Publications by authors named "Leo Leung"

27 Publications

  • Page 1 of 1

Social and cultural construction processes involved in HPV vaccine hesitancy among Chinese women: a qualitative study.

Int J Equity Health 2019 09 18;18(1):147. Epub 2019 Sep 18.

Department of Applied Social Sciences, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Hong Kong.

Background: HPV vaccine is a prophylactic vaccine to prevent HPV infections. Recommended by the World Health Organization, this vaccine is clinically proven to be one of the most effective preventive measures against the prevalence of cervical cancer and other HPV-associated cancers and chronic genital conditions. However, its uptake rate among women in Hong Kong is insignificant-only approximately 2.9% adolescent girls and 9.7% female university students received HPV vaccination in 2014. With the notion of Critical Medical Anthropology, we aimed to identify if different influential factors, ranging from individual, societal, and cultural, are involved in the decision-making process of whether to receive HPV vaccination.

Methods: We adopted a qualitative approach and conducted in-depth individual semistructured interviews with 40 women in Hong Kong between May and August 2017.

Results: We noted that the following factors intertwined to influence the decision-making process: perceptions of HPV and HPV vaccine; perceived worthiness of HPV vaccines, which was in turn influenced by vaccine cost, marriage plans, and experiences of sexual activities; history of experiencing gynecological conditions, stigma associated with HPV vaccination, acquisition of information on HPV vaccines, distrust on HPV vaccines, and absence of preventive care in the healthcare practice.

Conclusions: HPV vaccination is promoted in a manner that is "feminized" and "moralized" under the patriarchal value system, further imposing the burden of disease on women, and leading to health inequality of women in pursuing the vaccination as a preventive health behaviour as a result. We believe that this ultimately results in an incomplete understanding of HPV, consequently influencing the decision-making process. The "mixed-economy" medical system adopting capitalist logic also molds a weak doctor-patient relationship, leading to distrust in private practice medical system, which affects the accessibility of information regarding HPV vaccination for participants to make the decision.
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http://dx.doi.org/10.1186/s12939-019-1052-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6751778PMC
September 2019

2-Aminomethylene-5-sulfonylthiazole Inhibitors of Lysyl Oxidase (LOX) and LOXL2 Show Significant Efficacy in Delaying Tumor Growth.

J Med Chem 2020 03 4;63(5):2308-2324. Epub 2019 Sep 4.

Drug Discovery Unit, Cancer Research UK Manchester Institute, University of Manchester, Alderley Park, Macclesfield SK10 4TG, United Kingdom.

The lysyl oxidase (LOX) family of extracellular proteins plays a vital role in catalyzing the formation of cross-links in fibrillar elastin and collagens leading to extracellular matrix (ECM) stabilization. These enzymes have also been implicated in tumor progression and metastatic disease and have thus become an attractive therapeutic target for many types of invasive cancers. Following our recently published work on the discovery of aminomethylenethiophenes (AMTs) as potent, orally bioavailable LOX/LOXL2 inhibitors, we report herein the discovery of a series of dual LOX/LOXL2 inhibitors, as well as a subseries of LOXL2-selective inhibitors, bearing an aminomethylenethiazole (AMTz) scaffold. Incorporation of a thiazole core leads to improved potency toward LOXL2 inhibition via an irreversible binding mode of inhibition. SAR studies have enabled the discovery of a predictive 3DQSAR model. Lead AMTz inhibitors exhibit improved pharmacokinetic properties and excellent antitumor efficacy, with significantly reduced tumor growth in a spontaneous breast cancer genetically engineered mouse model.
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http://dx.doi.org/10.1021/acs.jmedchem.9b01112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073924PMC
March 2020

Author Correction: Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface.

Nat Commun 2019 Jul 18;10(1):3151. Epub 2019 Jul 18.

Molecular Oncology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, M20 4BX, UK.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41467-019-11220-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639354PMC
July 2019

Anti-metastatic Inhibitors of Lysyl Oxidase (LOX): Design and Structure-Activity Relationships.

J Med Chem 2019 06 23;62(12):5863-5884. Epub 2019 May 23.

Cancer Research UK Centre for Cancer Therapeutics , The Institute of Cancer Research , 15 Cotswold Road , London SM2 5NG , United Kingdom.

