bluuebunny/crossref_metadata_2025 huggingface dataset:
Research Upregulation of CD23 (FcεRII) Expression in Human Airway Smooth Muscle Cells (huASMC) in Response to IL-4, GM-CSF, and IL-4/GM-CSF
Authors: Belleau Joseph T , Gandhi Radha K , McPherson Holly M , Lew D Betty
Published: May 2005

Background

Airway smooth muscle cells play a key role in remodeling that contributes to airway hyperreactivity. Airway smooth muscle remodeling includes hypertrophy and hyperplasia. It has been previously shown that the expression of CD23 on ASMC in rabbits can be induced by the IgE component of the atopic serum. We examined if other components of atopic serum are capable of inducing CD23 expression independent of IgE.

Methods

Serum starved huASMC were stimulated with either IL-4, GM-CSF, IL-13, IL-5, PGD2, LTD4, tryptase or a combination of IL-4, IL-5, IL-13 each with GM-CSF for a period of 24 h. CD23 expression was analyzed by flow cytometry, western blot, and indirect immunofluorescence.

Results

The CD23 protein expression was upregulated in huASMC in response to IL-4, GM-CSF, and IL-4/GM-CSF. The percentage of cells with increased fluorescence intensity above the control was 25.1 ± 4.2% (IL-4), 15.6 ± 2.7% (GM-CSF) and 32.9 ± 13.9% (IL-4/GMCSF combination)(n = 3). The protein content of IL-4/GMCSF stimulated cells was significantly elevated. Expression of CD23 in response to IL-4, GM-CSF, IL-4/GM-CSF was accompanied by changes in cell morphology including depolymerization of isoactin fibers, cell spreading, and membrane ruffling. Western blot revealed abundant expression of the IL-4Rα and a low level expression of IL-2Rγc in huASMC. Stimulation with IL-4 resulted in the phosphorylation of STAT-6 and an increase in the expression of the IL-2Rγc.

Conclusion

CD23 on huASMC is upregulated by IL-4, GM-CSF, and IL-4/GM-CSF. The expression of CD23 is accompanied by an increase in cell volume and an increase in protein content per cell, suggesting hypertrophy. Upregulation of CD23 by IL-4/GM-CSF results in phenotypic changes in huASMC that could play a role in cell migration or a change in the synthetic function of the cells. Upregulation of CD23 in huASMC by IL-4 and GM-CSF can contribute to changes in huASMC and may provide an avenue for new therapeutic options in asthma targeting ASMC.
Minimal Important Difference (MID) of the Dermatology Life Quality Index (DLQI): Results from patients with chronic idiopathic urticaria
Authors: Shikiar Richard , Harding Gale , Leahy Michael , Lennox Richard D
Published: May 2005

Background

The Dermatology Quality Life Index (DLQI) has seen widespread use as a health-related quality of life measure for a variety of dermatological diseases. The purpose of this study was to estimate the minimal important difference (MID) on the DLQI for patients with chronic idiopathic urticaria (CIU).

Methods

Data from 2 Phase III clinical trials of patients (N = 476 for Study A; N = 468 for Study B) with CIU were analyzed separately to estimate the MID for the DLQI for these populations. Both distributional based and anchor based approaches were used for deriving estimates. The anchor based approach relied upon patient self assessments of pruritus severity; the distributional based approaches relied upon estimating the standard error of measurement, as well as one-half the standard deviation of the DLQI from each study.

Results

The distributional approaches resulted in estimates of MID ranging from 2.24 to 3.10 for the two studies. The anchor based approach resulted in estimates of 3.21 and 2.97 for the two studies.

Conclusion

An MID for the DLQI in the range of 2.24 to 3.10 is recommended in interpreting results for patients with CIU.
Quantification of the glycogen cascade system: the ultrasensitive responses of liver glycogen synthase and muscle phosphorylase are due to distinctive regulatory designs
Authors: Mutalik Vivek K , Venkatesh KV
Published: May 2005

Background

Signaling pathways include intricate networks of reversible covalent modification cycles. Such multicyclic enzyme cascades amplify the input stimulus, cause integration of multiple signals and exhibit sensitive output responses. Regulation of glycogen synthase and phosphorylase by reversible covalent modification cycles exemplifies signal transduction by enzyme cascades. Although this system for regulating glycogen synthesis and breakdown appears similar in all tissues, subtle differences have been identified. For example, phosphatase-1, a dephosphorylating enzyme of the system, is regulated quite differently in muscle and liver. Do these small differences in regulatory architecture affect the overall performance of the glycogen cascade in a specific tissue? We address this question by analyzing the regulatory structure of the glycogen cascade system in liver and muscle cells at steady state.

Results

The glycogen cascade system in liver and muscle cells was analyzed at steady state and the results were compared with literature data. We found that the cascade system exhibits highly sensitive switch-like responses to changes in cyclic AMP concentration and the outputs are surprisingly different in the two tissues. In muscle, glycogen phosphorylase is more sensitive than glycogen synthase to cyclic AMP, while the opposite is observed in liver. Furthermore, when the liver undergoes a transition from starved to fed-state, the futile cycle of simultaneous glycogen synthesis and degradation switches to reciprocal regulation. Under such a transition, different proportions of active glycogen synthase and phosphorylase can coexist due to the varying inhibition of glycogen-synthase phosphatase by active phosphorylase.

