RESEARCH PROJECTS
Transcription
RESEARCH PROJECTS
Dept of Anaesthesia & Intensive Care In RESEARCH PROJECTS this proposed randomized, double-blind, multicenter trial, 1,000 elderly (> 60 years) patients who are undergoing major non-cardiac surgery will Cognitive Dysfunction after Anesthesia (CoDA) be randomly allocated to receive additional BIS Study monitoring or routine anesthetic care. Postoperative cognitive functioning will be assessed at the baseline, CHAN Matthew Tak Vai GIN Tony LEE Tatia M C* POON Wai Sang (Surgery) 1 week, and 3 months after surgery using a battery of established neurocognitive tests. NG (CU06400) Ho Keung (Anatomical & Cellular Pathology) 1 January 2007 PeriOperative Research Grants Council (Earmarked Grants) Study. ISchemic How Does Evaluation (POISE) Metoprolol Prevent Postoperative Cardiac Complications? It is widely believed among clinicians that anesthetic effects such as unconsciousness, amnesia, and areflexia are transient phenomena. CHAN Matthew Tak Vai Therefore, patients who receive a general anesthetic should GIN Tony recover completely as the drugs are eliminated from DEVEREAUX Philip J* the body. However, there are now compelling data LESILE, Kate* CHOI Yuk Sang Gordon 1 January 2007 to suggest that standard doses of routine anesthetics Australian and New Zealand College of induce profound neurochemical changes that last for days or months. Anaesthetists, Research Grant These “anesthetic imprints” in the brain may contribute to postoperative cognitive Patients with coronary artery disease suffer cardiac impairment. complications after surgery that may result in death. Such “toxicity” is more apparent in surgery. Giving β blockers, such as metoprolol around the Intuitively, a technique that decreases anesthetic period of surgery may prevent these events. We are exposure currently participating a large clinical trial (the elderly patients may who prevent undergo major postoperative cognitive dysfunction. PeriOperative ISchemia Evaluation study, POISE) to Intraoperative monitoring of anesthetic depth, such as re-evaluate the benefits of metoprolol to prevent the bispectral electroencephalogram (BIS) index, may major cardiac events in moderate to high risk patients be useful in assisting anesthesiologists to optimize undergoing surgery. anesthetic drug It is however still unclear as to how metoprolol may anesthesia guided administration. by depth Specifically, monitoring modify the risk. was Previous studies in non-surgical associated with lower drug consumption, fewer settings suggested that dampening inflammation may perioperative complications, and a faster and better play be important in preventing acute coronary quality syndrome or heart attack. of recovery. We hypothesize that BIS-guided drug delivery avoids excessively deep metoprolol anesthesia, and will potentially reduce the incidence inflammatory of cognitive dysfunction after anesthesia. complications after surgery. Faculty of Medicine 164 We hypothesize that administration, response, will by changing decrease the cardiac Dept of Anaesthesia & Intensive Care We propose to undertake a substudy within the POISE We have recently developed a novel technique to trial to define the protective mechanism of metoprolol. document the dispersion of expired air from a In this study, 110 moderate to high risk patients will high-fidelity human patient simulator, using smoke receive either metoprolol or placebo before and then tracers illuminated by strong laser light. for 30 days after surgery. Serial blood samples will proposed study, we will apply the laser visualization be method to characterize aerosol dispersion throughout taken to determine the blood levels of In this inflammatory markers after surgery. a volume over time, during common respiratory The study will characterize the mechanism of therapies. perioperative cardiac complications. The data will influenza (H5N1) infection since 2004 in Asia and enhance our understanding of the benefits of recently in the Middle East, there is an urgent need to metoprolol and provide new insights into the study the safety of various respiratory therapies. development of potential interventions for the This study will provide clinicians with data to develop prevention of cardiac events after surgery. strategies for preventing spread of infection. (MD06734) will greatly enhance potential therapeutic options Given the re-emergence of avian This during treatment of chest infection. The expected During results will allow engineers and architects to design a Common Respiratory Therapy : A Simulator work environment that is safe for healthcare workers. Model to Assess the Risk of Nosocomial Infection (MD06974) CHAN Matthew Tak Vai GIN Tony Stephen Vascular events In noncardiac Surgery patIents Visualizing HALL* Expired Air Dispersion HUI Shu Cheong David (Medicine & cOhort evaluatioN Study (The VISION study) Therapeutics) CHAN Matthew Tak Vai 1 January 2007 GIN Tony CHOI Yuk Sang Gordon Australian and New Zealand College of 1 April 2007 Anaesthetists, Research Grant Public Policy Research Funding Scheme Patients with chest infections often require supportive therapies such as supplemental oxygen, nebulised Recent advances in medicine have allowed patients to medications, chest physiotherapy and mechanical undergo complex noncardiac surgery. ventilation. these patients, however have significant coronary These procedures may however, disease and may suffer Many of generate large amount of potentially infected aerosols artery from major in patient’s exhaled air that can be inhaled by perioperative cardiac events such as vascular death, healthcare workers, visitors and other patients to myocardial infarction, nonfatal cardiac arrest, and produce cross infection. This problem is highlighted stroke. In this regard, it should be considered as a with the recent SARS outbreak in 2003. In order to greater loss to individuals who may have gone prevent cross infection, it is important to visualize through otherwise successful and curative surgery. and understand how the infected aerosols may spread There are now compelling data to suggest that during respiratory therapies. perioperative cardiac events are in the rising trend. Unfortunately, much of the existing data are limited in 165 Faculty of Medicine Dept of Anaesthesia & Intensive Care their methodology and generalizability. Therefore, it induce profound neurochemical changes that last for is still uncertainty about the current incidence of major days or months. These “anesthetic imprints” in the cardiac events and the optimal risk model to predict brain may adversely affect mental health outcome these events in patients undergoing noncardiac after surgery. Intuitively, a technique that decreases surgery. We propose to conduct a large prospective anesthetic exposure may prevent postoperative mental multicentre patients disturbance. We have previously demonstrated that undergoing noncardiac surgery to determine the the intraoperative monitoring of anesthetic depth, incidence of major vascular events, the optimal such as the bispectral electroencephalogram (BIS) clinical model to predict major perioperative vascular index, is useful in assisting anesthesiologists to events, and whether postoperative measurements of optimize anesthetic drug administration. plasma hypothesize that BIS-guided drug delivery avoids cohort troponin myocardial study 20,000 concentrations infarctions unrecognized. in that are can identify likely to We go excessively deep anesthesia, and will potentially The VISION study allows us to reduce the incidence of postoperative delirium and address the fundamental questions with immense cognitive decline. public health implications. Given that hundreds of Design: Randomized control trial in which elderly thousands of patients in Hong Kong (and millions patients undergoing major colorectal surgery will be worldwide) undergo noncardiac surgery each year, assigned to receive general anesthesia with additional the BIS monitoring or routine anesthetic care. expected results will inform clinicians, administrators, and the government about resource Setting: Tertiary and district hospitals (Prince of allocation. We will also derive an accurate model to Wales Hospital, North District Hospital) in the New estimate the risk of perioperative cardiac event that Territories East cluster. will facilitate informed decision-making between Participants: Elderly (≥ 65 years) patients undergoing clinicians and patients regarding the appropriateness major elective colorectal (> 2 hours) surgery. of noncardiac surgery. Main Outcome Measures: The primary endpoint is (MD06465) postoperative mental disturbance (including either delirium or cognitive decline or both) using confusion Delirium and Cognitive Decline after Surgery : A assessment method, cognitive failure questionnaires Randomized and Controlled Trial of Anesthetic objective neuropsychological test battery, Management to Improve Postoperative Mental respectively. Other outcome measures include speed Health Outcome and quality of recovery from general anesthesia, incidence of perioperative morbidities, and health CHAN Matthew Tak Vai GIN Tony related quality of life measures. 