Lysyl oxidase (LOX) is a secreted copper-dependent amine oxidase that cross-links collagens and elastin in the extracellular matrix and is a critical mediator of tumor growth and metastatic spread. LOX is a target for cancer therapy, and thus the search for therapeutic agents against LOX has been widely sought. We report herein the medicinal chemistry discovery of a series of LOX inhibitors bearing an aminomethylenethiophene (AMT) scaffold. High-throughput screening provided the initial hits. Structure-activity relationship (SAR) studies led to the discovery of AMT inhibitors with sub-micromolar half-maximal inhibitory concentrations (IC) in a LOX enzyme activity assay. Further SAR optimization yielded the orally bioavailable LOX inhibitor CCT365623 with good anti-LOX potency, selectivity, pharmacokinetic properties, as well as anti-metastatic efficacy.
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http://dx.doi.org/10.1021/acs.jmedchem.9b00335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937593PMC
June 2019

Barriers to Receiving HPV Vaccination Among Men in a Chinese Community: A Qualitative Study in Hong Kong.

Am J Mens Health 2019 Jan-Feb;13(1):1557988319831912

1 Department of Applied Social Sciences, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hong Kong.

Human papillomavirus (HPV) can cause various diseases; low-risk strains can cause genital warts, whereas high-risk strains can cause cervical cancer and cancer of the vulva in women and cancers of the penis, anus, and oropharynx in men. Although HPV affects men, literature has reported that the prevalence of HPV vaccination is far lower among men than among women. Few studies have examined perceptions and acceptability of the HPV vaccine among men, particularly in Chinese communities. In this study, the acceptability of the HPV vaccine to men was investigated using Hong Kong men as a case group. A qualitative research approach was adopted. Thirty-nine men were purposively sampled for the in-depth individual semistructured interviews from June to October 2017 to investigate their perceptions of the HPV vaccine and the barriers for them to receive the vaccination. Limited knowledge and awareness of HPV-related issues, low perceived risk of HPV infection, perceived association between HPV vaccine and promiscuity, and lack of accessible official information on HPV-related topics were identified as the key barriers. These barriers intermingled with the sociocultural environment, cultural values of sexuality, and patriarchal gender values. HPV vaccine is shown to be socially constructed as a vaccine for women exclusively and for promiscuity. The participants were discouraged from receiving HPV vaccination because of its signaling of socially deviant promiscuity. Cultural taboo on sex served as a social oppression of open discussion about HPV vaccine and affected the participants' perceived need of vaccination. Perceived insignificance of reproductive organs also influenced the participants' perceived need of vaccination.
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http://dx.doi.org/10.1177/1557988319831912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775547PMC
April 2020

Bridging the gap: An evaluation of self-paced online transition modules for advanced pharmacy practice experience students.

Curr Pharm Teach Learn 2018 10 10;10(10):1375-1383. Epub 2018 Aug 10.

Faculty of Pharmaceutical Sciences, University of British Columbia, 2405 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada. Electronic address:

Background And Purpose: A three module online self-paced educational resource was developed for entry to practice students transitioning from the classroom to their inpatient practicums. The objective of this study was to determine the benefits of the transition modules on students' self-perceived competency as related to onsite performance and reduction in anxiety during their inpatient practicum.

Educational Activity And Setting: Evaluations of the three transition modules were conducted in two phases via electronic surveys distributed to final year advanced pharmacy practice students and focus group members including faculty, pharmacy practice educators, and pharmacy residents.

Findings: Based on our findings, the modules addressed common learning needs. While 69.7% of student respondents from Phase II of the evaluation found the modules to have positively impacted their onsite performance, only 24.7% believed the modules reduced their anxiety.

Discussion: The study indicates that students found the modules to be relevant to inpatient practice and of appropriate difficulty. Although most students perceived the modules to enhance performance on practicum, student anxiety levels appeared to remain unchanged.

Summary: Based on feedback and results, it may be beneficial to expose students to transition modules earlier in the curriculum in tandem with other inpatient preparatory activities. The results from this study may be of interest or benefit other universities and healthcare educators pursuing work on transition activities.
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http://dx.doi.org/10.1016/j.cptl.2018.07.006DOI Listing
October 2018

Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface.

Nat Commun 2017 04 18;8:14909. Epub 2017 Apr 18.