Conclusion

The highly sensitive responses of glycogen synthase in liver and phosphorylase in muscle to primary stimuli can be attributed to distinctive regulatory designs in the glycogen cascade system. The different sensitivities of these two enzymes may exemplify the adaptive strategies employed by liver and muscle cells to meet specific cellular demands.
Evaluation of the proficiency of trained non-laboratory health staffs and laboratory technicians using a rapid and simple HIV antibody test
Authors: Kanal Koum , Chou Thai Leang , Sovann Ly , Morikawa Yasuo , Mukoyama Yumi , Kakimoto Kazuhiro
Published: May 2005

In Cambodia, nearly half of pregnant women attend antenatal care (ANC), which is an entry point of services for prevention of mother-to-child transmission of HIV (PMTCT). However, most of ANC services are provided in health centres or fields, where laboratory services by technicians are not available. In this study, those voluntary confidential counselling and testing (VCCT) counsellors involved in PMTCT were trained by experienced laboratory technicians in our centre on HIV testing using Determine (Abbot Laboratories) HIV1/2 test kits through a half-day training course, which consisted of use of a pipette, how to process whole blood samples, and how to read test result. The trained counsellors were midwives working for ANC and delivery ward in our centre without any experience on laboratory works. The objective of this study was to assess the feasibility of the training by evaluating the proficiency of the trained non-laboratory staffs. The trained counsellors withdrew blood sample after pre-test counselling following ANC, and performed the rapid test. Laboratory technicians routinely did the same test and returned reports of the test results to counsellors. Reports by the counsellors and the laboratory technicians were compared, and discordant reports in two groups were re-tested with the same rapid test kit using the same blood sample. Cause of discordance was detected in discussion with both groups. Of 563 blood samples tested by six trained VCCT counsellors and three laboratory technicians, 11 samples (2.0%) were reported positive in each group, however four discordant reports (0.7%) between the groups were observed, in which two positive reports and two negative reports by the counsellors were negative and positive by the laboratory technicians, respectively. Further investigation confirmed that all the reports by the counsellors were correct, and that human error in writing reports in the laboratory was a cause of these discordant reports. These findings lead us the conclusion that the half-day training using the rapid and simple test was feasible for non-laboratory staffs to attain enough proficiency to implement VCCT services for PMTCT in resource-limited settings, and that human error was more likely to occur in laboratory before giving reports to counsellors.
Prolonged exercise testing in two children with a mild Multiple Acyl-CoA-Dehydrogenase deficiency
Authors: Takken T , Custers JWH , Visser G , Dorland L , Helders PJM , de Koning TJ
Published: May 2005

Background

Multiple Acyl-CoA-Dehydrogenase deficiency (MADD) is an inherited metabolic disorder characterized by impaired oxidation of fatty acids and some amino acids.

Methods

We were interested whether children with MADD could tolerate a prolonged low-intensity exercise test and if this test could have any additional diagnostic value. Therefore, we performed a maximal exercise test and a low-intensity prolonged exercise test in 2 patients with MADD and in 5 control subjects. During a prolonged exercise test the subjects exercised on a cycle ergometer at a constant workload of 30% of their maximum for 90 minutes and heart rate, oxygen uptake, fuel utilization and changes in relevant blood and urinary parameters were monitored.

Results

The tests were tolerated well. During the prolonged exercise test the fatty acid oxidation (FAO) was quite low compared to 5 control subjects, while characteristic metabolites of MADD appeared in plasma and urine.

Conclusion

We suggest that the prolonged exercise test could be of diagnostic importance and might replace the fasting test as a diagnostic procedure in some cases, particularly in patients with anamnestic signs of intolerance for prolonged exercise.
Perforin deficiency attenuates collagen-induced arthritis
Authors: Bauer Kristin , Knipper Annika , Tu-Rapp Hoang , Koczan Dirk , Kreutzer Hans-Jürgen , Nizze Horst , Mix Eilhard , Thiesen Hans-Juergen , Holmdahl Rikard , Ibrahim Saleh M
Published: May 2005

Collagen-induced arthritis (CIA), an approved animal model for rheumatoid arthritis, is thought to be a T cell-dependent disease. There is evidence that CD8+ T cells are a major subset controlling the pathogenesis of CIA. They probably contribute to certain features of disease, namely tissue destruction and synovial hyperplasia. In this study we examined the role of perforin (pfp), a key molecule of the cytotoxic death pathway that is expressed mainly in CD8+ T cells, for the pathogenesis of CIA. We generated DBA/1J mice suffering from mutations of the pfp molecule, DBA/1J-pfp-/-, and studied their susceptibility to arthritis. As a result, pfp-deficient mice showed a reduced incidence (DBA/1J-pfp+/+, 64%; DBA/1J-pfp-/-, 54%), a slightly delayed onset (onset of disease: DBA/1J-pfp+/+, 53 ± 3.6; DBA/1J-pfp-/-, 59 ± 4.9 (mean ± SEM), and milder form of the disease (maximum disease score: DBA/1J-pfp+/+, 7.3 ± 1.1; DBA/1J-pfp-/-, 3.4 ± 1.4 (mean ± SEM); P < 0.05). Concomitantly, peripheral T cell proliferation in response to the specific antigen bovine collagen II was increased in pfp-/- mice compared with pfp+/+ mice, arguing for an impaired killing of autoreactive T cells caused by pfp deficiency. Thus, pfp-mediated cytotoxicity is involved in the initiation of tissue damage in arthritis, but pfp-independent cytotoxic death pathways might also contribute to CIA.
Screening of an endothelial cDNA library identifies the C-terminal region of Nedd5 as a novel autoantigen in systemic lupus erythematosus with psychiatric manifestations
Authors: Margutti Paola , Sorice Maurizio , Conti Fabrizio , Delunardo Federica , Racaniello Mauro , Alessandri Cristiano , Siracusano Alessandra , Riganò Rachele , Profumo Elisabetta , Valesini Guido , Ortona Elena
Published: May 2005