2 May 2007 (MD06426) Health and Health Services Research Fund Vascular Endothelial Dysfunction after Nitrous Objectives: Postoperative delirium and cognitive Oxide Administration decline are adverse events that occur frequently in elderly patients. CHAN Matthew Tak Vai GIN Tony There are now compelling data to suggest that standard doses of routine anesthetics Faculty of Medicine 166 Dept of Anaesthesia & Intensive Care 30 June 2007 The ENIGMA trial was a large, double-blind CUHK Research Committee Funding (Direct randomized controlled trial (n = 2,050) comparing nitrous Grants) oxide-free anesthesia with nitrous oxide-containing anesthesia. The results of this trial Myocardial infarction, heart failure, cardiac arrest were presented in international meetings and were (“cardiac events”) and death are amongst the most accepted for publication in Anesthesiology, 2007. It serious complications after surgery. has received lots of international attention. We have Patients recently completed a large multicenter clinical trial, receiving nitrous oxide had significantly higher rates the “ENIGMA Trial”. The study identified nitrous of major complications including severe vomiting, oxide (N2O) anesthesia as a probable contributor to a fever, wound infection, pneumonia and atelectasis. number of serious adverse outcomes, including There were also trends towards increased rates of postoperative cardiac events and mortality. There is myocardial infarction and death in the nitrous oxide substantial biologic rationale to suggest that N2O group. A plausible pathophysiologic rationale exists administration produces an acute state of folate for increased long-term morbidity and mortality in deficiency These patients receiving significant doses of nitrous oxide biochemical changes impair endothelial dysfunction during anesthesia, owing to the inhibition of and may predispose patients to adverse cardiac events. methionine synthase, folate metabolism and DNA In this proposed study, we aim to evaluate the synthesis. In addition, the administration of nitrous changes of endothelial function using brachial artery oxide is associated with hyperhomocysteinemia, an flow-mediated independent risk factor for coronary artery disease and hyperhomocysteinemia. dilatation in patients receiving anesthesia with or without N2O. We wish to and stroke. These problems may arise up to one correlate these changes with plasma concentrations of year after the operation. We therefore hypothesized folate, vitamin B12 and homocysteine. that nitrous oxide administration is associated with The proposed study will provide mechanistic information long term morbidity and mortality. on the possible cardiac complication after N2O follow up all the patients in the ENIGMA Trial to find administration. The expected results of this study out about their health after surgery. will provide the essential scientific basis for a future (MD06357) We plan to large randomized study to study the safety of N2O in contemporary anesthesia. The Effect of Acidosis on Coagulation and Platelet (MD06654) Functions before and after Neutralization, and in the ENIGMA Trial Long-term Follow-up Study Absence or Presence of Recombinant Activated Factor VII (Novoseven, NovoNordisk, Denmark) GIN Tony CHAN Matthew Tak Vai HO Ming Hei Anthony Dai, Yue* LEE Anna 30 June 2007 CUHK Research Committee Funding (Direct CRITCHLEY Lester Augustus Hall JOYNT Gavin Matthew KARMAKAR Manoj Kumar Grants) 1 March 2007 167 Faculty of Medicine Dept of Anaesthesia & Intensive Care CUHK Research Committee Funding (Direct rapid shift from inpatient to same day admission Grants) surgery and day only surgery admissions, thereby increasing Despite an impressive record of arresting refractory healthcare costs. bleeding in numerous clinical situations, recombinant unresponsiveness. may cause cost-effective from the hospital’s perspective and Clinically, in severe acidosis, how much patients are willing to pay for a preanaesthetic consultation at the clinic or on the However, neutralization of acidosis with ward. NaHCO3 alone in vitro does not reverse acidosis induced haemostatic deficiencies. A prospective study of 560 patients undergoing elective surgery receiving OPC or Whether the traditional preoperative visit intervention (noOPC) addition of rFVIIa improves haemostatic function in will be conducted. NaHCO3 treated acidic blood remains unexplored. The main outcomes measures are costs to the Hospital Authority (non-profit We intend to quantify coagulation and platelet making and the largest public health organization in function parameters using thrombelastography and Hong Kong), patient’s willingness to pay for a platelet function analyzer of donated blood from preanaesthetic consultation, Quality of Recovery healthy volunteers not on any food or medications known to influence haemostasis. However, the development of this study will be to determine if an OPC is rFVIIa NaHCO3 is sometimes given to bring the pH closer to normal. reducing Hong Kong has been carried out. The objectives of Acidosis, in itself a cause of impaired coagulation functions, and No formal cost-effectiveness analysis of an OPC in ineffective in some patients with refractory bleeding. platelet efficiency OPCs in Hong Kong public hospitals has been slow. activated factor VII (rFVIIa) has been reported to be and hospital scores, health-related quality of life and patient The blood samples satisfaction with preoperative assessment. will be studied in vitro before acidification with lactic The results of the study will be used to determine whether acid, after acidification, and after neutralization with it will be feasible to establish and expand OPC in NaHCO3. In the latter two situations, the effect of public hospitals. adding rFVIIa will also be studied. (MD06440) (MD06448) Please refer to previous issues of this publication Cost-effectiveness of an Outpatient Preanaesthetic for more details of the following ongoing research Clinic at the department: LEE Anna GIN Tony CHUI Po Tong HO Edition Ming Hei Anthony 1 April 2007 2002-03 Perioperative Ischemic Evaluation Study Public Policy Research Funding Scheme Overseas, anaesthesiologist-led (MD02634) CHAN Matthew Tak Vai preoperative Kwok Gabriel* medicine clinics prepare most elective surgical patients for anaesthesia and surgery. Benefits of an outpatient preanaesthetic clinic (OPC) include a Faculty of Medicine Title/Investigators 168 YIP Wai Dept of Anaesthesia & Intensive Care 2004-05 Improving Perioperative Outcome in the 2005-06 A Randomized, Double-Blind, Placebo Elderly Surgical Patients. An Evaluation Controlled, Multicenter Phase IIb Study of Nitrous Oxide in the Gas Mixture for to Evaluate the Efficacy and Safety of Anesthesia (MD04736) Multiple Alvimopan Dosage Regimens CHAN Matthew Tak Vai for the Treatment of Opioid-Induced GIN Bowel Tony Dysfunctin in Cancer Pain Subjects (SB-767905/008) (MD05894) 2005-06 PeriOperative Ischemic GIN Tony Evaluation (POISE) Study - How Does Metoprolol Prevent Postoperative Cardiac 2005-06 A Phase III, Multicenter, Randomized, CHAN Matthew Tak Vai LAM Wai CHAN Matthew Tak Vai RHEE Seongha* Complications (MD05329) Yuk Sang Gordon Evaluate the Safety and Efficacy of 50 Christopher mg Oral Dosing with the Neurokinin-1 GIN Tony Kei Double-Blind, Parallel Group Study to CHOI Receptor Antagonist GW679769 for the (Chemical Pathology) Prevention of Postoperative Nausea and 2005-06 A Randomized, Vomiting in Female Subjects at High Double-Blind, Placebo-Controlled, Multicenter Phase 3 Risk Study to Evaluate the Long-Term Safety (MD05357) of Alvimopan 0.5 mg Twice Daily for 12 GIN Tony months for the Treatment of for Emesis (NKT102553) CHAN Matthew Tak Vai Opioid-Induced Bowel Dysfunction in Adults taking Persistent Opioid Therapy Non-Cancer for 2005-06 A Phase III Multicenter, Randomized, Pain. Double-Blind, Parallel Group Study to (SB-767905/014) (MD05467) Evaluate the Safety and Efficacy of the GIN Tony Intravenous CHAN Matthew Tak Neurokinin-1 Vai RHEE Seongha* GW679769 Formulation Receptor for of the Antagonist Prevention of Placebo-Controlled, Postoperative Nausea and Vomiting in Multicenter Phase IIb Extension Study to Female Subjects at High Risk for Emesis Evaluate the Safety and Efficacy of (NKT102552) (MD05569) Multiple Alvimopan Dosage Regimens GIN Tony 2005-06 A Double-Blind, for the Treatment of Opioid-Induced CHAN Matthew Tak Vai Bowel Dysfunction