Publications by authors named "Eugene Choo"

31 Publications

Impact of Rapid Transition to Telemedicine-Based Delivery on Allergy/Immunology Care During COVID-19.

J Allergy Clin Immunol Pract 2021 Jul 22;9(7):2672-2679.e2. Epub 2021 Apr 22.

UCSF Department of Medicine, Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, San Francisco, Calif.

Background: Coronavirus disease 2019 (COVID-19) necessitated wide-scale adoption of telemedicine (TM) and restriction of in-person care. The impacts on allergy/immunology (A/I) care delivery are still being studied.

Objective: To describe the outcomes of rapid transition to TM-based care (video visit followed by in-person visits dedicated to diagnostic and therapeutic procedures when needed) at an academic A/I practice during COVID-19.

Methods: Demographic data were compared for patients originally scheduled for in-person visits between March 10, 2020, and April 30, 2020, who completed a video visit instead between March 10, 2020, and June 30, 2020, and those who did not. Appointment completion, diagnoses, and drug allergy and skin testing completion were compared for visits between March 10, 2020, and June 30, 2020, and 1 year prior (March 10, 2019-June 30, 2019).

Results: Sixty-nine percent (265 of 382) of patients originally scheduled between March 10, 2020, and April 30, 2020, were able to complete video visits. Patients who completed video visits were more likely to be white (52% vs 33%; P < .001), English-speaking (96% vs 89%; P = .01), and privately insured (70% vs 54%; P = .004). With TM-based care compared with in-person care, there were significant decreases in environmental and food skin testing completion rates (91% and 92% in 2019 vs 60% and 64% in 2020, respectively, P < .001). Drug allergy testing completed after internal referral remained low but comparable (51% in 2019 vs 52% in 2020). Transitioning nonprocedural visits to video allowed allergen immunotherapy and biologic injection visits to resume at a volume similar to pre-COVID. No COVID-19 infections resulted from in-clinic exposure.

Conclusions: Although transitioning to TM-based care allowed continued A/I care delivery, strategies are needed to achieve higher testing completion rates and ensure video visits do not exacerbate existing health disparities.
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http://dx.doi.org/10.1016/j.jaip.2021.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061180PMC
July 2021

No difference in omalizumab efficacy in patients with asthma by number of asthma-related and allergic comorbidities.

Ann Allergy Asthma Immunol 2021 06 17;126(6):666-673. Epub 2021 Jan 17.

Albert Einstein College of Medicine, Bronx, New York.

Background: Comorbidities are common in asthma and may complicate treatment response.

Objective: To examine response to omalizumab in patients with moderate-to-severe allergic asthma by asthma-related and allergic comorbidities.

Methods: Patients aged 12 years or more from placebo-controlled 008/009 (n = 1071), EXTRA (n = 848), and INNOVATE (n = 419), and single-armed PROSPERO (n = 801) omalizumab studies were included. Poisson regression/analysis of covariance models were used to estimate adjusted exacerbation rates and forced expiratory volume in 1 second (FEV1) change from baseline after omalizumab initiation for subgroups by number of comorbidities (0, 1 [008/009]; 0, 1, ≥2 [EXTRA and INNOVATE]; 0, 1, 2, ≥3 [PROSPERO]). Self-reported comorbidities included allergic rhinoconjunctivitis, chronic rhinosinusitis, recurrent acute sinusitis, nasal polyps, atopic and contact dermatitis, urticaria, food allergy, anaphylaxis, other allergies, gastroesophageal reflux disease, eosinophilic esophagitis, and eosinophilic granulomatosis with polyangiitis.

Results: In the EXTRA and INNOVATE studies, no consistent pattern was observed for placebo-corrected relative rate reduction in normalized asthma exacerbations among omalizumab-treated comorbidity subgroups. In PROSPERO, on-study exacerbation rates in the comorbidity subgroups were similar (0, 0.68; 1, 0.70; 2, 0.77; ≥3, 0.80). FEV1 improvements were observed throughout the study for omalizumab vs placebo for all comorbidity subgroups. There were no consistent differences in FEV1 improvements among comorbidity subgroups in 008/009, EXTRA, or INNOVATE. Similarly, no among-group differences were observed for FEV1 change from baseline at month 12 in PROSPERO (0, 0.05 L; 1, 0.08 L; 2, 0.00 L; ≥3, 0.04 L). The 95% confidence intervals overlapped substantially in all instances.

Conclusion: In these analyses of placebo-controlled/single-armed studies, on-study exacerbation rates and FEV1 improvements with omalizumab treatment were similar irrespective of comorbidity burden.

Trial Registration: ClinicalTrials.gov identifiers are as follows: EXTRA, NCT00314574 (https://clinicaltrials.gov/ct2/show/NCT00314574); INNOVATE, NCT00046748 (https://clinicaltrials.gov/ct2/show/NCT00046748); and PROSPERO, NCT01922037 (https://clinicaltrials.gov/ct2/show/NCT01922037).
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http://dx.doi.org/10.1016/j.anai.2021.01.015DOI Listing
June 2021

COVID-19 intubation teams-the Saskatoon experience.

Can J Anaesth 2021 04 6;68(4):591-592. Epub 2021 Jan 6.

Department of Anesthesiology, Perioperative Medicine, and Pain Management, University of Saskatchewan, Saskatoon, SK, Canada.

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http://dx.doi.org/10.1007/s12630-020-01897-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785328PMC
April 2021

Overlap of allergic, eosinophilic and type 2 inflammatory subtypes in moderate-to-severe asthma.

