from 5 to 20 m with target-to-target angular separations of 45°, 90°, and 135°. Observers judged exocentric direction using two methods: (i) by judging which point on a distant fence appeared collinear with the two targets, and (ii) by orienting their body in a direction parallel with the perceived line segment. In the collinearity task, observers had to imagine the line connecting the targets and then extrapolate this imagined line out to the fence. Observers indicated the perceived point of collinearity on a handheld 360° panoramic cylinder representing their vista. The two judgment methods gave similar results except for a constant bias associated with the body-pointing response. Aside from this bias, the results of these two methods agree with other existing research indicating an effect of relative egocentric distance to the targets on judgment error—line segments are perceived as being rotated in depth. Additionally, verbal estimates of egocentric and exocentric distance suggest that perceived distance is not the cause for the systematic errors in judging exocentric direction.
The evolution of a pleiotropic fitness tradeoff in
Pseudomonas fluorescens
Authors: MacLean R. Craig , Bell Graham , Rainey Paul B.
Published: May 2004

The evolution of ecological specialization is expected to carry a cost, due to either antagonistic pleiotropy or mutation accumulation. In general, it has been difficult to distinguish between these two possibilities. Here, we demonstrate that the experimental evolution of niche-specialist genotypes of the bacterium
Pseudomonas fluorescens
that colonize the air–broth interface of spatially structured microcosms is accompanied by pleiotropic fitness costs in terms of reduced carbon catabolism. Prolonged selection in spatially structured microcosms caused the cost of specialization to decline without loss of the benefits associated with specialization. The decline in the cost of specialization can be explained by either compensatory adaptation within specialist lineages or clonal competition among specialist lineages. These results provide a possible explanation of conflicting accounts for the cost of specialization.
Global analysis of predicted proteomes: Functional adaptation of physical properties
Authors: Knight Christopher G. , Kassen Rees , Hebestreit Holger , Rainey Paul B.
Published: May 2004

The physical characteristics of proteins are fundamentally important in organismal function. We used the complete predicted proteomes of >100 organisms spanning the three domains of life to investigate the comparative biology and evolution of proteomes. Theoretical 2D gels were constructed with axes of protein mass and charge (pI) and converted to density estimates comparable across all types and sizes of proteome. We asked whether we could detect general patterns of proteome conservation and variation. The overall pattern of theoretical 2D gels was strongly conserved across all life forms. Nevertheless, coevolved replicons from the same organism (different chromosomes or plasmid and host chromosomes) encode proteomes more similar to each other than those from different organisms. Furthermore, there was disparity between the membrane and nonmembrane subproteomes within organisms (proteins of membrane proteomes are on the average more basic and heavier) and their variation across organisms, suggesting that membrane proteomes evolve most rapidly. Experimentally, a significant positive relationship independent of phylogeny was found between the predicted proteome and Biolog profile, a measure associated with the ecological niche. Finally, we show that, for the smallest and most alkaline proteomes, there is a negative relationship between proteome size and basicity. This relationship is not adequately explained by AT bias at the DNA sequence level. Together, these data provide evidence of functional adaptation in the properties of complete proteomes.
Φ-Value analysis and the nature of protein-folding transition states
Authors: Fersht Alan R. , Sato Satoshi
Published: May 2004