in Cancer Pain Subjects (ABD101684) (MD05661) GIN Tony 2005-06 B-Aware Trial Long-Term Follow-Up Study (MD05969) CHAN Matthew Tak GIN Tony Vai RHEE Seongha* CHAN Matthew Tak Vai 169 Faculty of Medicine Dept of Anaesthesia & Intensive Care LEE Anna 2005-06 Linezolid in the Treatment of Subjects GIN Tony with Nosocomial Pneumonia Proven to Simon Kin Cheong be Ping Due to Methicillin-Resistant CHAN CHEN Phoon Staphylococcus Aureus (MD05785) GOMERSALL Charles David 2003-04 The Effect of Vasopressor Choice on Fetal Acid-Base Status During Spinal JOYNT Gavin Matthew Anaesthesia for Emergency Caesarean Section (CU03406) 2005-06 Continuous Thoracic Paravertebral Block: NGAN KEE Warwick Dean Effects on Acute and Chronic Pain and Quality of Life after Breast Cancer KHAW Kim Sun Surgery (CU05406) (Obstetrics & Gynaecology) KARMAKAR Manoj Kumar Ming Hei Anthony LAU Tze Kin HO GIN Tony CHAN Wing Cheong (Surgery) 2004-05 Vasopressor Drugs Anaesthesia for in Regional Obstetrics: Quantification of Transplacental Transfer and Determination of Metabolic Effects 1998-99 Ropivacaine as an Intrathecal Agent: Part I – A Dose Response Study (MD98153) on the Fetus (CU04467) KHAW Kim Sun NGAN KEE Warwick Dean Warwick Dean NGAN KEE KHAW Kim Sun CRITCHLEY Lester Augustus Hall 2005-06 Maintenance of Maternal Arterial Blood 2003-04 External Cephalic Version for Breech Pressure during Spinal Anaesthesia for Presentation : A Randomised Controlled Caesarean Section: Development of a Trial Novel Computer-Controlled Closed-loop of Anaesthetic Interventions Feedback Vasopressor Infusion Control (CU03405) KHAW Kim Sun System (CU05408) LAU Tze Kin NGAN KEE Warwick Dean LEUNG Tak Yeung (Obstetrics & KHAW Kim Sun TAM Yuk Ho (Obstetrics & Gynaecology) Gynaecology) NGAN KEE Warwick Dean 2005-06 Cost-Effectiveness Analysis of an Acute Pain Service (MD05312) Faculty of Medicine 170 Dept of Anatomical & Cellular Pathology potential to serve as a prognostic marker as well as a RESEARCH PROJECTS drug target for anti-cancer therapeutic. (MD06912) To Investigate the Role of OREBP/NFAT5 in Elucidation of Mechanisms of ERβ-mediated Cell Hepatocellular Carcinoma Growth Inhibition by Diarylpropionitrile in Prostate Cancer Cells KO Chi Bun 20 June 2007 LAU Kin Mang CUHK Research Committee Funding (Direct NG Heung Ling Margaret NG Chi Fai (Surgery) Grants) MAC-MOUNE LAI Fernand HO Shuk Mei* Hepatocellular carcinoma (HCC) is the fifth most 1 April 2007 common cancer worldwide. CUHK Research Committee Funding (Direct In Hong Kong, where there is a high prevalence of hepatitis B injection, Grants) HCC is the third most common cancer. It is also the major cause of cancer death, ranked the second and Prostate cancer (PCa) incidence has been rapidly forth amongst males and females, respectively. rising in last two decades and now it is the 4th Nonetheless, the molecular events linked to the common male cancer in Hong Kong. Discovery of development and progression of HCC remains estrogen receptor-beta (ERβ) opened new therapeutic unknown. We have been studying the role of a avenues to manage the disease. Our previous studies transcription factor, namely the Osmotic Response demonstrated the importance of ERβ in normal Element-Binding Protein (OREBP), also known as prostate and lesions and the ERβ-dependent inhibition NFAT5, in the regulation of osmotic balance in of PCa cell growth by antiestrogen. Following these mammalian cells. Recently we have demonstrated a findings, phytoestrogens and selective estrogen crucial role for OREBP in the regulation of normal receptor modulators (SERMs) targeting ERβ were cell growth. Furthermore, we have shown that this recently tested in clinical trials, preliminarily with transcription factor is upregulated in the human HCC, promising results. With the advancements of SERM suggesting that it might also have a role in the development, a highly selective ERβ agonist, pathogenesis of cancer. diarylpropionitrile Consistent with our (DPN), was developed and hypothesis, evidence from cell culture studies has exhibited inhibitory effects on PCa cell growth. In revealed that gene silencing of OREBP remarkably this regard, studying DPN in PCa cells could reveal inhibits cell proliferation. We therefore propose: 1) the ERβ regulated genes and the ERβ functional to establish a cell culture model to investigate the involvements in control of PCa but this information molecular basis of OREBP-dependent cell growth; 2) remains lacking. to identify the gene targets of OREBP; and 3) to determine whether cell cycle arrest or/and induction investigate the mechanism responsible for OREBP of apoptosis is/are involved in the DPN-induced cell overexpression in HCC. growth Our study aims to inhibition; In the proposal, we will 1) 2) elucidate the molecular mechanisms by identification of DPN regulated genes elucidate the role of OREBP in HCC and explore its using DNA microarray; and 3) determine the 171 Faculty of Medicine Dept of Anatomical & Cellular Pathology functional involvements of these DPN regulated function. Firstly, we will investigate the expression genes in control of PCa cell growth by gene of ID2 in the precancerous lesions and access the knock-down approach. The outcomes of this prognostic value of ID2 overexpression in NPC. proposal could further enhance our understanding of Secondly, we will elucidate the effects of ID2 ERβ functions in PCa and facilitate the development overexpression of novel ERβ-targeting drugs in PCa treatments. chromosomal stability, and tumorigeneic potential of (MD06611) NPC. on differentiation, proliferation, By gene expression microarray analysis, the ID2 down-stream targets and associated pathway(s) Investigation of the Role of ID2 will in be identified on nasopharyngeal cells. Nasopharyngeal Carcinoma (NPC) Tumorigenesis the ID2 transfected The findings of these studies will contribute to a much better understanding of die molecular pathogenesis of NPC. LO Kwok Wai TO Ka Fai LAU Kin Mang (CU06406) CHUNG Tin Yun Grace TSAO Sai Wah* 1 October 2006 Characterization Research Grants Council (Earmarked Grants) of Phosphoproteome in EBV-positive Nasopharyngeal Carcinoma Nasopharyngeal carcinoma (NPC) poses a serious health problem in Hong Kong. LO Kwok Wai Through gene expression profiling of normal and malignant CHUNG Tin Yun Grace POON Chuen Wai (Medicine & Therapeutics) nasopharyngeal epithelial cells, we have found that 1 April 2007 ID2 (Inhibitor of DNA binding 2), an ID family CUHK Research Committee Funding (Direct member, was upregulated in NPC cell lines and xenografts. Grants) The overexpression of ID2 was further confirmed in majority of primary tumors by Nasopharyngeal carcinoma (NPC) is one the common immunohistochemical staining. Strikingly, in vitro cancers in Hong Kong. It ranked first in terms of studies have showed that expression of ID2 is cancer incidence in the young population (20-44 specifically elevated in nasopharyngeal epithelia with years) and poses a special health concern to our EBV infection and RASSF1A inactivation. community. We Aside from genetic alterations, EBV have previously shown that EBV latent infection and latent infection is important in the development of loss of RASSFIA locus are early events during NPC this endemic cancer. development. Thus, the findings demonstrated a tumors harbors EBV and expresses a number of latent possible link between ID2 overexpression and genes. Our recent study first demonstrated that in initiation of this cancer. Since ID proteins are vitro EBV infection in nasopharyngeal epithelial cells important parts of signaling pathways involved in resulted in the activation multiple signal cascades development, cell growth and tumorigenesis, we which are critical for transformation. hypothesize that ID2 play a critical role in NPC proposal, we plan to undertake comprehensive tumorigenesis. In this proposal, we aim to elucidate investigations on the global protein expression profile the roles of ID2 in the genesis of NPC, and the and phosphoproteome in EBV-positive NPC cells. molecular mechanisms responsible for its oncogenic By using our EBV-infected NPC cells and 2-D gel Faculty of Medicine 172 Virtually almost all NPC In this Dept of Anatomical & Cellular Pathology electrophoresis, we will identify the proteins that are We have conducted mutational analysis of EGFR specific phosphorylated by EBV latent infection and gene from exon 18 to exon 21 in a series of 71 elucidate their associated pathways. surgically identify proteins that are We aim to important in development of this EBV-associated cancer. the resected chemotherapy or NSCLCs gefitinib with no prior treatment. Our These preliminary results demonstrated a high and wide proposed studies will improve our understanding on spectrum of EGFR mutation rate (34.2%, 25/71) in the molecular