Clin Exp Allergy 2021 04 7;51(4):546-555. Epub 2021 Jan 7.

University of California, San Francisco, CA, USA.

Background: Current biologic therapies target allergic, eosinophilic or type 2 inflammation phenotypic asthma. However, frequency and degree of overlap among these subtypes is unclear.

Objective: To characterize overlap among allergic, eosinophilic and type 2 asthma phenotypes.

Methods: Post hoc analyses of baseline data were performed in two adult populations: (a) not selected for any asthma subtype (N = 935) and (b) selected for allergic asthma (N = 1049). Degree of overlap was examined using commonly accepted phenotypic definitions to guide treatment for allergic asthma (skin prick-positive and/or positive serum-specific immunoglobulin E > 0.35 kU/L) and eosinophilic asthma (blood eosinophil high count ≥ 300 cells/µL; low cut-off ≥ 150 cells/µL). Consistent with previous studies, fractional exhaled nitric oxide high level of ≥ 35 ppb and low cut-off of ≥ 25 ppb were selected as local markers of type 2 inflammation and to prevent overlap with the systemic eosinophilic asthma definition.

Results: In the non-subtype-selected population, 78.0% had allergic asthma; of these, 39.5% had eosinophilic asthma and 29.5% had type 2 asthma. Within patients with eosinophilic asthma (40.6% of total), 75.8% had allergic asthma and 41.3% had type 2 asthma. Within patients with type 2 asthma (28.3% of total), 81.1% had allergic asthma and 59.2% had eosinophilic asthma. In the allergic asthma-selected population, 38.3% had eosinophilic asthma and 29.2% had type 2 asthma. Within patients with eosinophilic asthma, 46.3% had type 2 asthma. Within patients with type 2 asthma, 60.8% had eosinophilic asthma. Overlaps among subtypes increased at low cut-off values.

Conclusions And Clinical Relevance: In this post hoc analysis in adults with moderate-to-severe asthma, allergic asthma was the most prevalent phenotype, followed by eosinophilic and type 2 asthma. Despite observed overlaps, a considerable proportion of patients had only a predominantly allergic subtype. Understanding the degree of overlap across phenotypes will help patient management and guide treatment options.
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http://dx.doi.org/10.1111/cea.13790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048421PMC
April 2021

Remote solutions for telementoring point-of-care ultrasound echocardiography: The RESOLUTE study.

Can J Anaesth 2017 10 5;64(10):1077-1078. Epub 2017 Jul 5.

Division of Cardiac Anesthesiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.

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http://dx.doi.org/10.1007/s12630-017-0927-8DOI Listing
October 2017

Nanoscaled self-alignment of Fe3O4 nanodiscs in ultrathin rGO films with engineered conductivity for electromagnetic interference shielding.

Nanoscale 2016 Sep 19;8(35):15989-98. Epub 2016 Aug 19.

Temasek Laboratories, National University of Singapore, 5A Engineering Drive 1, Singapore 117411, Singapore.

Ultrathin (∼2 μm) reduced graphene oxide (rGO) film embedded with self-aligned Fe3O4 nanodiscs were successfully fabricated through the filtration-assisted self-assembly method. In the as-fabricated hybrid film, Fe3O4 nanodiscs with thin thickness (26 nm) and high aspect ratio (∼9) were readily self-assembled and aligned in rGO intersheets under the assistance of hydrostatic forces. Compared with spherical Fe3O4 nanoparticles, introducing the Fe3O4 nanodiscs into rGO paper could not only offer high magnetic permeability and magnetic loss in a broad frequency range at the gigahertz level, but also increase the electrical conductivity of rGO film by means of improving the surface roughness without disrupting the conductive network of the rGO layers. Due to the above advantages, the free-standing rGO/Fe3O4 nanodisc magnetic hybrid film (56 wt%) exhibited an EMI shielding effectiveness (SE) of around 11.2 dB in the frequency range of 2-10 GHz, which is about 50% and 72% higher than that of neat rGO film and rGO/Fe3O4 nanosphere hybrid films (with similar particle size and loading weight fraction) prepared under the same conditions, respectively. Furthermore, compared with non-magnetic neat rGO film, the outstanding magnetic properties of the rGO/Fe3O4 nanodisc film paves the way for it to be used as a multifunctional material that can be controlled by magnetic fields. Additionally, the moderate thermal reduction temperature (420 °C) would be meaningful for large scale fabrication. Meanwhile, the strategy of achieving good alignment at the nanoscale could shed light on developing heterogeneous structures with self-aligned two-dimensional (2D) (magnetic or non-magnetic) nano-inclusions for various applications.
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http://dx.doi.org/10.1039/c6nr04539aDOI Listing
September 2016

Designed Construction of a Graphene and Iron Oxide Freestanding Electrode with Enhanced Flexible Energy-Storage Performance.

ACS Appl Mater Interfaces 2016 Mar 14;8(11):6972-81. Epub 2016 Mar 14.

Department of Materials Science and Engineering, National University of Singapore , Singapore 117573, Singapore.