Φ values are used to map structures of protein-folding transition states from changes in free energies of denaturation (ΔΔ
G
D-N
) and activation on mutation. A recent reappraisal proposed that Φ values for ΔΔ
G
D-N
< 1.7 kcal/mol are artifactual. On discarding such derived Φ values from published studies, the authors concluded that there are no high Φ values in diffuse transition states, which are consequently uniformly diffuse with no evidence for nucleation. However, values of ΔΔ
G
D-N
> 1.7 kcal/mol are often found for large side chains that make dispersed tertiary interactions, especially in hydrophobic cores that are in the process of being formed in the transition state. Conversely, specific local interactions that probe secondary structure tend to have ΔΔ
G
D-N
≈ 0.5–2 kcal/mol. Discarding Φ values from lower-energy changes discards the crucial information about local interactions and makes transition states appear uniformly diffuse by overemphasizing the dispersed tertiary interactions. The evidence for the 1.7 kcal/mol cutoff was based on mutations that had been deliberately designed to be unsuitable for Φ-value analysis because they are structurally disruptive. We confirm that reliable Φ values can be derived from the recommended mutations in suitable proteins with 0.6 < ΔΔ
G
D-N
< 1.7 kcal/mol, and there are many reliable high Φ values. Transition states vary from being rather diffuse to being well formed with islands of near-complete secondary structure. We also confirm that the structures of transition-state ensembles can be perturbed by mutations with ΔΔ
G
D-N
» 2 kcal/mol and that protein-folding transition states do move on the energy surface on mutation.
Trafficking of ODV-E66 is mediated via a sorting motif and other viral proteins: Facilitated trafficking to the inner nuclear membrane
Authors: Braunagel Sharon C. , Williamson Shawn T. , Saksena Suraj , Zhong Zhenping , Russell William K. , Russell David H. , Summers Max D.
Published: May 2004

The N-terminal 33 aa of the envelope protein ODV-E66 are sufficient to traffic fusion proteins to intranuclear membranes and the ODV envelope during infection with
Autographa californica
nucleopolyhedrovirus. This sequence has two distinct features: (
i
) an extremely hydrophobic sequence of 18 aa and (
ii
) positively charged amino acids close to the C-terminal end of the hydrophobic sequence. In the absence of infection, this sequence is sufficient to promote protein accumulation at the inner nuclear membrane. Covalent cross-linking results show that the lysines of the motif are proximal to FP25K and/or BV/ODV-E26 during transit from the endoplasmic reticulum to the nuclear envelope. We propose that the 33 aa comprise a signature for sorting proteins to the inner nuclear membrane (sorting motif) and that, unlike other resident proteins of the inner nuclear membrane, ODV-E66 and sortingmotif fusions do not randomly diffuse from their site of insertion at the endoplasmic reticulum to the nuclear envelope and viral-induced intranuclear membranes. Rather, during infection, trafficking is mediated by protein-protein interactions.
Intraoperative Hyperglycemia during Infant Cardiac Surgery Is Not Associated with Adverse Neurodevelopmental Outcomes at 1, 4, and 8 Years
Authors: de Ferranti Sarah , Gauvreau Kimberlee , Hickey Paul R. , Jonas Richard A. , Wypij David , du Plessis Adre , Bellinger David C. , Kuban Karl , Newburger Jane W. , Laussen Peter C.
Published: May 2004

Background

It is unknown whether intraoperative hyperglycemia in infants is associated with worse neurodevelopmental outcomes after low-flow cardiopulmonary bypass (LF), deep hypothermic circulatory arrest (CA), or both.

Methods

In a database review of a prospective trial of 171 infants undergoing arterial switch for D-transposition of the great arteries who were randomly assigned to predominantly LF or CA, glucose was measured after induction (T1), 5 min after cardiopulmonary bypass onset (T2), at the onset of CA or LF (T3), 5 min after CPB resumption (T4), at rewarming to 32 degrees C (T5), 10 min after cardiopulmonary bypass weaning (T6), and 90 min after CA or LF (T7). Outcomes included seizures, electroencephalographic findings, and neurodevelopmental evaluation at 1, 4, and 8 yr.

Results

Glucose concentrations were affected by support strategy and age at surgery. Lower glucose in the entire group at T6-T7 tended to predict electroencephalographic seizures (P = 0.06 and P = 0.007) but was not related to clinical seizures. Within the predominantly CA group, higher glucose did not correlate with worse outcomes. Rather, it was associated with more rapid electroencephalographic normalization of "close burst" and "relative continuous" activity at all times except T2 (P < or = 0.03), a finding more pronounced in infants aged 7 days old or younger. Intraoperative serum glucose concentrations were unrelated to neurodevelopmental outcomes at ages 1, 4, and 8 yr.