basis for development of NPC, Hong Kong. However, the functional significances elucidate the role EBV plays in the cancer, and of those novel mutations have not been properly discover new therapeutic targets, findings of which evaluated. will help us to better control this common malignant mutations and the sensitivity of these novel mutants disease in our population. to gefitinib might not be identical. (MD06852) aim to examine the functional properties of these The biochemical properties of these In this study, we novel EGFR mutants and also its responsiveness to Functional Characterization of Epidermal Growth gefitinib in culture cells. Factor molecular basis of responsiveness to gefitinib has Receptor (EGFR) Novel Mutations Understanding the immediate clinical implications, which permit the Detected from Lung Cancer in Hong Kong customization of treatment using EGFR tyrosine LUI Chi Wai TO Ka Fai kinase TONG Hung Man inhibitors as front-line treatment in neoadjuvant, adjuvant, or metastatic settings. Joanna (MD07392) 15 June 2007 CUHK Research Committee Funding (Direct Study of Minimal Residual Disease (MRD) in Grants) Hong In Asia, lung cancer ranks first in the overall Kong Chinese Children with Acute Lymphoblastic Leukemia (ALL) incidence and represent the major cause of cancer death in our locality. NG Heung Ling Margaret The prognosis remains poor especially in advanced stage diseases. HRUSAK Ondrej* Recent advancement in therapy targeting EGFR-tyrosine kinase (EGFR-TK) is advocated as promising Family Medicine) therapeutic strategy for advanced non-small cell lung cancer (NSCLC). LAU Kin Mang LI Chi Kong (Paediatrics) ZEE Chung Ying Benny (Community and 1 January 2007 Among EGFR-targeting agents, Research Grants Council (Earmarked Grants) gefitinib is an orally active small molecule drag with evidence of anti-tumor activity in NSCLC. The It has been demonstrated that early leukemic cell clinical responsiveness to gefitinib is closely clearance with induction therapy is the best indicator associated with EGFR mutations. In particular, of the efficacy of cytostatic treatment and highly adenocarcinoma in Asia harbor a much higher sensitive and specific detection and quantification of incidence of EGFR mutations and which may explain these minimal residual leukemic cells during the first why EGFR-tyrosine kinase targeting therapy is more month of therapy has critical bearing in risk effective in Asia as compare to western populations. stratification 173 and post-induction therapies. Faculty of Medicine Dept of Anatomical & Cellular Pathology Currently, the two problems in minimal residual 4q Loss is Potentially an Important Genetic Event disease (MRD) investigation that need to be tackled in MM Tumorigenesis : Identification of a Tumor are the identification and selection of the most Suppressor cost-effective Methylation at 4q13.3, Platelet Factor 4 platform of assessment and an Gene Regulated by Promoter non-invasive approach that could afford easier and more frequent assessments on the children. For the NG Heung Ling Margaret latter, the recent finding of relative increase in leukemia-specific DNA in peripheral blood plasma Keung with detectable rearranged Ig heavy chain DNA in LAU Kin Mang CHENG Suk Hang LO Kwok Wai NG Ho 30 June 2007 acute leukemia suggests that molecular studies in this CUHK Research Committee Funding (Direct cell-free blood samples may be a promising means of Grants) non-invasive approach for children with BCP-ALL. For the former, with the initial supports by Children Multiple myeloma (MM) is a clonal plasma cell Cancer’s Foundation, we conducted a multicentre malignancy with no effective treatment for cure. MRD study by 3-color flow cytometry and real-time The critical genetic triggers associated with MM quantitative polymerase chain reaction (RQ-PCR) transformation and disease progression remains analysis unidentified. In this proposal, we will elucidate the of leukemia-clonogenic rearranged immunoglobulin (Ig) and T-cell receptor (TCR) chromosomal genes on childhood ALL as participation in the pathogenesis and search for tumor suppressor gene Intercontinental-Berlin-Frankfurt-Münster (TSG) loci in MM. (I-BFM) imbalances in the multistep We aim to comprehensively study. The current proposal builds on the previous investigate the genome of MM and its precursor study with an extension to 4-color approach using condition (monoclonal gammopathy of undetermined simple but cost-effective panels of antibodies (CD10, significance, CD19, CD20, CD34, CD45, CD58, CD66c and hybridization (CGH) and allelotyping on chromosome sytol6) 4q and 13q. to enhance coverage, specificity for MRD investigation. assessment by RQ-PCR sensitivity and Simultaneous analysis MGUS) by comparative genomic The searches focusing on these two chromosomal regions are based on our preliminary of findings of high incidence of 4q and 13 q losses in 3 leukemia-clonogenic rearranged Ig and TCR genes MGUS and 9 MM bone marrow samples. on bone marrow and both cellular and plasma further investigate the involvements of these two fractions of peripheral blood will also be performed. genetic alterations in MM, we will perform Findings from the study will lead to the development fluoresecent in situ hybridization analysis on bone of the best MRD detection strategy in Chinese marrow smear samples to determine the population children with BCP-ALL. sizes with 4q/13q loss in the clonal plasma cells of The ultimate goal is to To incorporate clinically relevant MRD data into relapse the patients. risk stratification on the patients as planned in the will define the minimal deletion regions. I-BFM study group for the best risk adapted personal expression of the candidate genes located at the therapy. regions will be profiled and compared between MM (CU06408) and normal bone marrow cells to identify the By high resolution allelotyping, we The candidate TSG. The genes with absence/reduction Faculty of Medicine 174 Dept of Anatomical & Cellular Pathology of the expression in MM cells will be further studied Moreover, loss of REOTl transcript was also found in to determine whether DNA methylation is involved gastric and ovarian carcinoma cell lines, suggesting in the transcriptional silencing. The outcomes of the that REOTl inactivation may be involved in human proposal could generate novel targets for the cancers other than OTs. Importantly, a significant development of molecular markers in diagnosis and association was observed between down-regulated prognosis, pharmaceutical intervention, gene therapy REOTl expression and the chromosome lp deletion or adjunct therapy. status in OTs (P<0.0001). (MD06766) REOTl is a major tumor suppressor gene on We hypothesize that chromosome lp36.3. The objectives of this proposal Molecular and Functional Characterization of a are to investigate the biological functions of REOTl Novel Candidate Tumor Suppressor Gene REOT1 in relation to oncogenesis and to evaluate its clinical on significance in oligodendrogliomas. Chromosome 1p36.3 and Its Clinical It is anticipated that results from this study will shed light on the Significance in Oligodendroglial Tumors pathogenesis of human cancers carrying lp deletion NG Ho Keung PANG Chung Sean Jesse POON Wai Sang (Surgery) and may potentially generate novel targets for prognosis and treatment. CHUI Yiu Loon (CU06407) (Clinical Immunology Unit) 1 September 2006 Identification of Gene Targets Modulated by Research Grants Council (Earmarked Grants) Dysregulated MicroRNAs in Medulloblastoma Oligodendroglial tumors (OTs) are primary brain tumors of adults. tumors is the NG Ho Keung PANG Chung Sean Jesse A genetic hallmark of these combined allelic deletion of 15 June 2007 chromosomes lp and 19q, suggesting that these CUHK Research Committee Funding (Direct chromosome arms carry critical tumor suppressor genes involved in OT formation. Grants) No tumor suppressor genes have yet been isolated from these Medulloblastoma is a common malignant brain tumor chromosomes. in children. Recently, loss of chromosome lp has Despite advances in multimodality been demonstrated to be a significant predictor of therapy, 30-50% of medulloblastoma patients do not chemosensitivity and better patient survival in OTs. survive and post-treatment cognitive deficits are The identity of gene(s) mediating these effects is also common in long-term survivors. undefined. We recently isolated from chromosome therapies lp36.32 a novel gene named REOTl, whose pathogenesis expression is either lost or significantly reduced in MicroRNAs are a recently discovered class of ~60% of OTs. Aberrant promoter hypermethylation non-coding and loss of REOTl allele are demonstrated to be the expression of hundreds of genes with functions in major mechanisms contributing to such aberrant diverse