In this work, a bendable [email protected] oxide hybrid film (GFeF) electrode was fabricated through a filtration-assisted self-assembly method. Morphological characterization of GFeF revealed a uniform distribution of iron oxide nanoparticles between graphene nanosheets. Surface chemical characterization confirmed that graphene oxide in the as-prepared hybrid film was effectively reduced after thermal reduction. The electrochemical performance of a GFeF half-cell versus Li/Li(+) exhibited high gravimetric capacity (855.2 mAh g(-1) at 0.02 A g(-1)), high volumetric capacity (1949.9 mAh cm(-3) at 0.02 A g(-1)), and superior cycling stability (93% capacitance retention after 500 cycles). On the basis of such a bendable electrode, a hybrid Li-ion supercapacitor that offers an operation voltage of 3.5 V and delivers a high energy density (129.6 Wh kg(-1)) like a Li-ion battery combined with a high power density (1870 W kg(-1)) like a supercapacitor was fabricated. In addition to the superior energy-storage capability, the as-fabricated prototype pouch cell also exhibited excellent mechanical flexibility and stable electrochemical performances under dynamic bending. The viability of such an energy-storage device provides a possible design pathway for future wearable electronics.
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http://dx.doi.org/10.1021/acsami.5b10853DOI Listing
March 2016

Tracheobronchomalacia and Hyperdynamic Airway Collapse.

J Allergy Clin Immunol Pract 2015 Jul-Aug;3(4):644-5; quiz 646

Allergy, Asthma & Immunology Associates of Tampa Bay, Tampa, Fla; Morsani College of Medicine, University of South Florida, Tampa, Fla.

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http://dx.doi.org/10.1016/j.jaip.2015.01.018DOI Listing
April 2016

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss vasculitis).

J Allergy Clin Immunol Pract 2015 May-Jun;3(3):466-7; quiz 468

Allergy, Asthma & Immunology Associates of Tampa Bay, Tampa, Fla; Ellsworth and Mabel Simmons Professor of Allergy/Immunology, Tampa, Fla; Past-President of Medical Faculty, University of South Florida College of Medicine, Tampa, Fla.

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http://dx.doi.org/10.1016/j.jaip.2015.02.010DOI Listing
February 2016

Magnetic nanoparticle-loaded polymer nanospheres as magnetic hyperthermia agents.

J Mater Chem B 2014 Jan 19;2(1):120-128. Epub 2013 Nov 19.

Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Xi'an, Shaanxi 710069, China.

Uniform magnetic nanoparticle-loaded polymer nanospheres with different loading contents of manganese ferrite nanoparticles were successfully synthesized using a flexible emulsion process. The MnFeO-loaded polymer nanospheres displayed an excellent dispersibility in both water and phosphate buffer saline. The effect of loading ratio and size of MnFeO nanoparticles within the nanospheres on the specific absorption rate (SAR) under an alternating magnetic field was investigated. Our results indicate that a large size (here 18 nm) and a low loading ratio are preferable for a high SAR. For a smaller particle size (6 nm), the low loading ratio did not result in an enhancement of the SAR value, while a very low SAR value is expected for 6 nm. In addition, the SAR of low-content MnFeO (18 nm)-loaded polymer nanospheres in the agarose gel which is simulated for in vivo environment is the highest among the samples and does not change substantially in physiological environments. This differs largely from the behaviour of singly dispersed nanoparticles. Our results have paved the way for the design of MnFeO-loaded polymer nanospheres as magnetic hyperthermia agents for in vivo bio-applications.
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http://dx.doi.org/10.1039/c3tb21146kDOI Listing
January 2014

IL-4 confers resistance to IL-27-mediated suppression on CD4+ T cells by impairing signal transducer and activator of transcription 1 signaling.

J Allergy Clin Immunol 2013 Oct 16;132(4):912-21.e1-5. Epub 2013 Aug 16.

Division of Allergy and Immunology, Department of Medicine, National Jewish Health, Denver, Colo; Zhangshan Hospital, Fudan University, Shanghai, China.

Background: TH2 cells play a critical role in the pathogenesis of allergic asthma. Established TH2 cells have been shown to resist reprogramming into TH1 cells. The inherent stability of TH2 cells poses a significant barrier to treating allergic diseases.

Objective: We sought to understand the mechanisms by which CD4(+) T cells from asthmatic patients resist the IL-27-mediated inhibition.

Methods: We isolated and cultured CD4(+) T cells from both healthy subjects and allergic asthmatic patients to test whether IL-27 can inhibit IL-4 production by the cultured CD4(+) T cells using ELISA. Culturing conditions that resulted in resistance to IL-27 were determined by using both murine and human CD4(+) T-cell culture systems. Signal transducer and activator of transcription (STAT) 1 phosphorylation was analyzed by means of Western blotting and flow cytometry. Suppressor of cytokine signaling (Socs) mRNA expression was measured by using quantitative PCR. The small interfering RNA method was used to knockdown the expression of Socs3 mRNA.

Results: We demonstrated that CD4(+) T cells from asthmatic patients resisted the suppression of IL-4 production mediated by IL-27. We observed that repeated exposure to TH2-inducing conditions rendered healthy human CD4(+) T cells resistant to IL-27-mediated inhibition. Using an in vitro murine culture system, we further demonstrated that repeated or higher doses of IL-4 stimulation, but not IL-2 stimulation, upregulated Socs3 mRNA expression and impaired IL-27-induced STAT1 phosphorylation. The knockdown of Socs3 mRNA expression restored IL-27-induced STAT1 phosphorylation and IL-27-mediated inhibition of IL-4 production.

Conclusions: Our findings demonstrate that differentiated TH2 cells can resist IL-27-induced reprogramming toward TH1 cells by downregulating STAT1 phosphorylation and likely explain why the CD4(+) T cells of asthmatic patients are resistant to IL-27-mediated inhibition.
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http://dx.doi.org/10.1016/j.jaci.2013.06.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3788709PMC
October 2013

Multifunctional PEGylated nanoclusters for biomedical applications.

Nanoscale 2013 Jul 28;5(13):5994-6005. Epub 2013 May 28.