Molecular Oncology Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester M20 4BX, UK.

Lysyl oxidase (LOX) remodels the tumour microenvironment by cross-linking the extracellular matrix. LOX overexpression is associated with poor cancer outcomes. Here, we find that LOX regulates the epidermal growth factor receptor (EGFR) to drive tumour progression. We show that LOX regulates EGFR by suppressing TGFβ1 signalling through the secreted protease HTRA1. This increases the expression of Matrilin2 (MATN2), an EGF-like domain-containing protein that traps EGFR at the cell surface to facilitate its activation by EGF. We describe a pharmacological inhibitor of LOX, CCT365623, which disrupts EGFR cell surface retention and delays the growth of primary and metastatic tumour cells in vivo. Thus, we show that LOX regulates EGFR cell surface retention to drive tumour progression, and we validate the therapeutic potential of inhibiting this pathway with the small molecule inhibitor CCT365623.
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http://dx.doi.org/10.1038/ncomms14909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399287PMC
April 2017

Improving the stability of C-labeled L-methionine with ascorbate.

EJNMMI Radiopharm Chem 2017 4;2(1):13. Epub 2017 Oct 4.

1Department of Functional Imaging, BC Cancer Agency, Vancouver, BC Canada.

Background: Carbon-11 labeled L-methionine (C-MET) is a popular tracer used in the clinic for imaging brain tumors with positron emission tomography. However, the stability of C-MET in its final formulation is not well documented in literature. Recently, we observed fast degradation of HPLC-purified C-MET over time, and systematic investigation was conducted to identify the cause.

Results: In this study, we verified the degraded product as C-labeled methionine sulfoxide (C-METSO). To minimize oxidation, ascorbate (100 ppm) was added to the HPLC eluant, and the resulting HPLC-purified C-MET was stable in the final formulation solution without noticeable degradation for up to 1 h after the end of synthesis.

Conclusions: Our data suggest that to minimize degradation, ascorbate can be added to the C-MET formulation solution especially if it is not administered into patients soon after the end of synthesis.
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http://dx.doi.org/10.1186/s41181-017-0032-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824703PMC
October 2017

Repeatability of a novel corneal indentation device for corneal biomechanical measurement.

Ophthalmic Physiol Opt 2015 Jul;35(4):455-61

Department of Mechanical and Aerospace Engineering, The Hong Kong University of Science and Technology, Hong Kong.

Purpose: The aim of the study was to evaluate the repeatability of a new device for measuring corneal biomechanics.

Methods: Twenty-nine normal subjects aged 20-28 years (23.4 ± 1.7 years) underwent measurements of corneal stiffness and tangent elastic modulus using a novel corneal indentation device. Corneal topography, axial biometry and Goldmann applanation tonometry were also performed during the visit. Subjects returned after about 1 week, at approximately the same time, and with the corneal biomechanics, corneal topography and Goldmann applanation tonometry measured again. Both the intrasession and intersession repeatability was assessed.

Results: Both the corneal stiffness and tangent elastic modulus demonstrated good intrasession repeatability (corneal stiffness: coefficient of variation = 7.32%, intraclass correlation coefficient = 0.75; tangent elastic modulus: coefficient of variation = 7.34%, intraclass correlation coefficient = 0.84). The mean modulus after normalised to normal intraocular pressure of 15.5 mmHg was 0.755 ± 0.159 MPa. There was no significant difference between the two visits (paired t-tests: p > 0.05). The repeatability [1.96 times the standard deviation (S.D.) of the intersession difference] of the corneal stiffness and the tangent elastic modulus was 0.0022 N mm(-1) and 0.197 MPa, respectively.

Conclusion: The corneal indentation device has good intrasession and intersession repeatability. It has good potential to measure corneal biomechanics clinically, even at different corneal regions.
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http://dx.doi.org/10.1111/opo.12219DOI Listing
July 2015

Soft wearable contact lens sensor for continuous intraocular pressure monitoring.

Med Eng Phys 2014 Sep 15;36(9):1134-9. Epub 2014 Jul 15.