biological processes. expression pattern. These results suggest that indicates that microRNAs also play an important role REOTl may play a role in the development of OTs. in oncogenesis. We evaluated the involvement of 3 175 targeting of the underlying medulloblastoma RNAs Thus novel which are negatively molecular needed. regulate Mounting evidence Faculty of Medicine Dept of Anatomical & Cellular Pathology microRNAs, which are mapped to the frequently that multiple EBV encoded miRNAs are consistently deleted in expressed in NPC samples. However, only scanty Our results demonstrated that data is available for EBV miRNA. The currently expressions of microRNAs mir-124a (8p23.1) and identified EBV miRNA are all cloned from a mir-383 (8p22) were either lost or reduced in 40-60% Burkitt’s lymphoma cell line BL41/95 latently of medulloblastoma, whereas that of mir-320 (8p21.3) infected with EBV strain B95-8. was newly identified EBV miRNAs are present in both regions on medulloblastoma. not altered. expression of chromosome More importantly, mir-124a or 8p, forced mir-383 Although those in NPC and lymphoma cells, distinct expression medulloblastoma cells deficient of such miRNAs patterns were found in NPC according to our resulted in suppression of cell proliferation and preliminary study. The EBV miRNA profile might induction of cell death. Taken together, our results be different in different disease entities, cellular strongly suggest that mir-124a and mir-383 may act backgrounds, EBV strains and latency status. The as tumor suppressors in medulloblastoma oncogenesis. NPC cell line C666-1 carries a relatively wild-type The aim of this study was to identify the gene targets EBV strain. modulated by the dysregulated microRNAs during miRNA expression profile in NPC cells and novel medulloblastoma tumorigenesis. EBV miRNAs may be detected. It is anticipated that results from this study will provide insights into Objectives: the underlying genetic pathways associated with 1. mir-124a and mir-383 in medulloblastoma and We aimed to investigate the EBV To construct miRNA libraries from EBV positive NPC cell line and xenografts. potentially generate novel therapeutic targets for 2. improved outcome of this malignant pediatric To document the EBV miRNA profile in NPC in order to identify novel EBV miRNAs. disease. 3. (MD06999) To confirm the expression of detected EBV miRNA in NPC cell lines, xenografts and primary tumor samples. Identification of Epstein-Barr Virus miRNA in Study designs: miRNA libraries from EBV positive Nasopharyngeal Carcinoma Cells NPC cell line C666-1 and xenografts X-2117 will be constructed. The small RNA clones will be screened and sequenced to document the EBV TO Ka Fai LO Kwok Wai TONG Hung Man miRNA profiles and to detect novel EBV miRNAs. Joanna And the existence of the novel EBV miRNA will be 2 January 2007 confirmed by Northern blotting in NPC tumor Research Fund for the Control of Infectious samples. Diseases Main outcome measure: Such information may no Recent advances in cancer biology have strong doubt implications for the alterations of microRNAs tumorigenesis and provide new therapeutic prospects (miRNAs) as one of the most important events in for future developments. human tumorigenesis. (MD06848) Nasopharyngeal carcinoma (NPC) is well-known to be associated with Epstein-Barr virus (EBV) and we have demonstrated Faculty of Medicine 176 enhance our understanding on NPC Dept of Anatomical & Cellular Pathology Research Centre for Gastric Cancer Epigenetics : treatment. However, such data in gastric cancer is Molecular Basis and Clinical Applications limited. In this proposal, we focused on comprehensive analysis of these two epigenetic TO Ka Fai LO Kwok Wai Keung (Medicine & Therapeutics) Wai (Medicine & Therapeutics) By which we could identify target cancer associated genes regulated by these CHAN Ka Leung Francis (Medicine & Therapeutics) Enders Kwok-wai (Surgery) mechanisms in GC. LEUNG Wai epigenetic mechanisms. NG These not only enhance POON Chuen our understanding of gastric cancer carcinogenesis, CHIU Wai but may also lead to discovery of new cancer biomarkers. In vivo and in-vitro anticancer effect of Yan Philip (Surgery) CHOW K C Billy* various HDAC inhibitors will be assessed. 1 April 2007 The results will enhance our understanding of this new Supplementary Funding for RGC Central class of anti-cancer agents and provide laboratory Allocation evidence and information for future clinical trials Gastric carcinoma (GC) is the second most common against gastric cancer. and often fatal malignant cancer worldwide and it is (MD06765) particular prevalent in China including Hong Kong. Gastric cancer accounts for 3% to 10% of all cancer Role of Small Non-Coding miR-221 and miR-222 related deaths. in the Oncogenesis of Human Hepatocellular More than 700,000 people died of gastric cancer per year and more than 40% occur in China. Carcinoma Gastric cancers are often detected at an The WONG Nathalie POON Chuen Wai (Medicine mortality rates have remained relatively unchanged & Therapeutics) TO Ka Fai LAI Bo San Paul over the past 30 years and overall 5-years survival (Surgery) rate is only 10-20%. Thus, cancer biomarkers for 1 January 2007 advanced stage, the prognosis remains poor. early cancer detection, prediction of prognosis and Research Grants Council (Earmarked Grants) effective therapeutic approach are urgently needed. Epigenetic mechanisms are important in regulation of Hepatocellular gene epigenetic malignant tumor that is prevalent in Southeast China regulatory mechanisms, namely gene promoter including Hong Kong, where it is associated with a methylation and histone modifications are implicated high in cancer development. Other and our investigative understanding of genetic changes leading to the team have shown that epigenetic alterations are development and progression of HCC hence holds common gastric much value from a biological and clinical standpoint. Identification of abnormal gene Recent emergence of microRNA (miRNA) as an expression. and carcinogenesis. Two important important events in cancer carcinoma mortality in and the is a morbidity. control of highly The methylation may also serve as potential cancer important markers for gastric cancer detection and predict oncogenesis has led to our speculation of differential prognosis. miRNA expressions in HCC. Moreover, by using histone deacetylase element (HCC) cancer We therefore (HDAC) inhibitors modifying the histone acetylation performed array-based miRNA expression analysis status is emerged as an effect and safe anti-cancer and found marked elevations of miR-221 and 177 Faculty of Medicine Dept of Anatomical & Cellular Pathology miR-222 in HCC tumors, early-passages of HCC new approaches of early diagnosis and disease cultures and established cell lines. In addition, our monitoring in patients with HCC. data also indicated distinct over-expressions of (MD06674) miR-221 and miR-222 in primary HCC whereas absence or negligible detection was suggested in the Please refer to previous issues of this publication putative pre-malignant lesion i.e. the cirrhotic liver for more details of the following ongoing research adjacent to the tumor. Given that little is known at the department: about the function(s) of miR-221 and miR-222, the aim of this work is to define the role of these miRNAs Edition Title/Investigators in HCC oncogenesis. (CU06410) 2003-04 The Role of Pif1 DNA Helicase Homolog in Telomere Maintenance and Hepatocellular Carcinoma Research Group : Chromosome Stability in Mammalian Clinical Applications of Functional Genomics Cells (CU03411) Anthony W.I. LO WONG Nathalie LAI Bo San Paul (Surgery) POON Chuen Wai (Medicine & Therapeutics) CHAN Lik Therapeutics) Yuen Henry TO Ka Fai (Medicine John P.