Conclusions

Low glucose after cardiopulmonary bypass tended to relate to electroencephalographic seizures and slower electroencephalogram recovery, independent of CA duration. High glucose concentrations were not associated with worse neurodevelopmental outcomes. Avoiding hypoglycemia may be preferable to restricting glucose in infants undergoing heart surgery.
A Response Surface Analysis of Propofol–Remifentanil Pharmacodynamic Interaction in Volunteers
Authors: Kern Steven E. , Xie Guoming , White Julia L. , Egan Talmage D.
Published: May 2004

Background

Characterizing drug interactions using a response surface allows for the determination of the interaction over a complete range of clinically relevant concentrations. Gathering the data necessary to create this surface is difficult to do in a clinical setting and requires the use of volunteer experiments with surrogate noxious stimuli to adequately control the process for data collection. The pharmacodynamic synergy of opioids and hypnotics was investigated using a volunteer study paradigm.

Methods

Twenty-four volunteer subjects (12 male, 12 female) were studied using computer-controlled infusions of propofol and remifentanil to create an increasing staircase drug concentration profile in each subject. Three different drug delivery profiles were administered to subjects, one with a single agent and two with combinations of propofol and remifentanil. At each plateau of the staircase profile, drug effect was assessed using four surrogate measures: Observer Assessment of Alertness/Sedation score, tibial pressure algometry, electrical tetany, and response to laryngoscopy. Response surfaces were developed that mapped the interaction of propofol and remifentanil to these surrogate effect measures in all subjects. An interaction parameter was used to assess whether these two drugs behave synergistically to blunt response to noxious stimuli.

Results

The response surfaces showed considerable synergy between remifentanil and propofol for blunting response to the noxious stimuli. The interaction index, a measure of synergy, was 8.2 and 14.7 for response to algometry and tetany, respectively (P < 0.001), and 5.1 and 33.2 for sedation and laryngoscopy, respectively (P < 0.001), using the Greco interaction model. The surrogate stimuli mapped to clinically relevant concentrations for these agents in combination.

Conclusions

The response surface models reveal the tremendous synergy between remifentanil and propofol. The surface morphologic features give some indication of the relative contribution of sedation and analgesia to blunting subject response. Further, the results of this investigation validate the volunteer study paradigm and use of surrogate effect measures for its clinical relevance.
Determination of the Pharmacodynamic Interaction of Propofol and Remifentanil during Esophagogastroduodenoscopy in Children
Authors: Drover David R. , Litalien Catherine , Wellis Vinit , Shafer Steven L. , Hammer Gregory B.
Published: May 2004

Background

Propofol is commonly used to anesthetize children undergoing esophagogastroduodenoscopy. Opioids are often used in combination with propofol to provide total intravenous anesthesia. Because both propofol and remifentanil are associated with rapid onset and offset, the combination of these two drugs may be particularly useful for procedures of short duration, including esophagogastroduodenoscopy. The authors previously demonstrated that the median effective concentration (C50) of propofol during esophagogastroduodenoscopy in children is 3.55 microg/ml. The purpose of this study was to describe the pharmacodynamic interaction of remifentanil and propofol when used in combination for esophagogastroduodenoscopy in pediatric patients.

Methods

The authors studied 32 children aged between 3 and 10 yr who were scheduled to undergo esophagogastroduodenoscopy. Propofol was administered via a target-controlled infusion system using the STANPUMP software based on a pediatric pharmacokinetic model. Remifentanil was administered as a constant rate infusion of 25, 50, and 100 ng.kg(-1).min(-1) to each of three study groups, respectively. A sigmoid Emax model was developed to describe the interaction of remifentanil and propofol.

Results

There was a positive interaction between remifentanil and propofol when used in combination. The concentration of propofol alone associated with 50% probability of no response was 3.7 microg/ml (SE, 0.4 microg/ml), and this was decreased to 2.8 microg/ml (SE, 0.1 microg/ml) when used in combination with remifentanil.

Conclusion

A remifentanil infusion of 25 ng.kg(-1).min(-1) reduces the concentration of propofol required for adequate anesthesia for esophagogastroduodenoscopy from 3.7 to 2.8 microg/ml. Increasing the remifentanil infusion yields minimal additional decrease in propofol concentration and may increase the risk of side effects.
Evidence for Development of Capillary Leak Syndrome Associated with Cardiopulmonary Bypass in Pediatric Patients with the Homozygous C4A Null Phenotype
Authors: Zhang Shihai , Wang Shouyong , Yao Shanglong
Published: May 2004

Background

The mechanism of postoperative capillary leak syndrome related to cardiopulmonary bypass (CPB) is unknown. The authors hypothesized that C4 gene polymorphism might be involved in the development of the syndrome because complement activation is associated with CPB and protamine administration, and the two isotypes of C4 (C4A and C4B) differ in their biochemical and functional properties after activation.