The Department of Mechanical and Aerospace Engineering, The Hong Kong University of Science and Technology, Hong Kong. Electronic address:

Intraocular pressure (IOP) is a primary indicator of glaucoma, but measurements from a single visit to the clinic miss the peak IOP that may occur at night during sleep. A soft chipless contact lens sensor that allows the IOP to be monitored throughout the day and at night is developed in this study. A resonance circuit composed of a thin film capacitor coupled with a sensing coil that can sense corneal curvature deformation is designed, fabricated and embedded into a soft contact lens. The resonance frequency of the sensor is designed to vary with the lens curvature as it changes with the IOP. The frequency responses and the ability of the sensor to track IOP cycles were tested using a silicone rubber model eye. The results showed that the sensor has excellent linearity with a frequency response of ∼8 kHz/mmHg, and the sensor can accurately track fluctuating IOP. These results showed that the chipless contact lens sensor can potentially be used to monitor IOP to improve diagnosis accuracy and treatment of glaucoma.
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http://dx.doi.org/10.1016/j.medengphy.2014.06.005DOI Listing
September 2014

Comparative study of corneal tangent elastic modulus measurement using corneal indentation device.

Med Eng Phys 2014 Sep 28;36(9):1115-21. Epub 2014 Jun 28.

Department of Mechanical and Aerospace Engineering, Hong Kong University of Science and Technology, Hong Kong. Electronic address:

The aim of this study is to examine the corneal tangent modulus measurement repeatability and performance of the corneal indentation device (CID). Twenty enucleated porcine eyes were measured and the eyes were pressurized using saline solution-filled manometer to 15 and 30 mmHg. Corneal tangent moduli measured using the CID were compared with those measured using high precision universal testing machine (UTM). The within-subject standard deviation (Sw), repeatability (2.77×Sw), coefficient of variation (CV) (Sw/overall mean), and intraclass correlation coefficient (ICC) were determined. The mean corneal tangent moduli measured using UTM and CID were 0.094±0.030 and 0.094±0.028 MPa at 15 mmHg, and 0.207±0.056 and 0.207±0.055 MPa at 30 mmHg, respectively, with a difference less than 0.13%. The 95% limit of agreement was between -0.009 and 0.009 MPa. The Sw, repeatability, CV and ICC of corneal tangent moduli measured by the CID were 0.006 MPa, 0.015 MPa, 4.3% and 0.993, respectively. The results showed that the corneal tangent moduli measured by the CID are repeatable and are in good agreement with the results measured by the high precision UTM.
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http://dx.doi.org/10.1016/j.medengphy.2014.06.003DOI Listing
September 2014

Noninvasive measurement of scleral stiffness and tangent modulus in porcine eyes.

Invest Ophthalmol Vis Sci 2014 May 15;55(6):3721-6. Epub 2014 May 15.

Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, People's Republic of China.

Purpose: We investigated an indentation technique to measure the scleral stiffness and tangent modulus of porcine eyes.

Methods: The scleral load-displacement responses were measured with a universal testing machine as a function of IOP in 15 porcine eyes ex vivo using a 5-mm diameter cylindrical flat-punch indenter. The scleral radius of curvature and scleral thickness were measured using a DSLR camera (Alpha 900) and a camera-mounted stereomicroscope (M205C), respectively. The relationships between scleral stiffness, tangent modulus, and IOP were examined.

Results: The mean local scleral radius of curvature and scleral thickness were 7.86 ± 0.49 and 1.03 ± 0.14 mm, respectively. The average scleral stiffness and scleral tangent modulus of porcine eyes were 0.13 ± 0.02 N/mm and 0.20 ± 0.04 MPa at 15 mm Hg, respectively. The scleral stiffness and scleral tangent modulus were correlated positively with IOP (scleral stiffness, 0.989 < r < 0.999, P < 0.001; scleral tangent modulus, 0.989 < r < 0.999, P < 0.001).

Conclusions: The scleral indentation technique can provide a noninvasive approach to measure scleral stiffness and tangent modulus.
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http://dx.doi.org/10.1167/iovs.13-13674DOI Listing
May 2014

Individual-specific tonometry on porcine eyes.

Med Eng Phys 2014 Jan 5;36(1):96-101. Epub 2013 Nov 5.