Anti-endothelial-cell antibodies are associated with psychiatric manifestations in systemic lupus erythematosus (SLE). Our primary aim in this study was to seek and characterize molecules that behave as endothelial autoantigens in SLE patients with psychiatric manifestations. By screening a cDNA library from human umbilical artery endothelial cells with serum from an SLE patient with psychosis, we identified one positive strongly reactive clone encoding the C-terminal region (C-ter) of Nedd5, an intracytoplasmatic protein of the septin family. To evaluate anti-Nedd5 serum immunoreactivity, we analyzed by ELISA specific IgG responses in 17 patients with SLE and psychiatric manifestations (group A), 34 patients with SLE without psychiatric manifestations (group B), 20 patients with systemic sclerosis, 20 patients with infectious mononucleosis, and 35 healthy subjects. IgG specific to Nedd5 C-ter was present in 14 (27%) of the 51 SLE patients. The mean optical density value for IgG immunoreactivity to Nedd5 C-ter was significantly higher in patients of group A than in those of group B, those with infectious mononucleosis, or healthy subjects (0.17 ± 0.14 vs, respectively, 0.11 ± 0.07, P = 0.04; 0.11 ± 0.06, P = 0.034; and 0.09 ± 0.045, P = 0.003, on Student's t-test). Moreover, IgG immunoreactivity to Nedd5 C-ter was significantly higher in patients with systemic sclerosis than in patients of group B or healthy subjects (0.18 ± 0.18 vs, respectively, 0.11 ± 0.07, P = 0.046; and 0.09 ± 0.045, P = 0.003). The percentage of patients with anti-Nedd5 C-ter serum IgG was higher in group A than in group B (8 (47%) of 17, vs 6 (17%) of 34, P = 0.045, on Fisher's exact test). In order to clarify a possible mechanism by which Nedd5 might be autoantigenic, we observed that Nedd5 relocated from cytoplasm to the plasma membrane of EAhy926 endothelial cells after apoptotic stimuli. In conclusion, Nedd5 is a novel autoantigen of potential clinical importance that could be successfully used for a more thorough investigation of the pathogenesis of psychiatric manifestations in SLE. Although anti-Nedd5 autoantibodies are not specific to SLE, they are significantly associated with neuropsychiatric SLE and may represent immunological markers of psychiatric manifestations in this pathology.
NADPH-oxidase-driven oxygen radical production determines chondrocyte death and partly regulates metalloproteinase-mediated cartilage matrix degradation during interferon-γ-stimulated immune complex arthritis
Authors: van Lent Peter LEM , Nabbe Karin CAM , Blom Arjen B , Sloetjes Annet , Holthuysen Astrid EM , Kolls Jay , Van De Loo Fons AJ , Holland Steven M , Van Den Berg Wim B
Published: May 2005

In previous studies we have found that FcγRI determines chondrocyte death and matrix metalloproteinase (MMP)-mediated cartilage destruction during IFN-γ-regulated immune complex arthritis (ICA). Binding of immune complexes (ICs) to FcγRI leads to the prominent production of oxygen radicals. In the present study we investigated the contribution of NADPH-oxidase-driven oxygen radicals to cartilage destruction by using p47phox-/- mice lacking a functional NADPH oxidase complex. Induction of a passive ICA in the knee joints of p47phox-/- mice resulted in a significant elevation of joint inflammation at day 3 when compared with wild-type (WT) controls as studied by histology. However, when IFN-γ was overexpressed by injection of adenoviral IFN-γ in the knee joint before ICA induction, a similar influx of inflammatory cells was found at days 3 and 7, comprising mainly macrophages in both mouse strains. Proteoglycan depletion from the cartilage layers of the knee joints in both groups was similar at days 3 and 7. Aggrecan breakdown in cartilage caused by MMPs was further studied by immunolocalisation of MMP-mediated neoepitopes (VDIPEN). VDIPEN expression in the cartilage layers of arthritic knee joints was markedly lower (between 30 and 60%) in IFN-γ-stimulated arthritic p47phox-/- mice at day 7 than in WT controls, despite significant upregulation of mRNA levels of various MMPs such as MMP-3, MMP-9, MMP-12 and MMP-13 in synovia and MMP-13 in cartilage layers as measured with quantitative RT-PCR. The latter observation suggests that oxygen radicals are involved in the activation of latent MMPs. Chondrocyte death, determined as the percentage of empty lacunae in articular cartilage, ranged between 20 and 60% at day 3 and between 30 and 80% at day 7 in WT mice, and was completely blocked in p47phox-/- mice at both time points. FcγRI mRNA expression was significantly lower, and FcγRII and FcγRIII were higher, in p47phox-/- mice than in controls. NADPH-oxidase-driven oxygen radical production determines chondrocyte death and aggravates MMP-mediated cartilage destruction during IFN-γ-stimulated IC-mediated arthritis. Upregulation of FcγRI by oxygen radicals may contribute to cartilage destruction.
DNase and atelectasis in non-cystic fibrosis pediatric patients
Authors: Hendriks Tom , de Hoog Matthijs , Lequin Maarten H , Devos Annick S , Merkus Peter JFM
Published: May 2005

Introduction

No evidence based treatment is available for atelectasis. We aimed to evaluate the clinical and radiologic changes in pediatric patients who received DNase for persistent atelectasis that could not be attributed to cardiovascular causes, and who were unresponsive to treatment with inhaled bronchodilators and physiotherapy.