Methods

One hundred fifty-six pediatric patients referred for elective cardiac surgery with CPB were included in the study. C4 isotype studies were performed in plasma samples obtained before surgery, with use of agarose gel immunofixation and crossed immunoelectrophoresis. Five possible C4 phenotype groups were observed, which were abbreviated as follows: (1) AABB = no detectable null alleles, (2) A0BB = a single null allele (heterozygous) at the C4A locus, (3) 00BB = a homozygous C4A null allele, (4) AAB0 = a single null allele (heterozygous) at the C4B locus, and (5) AA00 = a homozygous C4B null allele. The patients were classified into five groups according to their C4 phenotypes. Before CPB and at 1 h after CPB, plasma protein was measured with a biuret test kit. Plasma colloid osmotic pressure was determined with a membrane osmometer. Evans blue dye was used to measure plasma volume, serum protein, intravenous protein pool, and transvascular escape rate of Evans blue dye.

Results

Of 156 pediatric patients enrolled, 80 were assigned to the AABB group, 28 were assigned to the A0BB group, 7 were assigned to the 00BB group, 31 were assigned to the AAB0 group, and 10 were assigned to the AA00 group, according to their C4 phenotypes. At 1 h after CPB, serum protein concentrations averaged 3.6 +/- 0.4 g/dl in patients with the 00BB C4 phenotype; this value was significantly lower (P < 0.01) than that in patients with other C4 phenotypes. The changes of intravenous protein pool and colloid osmotic pressure were comparable with the change in serum protein concentration. At 1 h after CPB, the transvascular escape rate of Evans blue dye averaged 11.5 +/- 1.3%/h in patients with the 00BB C4 phenotype; this value was significantly higher (P < 0.01) than that in patients with other C4 phenotypes.

Conclusions

In this study, capillary leak syndrome induced by CPB occurred only in patients with the homozygous C4A null phenotype.
Injuries and Liability Related to Central Vascular Catheters
Authors: Domino Karen B. , Bowdle T. Andrew , Posner Karen L. , Spitellie Pete H. , Lee Lorri A. , Cheney Frederick W.
Published: May 2004

Background

To assess changing patterns of injury and liability associated with central venous or pulmonary artery catheters, the authors analyzed closed malpractice claims for central catheter injuries in the American Society of Anesthesiologists Closed Claims database.

Methods

All claims for which a central catheter (i.e., central venous or pulmonary artery catheter) was the primary damaging event for the injury were compared with the rest of the claims in the database. Central catheter complications were defined as being related to vascular access or catheter use or maintenance. Statistical analysis was performed using the chi-square test, Fisher exact test, or Z test (proportions) and the Kolmogorov-Smirnov test (payments).

Results

The database included 110 claims for injuries related to central catheters (1.7% of 6,449 claims). Claims for central catheter injuries had a higher severity of injury, with an increased proportion of death (47%) compared with other claims in the database (29%, P < 0.01). The most common complications were wire/catheter embolus (n = 20), cardiac tamponade (n = 16), carotid artery puncture/cannulation (n =16), hemothorax (n =15), and pneumothorax (n =14). Cardiac tamponade, hemothorax, and pulmonary artery rupture had a higher proportion of death (P < 0.05) compared with the rest of the central catheter injures. The proportion of claims for vascular access injury increased (47% to 84%) and use/maintenance injury decreased (53% to 16%) in 1994-1999 compared with 1978-1983 (P < 0.05).