The Department of Mechanical Engineering, The Hong Kong University of Science and Technology, Hong Kong. Electronic address:

Intraocular pressure (IOP) monitoring is important in the diagnosis and management of glaucoma. The measurement of IOP is affected by corneal properties, but the effect of corneal stiffness on IOP measurement is unaccounted for in pressure measurement instruments such as the Goldmann Applanation Tonometer (GAT). A new instrumented non-invasive indentation tonometry that can measure IOPIST, a corneal stiffness-corrected intraocular pressure is developed. The inter-individual corneal variations of 12 porcine eyes ex vivo were independently characterized; and their true intraocular pressure, IOPT's, were set using a manometer before indentation using the new indentation tonometry. Analyses of the load-displacement data showed that porcine corneal stiffness varied more than five times from 0.045 to 0.253N/mm. Analysis showed that, without individual stiffness correction, inter-individual variation of IOPGAT can vary up to 8mmHg from IOPT at 15mmHg; the error becomes larger at high IOPT. In comparison when corneal stiffness is accounted for, IOPIST has a significantly smaller error of 1.82±1.70mmHg for IOPT between 12 and 40mmHg than IOPGAT. The results showed that the new tonometry successfully accounted for inter-individual variations in IOP measurement.
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http://dx.doi.org/10.1016/j.medengphy.2013.10.001DOI Listing
January 2014

Characterization of pressure reduction in coil-filled aneurysm under flow of human blood with and without anti-coagulant.

Annu Int Conf IEEE Eng Med Biol Soc 2013 ;2013:739-42

Filling aneurysms with embolization coils is a widely used part of the treatment to stop intracranial aneurysm from rupturing. However, the effect of coiling on aneurysmal pressure has not been established. In this study, the effect of intra-aneurysmal coiling on pressure reduction was characterized. Coil deployment in the aneurysm will disturb flow and may induce aneurysmal coagulation. These effects were experimentally examined in this study using silicone rubber saccular aneurysm models. Changes in aneurysmal blood pressure under pulsatile flow were characterized. With coils in the aneurysm, results showed that flow reduction of anti-coagulated blood in the aneurysm did not reduce aneurysmal pressure. Significant pressure reduction was observed only when the blood's coagulation ability is restored to normal. These results suggest that blood coagulation is pivotal to pressure reduction and concomitant with rupture risk reduction in treatments of aneurysm with coils.
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http://dx.doi.org/10.1109/EMBC.2013.6609606DOI Listing
July 2015

Partial contact indentation tonometry for measurement of corneal properties-independent intraocular pressure.

Mol Cell Biomech 2012 Dec;9(4):251-68

Department of Mechanical Engineering, The Hong Kong University of Science and Technology, Hong Kong, People Republic of China.

Inter-individual differences in corneal properties are ignored in existing methods for measuring intraocular pressure IOP, a primary parameter used in screening and monitoring of glaucoma. The differences in the corneal stiffness between individuals can be more than double and this difference would lead to IOP measurement errors up to 10 mmHg. In this study, an instrumented partial-contact indentation measurement and analysis method that can account for inter-individual corneal difference in stiffness is developed. The method was tested on 12 porcine eyes ex vivo and 7 rabbit eyes in vivo, and the results were compared to the controlled IOPs to determine the method's validity. Analyses showed that without corneal stiffness correction, up to 10 mmHg of measurement error was found between the existing approach and the controlled IOP. With the instrumented indentation and analysis method, less than 2 mmHg of differences were founded between the measured IOP and the controlled IOP. These results showed that instrumented partial-contact indentation can effectively account for inter-individual corneal variations in IOP measurement.
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December 2012

Characterization of corneal tangent modulus in vivo.

Acta Ophthalmol 2013 Jun 22;91(4):e263-9. Epub 2013 Jan 22.

Department of Mechanical Engineering, Hong Kong University of Science and Technology, Hong Kong, China.

Purpose: Intraocular pressure (IOP) measured using Goldmann Applanation Tonometry (GAT) changes with individual's corneal properties, but the method to measure the in vivo corneal material properties to account for individual variation in GAT IOP is not available. In this study, a new method to measure the IOP-dependent corneal tangent modulus in vivo is developed to address this research gap.

Methods: Instrumented indentation and analysis were developed to measure the corneal tangent modulus. The validity of the method and procedure was verified using model silicone eye pressurized to different IOP. In addition, 15 porcine eyes and 3 rabbit eyes were tested using the corneal indentation at different set intraocular pressure and different indentation rates.