Department of Materials Science & Engineering, Faculty of Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576.

A simple and versatile synthesis method to form water soluble multifunctional nanoclusters using polyethylene glycol (PEG) functionalized poly(maleic anhydride-alt-1-octadecene) amphiphilic brush copolymers (PMAO-g-PEG) was presented. Simply by tuning the core size and the initial nanocrystal concentration, manganese ferrite nanoparticles (MFNPs) were used to demonstrate the versatility of tuning the loading amount of the nanoclusters. The resultant nanoclusters were found to have a well-controlled spherical shape. When Zn-doped AgInS2 quantum dots (AIZS QDs) were loaded together with the MFNP nanocrystals, bi-functional nanoclusters with fluorescent and magnetic behaviors were obtained. Such bi-functional nanoclusters were also successfully demonstrated for cellular bio-imaging. Moreover, the presence of another type of nanocrystals together with MFNPs was found to have a negligible effect on the overall properties of the nanoclusters as demonstrated by the MR relaxivity test. From the time-dependent colloidal stability test, it was found that the presence of the PEG chain grafted onto PMAO was able to reduce protein adsorption onto the nanocluster surface. An in vitro study on NIH/3T3 demonstrated the biocompatibility of the nanoclusters. Such biocompatible and colloidally stable nanoclusters with an approximate size of 80-120 nm were suitable for both MRI and cell labeling applications.
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http://dx.doi.org/10.1039/c3nr00774jDOI Listing
July 2013

Asthma, one of the most common diseases seen by physicians. Preface.

Authors:
Eugene M Choo

Immunol Allergy Clin North Am 2013 Feb;33(1):xi-xii

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http://dx.doi.org/10.1016/j.iac.2012.12.001DOI Listing
February 2013

Tracheomalacia/Tracheobronchomalacia and hyperdynamic airway collapse.

Immunol Allergy Clin North Am 2013 Feb 27;33(1):23-34. Epub 2012 Nov 27.

Division of Allergy and Immunology, Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.

Tracheobronchomalacia (TBM) and hyperdynamic airway collapse (HDAC) can be debilitating diseases associated with decreased functional capacity and poor quality of life, although there is no standard definition of this complex condition, and there are numerous terms used to describe it. The diverse etiology associated with TBM and HDAC can obscure and delay an accurate diagnosis for years. A thorough medical history is important in understanding possible causes and in guiding diagnostic testing. Medical history may also suggest what treatments may be most beneficial.
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http://dx.doi.org/10.1016/j.iac.2012.10.005DOI Listing
February 2013

Synthesis of manganese ferrite/graphene oxide nanocomposites for biomedical applications.

Small 2012 Dec 7;8(23):3620-30. Epub 2012 Sep 7.

Department of Materials Science & Engineering, Faculty of Engineering, National University of Singapore (NUS), 7 Engineering Drive 1, Singapore.

In this study, MnFe(2)O(4) nanoparticle (MFNP)-decorated graphene oxide nanocomposites (MGONCs) are prepared through a simple mini-emulsion and solvent evaporation process. It is demonstrated that the loading of magnetic nanocrystals can be tuned by varying the ratio of graphene oxide/magnetic nanoparticles. On top of that, the hydrodynamic size range of the obtained nanocomposites can be optimized by varying the sonication time during the emulsion process. By fine-tuning the sonication time, MGONCs as small as 56.8 ± 1.1 nm, 55.0 ± 0.6 nm and 56.2 ± 0.4 nm loaded with 6 nm, 11 nm, and 14 nm MFNPs, respectively, are successfully fabricated. In order to improve the colloidal stability of MGONCs in physiological solutions (e.g., phosphate buffered saline or PBS solution), MGONCs are further conjugated with polyethylene glycol (PEG). Heating by exposing MGONCs samples to an alternating magnetic field (AMF) show that the obtained nanocomposites are efficient hyperthermia agents. At concentrations as low as 0.1 mg Fe mL(-1) and under an 59.99 kA m(-1) field, the highest specific absorption rate (SAR) recorded is 1588.83 W g(-1) for MGONCs loaded with 14 nm MFNPs. It is also demonstrated that MGONCs are promising as magnetic resonance imaging (MRI) T(2) contrast agents. A T(2) relaxivity value (r(2) ) as high as 256.2 (mM Fe)(-1) s(-1) could be achieved with MGONCs loaded with 14 nm MFNPs. The cytotoxicity results show that PEGylated MGONCs exhibit an excellent biocompatibility that is suitable for biomedical applications.
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http://dx.doi.org/10.1002/smll.201201427DOI Listing
December 2012

Synthesis of poly(acrylic acid) (PAA) modified Pluronic P123 copolymers for pH-stimulated release of doxorubicin.

J Colloid Interface Sci 2011 Jun 21;358(2):462-70. Epub 2011 Mar 21.

Department of Materials Science and Engineering, Faculty of Engineering, National University of Singapore (NUS), 7 Engineering Drive 1, Singapore 117574, Singapore.

Pluronic P123 was chain-extended at their terminal groups using atom transfer radical polymerization to form poly(acrylic acid) (PAA) tails and obtain the PAA-b-P123-b-PAA (P123-PAA) copolymer. The incorporation of PAA had the effect of increasing the carrier's drug loading capacity of an anti-cancer drug, Doxorubicin (DOX), and also allowed for pH-controlled release of the drug. Drug release assays showed that up to 60% of DOX cargo could be retained in the DOX/P123-PAA complex for 3 days at normal physiological pH (7.4). This was then followed by a secondary burst release of DOX when the environment became more acidic (pH 5). Therefore, it was possible that the more acidic physiological environment of tumor sites could be used to trigger an accelerated release of DOX from the drug carriers. The material was demonstrated for potential application in the delivery of cationic drugs for cancer treatment.
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http://dx.doi.org/10.1016/j.jcis.2011.03.047DOI Listing
June 2011

Synthesis of CuInS2-ZnS alloyed nanocubes with high luminescence.