Conclusions

Claims related to central catheters had a high severity of patient injury. The most common complications causing injury were wire/catheter embolus, cardiac tamponade, carotid artery puncture/cannulation, hemothorax, and pneumothorax.
Measurement of Oxygen Uptake and Carbon Dioxide Elimination Using the Bymixer
Authors: Rosenbaum Abraham , Kirby Christopher , Breen Peter H.
Published: May 2004

Background

The authors have developed a new clinical bymixer that bypasses a constant fraction of gas flow through a mixing arm. A separate bymixer was interposed in the expiratory and inspiratory limbs of the ventilation circuit to measure mixed gas fractions. By utilizing nitrogen conservation, the clinical bymixer allows the determination of airway carbon dioxide elimination (VCO2) and oxygen uptake (VO2), whenever basic expired flow and gas monitoring measurements are used for the patient. Neither an expiratory exhaust gas collection bag nor expensive, complex equipment are needed. This study tested the accuracy of airway bymixer-flow measurements of VCO2 and VO2 in a new bench apparatus.

Methods

The authors compared airway bymixer-flow measurements of VCO2 and VO2 over a range of reference values generated by ethanol combustion in a new metabolic lung simulator, which was ventilated by a volume-cycled respirator. An airway humidity and temperature sensor permitted standard temperature and pressure, dry, correction of airway VCO2 and VO2.

Results

Bymixer-flow airway measurements of VCO2 and VO2 correlated closely (R2 = 0.999 and 0.998, respectively) with the stoichiometric values generated by ethanol combustion. Limits of agreement for VCO2 and VO2 were 0.1 +/- 4.7 and 1.1 +/- 5.7%, respectively. The average (+/- SD) percent error for airway VCO2 (compared with the stoichiometric value) was 0.1 +/- 2.4%. The same error for airway VO2 was 1.1 +/- 2.9%.

Conclusions

The new clinical bymixer, plus basic expired flow and gas fraction measurements, generated clinically accurate determinations of VCO2 and VO2. These measurements are helpful in the assessment of metabolic gas exchange in the critical care unit. In contrast to using the gas collection bag or complex metabolic monitor, the bymixer should measure mixed gas concentrations in the inspired or expired limb of the common anesthesia circle ventilation circuit.
Measurement of Cardiac Output with Indocyanine Green Transcutaneous Fluorescence Dilution Technique
Authors: Maarek Jean-Michel I. , Holschneider Daniel P. , Harimoto Juji , Yang Jun , Scremin Oscar U. , Rubinstein Eduardo H.
Published: May 2004

Background

Cardiac output is an essential parameter for the hemodynamic assessment of patients with cardiovascular disease. The authors tested in an animal model the feasibility of measuring cardiac output by transcutaneous fluorescence monitoring of an intravenous bolus injection of indocyanine green.

Methods

Fluorescence dilution cardiac output was measured in 10 anesthetized rabbits and compared with cardiac output measured with a pulmonary thermodilution catheter and to aortic velocity measured by Doppler ultrasound. Indocyanine green fluorescence was excited with a near-infrared laser and measured with an optical probe positioned on the central ear artery. Measurements were obtained during baseline conditions as well as during short-term decreases and increases of the cardiac output.

Results

The fluorescence of circulating indocyanine green detected transcutaneously varied proportionally to that of arterial blood samples, which allowed for calibration in terms of blood concentration of indocyanine green. Average values of fluorescence dilution cardiac output and thermodilution cardiac output measured in baseline conditions were 412 (+/- 13) and 366 (+/- 11) ml/min, respectively. Fluorescence dilution cardiac output showed a close, one-to-one linear relation with thermodilution cardiac output in each animal and in the pooled data from all animals (slope = 0.95 x 0.03; R = 0.94). Fluorescence dilution cardiac output overestimated thermodilution cardiac output by an average of 46 (+/- 6) ml/min during baseline conditions. Fluorescence dilution cardiac output was tightly correlated with aortic velocity.

Conclusions

The proposed technique yielded accurate estimates of the cardiac output in experimental animals. This study should provide an initial framework for clinical testing of this new minimally invasive method for measuring cardiac output.
Epidural Catheter Penetration of Human Dural Tissue
Authors: Angle Pamela J. , Kronberg Jean E. , Thompson Dorothy E. , Duffin James , Faure Peter , Balasubramaniam Shan , Szalai John Paul , Cromwell Susan
Published: May 2004

Background

Factors contributing to subarachnoid catheter passage after epidural placement are not well understood. This study explored mechanisms that might explain its occurrence.