Methods

All non-cystic fibrosis pediatric patients who received nebulised or endotracheally instilled DNase for atelectasis between 1998 and 2002, with and without mechanical ventilation, were analysed in a retrospective descriptive study. The endpoints were the blood pCO2, the heart rate, the respiratory rate, the FiO2 and the chest X-ray scores before and after treatment.

Results

In 25 of 30 patients (median [range] age, 1.6 [0.1–11] years) who met inclusion criteria, paired data of at least three endpoints were available. All clinical parameters improved significantly within 2 hours (P < 0.01), except for the heart rate (P = 0.06). Chest X-ray scores improved significantly within 24 hours after DNase treatment (P < 0.001). Individual improvement was observed in 17 patients and no clinical change was observed in five patients. Temporary deterioration (n = 3) was associated with increased airway obstruction and desaturations. No other complications were observed.

Conclusion

After treatment with DNase for atelectasis of presumably infectious origin in non-cystic fibrosis pediatric patients, rapid clinical improvement was observed within 2 hours and radiologic improvement was documented within 24 hours in the large majority of children, and increased airway obstruction and ventilation–perfusion mismatch occurred in three children, possibly due to rapid mobilisation of mucus. DNase may be an effective treatment for infectious atelectasis in non-cystic fibrosis pediatric patients.
Decrease in serum procalcitonin levels over time during treatment of acute bacterial meningitis
Authors: Viallon Alain , Guyomarc'h Pantéa , Guyomarc'h Stéphane , Tardy Bernard , Robert Florianne , Marjollet Olivier , Caricajo Anne , Lambert Claude , Zéni Fabrice , Bertrand Jean-Claude
Published: May 2005

Introduction

The aim of this study was to describe the change in serum procalcitonin levels during treatment for community-acquired acute bacterial meningitis.

Methods

Out of 50 consecutive patients presenting with bacterial meningitis and infection at no other site, and who had received no prior antibiotic treatment, 48 had a serum procalcitonin level above 0.5 ng/ml on admission and were enrolled in the study.

Results

The mean age of the patients was 55 years, and mean Glasgow Coma Scale score on admission was 13. The time from symptom onset to admission was less than 24 hours in 40% of the patients, 24–48 hours in 20%, and more than 48 hours in 40%. The median (interquartile) interval between admission and initial antibiotic treatment was 160 min (60–280 min). Bacterial infection was documented in 45 patients. Causative agents included Streptococcus pneumoniae (n = 21), Neisseria meningitidis (n = 9), Listeria monocytogenes (n = 6), other streptococci (n = 5), Haemophilus influenzae (n = 2) and other bacteria (n = 2). The initial antibiotic treatment was effective in all patients. A lumbar puncture performed 48–72 hours after admission in 34 patients showed sterilization of cerebrospinal fluid. Median (interquartile) serum procalcitonin levels on admission and at day 2 were 4.5 (2.8–10.8) mg/ml and 2 (0.9–5.0) mg/ml, respectively (P < 0.0001). The corresponding values for C-reactive protein were 120 (21–241) mg/ml and 156 (121–240) mg/ml, respectively. Five patients (10%) died from noninfectious causes during their hospitalization.

Conclusions

Serum procalcitonin levels decrease rapidly with appropriate antibiotic treatment, diminishing the value of lumbar puncture performed 48–72 hours after admission to assess treatment efficacy.
A Rational Approach for Determining Response Modification Factors for Seismic Design of Buildings Using Current Code Provisions
Authors: Foutch Douglas A. , Wilcoski James
Published: May 2005

A short review of response modification factors currently found in code design provisions for seismic design of buildings is given. A proposal for a new, rational procedure for determining R factors is presented. It requires both experimental and analyses for implementation. It is based on a probabilistic foundation developed for the SAC Phase 2 project. The target threshold is to provide a 90% confidence level for satisfying the Collapse Prevention performance objective for an earthquake with a 2,475-year return period. Adoption of this procedure would result in a uniform level of safety against collapse over all materials and building systems. The method is applied to steel moment-resisting frame buildings as an example.
Mapping NEHRP VS30 Site Classes
Authors: Holzer Thomas L. , Padovani Amy C. , Bennett Michael J. , Noce Thomas E. , Tinsley John C.
Published: May 2005

Site-amplification potential in a 140-km2 area on the eastern shore of San Francisco Bay, California, was mapped with data from 210 seismic cone penetration test (SCPT) soundings. NEHRP VS30 values were computed on a 50-m grid by both taking into account the thickness and using mean values of locally measured shear-wave velocities of shallow geologic units. The resulting map of NEHRP VS30 site classes differs from other published maps that (1) do not include unit thickness and (2) are based on regional compilations of velocity. Although much of the area in the new map is now classified as NEHRP Site Class D, the velocities of the geologic deposits within this area are either near the upper or lower VS30 boundary of Class D. If maps of NEHRP site classes are to be based on geologic maps, velocity distributions of geologic units may need to be considered in the definition of VS30 boundaries of NEHRP site classes.
Damage-based Seismic Design of Structures
Authors: Khashaee Payam
Published: May 2005