* MURNANE NG Ho Keung PANG Chung Sean Jesse & YEO Winnie 2004-05 The Role of Pif1 DNA Helicase (Clinical Oncology) CHAN Kwan Chee (Chemical Pathology) LO Yuk Ming Dennis Chromosome (Chemical Pathology) POON Y. C. Randy* Embryonic Stem Cells (MD04324) CHEUNG Siu Tim* LUK John* Homolog in Telomere Maintenance and NGAI Stability in Mouse Anthony W.I. LO Jenny* CHINNAIYAN, Arul* 2003-04 Interleukin-10 Gene Polymorphisms in 30 June 2007 Malignancies Associated with Infectious Supplementary Funding for RGC Central Agents in Hong Kong (CU03408) Allocation CHAN Bik Wan CHAN Wing Despite advances made in clarifying the genetic and Yee# LEI Ieng Kit Kenny (Clinical cellular changes associated with Hepatocellular Oncology) Carcinoma (HCC), the implications of these changes in clinical utilities and targeted therapies remained largely unexplored. This project aims 2005-06 Investigation at of Medulloblastoma Related MicroRNAs (MD05300) establishing a comprehensive integrated map of HCC CHAN Bik Wan HUI Bik Yu LO at the molecular, proteome and cellular levels. Kwok Wai Information derived is expected to consolidate our POON Wai Sang (Surgery) NG Ho understandings on the tumor biology of HCC. Keung Promising biomarkers and expression patterns will be further examined for their potential applications as Faculty of Medicine 178 LAU Kin Mang Dept of Anatomical & Cellular Pathology 2005-06 Mechanism of Institute)# Nucleocytoplasmic LAM Ching Wan Shuttling of OREBP/TonEBP (BL03315) (Chemical Pathology) KO Chi Bun Wah* HUI Bik Yu CHUNG Stephen S TSAO Sai M* 2004-05 Study on Nasopharyngeal Carcinoma 2005-06 The Mechanism of Genetics (MD04387) LO Kwok Wai OREBP/TonEBP/NFAT5-dependent Transcription – Role of Signaling HUANG POON Wai Sin Dolly (Hong Kong Cancer Pathway and Chromatin Remodeling Institute)# (BL04799) Yu TSAO Sai Wah* KO Chi Bun 2005-06 Histone Acetylation Molecular 2005-06 Characterization of T-Cells Carcinoma Patients Kong Novel Target for HUANG POON TO Ka Fai HUI Bik WOO Sang 2005-06 Characterization John (Otorhinolaryngology, Neck S) a Yu TSAO George* NG Heung Ling LO Kwok Wai HUI Bik Wai Sin Dolly (Hong Kong Cancer Institute)# LAU Kin Mang as Therapeutic LO Kwok Wai in (MD05375) Margaret Nasopharyngeal Carcinoma (CU05413) Circulating Regulatory Nasopharyngeal TO Ka Fai CHUNG Stephen S M* RAO Anjanna* CD4+CD25+ Head of MicroRNAs in Nasopharyngeal Carcinoma (MD05731) and LO Kwok Wai VAN HASSELT Charles Andrew (Otorhinolaryngology, Head CHUNG Tin Yun Grace and Neck S) 2005-06 Evaluation 2003-04 Comprehensive Characterization of Prognostic Molecular of Immunohistochemical Markers of Ductal Common Amplicons in Nasopharyngeal Carcinoma in Situ in Asian Women Carcinoma (CU03410) (MD05882) LO Kwok Wai LUI Chi Wai TSE Man Kit Gary HUANG POON Wai Sin Dolly (Hong Kong Cancer Institute)# HUI Bik Yu LAU Kin Mang TEO 2005-06 Metabolic Man Lung Peter (Clinical Oncology) Characterization of a Pre-Diabetes Renal Lesion – Isolated TO Ka Fai Thick Glomerular Capillary Basement 2004-05 Functional Role of in Membrane (TGCBM), a Marker for the Carcinoma Prevention of Diabetic Nephropathy? RASSF1A Nasopharyngeal Tumorigenesis (CU04255) (CU05411) LO Kwok Wai MAC-MOUNE HUANG POON Wai Sin Dolly (Hong Kong Cancer LAI Fernand SZETO Cheuk Chun (Medicine & 179 Faculty of Medicine Dept of Anatomical & Cellular Pathology Therapeutics) Growth Inhibition in Childhood Acute CHAN Chung Ngor Juliana (Medicine & Therapeutics) Lymphoblastic Leukemia (CU05415) NG Heung Ling Margaret TO Ka Fai Kin Mang 2004-05 Immunogenetic Study of Nasopharyngeal (Chemical Pathology) (Paediatrics)# (MD04572) (Paediatrics) NG Heung Ling Margaret Kin Mang LO Kwok Wai LAM Ching Wan Carcinoma in Hong Kong Chinese LAU YANG Mo CHIK Ki Wai ZEE Chung Ying LAU Benny (Community ZEE Medicine) and Family Chung Ying Benny (Community and Family Medicine) 2005-06 Molecular WOO Kong and Functional Sang John (Otorhinolaryngology, Characterization of Tazarotene Induced Head and Neck Gene HASSELT S) Charles (Otorhinolaryngology, VAN (TIG1) Carcinoma Andrew Head 1 in and Nasopharyngeal Medulloblastoma (CU05409) and NG Ho Keung Neck S) CHAN Bik Wan LO Kwok Wai PANG Chung Sean 2004-05 A Family Based Case-Control Study of Immunogenetics Respiratory in Severe Syndrome Jesse Acute (SARS) 2005-06 Research into Asian Cancers – Integrated (MD04752) Genomic Research (MD05591) NG Heung Ling Margaret Kin Mang* NG Ho Keung LAU and TO Ka Fai LO Kwok Wai WONG Nathalie ZEE Chung Ying Benny (Community Medicine) Family 2005-06 The SUNG Joseph Jao Yiu Clinical Significance (Medicine & Therapeutics) and of Pathological Chromosome 1p Genotyping in Gliomas (CU05416) NG Ho Keung 2005-06 Immunogenetics and Viral Genotyping of POON Wai Sang Hong Kong Hepatitis B Virus Carriers (Surgery) for the Increased Risk of Hepatocellular PANG Chung Sean Jesse ZHOU Liang Fu* Carcinoma (MD05399) NG Heung Ling Margaret Kin Mang (Surgery) 2005-06 Molecular LAU Functional Characterization of a Novel Candidate LAI Bo San Paul WONG Nathalie and Tumor Suppressor Gene REOT1 Located ZEE Chung Ying Benny (Community and on Chromosome 1p36.3 (MD05747) Family Medicine) NG Ho Keung Jesse 2005-06 Elucidation of Molecular Mechanisms of Thrombospondin (TSP-1)-Induced Cell Faculty of Medicine 180 PANG Chung Sean Dept of Anatomical & Cellular Pathology 2003-04 Identification of Multiple Suppressor Genes 8p21-23.1 in on Hydroxamic Acid (SAHA) in Gastric Tumor Cancer Cells (MD05765) Chromosome TO Ka Fai Medulloblastoma (CU03414) TONG Hung Man Joanna PANG Chung Sean Jesse NG Ho 2003-04 Characterisation of Genomic Amplicons Keung POON Wai Sang (Surgery) in Hepatocellular Carcinoma : Targeting Candidate 2005-06 Epigenetic Silencing of DOC2-hDAB2 and Tumor Suppressor DOC2-hDAB2 in Activity by Array-CGH, Transcriptional Profiling and Functional of Study (CU03467) Nasopharyngeal WONG Nathalie CHAN Yuen Yee Carcinoma (CU05417) TO Ka Fai Genes (Paediatrics) HUANG POON Wai LAI Bo San Paul Sin Dolly (Hong Kong Cancer (Surgery) Institute)# LO Kwok Wai (Community and Family Medicine) 2004-05 Characterization 2005-06 Sequencing Analysis of 3' Region of CagA Isolated Gene in from Patients Helicobacter Hong with Suppressive Pylori Kong of Tumor Activating Factor, ATF5, in WONG Nathalie CHAN Yuen Yee (Paediatrics) LEUNG Wai Keung (Medicine & Therapeutics) the Hepatocellular Carcinoma (CU04289) H. Pylori-Associated Diseases (MD05832) TO Ka Fai of Role Transcriptional Chinese Different ZEE Chung Ying Benny LAI Bo San Paul (Surgery) NG Enders Kwok-wai (Surgery) 2004-05 Characterizing the Viral Hepatitis B Integrants 2005-06 Centre for MicroRNA Study - Basic in Human Research and Clinical Applications in Carcinoma (MD04723) Nasopharyngeal Cancer and Liver Cancer WONG Nathalie (MD05698) WONG Nathalie LO Kwok Wai SMITH David I.* 2005-06 Functional Characterization of PFTK1 in TONG Chi Fai Michael Head the and Cellular Invasion WONG Nathalie Bazan J. Fernando* NG Ho Keung Human POON Chuen Wai (Medicine & Therapeutics) POON Y C Randy* 2005-06 In Vivo Anticancer Effect of Histone Inhibitor of Hepatocellular Carcinoma (CU05418) POON Chuen Wai (Medicine & Therapeutics) Deacetylase LAI Bo San Paul (Otorhinolaryngology, Neck S) CHAN Lik Yuen Henry (Medicine & Therapeutics) TO Ka Fai (Surgery) Hepatocellular LAI Bo San Paul (Surgery) Suberoylanilide 181 Faculty of Medicine Dept of Anatomical & Cellular Pathology WONG Nathalie SY Ming Hui# 2005-06 Elucidation of Candidate Genes on chr 7q34-q36 in the Progression of Hepatocellular Carcinoma (MD05864) Faculty of Medicine 182 Dept of Anatomy members of ligand-independent orphan nuclear RESEARCH PROJECTS receptors are important regulators of many basic cellular functions and involved widely in many A Functional Study of Estrogen Receptor-Related physiological processes via their transcriptional Receptor β in Prostate Cancer regulation of gene expression. Among these orphan receptors, we are particularly interested on the CHAN Leung Franky estrogen receptor-related receptors (ERRs) as they 1 January 2007 are close relative of ERs and also involved in similar ER-mediated regulatory pathways in target cells. Research Grants Council (Earmarked Grants) ERRs consist of three closely related subtypes (α, β Prostate cancer is the most commonly diagnosed and γ), which are encoded by different genes. cancer in men in many Western countries. Recently, Although ERRs are homologous to ERs in their its incidence rates are increasing rapidly in Asia, protein structures, ERRs do not bind to estrogens and including China and Hong Kong. thus they are classified as orphan nuclear receptor. prostate are heterogeneous in their Similar to ERs, ERRs can bind to the consensus and responses hormonal estrogen response element (ERE) and ERE-related Most prostate cancers grow slowly DNA elements, which are also recognized by other cancers progression rates interventions. The clinical to and depend on androgens, and thus androgen ablation nuclear receptors. therapy is effective but only temporarily. cross-talk with ERs or other nuclear receptors at Many Therefore, ERRs can interact or patients under hormone therapy will progress to an transcription level in target cells. advanced androgen-independent and metastatic stage background, we hypothesize that besides ERs, ERRs in few years, and resulted in high mortalities. may be critically involved in the regulation of normal Despite much research works conducted in this area, prostatic growth and prostate cancer development via the mechanisms underlying the initiation and similar progression of both latent and clinical prostate cancers independent pathways. are still not well understood. Steroid hormones, [J Clin Endocrinol Metab (2005) 90:1830-1844], we particularly androgens, play a major role in the demonstrate that members of ERRs are co-expressed growth and function of prostate gland, and also its with ERs in normal