Chem Commun (Camb) 2011 May 23;47(18):5217-9. Epub 2011 Mar 23.

Department of Materials Science and Engineering, National University of Singapore, Singapore, 117576.

CuInS(2)-ZnS alloyed nanocubes with high luminescence were synthesized through a solution-based diffusion method.
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http://dx.doi.org/10.1039/c1cc10417aDOI Listing
May 2011

Skin conductance fluctuations correlate poorly with postoperative self-report pain measures in school-aged children.

Anesthesiology 2010 Jul;113(1):175-82

Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.

Background: The number of fluctuations of skin conductance per second (NFSC) has been shown to correlate with induced pain and self-report pain scales. This study aimed to evaluate the validity and feasibility of NFSC as an objective measurement of nociception intensity in school-aged children after surgery.

Methods: After approval by the research ethics board and obtaining consent, 100 subjects participated in this prospective observational study. Preoperatively, NFSC was measured for 60 s at rest and during response to a self-report pain scale (numeric rating scale [NRS], Faces Pain Scale-Revised) and anxiety scoring (NRS). Postoperative measurements were repeated every 10 min for 30 min or until NRS pain score was
Results: Data from 90 subjects (64.4% male) aged 7-17 yr (median age 13 yr) were analyzed (217 postoperative datasets). NFSC correlated weakly with NRS pain scores (P = 0.21; P < 0.002). NFSC did not correlate with NRS anxiety scores (P = 0.15, P < 0.03). NRS pain scores correlated strongly with Faces Pain Scale-Revised (P = 0.89, P < 0.0001) and weakly with NRS anxiety scores (P = 0.34, P < 0.0001). A threshold of 0.23 NFSC predicted severe pain (NRS >or= 7) with 56.3% sensitivity (95% CI = 37.7-73.6%) and 78.4% specificity (95% CI = 71.7-84.1%). The area under receiver operator characteristic curve for NFSC was 69.1%.

Conclusions: NFSC measurement is feasible in a perioperative setting but was not specific for postoperative pain intensity and was unable to identify analgesia requirements when compared with self-report measures.
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http://dx.doi.org/10.1097/ALN.0b013e3181de6ce9DOI Listing
July 2010

Designing poly[(R)-3-hydroxybutyrate]-based polyurethane block copolymers for electrospun nanofiber scaffolds with improved mechanical properties and enhanced mineralization capability.

J Phys Chem B 2010 Jun;114(22):7489-98

Institute of Materials Research and Engineering, Agency for Science, Technology and Research, 3 Research Link, Singapore 117602.

Efforts to mineralize electrospun hydrophobic polyester scaffold often require prior surface modification such as plasma or alkaline treatment, which may affect the mechanical integrity of the resultant scaffold. Here through rational design we developed a series of polyurethane block copolymers containing poly[(R)-3-hydroxybutyrate] (PHB) as hard segment and poly(ethylene glycol) (PEG) as soft segment that could be easily fabricated into mineralizable electrospun scaffold without the need of additional surface treatment. To ensure that the block copolymers do not swell excessively in water, PEG content in the polymers was kept below 50 wt %. To obtain good dry and hydrated state mechanical properties with limited PEG, low-molecular-weight PHB-diol with M(n) 1230 and 1790 were used in various molar feed ratios. The macromolecular characteristics of the block copolymers were confirmed by (1)H NMR spectroscopy, gel permeation chromatography (GPC), and thermal gravimetric analyses (TGA). With the incorporation of the hydrophilic PEG segments, the surface and bulk hydrophilicity of the block copolymers were significantly improved. Differential scanning calorimetry (DSC) revealed that the block copolymers had low PHB crystallinity and no PEG crystallinity. This was further confirmed by X-ray diffraction analyses (XRD) in both dry and hydrated states. With short PHB segments and soft PEG coupled together, the block copolymers were no longer brittle. Tensile measurements showed that the block copolymers with higher PEG content or shorter PHB segments were more ductile. Furthermore, their ductility was enhanced in hydrated states with one particular example showing increment in strain at break from 1090 to 1962%. The block copolymers were fabricated into an electrospun fibrous scaffold that was easily mineralized by simple incubation in simulated body fluid. The materials have good potential for bone regeneration application and may be extended to other applications by simply coating them with other biologically active substances.
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http://dx.doi.org/10.1021/jp1018247DOI Listing
June 2010

Synthesis of ZnO-Pt nanoflowers and their photocatalytic applications.

Nanotechnology 2010 May 14;21(18):185606. Epub 2010 Apr 14.

Department of Materials Science and Engineering, National University of Singapore, 7 Engineering Drive 1, 117574, Singapore.