The influences of the ground motion and structural characteristics on damage potential of a 7-, a 13-, and a 20-story steel building are examined using four sets of 40 accelerograms each, classified as soil sites B, C, D, and E according to the 2003 International Building Code. The Park-Ang damage index that has been used extensively during the past two decades is examined. A new damage index based on ductility and stiffness degradation is proposed. Results indicate that the proposed index correlates strongly with the energy dissipated through inelastic action. The advantages and disadvantages of the strength-based design approach are discussed and a seismic design procedure based on damage is outlined.
Strength Demand Issues Relevant for the Seismic Design of Moment-Resisting Frames
Authors: Medina Ricardo A. , Krawinkler Helmut
Published: May 2005

This paper deals with the evaluation of strength demands relevant for the seismic design of columns that are part of moment-resisting frames. Regular frames with fundamental periods from 0.3 sec. to 3.6 sec. and number of stories from 3 to 18 are investigated. An evaluation of the relationships between strength demands (e.g., story shear forces, story overturning moments, and moments in columns), ground motion intensity, fundamental period, and number of stories is the focus of this paper. The results from this study demonstrate that the magnitude and distribution over the height of maximum axial and shear forces in columns exposed to severe earthquakes often are not adequately estimated by current seismic design and analysis procedures (e.g., the nonlinear static pushover). Moreover, the potential of plastic hinging in columns is high for regular frames designed according to the strong-column/weak-beam requirements of current code provisions, and more stringent strong-column/weak-beam criteria appear to be called for. The presented results are intended to provide guidance for improvement of seismic design provisions to avoid brittle failure modes in columns of moment-resisting frames.
Optimizing Regional Earthquake Mitigation Investment Strategies
Authors: Dodo Atsuhiro , Xu Ningxiong , Davidson Rachel A. , Nozick Linda K.
Published: May 2005

Regional mitigation analysis is a systematic procedure to determine how much to spend on mitigation versus post-event reconstruction and to prioritize alternative mitigation strategies. It requires at least the following information: magnitude and character of the regional risk, costs and benefits associated with all possible mitigation alternatives, available budget, and specific regional objectives for risk management. Currently available loss estimation models provide increasingly comprehensive estimates of regional risk, but offer little guidance about how to use that information to make mitigation resource allocation decisions. This paper describes a linear program developed to support systematic regional earthquake mitigation analysis, and illustrates its application through a case study in Los Angeles County. Results suggest which buildings—by structural type, occupancy type, and census tract location—should be upgraded so as to minimize total mitigation and expected post-earthquake reconstruction costs.
Shape Memory Alloys for Seismic Response Modification: A State-of-the-Art Review
Authors: Wilson John C. , Wesolowsky Michael J.
Published: May 2005

Shape memory alloys (SMAs) are a remarkable class of metals that can offer high strength, large energy dissipation through hysteretic behavior, extraordinary strain capacity (up to 8%) with full shape recovery to zero residual strain, and a high resistance to corrosion and fatigue—aspects that are all desirable from an earthquake engineering perspective. Their various physical characteristics result from solid-solid transformation between austenite and martensite phases of the alloy that may be induced by stress or temperature. The most commercially successful SMA is a binary alloy of nickel and titanium (NiTi). Although SMAs are expensive relative to most other materials used in seismic engineering, in certain forms their capacity for high energy loss per unit volume means that comparatively small quantities can be made to be especially effective, for example when used in wire form as part of a seismic bracing system. This state-of-the-art paper presents current materials science aspects, material models, and mechanical behavior of SMAs relevant to seismic engineering, and examines the current state of design of SMA-based seismic response modification devices and their use in buildings and bridges. SMA-based devices offer promising advantages for development of next-generation seismic protection systems.
Seismic Vulnerability Assessment and Retrofit of a Major Natural Gas Pipeline System: A Case History
Authors: Wijewickreme Dharma , Honegger Douglas , Mitchell Allen , Fitzell Trevor
Published: May 2005

The performance of pipeline systems during earthquakes is a critical consideration in seismically active areas. Unique approaches to quantitative estimation of regional seismic vulnerability were developed for a seismic vulnerability assessment and upgrading program of a 500-km-long natural gas pipeline system in British Columbia, Canada. Liquefaction-induced lateral spreading was characterized in a probabilistic manner and generic pipeline configurations were modeled using finite elements. These approaches, developed during the early part of this 10-year program, are more robust than typical approaches currently used to assess energy pipeline systems. The methodology deployed within a GIS environment provided rational means of distinguishing between seismically vulnerable sites, and facilitated the prioritization of remedial works. While ground improvement or pipeline retrofit measures were appropriate for upgrading most of the vulnerable sites, replacement of pipeline segments using horizontal directional drilling to avoid liquefiable zones were required for others.
Loss Estimates for a Puente Hills Blind-Thrust Earthquake in Los Angeles, California
Authors: Field Edward H. , Seligson Hope A. , Gupta Nitin , Gupta Vipin , Jordan Thomas H. , Campbell Kenneth W.
Published: May 2005