Results: The results from silicone eye showed that the measured tangent modulus is in good agreement with the standard silicone rubber modulus. The results on the porcine eyes and rabbit eyes showed that the method can be used to measure corneal tangent modulus in vivo in the human range of intraocular pressure from 10 to 40 mmHg.

Conclusions: An indentation method to measure the corneal tangent modulus in vivo was developed, and the IOP dependence of the corneal tangent modulus was characterized. The developed indentation method provides a new means to measure the in vivo corneal tangent modulus to account for individual and pressure variations in measurement of intraocular pressure.
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http://dx.doi.org/10.1111/aos.12066DOI Listing
June 2013

Effect of age-stiffening tissues and intraocular pressure on optic nerve damages.

Mol Cell Biomech 2012 Jun;9(2):157-73

Department of Mechanical Engineering, The Hong Kong University of Science and Technology, Hong Kong, The People's Republic of China.

Age-stiffening of ocular tissues is statistically linked to glaucoma in the elderly. In this study, the effects of age-stiffening on the lamina cribrosa, the primary site of glaucomatous nerve damages, were modeled using computational finite element analysis. We showed that glaucomatous nerve damages and peripheral vision loss behavior can be phenomenologically modeled by shear-based damage criterion. Using this damage criterion, the potential vision loss for 30 years old with mild hypertension of 25 mmHg intraocular pressure (IOP) was estimated to be 4%. When the IOP was elevated to 35 mmHg, the potential vision loss rose to 45%; and age-stiffening from 35 to 60 years old increased the potential vision loss to 52%. These results showed that while IOP plays a central role in glaucomatous damages, age-stiffening facilitates glaucomatous damages and may be the principal factor that resulted in a higher rate of glaucoma in the elderly than the general population.
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June 2012

Synthesis and crystallographic analysis of meso-2,3-difluoro-1,4-butanediol and meso-1,4-dibenzyloxy-2,3-difluorobutane.

Beilstein J Org Chem 2010 Jun 8;6:62. Epub 2010 Jun 8.

School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK.

A large-scale synthesis of meso-2,3-difluoro-1,4-butanediol in 5 steps from (Z)-but-2-enediol is described. Crystallographic analysis of the diol and the corresponding benzyl ether reveals an anti conformation of the vicinal difluoride moiety. Monosilylation of the diol is high-yielding but all attempts to achieve chain extension through addition of alkyl Grignard and acetylide nucleophiles failed.
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http://dx.doi.org/10.3762/bjoc.6.62DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900908PMC
June 2010

The synthesis and in vivo evaluation of 2',2'-difluoro KRN7000.

ChemMedChem 2009 Mar;4(3):329-34

School of Chemistry, University of Southampton Highfield, Southampton SO17 1BJ, UK.

The synthesis of 2',2'-difluoro KRN7000 is described. In vivo evaluation demonstrates that this fluorinated glycolipid induces CD1d-dependent TCR activation of NKT cells, with a bias towards Th2 cytokine production.
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http://dx.doi.org/10.1002/cmdc.200800348DOI Listing
March 2009

A linchpin carbacyclization approach for the synthesis of carbanucleosides.

J Org Chem 2008 Dec;73(23):9197-206

School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK.

A convenient synthesis of carbanucleosides, with both enantiomers equally accessible, is reported. The key step is a tandem linchpin cyclization process to give access to substituted carbafuranose derivatives having the correct relative stereochemistry for subsequent nucleobase introduction with inversion of configuration at C1. This was illustrated by the synthesis of 2',3'-dideoxycarbathymidine via a convergent nucleobase introduction and of 2',3'-dideoxy-6'-hydroxycarbauridine via a linear nucleobase introduction. Both methods relied on Mitsunobu chemistry, and the first example of the Mukaiyama modification of the Mitsunobu reaction involving nucleobases as nucleophiles is reported.
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http://dx.doi.org/10.1021/jo801848hDOI Listing
December 2008

Synthesis and in vivo evaluation of 4-deoxy-4,4-difluoro-KRN7000.

Org Lett 2008 Oct 18;10(20):4433-6. Epub 2008 Sep 18.

School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK.