The photocatalytic behaviors of ZnO nanoparticles have been intensively studied recently. However, the photocatalytic efficiency of pure ZnO nanoparticles always suffers from the quick recombination of photoexcited electrons and holes. In order to suppress the electron-hole recombination and then raise the photocatalytic efficiency of ZnO, metal nanoparticles have been combined with ZnO to form ZnO-metal heterostructures. In this work, the feasibility of synthesizing ZnO-Pt composite nanoflowers for optimized catalytic properties was studied. Three different Pt nanocrystals, i.e. cubic Pt nanocrystals enclosed by {100} facets, octahedral Pt nanocrystals enclosed by {111} facets, and truncated octahedral Pt nanocrystals enclosed by both {111} and {100} facets, were selected as seeds for epitaxial growth of ZnO. A ZnO-Pt flowerlike nanostructure was formed by selective growth of ZnO nanolobes at {111} facets of the truncated octahedral Pt nanocrystals. The resultant nanoflowers had well defined ZnO-Pt interfaces and exposed Pt {100} facets, as confirmed by transmission electron microscopy (TEM) and high-resolution TEM (HRTEM) measurements. The photocatalytic behaviors of the resultant ZnO-Pt nanoflowers were demonstrated in the photodegradation of ethyl violet. In comparison with the commercial TiO(2) photocatalyst P25, the ZnO-Pt flowerlike nanostructures showed improved catalytic efficiency. Notable ferromagnetism of the obtained ZnO-Pt flowerlike nanostructures was also observed. It is believed that the ZnO-Pt interface played an important role in the enlarged magnetic coercivity of the ZnO-Pt nanoflowers.
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http://dx.doi.org/10.1088/0957-4484/21/18/185606DOI Listing
May 2010

One-pot synthesis of water-stable ZnO nanoparticles via a polyol hydrolysis route and their cell labeling applications.

Langmuir 2009 May;25(9):5271-5

Department of Materials Science and Engineering, National University of Singapore, Blk E3A, 04-10, 7 Engineering Drive 1, Singapore 117574.

ZnO nanoparticles have been identified as a new generation of biofriendly cell labeling agents since they are nontoxic, less expensive, and chemically stable in air. However, ZnO nanoparticles show poor water stability due to high equilibrium concentration of Zn species in water in a wide pH range. In this work, a one-pot polyol hydrolysis method was developed for synthesizing water-stable ZnO nanoparticles with blue emission. The as-synthesized ZnO nanoparticles were hydrophilic and stable in water, even at basic or acidic aqueous conditions. The PL properties of the ZnO nanoparticles stored at various pH values (i.e., 4.5-11) could be preserved for at least 3 days. The good water stability of the ZnO nanoparticles was offered by the surface attachment of an ester compound, which was formed as a result of the reaction between the stearic acid and triethylene glycol (TREG). This method provides a new approach to synthesize water-stable ZnO nanoparticles. The resultant ZnO nanoparticles demonstrated promising applications in cell labeling.
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http://dx.doi.org/10.1021/la900374bDOI Listing
May 2009

Three new datasets supporting use of the Numerical Rating Scale (NRS-11) for children's self-reports of pain intensity.

Pain 2009 Jun 8;143(3):223-227. Epub 2009 Apr 8.

Department of Psychology, University of Saskatchewan, 9 Campus Drive, Saskatoon, SK, Canada S7N 5A5 Department of Pediatrics, University of Saskatchewan, Saskatoon, Canada Faculty of Medicine, University of British Columbia, and British Columbia Children's and Women's Hospital, Vancouver, Canada Children's Mercy Hospital and Department of Pediatrics, University of Missouri - Kansas City School of Medicine, USA.

Despite wide usage of the Numerical Rating Scale (NRS) for self-report of pain intensity in clinical practice with children and adolescents, validation data are lacking. We present here three datasets from studies in which the NRS was used together with another self-report scale. Study A compared post-operative pain ratings on the NRS with scores on the Faces Pain Scale-Revised (FPS-R) in 69 children age 7-17 years who had undergone a variety of surgical procedures. Study B compared post-operative pain ratings on the NRS with scores on the Visual Analogue Scale (VAS) in 29 children age 9-17 years who had undergone pectus excavatum repair. Study C compared ratings of remembered immunization pain in 236 children who comprised an NRS group and a sex- and age-matched VAS group. Correlations of the NRS with the FPS-R and VAS were r=0.87 and 0.89 in Studies A and B, respectively. In Study C, the distributions of scores on the NRS and VAS were very similar except that scores closest to the no pain anchor were more likely to be selected on the VAS than the NRS. The NRS can be considered functionally equivalent to the VAS and FPS-R except for very mild pain (<1/10). We conclude that use of the NRS is tentatively supported for clinical practice with children of 8years and older, and we recommend further research on the lower age limit and on standardized age-appropriate anchors and instructions for this scale.
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http://dx.doi.org/10.1016/j.pain.2009.03.002DOI Listing
June 2009

A facile one-step route to synthesize cage-like silica hollow spheres loaded with superparamagnetic iron oxide nanoparticles in their shells.

Chem Commun (Camb) 2009 Feb 19(8):938-40. Epub 2008 Dec 19.

Department of Materials Science and Engineering, National University of Singapore, Singapore 117574.

Cage-like silica hollow spheres loaded with superparamagnetic iron oxide nanoparticles incorporated in their macroporous shells are synthesized in a facile manner through a one-step oil-in-diethylene glycol (DEG) microemulsion route.
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http://dx.doi.org/10.1039/b817937aDOI Listing
February 2009

Estimating a marriage matching model with spillover effects.

Demography 2006 Aug;43(3):463-90

Department of Economics, University of Toronto, 150 St. George Street, M5S 3G7 Toronto, Ontario, Canada.