prostate epithelial cells and they neoplastic growths. Besides androgens, estrogens display differential expression patterns in prostate have been suggested to play certain roles in these cancer cells. Among the three ERR subtypes, ERRβ regulatory processes and contribute differently at shows a distinct down-regulation pattern in most different developmental stages, largely based on the prostate cancer cell lines and clinical neoplastic positive expression of estrogen receptors (ERs) and tissues. estrogen metabolism related enzymes in this gland. study to investigate in-depth the functional role of However, and ERRβ in the growth regulation of prostate cancer ER-mediated signaling pathways in prostate gland cells, the epigenetic effects on its down-regulation in and prostate cancer are still undefined. prostate cancer cells and to identify its target genes in the exact roles of estrogens Recent ER-mediated pathways or In a recent expression study In this proposal, we plan to extend our prostatic cells. advances in nuclear receptors also indicate that regulatory Based on this Our preliminary results show that ectopic expression of ERRβ can inhibit significantly 183 Faculty of Medicine Dept of Anatomy the in vitro and in vivo prostate cancer cell growth, Hence, we hypothesize that other ER-related suggesting that ERRβ may play a tumor-suppressing receptors or alternative estrogen-signaling pathways function in prostate cancer cells. Through this could exist and be involved in the regulation of in-depth study, we strongly believe that valuable normal and neoplastic prostate growth and functions. information on the significance of ERRβ in prostatic Based on this background, we are interested to study function and prostate cancer development will be the estrogen receptor-related receptors (ERRs) in obtained. This information will not only be prostate and prostate cancer as these nuclear valuable to our understanding on the functional role receptors are structurally and functionally related to of ERRβ in prostate cancer but also its potential use ERs. as a novel biomarker or therapeutic target for this three closely related subtypes: α, β, γ. All ERRs are disease. highly homologous to ERs in their protein structure, (CU06411) particularly in their DNA- and ligand-binding ERRs are nuclear receptors and consist of domains. However, ERRs can constitutively A Functional and Molecular Characterization of transactivate target gene promoters without binding an Orphan Nuclear Receptor ERR as Putative to estrogens and thus they are classified as orphan Tumor Suppressor in Prostate Cancer nuclear receptors. Recent studies indicate that ERRs can cross-talk with the ligand-dependent ERs CHAN Leung Franky in many cell types via regulation of same target CHOY Kwong Wai genes or interfere with one another's functional (Obstetrics & Gynaecology) activity by competing for same coregulators and 29 June 2007 DNA binding sites. CUHK Research Committee Funding (Direct Based on this, we hypothesize that besides ERs, ERRs may also be involved in the Grants) estrogen signaling pathways, and piay certain Besides androgens, estrogens nave been suggested to regulatory roles in the normal and neoplastic play certain roles in normal and neoplastic growths prostates. of prostate gland, largely based on the positive the functional roles of ERR/and identify its target expression of estrogen receptors (ERs) and estrogen genes in prostate cancer cells with an ultimate goal of metabolism-related enzymes in this gland. It is understanding better its specific roles in the generally believed that direct estrogenic effects on regulation of prostate cancer cell growth and prostate the prostate or their possible roles in prostate cancer, carcinogenesis. benign prostatic hyperplasia and non-bacterial (MD06641) The main aim of this proposal is to study prostatitis are partially mediated by estrogen receptors, ERα and ERβ. However, studies from Genomic Approaches to Uncover Functionally ER-knockout mouse models raise a query on the Relevant Signaling Pathways in Craniofacial significance of ERs in adult prostate, as targeted Development disruption of ERs does not affect significantly the CHAN Wood Yee prostatic structure and functions, suggesting a CHEAH Kathryn S.E.* possible functional redundancy of ERs or other CHOW, K.L.* HUANG J.D.* SHAM M.H.* alternative signaling pathways are present in prostate. Faculty of Medicine 184 SMITH D.K.* Dept of Anatomy 30 March 2006 sulfate (CS) moieties of matrix proteoglycans have RGC-Central Allocation Scheme - Group recently emerged as a primary factor in restricting the path of growing axons. Our preliminary analysis of Research the E13.5 rat brain found difference in sulfation Many of the genes implicated in human deafness are pattern of CS between forebrain and hindbrain, in expressed in the ear during development. A correlation with axonal projections observable in the significant number of these have been discovered hindbrain in the hindbrain but not yet in the forebrain. through studying mouse models – either by At E13.5, chondroitinase digestion of hindbrain CS identifying mutations in existing mutants or by resulted in dispersed axonal projections that further gain-of or loss of function genetic manipulation of suggest axon-restrictiveness of the majority of matrix mouse genome. The theme of this study is focused on CS. We therefore hypothesize that the sulfation uncovering genetic relationships and functionally pattern of CSs in early embryonic environment relevant signaling pathways in ear development, confer restriction on axonal growth and that which is founded on the exciting results of our modification of their sulfation pattern is a mechanism current project. Working as a multidisciplinary team to allow axonal negotiation through an otherwise form HKU, HKUST and CUHK, we will use restrictive environment. To address this, we propose conditional and (1) to determine the change in sulfation pattern of transgenesis in mouse and worm models, embryology, hindbrain CS and to correlate the change with bioinformatics, advanced imaging and lineage tracing, expression pattern of chondroitin sulfotransferases in to address key issues on induction, patterning and the brain during early axonal projections; and (2) to morphogenesis in the mouse middle ear and inner ear. determine the spatiotemporal changes in expression Congenital deafness occurs in one in 800 live births of chondroitin sulfortransferases in relation to and hearing loss affects one in three elderly people. restrictions to commissural projections of vestibular Our studies will provide important insight into causes nuclear neurons in the developing hindbrain. Results of human deafness which may lead to the of the study will recognize sulfation of chondroitin development of therapies for hearing loss. moieties of proteoglycans as a means of fine-tuning (MD05575) the in vivo microenvironment for the layout of early gene activation/inactivation embryonic neuronal projections. Results will also be Role of Chondroitin Sulfates in the Regulation of significant for the design of strategy to target Axonal Growth and Patterning in the Developing specifically axon-restrictive CSs that build up in the Hindbrain injured neural environment. (MD06449) CHAN Wood Yee SHUM Daisy KY* FAWCELL JW* CHAN YS* Identifying the Tissue of Origin and Lineage of 1 September 2006 Microglial Progenitors in situ Research Grants Council (Earmarked Grants) CHAN Wood Yee REZAIE Payam* Establishing correct neuronal circuitry is an important 1 January 2007 goal in developmental neurobiology. The chondroitin 185 Faculty of Medicine Dept of Anatomy CUHK Research Committee Funding (Direct Research Grants Council (Earmarked Grants) Grants) Recent evidence suggests that microglia (the resident mononuclear phagocytes of the nervous system) may Hirschsprung’s exert neuroprotective and neurotrophic functions that megacolon, is the most common gastrointestinal are distinct from their potential to cause harm within motility disorder in newborns. the these feature of HD is an abnormal dilatation of the distal “newly-found” capabilities of microglia represents a colon resulting from a regional absence or reduction new era of research into the biological function of of enteric ganglion cells. It has been known that all these cells. However, despite intense study, the the intrinsic enteric ganglion cells are derived from precise tissue of origin and cell lineage of microglia neural crest cells, which migrate along defined still remain unclear. pathways from the neural tube (embryonic central nervous system. investigations by Tapping into Our own findings and others indicate that, unlike disease (HD), or congenital The prominent nervous system) to the gut during embryonic macroglia (astrocytes