The synthesis of 4-deoxy-4,4-difluoro-KRN7000 starting from phytosphingosine is described. Key steps include a regioselective benzylation of azidophytosphingosine and a deoxofluor-mediated fluorination of the corresponding 4-ketone. This fluorination failed completely when the adjacent 3-OH was protected as benzyl ether but proceeded well when a benzoyl group was used. The biological evaluation reveals a bias toward Th1 cytokine induction upon Natural Killer T cell activation.
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http://dx.doi.org/10.1021/ol801663mDOI Listing
October 2008

Factors distinguishing septic arthritis from transient synovitis of the hip in children. A prospective study.

J Bone Joint Surg Am 2006 Jun;88(6):1251-7

Division of Orthopaedics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

Background: Distinguishing septic arthritis from transient synovitis of the hip in children can be challenging. Authors of recent retrospective studies have used presenting factors to establish algorithms for predicting septic arthritis of the hip in children. This study differs from previous work in three ways: data were collected prospectively, C-reactive protein levels were recorded, and the focus was on children in whom the findings were so suspicious for septic arthritis that hip aspiration was performed.

Methods: Over four years, we prospectively collected data on every child (a total of fifty-three) who underwent hip aspiration because of a suspicion of septic arthritis at our institution. Diagnoses of confirmed septic arthritis, presumed septic arthritis, and transient synovitis were determined on the basis of the results of Gram staining, culture, and a cell count of the hip aspirate. Presenting factors and laboratory values were recorded. To evaluate the strength of predictors, we performed univariate and multivariate analysis on data from forty-eight patients who met the inclusion criteria.

Results: Univariate analysis showed that fever, the C-reactive protein level, and the erythrocyte sedimentation rate were strongly associated with the final diagnosis (p < 0.05). On multivariate analysis, the C-reactive protein level and erythrocyte sedimentation rate were found to be significant predictors. However, the erythrocyte sedimentation rate was not independent of the C-reactive protein level on backward elimination, and the C-reactive protein level was the only risk factor that was strongly associated with the outcome at a 5% significance level. Patients with five predictive factors had a 98% chance of having septic arthritis, those with four factors had a 93% chance, and those with three factors had an 83% chance.

Conclusions: This prospective study of children who presented with findings that were highly suspicious for septic arthritis of the hip builds on the work of previous authors. We found fever (an oral temperature >38.5 degrees C) was the best predictor of septic arthritis followed by an elevated C-reactive protein level, an elevated erythrocyte sedimentation rate, refusal to bear weight, and an elevated serum white blood-cell count. In our study group, a C-reactive protein level of >2.0 mg/dL (>20 mg/L) was a strong independent risk factor and a valuable tool for assessing and diagnosing children suspected of having septic arthritis of the hip.
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http://dx.doi.org/10.2106/JBJS.E.00216DOI Listing
June 2006

A stereoselective cyclization to carbafuranose derivatives starting from 1,4-bis-epoxides.

Org Lett 2005 Nov;7(23):5183-6

School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, United Kingdom.

[reactions: see text] A concise synthesis of highly functionalized cyclopentane derivatives via a Brook rearrangement mediated stereoselective linchpin cyclization reaction involving tert-butyldimethylsilyl-1,3-dithianyllithium and homochiral 1,4-bis-epoxides is described.
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http://dx.doi.org/10.1021/ol052009hDOI Listing
November 2005

Complications of wrist arthroscopy.

J Hand Surg Am 2004 May;29(3):406-11

Division of Hand Surgery, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Purpose: To determine the incidence and nature of complications after arthroscopy of the wrist joint.

Methods: The outpatient records and surgical reports of 211 patients who had wrist joint arthroscopy were reviewed to determine type of procedure, type of anesthetic, portals used, and incidence and nature of postsurgical complications.

Results: We identified a total of 11 complications in our patient group (5.2%). Of these, 2 patients (0.9%) developed major complications and 9 patients (4.3%) developed minor complications. Five complications 45% were identified in the immediate postsurgical period and 6 (55%) were delayed complications. All of the minor complications resolved at latest follow-up evaluation with conservative care.

Conclusions: Wrist arthroscopy is a safe procedure with a low rate of major and minor complications. In spite of its limitations wrist arthroscopy remains an invaluable tool in the diagnosis and treatment of wrist joint disorders.
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http://dx.doi.org/10.1016/j.jhsa.2003.12.020DOI Listing
May 2004

Human epidermal growth factor enhances healing of diabetic foot ulcers.