We use marriage matching functions to study how marital patterns change when population supplies change. Specifically, we use a behavioral marriage matching function with spillover effects to rationalize marriage and cohabitation behavior in contemporary Canada. The model can estimate a couple's systematic gains to marriage and cohabitation relative to remaining single. These gains are invariant to changes in population supplies. Instead, changes in population supplies redistribute these gains between a couple. Although the model is behavioral, it is nonparametric. It can fit any observed cross-sectional marriage matching distribution. We use the estimated model to quantify the impacts of gender differences in mortality rates and the baby boom on observed marital behavior in Canada. The higher mortality rate of men makes men scarcer than women. We show that the scarceness of men modestly reduced the welfare of women and increased the welfare of men in the marriage market. On the other hand, the baby boom increased older men's net gains to entering the marriage market and lowered middle-aged women's net gains.
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http://dx.doi.org/10.1353/dem.2006.0023DOI Listing
August 2006

Determining the critical micelle concentration of a novel lipid-lowering agent, disodium ascorbyl phytostanyl phosphate (FM-VP4), using a fluorescence depolarization procedure.

Drug Dev Ind Pharm 2004 Aug;30(7):725-30

Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, British Columbia, Canada.

The objective of this study was to determine the critical micelle concentration (CMC) of a novel water-soluble plant sterol derivative (FM-VP4) using a fluorescence depolarization method. The CMC was determined by 1,6-diphenyl-1,3,5-hexatriene (DPH) fluorescence depolarization. Test solutions of various concentrations of sodium dodecylsulphate (SDS) as a positive control or FM-VP4 in water were spiked with 2 microL of 4 mM DPH in tetrahydrofuran (THF) and left overnight to equilibrate in a dark chamber. Fluorescence of each solution was measured at room temperature using a Perseptive Biosystems Cytofluor Series 4000 multi-well plate reader. Fluorescence intensity increases as DPH is incorporated into the hydrophobic core of micelles. Thus, the CMC is the value at which an abrupt increase in intensity is observed. These points were observed at 8 mM and 0.014 mM for SDS and FM-VP4, respectively. Sodium dodecylsulphate was used as a positive control and supports the validity of our results, as the literature values of SDS are reported to be between 8-8.3 mM. The CMC of FM-VP4 is reported to be 0.014 mM.
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http://dx.doi.org/10.1081/ddc-120039509DOI Listing
August 2004

Safety, pharmacokinetics, pharmacodynamics, and plasma lipoprotein distribution of eritoran (E5564) during continuous intravenous infusion into healthy volunteers.

Antimicrob Agents Chemother 2004 Sep;48(9):3233-40

Eisai Medical Research, Inc., Glenpointe Centre West, 500 Frank W. Burr Blvd., Teaneck, NJ 07666-6741, USA.

Eritoran, a structural analogue of the lipid A portion of lipopolysaccharide (LPS), is an antagonist of LPS in animal and human endotoxemia models. Previous studies have shown that low doses (350 to 3,500 microg) of eritoran have demonstrated a long pharmacokinetic half-life but a short pharmacodynamic half-life. The present study describes the safety, pharmacokinetics and pharmacodynamics, and lipid distribution profile of eritoran during and after a 72-h intravenous infusion of 500, 2,000, or 3,500 microg/h into healthy volunteers. Except for the occurrence of phlebitis, eritoran administration over 72 h was safe and well tolerated. Eritoran demonstrated a slow plasma clearance (0.679 to 0.930 ml/h/kg of body weight), a small volume of distribution (45.6 to 49.8 ml/kg), and a relatively long half-life (50.4 to 62.7 h). In plasma, the majority (approximately 55%) of eritoran was bound to high-density lipoproteins. During infusion and for up to 72 h thereafter, ex vivo response of blood to 1- or 10-ng/ml LPS was inhibited by > or =85%, even when the lowest dose of eritoran (500 microg/h) was infused. Inhibition of response was dependent on eritoran dose and the concentration of LPS used as an agonist. Finally, in vitro analysis with purified lipoprotein and protein fractions from plasma obtained from healthy volunteers indicated that eritoran is inactivated by high-density but not low-density lipoproteins, very-low-density lipoproteins, or albumin. From these results, we conclude that up to 252 mg of eritoran can be safely infused into normal volunteers over 72 h and even though it associates extensively with high-density lipoproteins, antagonistic activity is maintained, even after infusion ceases.
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http://dx.doi.org/10.1128/AAC.48.9.3233-3240.2004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC514793PMC
September 2004

Assessing the antifungal activity and toxicity profile of amphotericin B lipid complex (ABLC; Abelcet) in combination with caspofungin in experimental systemic aspergillosis.

J Pharm Sci 2004 Jun;93(6):1382-9

Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.