Based on OpenSHA and HAZUS-MH, we present loss estimates for an earthquake rupture on the recently identified Puente Hills blind-thrust fault beneath Los Angeles. Given a range of possible magnitudes and ground motion models, and presuming a full fault rupture, we estimate the total economic loss to be between $82 and $252 billion. This range is not only considerably higher than a previous estimate of $69 billion, but also implies the event would be the costliest disaster in U.S. history. The analysis has also provided the following predictions: 3,000–18,000 fatalities, 142,000–735,000 displaced households, 42,000–211,000 in need of short-term public shelter, and 30,000–99,000 tons of debris generated. Finally, we show that the choice of ground motion model can be more influential than the earthquake magnitude, and that reducing this epistemic uncertainty (e.g., via model improvement and/or rejection) could reduce the uncertainty of the loss estimates by up to a factor of two. We note that a full Puente Hills fault rupture is a rare event (once every ∼3,000 years), and that other seismic sources pose significant risk as well.
Seismic Design of Steel Moment-Resisting Frame Structures Using Multiobjective Optimization
Authors: Liu Min
Published: May 2005

Design of seismic-resistant civil structural systems necessitates a balanced minimization of two general conflicting objective functions: the short-term construction investment and the long-term seismic risk. Many of the existing seismic design optimization procedures use single objectives of either the traditional minimum material usage (weight or cost) or the recent minimum expected life-cycle cost, while imposing constraints from relevant code specifications as well as additional seismic performance requirements. The resulting single optimized structural design may not always perform satisfactorily in terms of other important but competing merit objectives; the designer's individual risk-taking preference is not explicitly integrated into the design process. This paper presents a practical and general framework for design optimization of code-compliant seismic-resistant structures. Multiple objective functions, which reflect material usage, initial construction expenses, degree of design complexity, seismic structural performance, and lifetime seismic damage cost, respectively, are treated simultaneously as well as separately in the optimization process. Member-sizing problems of unbraced, regular planar, steel moment-resisting frames are selected as application examples. The resulting wide spread of optimized trade-off design alternatives enables structural engineers to actively select a cost-effective design solution that compromises conflicting merit objectives in a preferred manner.
Making a Difference: Stories of Successful Seismic Safety Advocates
Authors: Olshansky Robert B.
Published: May 2005

Promoting seismic safety is difficult. Earthquakes are not high on the political agenda, because they occur infrequently and are overshadowed by more immediate, visible issues. Nevertheless, seismic safety policies do get adopted and implemented by state and local governments. One important reason is the presence of effective advocates. This paper summarizes a study that reviewed eight examples of successful seismic safety advocacy throughout the United States. These stories exhibit a number of common themes. All of them show the importance of persistence (and patience) and the value of seeking partnerships. Personal contacts are crucial. The cases also show the importance of post-earthquake windows of opportunity. In several of the cases, community actions for seismic safety emanate from concerns about school safety. Finally, several of the cases demonstrate how initial efforts and seed funding provided by the Federal Emergency Management Agency and the U.S. Geological Survey can catalyze substantial community actions. The important lesson is that individuals can make a difference, especially if they are persistent, yet patient; have a clear message; understand the big picture; and work with others.
Geotechnical Aspects of the January 2003 Tecomán, Mexico, Earthquake
Authors: Wartman Joseph , Rodriguez-Marek Adrian , Macari Emir Jose , Deaton Scott , Ramírez-Reynaga Martín , Ochoa Carlos Navarro , Callan Sean , Keefer David , Repetto Pedro , Ovando-Shelley Efraín
Published: May 2005

Ground failure was the most prominent geotechnical engineering feature of the 21 January 2003 Mw 7.6 Tecomán earthquake. Ground failure impacted structures, industrial facilities, roads, water supply canals, and other critical infrastructure in the state of Colima and in parts of the neighboring states of Jalisco and Michoacán. Landslides and soil liquefaction were the most common type of ground failure, followed by seismic compression of unsaturated materials. Reinforced earth structures generally performed well during the earthquake, though some structures experienced permanent lateral deformations up to 10 cm. Different ground improvement techniques had been used to enhance the liquefaction resistance of several sites in the region, all of which performed well and exhibited no signs of damage or significant ground deformation. Earth dams in the region experienced some degree of permanent deformation but remained fully functional after the earthquake.
Evaluation and Design of Masonry Dwellings in Seismic Zones
Authors: Rodriguez Mario E.
Published: May 2005

Using an alternative approach, based on the demand and capacity of lateral deformations in the structure, an evaluation of seismic demand and capacity of masonry dwellings in seismic zones is performed in this paper. Recorded ground motions and general observed damage on masonry construction during several earthquakes that occurred mainly in Latin America are used in this evaluation. A seismic damage parameter previously proposed by the author is also used in a global evaluation of masonry dwelling responding to the analyzed earthquakes, in which the observed building response is correlated with the results of the damage parameter evaluation. Results of this correlation are considered in acceptable agreement.
Molecular Staging for Survival Prediction of Colorectal Cancer Patients
Authors: Eschrich Steven , Yang Ivana , Bloom Greg , Kwong Ka Yin , Boulware David , Cantor Alan , Coppola Domenico , Kruhøffer Mogens , Aaltonen Lauri , Orntoft Torben F. , Quackenbush John , Yeatman Timothy J.
Published: May 2005

Purpose

The Dukes' staging system is the gold standard for predicting colorectal cancer prognosis; however, accurate classification of intermediate-stage cases is problematic. We hypothesized that molecular fingerprints could provide more accurate staging and potentially assist in directing adjuvant therapy.

Methods

A 32,000 cDNA microarray was used to evaluate 78 human colon cancer specimens, and these results were correlated with survival. Molecular classifiers were produced to predict outcome.