Diabetes Care 2003 Jun;26(6):1856-61

Diabetes Ambulatory Care Center, Department of Medicine & Geriatrics, United Christian Hospital, Hong Kong, China.

Objective: To study the healing effect of recombinant human epidermal growth factor (hEGF) on diabetic foot ulcers.

Research Design And Methods: A total of 127 consecutive patients were screened and 61 diabetic subjects were recruited into this double-blind randomized controlled study. Predetermined criteria were used for diagnosis and classification of the diabetic wound. The patients were randomized into three groups. All patients attended our Diabetes Ambulatory Care Center every other week for joint consultation with the diabetologist and the podiatrist. Group 1 (control) was treated with Actovegin 5% cream (Actovegin), group 2 with Actovegin plus 0.02% (wt/wt) hEGF, and group 3 with Actovegin plus 0.04% (wt/wt) hEGF. The study end point was the complete closure of the wound. Failure to heal was arbitrarily defined as incomplete healing after 12 weeks.

Results: Final data were obtained from 61 patients randomly assigned into three groups. The mean ages of the patients, wound sizes, wound duration, metabolic measurements, and comorbidities were comparable within groups, except that group 3 had more female patients. Mean follow-up for the patients was 24 weeks. Data were cutoff at 12 weeks, and results were analyzed by intention to treat. After 12 weeks, in group 1 (control) eight patients had complete healing, two patients underwent toe amputation, and nine had nonhealing ulcers. In group 2 (0.02% [wt/wt] hEGF) 12 patients experienced wound healing, 2 had toe amputations, and 7 had nonhealing ulcers. Some 20 of 21 patients in group 3 (0.04% [wt/wt] hEGF) showed complete wound healing. Healing rates were 42.10, 57.14, and 95% for the control, 0.02% (wt/wt) hEGF, and 0.04% (wt/wt) hEGF groups, respectively. Kaplan-Meier survival analysis suggested that application of cream with 0.04% (wt/wt) hEGF caused more ulcers to heal by 12 weeks and increased the rate of healing compared with the other treatments (log-rank test, P = 0.0003).

Conclusions: Our data support the contention that application of hEGF-containing cream, in addition to good foot care from a multidisciplinary team, significantly enhances diabetic foot ulcer wound healing and reduces the healing time.
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http://dx.doi.org/10.2337/diacare.26.6.1856DOI Listing
June 2003

Neuropathic arthropathy of the digit: a case report.

J Hand Surg Am 2003 Mar;28(2):323-6

Division of Hand Surgery and Orthopaedic Oncology, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia, USA.

We present the case of a 60-year-old diabetic man who developed neuropathic arthropathy in the distal interphalangeal joint of the small finger. Neuropathic arthropathy is uncommon in the upper extremity, and only 2 cases of this condition occurring in the joints of the hand have been reported. The clinical presentation, diagnosis, and treatment options are discussed.
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http://dx.doi.org/10.1053/jhsu.2003.50037DOI Listing
March 2003

Radiographic assessment of small finger metacarpal neck fractures.

J Hand Surg Am 2002 May;27(3):443-8

Division of Hand Surgery, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Treatment recommendations for metacarpal neck fractures of the small finger are generally based on the degree of apex dorsal angulation at the fracture site. We evaluated the variability of measurement of fracture angulation and the effect this variability has on treatment recommendations for these injuries. A total of 96 radiographs (anteroposterior, lateral, oblique views) of 32 patients with fractures of the small finger metacarpal neck were evaluated independently by 3 fellowship-trained orthopedic hand surgeons. Treatment recommendations for each fracture were tabulated. This process was repeated 6 weeks later to evaluate intraobserver variability. Kappa coefficients of inter- and intraobserver reliability of fracture angulation measurement and treatment plans were generated. The mean reliability coefficient of the measurement of fracture angulation between the 3 different observers was slight. Similarly, the reproducibility of fracture angulation measurement within observers was fair. Agreement between observers for appropriate treatment recommendations for each fracture was fair and agreement within observers for treatment was only slightly better. The measurement of fracture angulation of small finger metacarpal neck fractures seems to be subject to a high degree of inter- and intraobserver variability.
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http://dx.doi.org/10.1053/s0363-5023(06)90001-xDOI Listing
May 2002