The purpose of this study was to assess the antifungal activity and renal and hepatic toxicity of amphotericin B lipid complex (ABLC; Abelcet) following co-administration of Caspofungin to rats infected with Aspergillus fumigatus. Aspergillus fumigatus inoculum (1.3-2.3 x 10(7) colony forming units [CFU]) was injected via the jugular vein; 48 h later male albino Sprague-Dawley rats (350-400 g) were administered either a single intravenous (i.v.) dose of Fungizone(R) (1 mg AmpB/kg), ABLC (1 or 5 mg AmpB/kg), or an equivalent volume of normal saline (NS) (vehicle control) once daily for 4 days. Rats were further randomized into groups to receive 3 mg/kg Caspofungin or physiologic saline i.v. once daily for 4 days. To assess antifungal activity, brain, lung, heart, liver, spleen, and kidney sections were homogenized with NS (2 mL; 1 g of each tissue/mL) and a 0.1-mL aliquot was spread plated onto a Sabouraud dextrose agar plate. The plates were incubated for 48 h at 37 degrees C, at which time the numbers of CFU were determined and corrected for tissue weight. To assess renal and hepatic toxicity, serum creatinine and aspartate aminotransferase levels were determined. Fungizone and ABLC at a dosing regimen of 1 mg/kg i.v. once daily for four consecutive days and Caspofungin at a dosing regimen of 3 mg/kg i.v. once daily for four consecutive days had similar effectiveness in decreasing the total number of Aspergillus fumigatus CFUs found in all organs analyzed compared to non-treated controls. A combination of ABLC (1 mg/kg i.v. x 4 days) and Caspofungin (3 mg/kg i.v. x 4 days) significantly decreased the total number of Aspergillus fumigatus CFUs found in all organs analyzed compared to Caspofungin alone and non-treated controls. ABLC at a dosing regiment of 5 mg/kg i.v. once daily for four consecutive days was more effective in decreasing the total number of Aspergillus fumigatus CFUs found in all organs analyzed compared to Fungizone or ABLC alone at 1 mg/kg and Caspofungin alone at 3 mg/kg. However, a combination of ABLC (5 mg/kg i.v. x 4 days) and Caspofungin (3 mg/kg i.v. x 4 days) was not more effective than ABLC at 5 mg/kg or the combination of ABLC at 1 mg/kg and Caspofungin 3 mg/kg in reducing the total number of Aspergillus fumigatus CFUs compared to controls. Except for non-treated infected control rats, none of the treatment groups tested displayed a greater than 50% increase in serum creatinine concentrations from baseline. In addition, only ABLC at a dosing regimen of 1 mg/kg i.v. once daily for four consecutive days displayed a greater than 50% increase in AST concentration from baseline. Taken together, these findings suggest that ABLC at 5 mg/kg once daily x 4 days appears to be the best therapeutic choice in this animal model.
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http://dx.doi.org/10.1002/jps.20080DOI Listing
June 2004

A stepwise surgical procedure to investigate the lymphatic transport of lipid-based oral drug formulations: Cannulation of the mesenteric and thoracic lymph ducts within the rat.

J Pharmacol Toxicol Methods 2004 Mar-Apr;49(2):115-20

Acute Care Animal Unit, Koerner Pavilion, University of British Columbia, Vancouver, BC, Canada.

Introduction: A number of animal models have been described for the assessment of intestinal lymphatic drug transport. Lymphatic transport studies are commonly first conducted in the laboratory rat, with larger more complicated models (i.e., dog or pig) subsequently investigated. However, the utility of lymph fistulation in large animals is limited by considerable logistical and economic constraints.

Methods: This paper describes a stepwise surgical procedure for cannulating the thoracic and mesenteric lymph ducts in male Sprague-Dawley rats.

Results: Following surgery, thoracic and mesenteric lymph flow rates during the 24-h period immediately following surgery averaged 12.5+/-2.5 and 2.4+/-1.1 ml/h, respectively. This flow rate is greater than that obtained with previously described methods, which require restraint of the animals and/or a 24-h recovery period and are reported to produce average intestinal lymph flow rates of 2 ml/h.

Discussion: This animal model can be utilized for the assessment of drug transport by the lymphatics and for determining what percentage of lymphatic transport is a result of only intestinal lymphatics.
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http://dx.doi.org/10.1016/j.vascn.2003.11.004DOI Listing
September 2004

Effects of lipid-based oral formulations on plasma and tissue amphotericin B concentrations and renal toxicity in male rats.

Antimicrob Agents Chemother 2003 Oct;47(10):3339-42

Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences. Acute Care Animal Unit, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.

The purpose of this study was to determine the effects of various lipid and mixed-micelle formulations on the oral absorption and renal toxicity of amphotericin B (AMB) in rats. The maximum concentration of AMB in plasma and the area under the concentration-time curve for 0 to 24 h for AMB were elevated in rats administered triglyceride (TG)-rich AMB formulations in comparison to those in rats given (i) AMB preformulated as a micelle containing sodium deoxycholate with sodium phosphate as a buffer (DOC-AMB), (ii) an AMB-lipid complex suspension, or (iii) AMB solubilized in methanol. Furthermore, our findings suggest that AMB incorporated into TG-based oral formulations has less renal toxicity than DOC-AMB.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC201114PMC
http://dx.doi.org/10.1128/AAC.47.10.3339-3342.2003DOI Listing
October 2003

Induction of caspase-dependent and -independent apoptosis in response to methionine restriction.

Int J Oncol 2003 Feb;22(2):415-20

Department of Medicine, Baylor College of Medicine and VA Medical Center, Houston, TX 77030, USA.

Tumor cells are more sensitive to methionine restriction than normal tissues, a phenomenon known as methionine auxotrophy. Previous studies have demonstrated that methionine restriction causes tumor cell growth arrest and eventually apoptosis. The current studies were undertaken to elucidate the molecular pathways leading to apoptosis induced by methionine restriction. We found that methionine restriction induced formation of oligonucleosomal DNA fragment and cytochrome c release from mitochondria in methionine-dependent PC3 and Hela cells. Methionine restriction also led to cleavage and activation of initiator and effector caspases in Hela cells but not PC3 cells. Furthermore, methionine restriction resulted in cleavage of BID and reduction in Bcl-2 levels in both cell lines. These data suggest that apoptosis induced by methionine restriction is mitochondria-dependent. Methionine restriction induced caspase-independent cell death in PC3 cells, whereas it stimulated caspase-dependent cell death in Hela cells. Cleavage of BID and decreased expression of Bcl-2 upon methionine deprivation may be the underlying mechanism to stimulate release of cytochrome c from mitochondria.
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February 2003