Results

Molecular staging, based on 43 core genes, was 90% accurate (93% sensitivity, 84% specificity) in predicting 36-month overall survival in 78 patients. This result was significantly better than Dukes' staging (P = .03878), discriminated patients into significantly different groups by survival time (P < .001, log-rank test), and was significantly different from chance (P < .001, 1,000 permutations). Furthermore, the classifier was able to discriminate a survival difference in an independent test set from Denmark. Molecular staging identifies patient prognosis (as represented by 36-month survival) more accurately than the traditional clinical staging, particularly for intermediate Dukes' stage B and C patients. The classifier was based on a core set of 43 genes, including osteopontin and neuregulin, which have biologic significance for this disease.

Conclusion

These data support further evaluation of molecular staging to discriminate good from poor prognosis patients, with the potential to direct adjuvant therapy.
Phase II Study of a Liposome-Entrapped Cisplatin Analog (L-NDDP) Administered Intrapleurally and Pathologic Response Rates in Patients With Malignant Pleural Mesothelioma
Authors: Lu Charles , Perez-Soler Roman , Piperdi Bilal , Walsh Garrett L. , Swisher Stephen G. , Smythe W. Roy , Shin Hyung J. , Ro Jae Y. , Feng Lei , Truong Mylene , Yalamanchili Adiseshu , Lopez-Berestein Gabriel , Hong Waun K. , Khokhar Abdul R. , Shin Dong M.
Published: May 2005

Purpose

To determine pathologic response rates to liposome-entrapped cis-bisneodecanoato-trans-R,R-1,2-diaminocyclohexane platinum(II) (L-NDDP) administered intrapleurally in patients with malignant pleural mesothelioma.

Patients and Methods

Thirty-three patients with malignant pleural mesothelioma and free-flowing pleural effusions received intrapleural L-NDDP once every 3 weeks at a dose of 450 mg/m2. Thoracoscopic evaluation with pleural biopsies was performed before therapy and then after every two cycles. The primary end point was pathologic response as determined by thoracoscopic biopsy.

Results

After at least two cycles, post-treatment pleural biopsy analysis was negative in 14 patients for a pathologic response rate of 42% (95% CI, 25% to 61%). Median survival was 11.2 months. There were three treatment-related deaths secondary to peritonitis, cellulitis at the thoracoscopy site, and empyema. Grade 3 nonhematologic toxicities included infection, fever, dyspnea, and anorexia, which occurred in five (15%), one (3%), one (3%), and one (3%) patients, respectively. There were no grade 4 nonhematologic toxicities. Grade 3 or 4 neutropenia, thrombocytopenia, and anemia occurred in five (15%), three (9%), and two (6%) patients, respectively. Two patients with pathologic responses subsequently underwent pleural decortication. Both surgical specimens revealed residual tumor in regions that were not in direct communication with the pleural space.

Conclusion

Intrapleural L-NDDP therapy in this patient population is feasible with significant but manageable toxicity. Although pathologic responses are highly encouraging, areas of mesothelioma that are not in direct communication with the pleural space will evade drug exposure and limit efficacy in some patients. The optimal role of intrapleural L-NDDP therapy currently remains to be determined.
Phase I Study of Hepatic Arterial Melphalan Infusion and Hepatic Venous Hemofiltration Using Percutaneously Placed Catheters in Patients With Unresectable Hepatic Malignancies
Authors: Pingpank James F. , Libutti Steven K. , Chang Richard , Wood Bradford J. , Neeman Ziv , Kam Anthony W. , Figg William D. , Zhai Souping , Beresneva Tatiana , Seidel Geoffrey D. , Alexander H. Richard
Published: May 2005

Purpose

We conducted a phase I study of a 30-minute hepatic artery infusion of melphalan via a percutaneously placed catheter and hepatic venous hemofiltration using a double balloon catheter positioned in the retrohepatic inferior vena cava to shunt hepatic venous effluent through an activated charcoal filter and then to the systemic circulation. The purpose of the study was to demonstrate feasibility in an initial cohort and subsequently determine the maximum tolerated dose and dose-limiting toxicity of melphalan.

Patients and Methods

The initial cohort (n = 12) was treated with 2.0 mg/kg of melphalan before dose escalation to 3.5 mg/kg (n = 16). Total hepatic drug delivery, systemic levels, and percent filter efficiency were determined. Patients were assessed for hepatic and systemic toxicity and response.

Results

A total of 74 treatments were administered to 28 patients. Twelve patients with primary and metastatic hepatic tumors received 30 treatments (mean, 2.5 per patient) at an initial melphalan dose of 2.0 mg/kg. At 3.5 mg/kg, a dose-limiting toxicity (neutropenia and/or thrombocytopenia) was observed in two of six patients. Transient grade 3/4 hepatic and systemic toxicity was seen after 19% and 66% of treatments, respectively. An overall radiographic response rate of 30% was observed in treated patients. In the 10 patients with ocular melanoma, a 50% overall response rate was observed, including two complete responses.