Methods

Human cadaveric dura was mounted on a model and pressurized to physiologic levels. In a standardized fashion, a 20-gauge Portex three-port, closed end (nonflexible) tip catheter was passed through an epidural needle mounted on a micromanipulator at a 90 degree angle, attempting to penetrate dura with the catheter. Attempts then followed with a 19-gauge Arrow Flex Tip Plus single-port catheter. Subarachnoid catheter passage was compared in (1) intact dura, (2) clinically occult versus obvious epidural needle punctures, and (3) single 25-gauge Whitacre spinal needle punctures after combined spinal-epidural placement.

Results

Neither catheter penetrated intact dura: Portex, 0 of 300 attempts (0.0000; 95% confidence interval [CI]: 0.0000, 0.0158); Arrow, 0 of 300 attempts (0.0000; 95% CI: 0.0000, 0.0158). In clinically occult epidural needle punctures, the 20-gauge Portex catheter penetrated 1 of 3 specimens in 1 of 14 attempts (0.0714; 95% CI: 0.0021, 0.3583). The 19-gauge Arrow did not pass (0 of 15 attempts, 0.0000; 95% CI: 0.0000, 0.2535). In clinically obvious epidural needle punctures, the Portex passed in 6 of 33 attempts (0.1818; 95% CI: 0.0760, 0.3608) and the Arrow passed in 1 of 35 attempts (0.0286; 95% CI: 0.0012, 0.1662). Neither catheter passed through a single 25-gauge spinal needle puncture after an uncomplicated combined spinal-epidural: Portex, 0 of 90 attempts (0.0000; 95% CI: 0.0000, 0.0510); Arrow, 0 of 90 attempts (0.0000; 95% CI: 0.0000, 0.0510).

Conclusions

Catheter passage is unlikely in the presence of intact dura or after an uncomplicated combined spinal-epidural. Unintentional subarachnoid passage suggests dural damage with the epidural needle.
Amitriptyline Neurotoxicity
Authors: Estebe Jean-Pierre , Myers Robert R.
Published: May 2004

Background

Amitriptyline is a tricyclic antidepressant drug used systemically for the management of neuropathic pain. Antidepressants, as a class of drugs with direct neurologic actions, are becoming widely used for the management of chronic pain, although their mechanisms are not entirely understood. Amitriptyline exerts potent effects on reuptake of norepinephrine and serotonin and blocks alpha 2A adrenoreceptors and N-methyl-D-aspartate receptors. Because amitriptyline is also a particularly potent blocker of sodium channels and voltage-gated potassium and calcium channels, it has been recommended as a long-acting local anesthetic agent. Unfortunately, amitriptyline has significant toxic side effects in the central nervous system and cardiovascular system that are dose-related to its systemic administration. Therefore, before amitriptyline can be used clinically as a local anesthetic agent, it should be thoroughly explored with respect to its direct neurotoxic effect in the peripheral nervous system.

Methods

The left sciatic nerve of Sprague-Dawley rats (12/ group) received a single topical amitriptyline dose of 0.625, 1.25, 2.5, or 5 mg; a saline group (n = 2) was used as control. Neuropathologic evaluations were conducted in separate animals (n = 4) 1, 3, and 7 days later.

Results

Amitriptyline topically applied in vivo to rat sciatic nerve causes a dose-related neurotoxic effect. Drug doses of 0.625-5 mg all caused Wallerian degeneration of peripheral nerve fibers, with the number of affected fibers and the severity of the injury directly related to the dose.

Conclusion

Because the effective local anesthetic dose is within this dose range, the authors strongly recommend that amitriptyline not be used as a local anesthetic agent.
Electrical Nerve Localization
Authors: Hadzic Admir , Vloka Jerry D. , Claudio Richard E. , Hadzic Nihad , Thys Daniel M. , Santos Alan C.
Published: May 2004

Background

Recommendations regarding the technical aspects of nerve stimulator-assisted nerve localization are conflicting. The objectives of this study were to determine whether the placement of the cutaneous electrode affects nerve stimulation and to determine the duration and intensity of an electrical stimulus that allows nerve stimulation with minimal discomfort.

Methods

Ten healthy volunteers underwent an interscalene and a femoral nerve block. After obtaining a clearly visible motor response of the biceps (interscalene) and quadriceps (femoral) muscles at the minimal current (0.1 ms, 2 Hz), the position of the cutaneous electrode was varied. Next, the duration of the stimulating current was set at 0.05, 0.1, 0.3, 0.5, or 1.0 ms, in random order. Intensity of the motor response and discomfort on stimulation were recorded.

Results

The minimal current at which a visible motor response was obtained was 0.32 +/- 0.1 mA (0.23-0.38 mA) for the inter-scalene block and 0.29 +/- 0.1 mA (0.15-0.4 mA) for the femoral block. Changing the position of the return electrodes did not result in any change in the grade of the motor response or in the current required to maintain it. Currents of longer duration caused discomfort and more forceful contraction at a lower current intensity as compared with currents of shorter duration (P < 0.01). When the current was adjusted to maintain the same visible motor response, there was no significant discomfort among studied current durations.

Conclusion

Site of placement of the cutaneous electrode is not important when constant current nerve stimulators are used during nerve localization in regional anesthesia. There is an inverse relation between the current required to obtain a visible motor response and current duration. Selecting a current duration between 0.05 and 1.0 ms to specifically stimulate sensory or motor components of a mixed nerve does not seem to be important in clinical practice.
Low Doses of Fentanyl Block Central Sensitization in the Rat Spinal Cord In Vivo
Authors: Benrath Justus , Brechtel Christina , Martin Eike , Sandkühler Jürgen
Published: May 2004

Background

mu-Opioid receptor agonists are strong analgesics. However, their usefulness for preemptive analgesia is controversial. The authors tested antinociceptive and preemptive properties of fentanyl as a mu-opioid receptor agonist in a model of spinal nociception in vivo.

Methods

C fiber-evoked potentials were recorded in the superficial laminae I-II of the rat lumbar spinal cord with glass microelectrodes in response to electrical stimulation of the sciatic nerve. High-frequency stimulation was applied on the sciatic nerve to induce long-term potentiation of C fiber-evoked field potentials, a form of central sensitization. To test the effect of fentanyl on acute nociception, fentanyl was infused intravenously at increasing doses (6-192 microg.kg(-1).h(-1)). One hour after start of infusion, high-frequency stimulation was applied to evaluate effects of fentanyl on the induction of long-term potentiation.

Results

In the absence of fentanyl, high-frequency stimulation potentiated C fiber-evoked field potentials to 149 +/-12% of controls (mean +/-SEM; n = 6) for at least 1 h. Increasing doses of fentanyl led to a significant reduction of C fiber-evoked potentials in a dose-dependent manner. The induction of long-term potentiation was blocked by low doses of fentanyl (infusion 12-48 microg.kg(1).h(-1)). At high doses, fentanyl did not block the induction of long-term potentiation (infusion 96-192 microg.kg(-1).h(-1)).

Conclusions

: Low doses of fentanyl block the synaptic form of central sensitization in the rat spinal cord in vivo, but higher doses do not have this effect.
Incorporation of the fluorescent amino acid 7‐azatryptophan into the core domain 1–47 of hirudin as a probe of hirudin folding and thrombin recognition
Authors: De Filippis Vincenzo , De Boni Silvia , De Dea Elisa , Dalzoppo Daniele , Grandi Claudio , Fontana Angelo
Published: May 2004