Conclusion

Delivery of melphalan via this system is feasible, with limited, manageable toxicity and evidence of substantial antitumor activity; 3 mg/kg is the maximum safe tolerated dose of melphalan administered via this technique.
Randomized Phase III Evaluation of Cisplatin Plus Fluorouracil Versus Cisplatin Plus Paclitaxel in Advanced Head and Neck Cancer (E1395): An Intergroup Trial of the Eastern Cooperative Oncology Group
Authors: Gibson Michael K. , Li Yi , Murphy Barbara , Hussain Maha H.A. , DeConti Ronald C. , Ensley John , Forastiere Arlene A.
Published: May 2005

Purpose

To determine the response rate, survival and toxicity of infusional cisplatin plus fluorouracil (CF) versus cisplatin plus paclitaxel (CP) in patients with incurable squamous cell cancer of the head and neck, with the hypothesis that CP is superior.

Patients and Methods

Two hundred eighteen patients with locally advanced, recurrent, or metastatic disease were randomly assigned to CF (cisplatin 100 mg/m2 day 1 and fluorouracil 1,000 mg/m2/24 hours by continuous intravenous infusion day 1 through 4) or CP (cisplatin 75 mg/m2 day 1 and paclitaxel 175 mg/m2 over 3 hours on day 1). Cycles were repeated every 3 weeks until progression or a minimum of 6 cycles with complete response or stable disease. The primary outcome was overall survival. Secondary outcomes included response rate and toxicity.

Results

No significant difference in overall survival or response rate was seen. Estimated median survival was 8.7 months in the CF group and 8.1 month in the CP group. Objective response rate (complete response plus partial response) was 27% in the CF group and 26% in the CP group. Toxicity was similar between groups, with the most frequent including myelosuppression, thrombocytopenia, anemia, nausea, vomiting, and stomatitis. A total of 12 deaths occurred (CF, seven; CP, five) during treatment; eight from infection, two from hemorrhage, one from cardiac causes and one from unknown causes. Gastrointestinal and hematologic toxicities were more common in the CF group, whereas neurotoxicity was equivalent between groups.

Conclusion

This phase III, randomized, multicenter trial showed no difference in survival between patients treated with CF or CP.
Phase II Study of Irinotecan Plus Cisplatin Induction Followed by Concurrent Twice-Daily Thoracic Irradiation With Etoposide Plus Cisplatin Chemotherapy for Limited-Disease Small-Cell Lung Cancer
Authors: Han Ji-Youn , Cho Kwan Ho , Lee Dae Ho , Kim Hyae Young , Kim Eun-A , Lee Sung Young , Lee Jin Soo
Published: May 2005

Purpose

Irinotecan plus cisplatin (IP) chemotherapy demonstrated a promising outcome with a high complete response (CR) rate in chemotherapy-naïve patients with extensive small-cell lung cancer (SCLC). We evaluated the efficacy of induction IP chemotherapy followed by concurrent etoposide plus cisplatin (EP) chemotherapy with twice-daily thoracic radiotherapy (TDTRT) in limited-disease SCLC (LD-SCLC).

Patients and Methods

Between November 2001 and May 2003, 35 chemotherapy-naïve patients with LD-SCLC were enrolled. Thirty-three patients (94%) were male, and 29 (83%) had an Eastern Cooperative Oncology Group performance status of 0 or 1. The median age was 63 years. Treatment consisted of two 21-day cycles of cisplatin 40 mg/m2 and irinotecan 80 mg/m2 intravenously (IV) on days 1 and 8 followed by two 21-day cycles of cisplatin 60 mg/m2 IV on days 43 and 64, and etoposide 100 mg/m2 IV on days 43 to 45 and 64 to 66, with concurrent TDTRT of total 45 Gy beginning on day 43.

Results

All 35 patients were assessable for response. The objective response rate was 97% (CR, 3; partial response [PR], 31) after induction chemotherapy and 100% (CR, 15; PR, 20) after concurrent chemoradiotherapy (CCRT). After a median follow-up of 26.5 months, the median survival was 25.0 months (95% CI, 19.0 to 30.9) with 1- and 2-year overall survival rates of 85.7% and 53.9%, respectively. Median progression-free survival (PFS) was 12.9 months with a 1- and 2-year PFS of 58.5% and 36.1%, respectively. The most common toxicities were grade 3 or 4 neutropenia in 68% of patients during induction chemotherapy and 100% during CCRT. Febrile neutropenia occurred in 20% of patients during induction chemotherapy and 60% during CCRT.

Conclusion

IP induction chemotherapy followed by concurrent TDTRT with EP chemotherapy showed a promising activity with favorable 1- and 2-year survival rates. Based on the favorable outcome in this trial, this regimen should be evaluated in a large phase III trial.
Neoplastic Meningitis
Authors: Chamberlain Marc C.
Published: May 2005

Neoplastic meningitis (NM) is a common problem in neuro-oncology occurring in approximately 5% of all patients with cancer, and is the third most common site of CNS metastases. NM is a disease affecting the entire neuraxis, and therefore clinical manifestations are pleomorphic affecting the spine, cranial nerves, and cerebral hemispheres. Because of craniospinal disease involvement, staging and treatment need to encompass all CSF compartments. Treatment of NM utilizes involved-field radiotherapy of bulky or symptomatic disease sites and intra-CSF drug therapy. The inclusion of concomitant systemic therapy may benefit patients with NM and may obviate the need for intra-CSF chemotherapy. At present, intra-CSF drug therapy is confined to three chemotherapeutic agents (ie, methotrexate, cytarabine, and thiotepa) administered by a variety of schedules either by intralumbar or intraventricular drug delivery. Although treatment of NM is palliative with an expected median patient survival of 2 to 6 months, it often affords stabilization and protection from further neurologic deterioration in patients with NM.