7‐Azatryptophan (AW), a noncoded isostere of tryptophan (W), possesses interesting spectral properties. In particular, the presence of a nitrogen atom at position 7 in the indolyl nucleus of AW results in a red shift of the absorption maximum and fluorescence emission by 10 and 46 nm, respectively, compared to W. In the present work, we report the chemical synthesis and the conformational and functional characterization of an analog (denoted as Y3AW) of the N‐terminal domain 1–47 of hirudin, a highly potent thrombin inhibitor, in which Tyr 3 has been replaced by AW. The results obtained were compared with those of the cooresponding Y3W analog. We found that the replacement W → AW reduces affinity for thrombin by 10‐fold, likely because of the lower hydrophobicity of AW compared with that of W. Measurements of the resonance energy transfer effect, which was observed between Tyr13 and the amino acid at position 3 upon disulfide‐coupled folding, demonstrate that AW behaves as a better energy acceptor than W for studying protein renaturation. The interaction of Y3AW with thrombin was studied by exciting the sample at 320 nm and recording the change in fluorescence of Y3AW on binding to the enzyme. Our results indicate that the fluorescence of AW of hirudin 1–47 in the Y3AW–thrombin complex is strongly quenched, possibly because of the presence of two structural water molecules at the hirudin–thrombin interface that can promote the nonradiative decay of AW in the excited state. The data herein reported demonstrate that the incorporation of AW can be of broad applicability in the study of protein folding and protein–protein interaction.
Identification of the N‐glycosylation sites on glutamate carboxypeptidase II necessary for proteolytic activity
Authors: Barinka Cyril , Šácha Pavel , Sklenář Jan , Man Petr , Bezouška Karel , Slusher Barbara S. , Konvalinka Jan
Published: May 2004

Glutamate carboxypeptidase II (GCPII) is a membrane peptidase expressed in the prostate, central and peripheral nervous system, kidney, small intestine, and tumor‐associated neovasculature. The GCPII form expressed in the central nervous system, termed NAALADase, is responsible for the cleavage of N‐acetylL‐aspartyl‐L‐glutamate (NAAG) yielding free glutamate in the synaptic cleft, and is implicated in various pathologic conditions associated with glutamate excitotoxicity. The prostate form of GCPII, termed prostate‐specific membrane antigen (PSMA), is up‐regulated in cancer and used as an effective prostate cancer marker. Little is known about the structure of this important pharmaceutical target. As a type II membrane protein, GCPII is heavily glycosylated. In this paper we show that N‐glycosylation is vital for proper folding and subsequent secretion of human GCPII. Analysis of the predicted N‐glycosylation sites also provides evidence that these sites are critical for GCPII carboxypeptidase activity. We confirm that all predicted N‐glycosylation sites are occupied by an oligosaccharide moiety and show that glycosylation at sites distant from the putative catalytic domain is critical for the NAAG‐hydrolyzing activity of GCPII calling the validity of previously described structural models of GCPII into question.
New enzymes from environmental cassette arrays: Functional attributes of a phosphotransferase and an RNA‐methyltransferase
Authors: Nield Blair S. , Willows Robert D. , Torda Andrew E. , Gillings Michael R. , Holmes Andrew J. , Nevalainen K.M. Helena , Stokes H.W. , Mabbutt Bridget C.
Published: May 2004

By targeting gene cassettes by polymerase chain reaction (PCR) directly from environmentally derived DNA, we are able to amplify entire open reading frames (ORFs) independently of prior sequence knowledge. Approximately 10% of the mobile genes recovered by these means can be attributed to known protein families. Here we describe the characterization of two ORFs which show moderate homology to known proteins: (1) an aminoglycoside phosphotransferase displaying 25% sequence identity with APH(7″) from Streptomyces hygroscopicus, and (2) an RNA methyltransferase sharing 25%–28% identity with a group of recently defined bacterial RNA methyltransferases distinct from the SpoU enzyme family. Our novel genes were expressed as recombinant products and assayed for appropriate enzyme activity. The aminoglycoside phosphotransferase displayed ATPase activity, consistent with the presence of characteristic Mg2+‐binding residues. Unlike related APH(4) or APH(7″) enzymes, however, this activity was not enhanced by hygromycin B or kanamycin, suggesting the normal substrate to be a different aminoglycoside. The RNA methyltransferase contains sequence motifs of the RNA methyltransferase superfamily, and our recombinant version showed methyltransferase activity with RNA. Our data confirm that gene cassettes present in the environment encode folded enzymes with novel sequence variation and demonstrable catalytic activity. Our PCR approach (cassette PCR) may be used to identify a diverse range of ORFs from any environmental sample, as well as to directly access the gene pool found in mobile gene cassettes commonly associated with integrons. This gene pool can be accessed from both cultured and uncultured microbial samples as a source of new enzymes and proteins.