and oligodendrocytes) and development. neurons, which arise from the neuroectoderm, HD is a developmental disorder related to the microglial progenitors arise from mesodermal tissues, abnormal development of neural crest cells. and colonise the nervous system during embryonic studies on avian embryos have also indicated that and fetal periods of development. This proposal neural crest cells at the sacral level contribute a aims to establish the tissue of origin and lineage of significant number of enteric neurons to the hindgut, microglial progenitors in situ in mouse embryos by the region of the gut where aganglionosis is usually means (immunohistochemical) detected in HD patients. In the present study, we characterization, in situ hybridization and in vivo cell aim to identify the anomalies in the migration of tracking. This information is critical not only from sacral neural crest cells in a mouse mutant model for a developmental perspective, but significantly from a HD by using a combination of techniques including therapeutic progenitors whole embryo culture, in situ cell labelling, gut specifically target the central nervous system, and explant culture, immunofluorescence staining and this becomes feasible only if the origin and cell 3-dimensional image reconstruction. lineage of the microglial progenitors are known and marker, eGFP, will also be used to label the migrating these cells can be isolated and manipulated in vitro (i.e. sacral neural crest cells. The results will provide us to express specific trophic factors) prior to therapeutic with the important information as to whether transfer in vivo. anomalies in the sacral neural crest cell migration are (CU06412) a cause of reduction in enteric ganglia in the mutant of phenotypic viewpoint - microglial Hence, it is generally believed that Recent A genetic mouse and possibly also in HD patients, and also give Towards a Better Understanding of us insight into the pathogenetic mechanism of HD. the Embryological Basis of Hirschsprung’s Disease (MD06995) CHAN Wood Yee Factors Influencing the Regeneration of Retinal 30 June 2007 Ganglion Cell Axons Studied by a Model of an Extensive Lesion of the Optic Nerve Faculty of Medicine 186 Dept of Anatomy 1 January 2007 CHO Yu Pang Eric Research Grants Council (Earmarked Grants) 1 June 2007 Pregnancies complicated by maternal diabetes are CUHK Research Committee Funding (Direct associated with an increased rate of birth defects. Grants) Interestingly, many of the organ systems commonly Damage to axons of the central nervous system (CNS) affected in the offspring of diabetic mothers are usually results in limited regeneration and poor similar to those affected by deficiency or excess recovery. intake of vitamin A, or its active metabolite, retinoic It is currently believed that the glial limiting acid. As retinoic acid is a key signaling molecule in regeneration but the relative contributions by the embryonic development, its concentration in the different glial cells remain controversial. We have embryo is tightly regulated, with both excess and recently observed that contrary to popular thinking, deficiency leading to malformation. While there is the lesion environment of the CNS may instead increasing evidence that vitamin A and retinoic acid possess properties supportive of axonal regeneration. concentrations are altered in patients with diabetes This conclusion is based on our finding that retinal mellitus, there are no reported studies on whether ganglion cell axons can be induced to regenerate in a retinoic acid signaling in the embryo is affected in lesion environment created by crushing the optic diabetic pregnancy. Recently, we have used a nerve for an extensive distance instead of a focal mouse demonstrate injury. This new experimental paradigm allows a diabetes/hyperglycemia can potentiate the effect of detailed analysis of the behavior of damaged axons in retinoic acid in causing birth defects. Moreover, we the lesion environment to be made. In this study, find that the expression level of Cyp26al, the key we propose to elucidate the relationships of axons enzyme for the breakdown (catabolism) of retinoic regenerating in the extensive lesion to that of glial acid, is significantly reduced in embryos of diabetic cells so as to identify which glial populations are mice compared with embryos of non-diabetic mice, involved in the process of regeneration. Moreover, both in the absence and in the presence of a experimental teratogenic dose of retinoic acid. environment plays a major conditions role which in may enhance model to that maternal regeneration will be tested in this lesion paradigm in To aim of this project is to test our hypothesis that order to understand more on the factors which down-regulation of Cyp26al by maternal diabetes promote axonal regeneration in the CNS. leads to reduced retinoic acid catabolism, resulting in (MD06632) a higher effective concentration of retinoic acid and thus an increase in teratogenic effect. Results of this The Role of Retinoic Acid Catabolism in project will provide fundamental information on the Increased pathogenic mechanism of diabetic embryopathy and Susceptibility to Retinoic Acid pave the way to derive preventive measures to reduce Teratogenicity in Diabetic Pregnancy the risk of congenital malformation in human diabetic SHUM Sau Wun Alisa MCCAFFERY Peter* COPP Andrew J.* pregnancy. (CU06416) WANG Chi Chiu (Obstetrics & Gynaecology) 187 Faculty of Medicine Dept of Anatomy An Investigation of Retinoid Homeostasis in the implantation in diabetic pregnancy, with an ultimate Female Reproductive System under Diatetes goal to design treatment to improve the reproductive performance of women with diabetes. (MD06369) SHUM Sau Wun Alisa 1 April 2007 South China National Research Centre for CUHK Research Committee Funding (Direct Integrated Biosciences in Collaboration with Grants) Zhongshan University – Aging & Degenerative The aim of this project is to determine whether Diseases (Group 1) diabetes will affect retinoid homeostasis in the female reproductive system. YEW Tai Wai David Diabetes is associated with reduced pregnancy rate 1 July 2005 and increased risk of having babies with congenital malformations. Development Grant Homeostasis of vitamin A and its active metabolites retinoic acid, regulated by The aging and degenerative diseases will target on balancing actions of the synthesizing enzymes, the study of Partkinsonism, Alzheimer diseases, catabolizing enzymes and binding proteins, is multiple essential for female reproduction and embryo psychobiological diseases. The studies would include development. There are emerging evidences that the both cell culture and on CNS tissue of human or plasma and liver concentrations of vitamin A, retinoic animals. The approaches would include biophysical acid and retinol binding protein are altered in diabetic (fMRI), biochemical and cytochemical evaluations. patients. Recently, using a mouse model, the Pi’s Changes and mechanisms involved are equally laboratory has demonstrated that maternal diabetes or stressed. We have established already several hyperglycemia changes the expression levels of both collaborating centers in Southern China, which would the retinoic acid synthesizing and catabolizing be fully functional in the coming few years. enzymes in the embryo. (MD05911) However, whether retinoid infarct dementia, normal aging and homeostasis in the female reproductive system is altered under diabetes remains to be determined. The specific objectives of this project are to carry out 人鼠腦衰老同源靶點基因的確立及相關基因藥物 a detailed comparison of the temporal and spatial 治療研究 expressions of the various retinoic acid synthesizing Anti-Aging Drug Screening, Using Aging-Related and catabolizing enzymes, and retinoid binding Homologous Genes between Human and SAM proteins in the female reproductive system between Mice diabetic and non-diabetic mice: (i) at different stages 姚大衛 YEW Tai Wai David of the ovarian cycle; (ii) under hormonal induction; FENG Zhong Tang* 路鋼 LU Gang (Surgery) and (iii) during early pregnancy. Results of this project will provide fundamental 1 December 2005 information for future study to investigate the role of retinoid homeostasis in the conception and embryo Faculty of Medicine 188 Dept of Anatomy Kunming Medical University Natural Science 2003-04 Developmental Controls of Axon Patterning in the Retinofugal Pathway of Foundation of Yunnan of China Mouse Embryos (CU03417) 目前認為腦衰老引起的變化主要是由於神經遞質 CHAN Sun On 的釋放、突觸的可塑性以及囊泡的運輸能力等相關 基因表達變化引起的。本項目計劃利用我們已有 2005-06 Roles of Protein Kinase C Mediated 的,國際上唯一公認的衰老哺乳動物模型—快速老 Inhibitory Mechanisms on Patterning the 化小鼠(Senescence Accelerated Mouse, SAM)做如 Axon Orders in the Mouse Retinofugal 下研究﹕1. 在功能明確的人類腦衰老相關的 15 個 Pathway (CU05420) 調控神經遞質釋放、突觸可塑性以及囊泡運輸的基 CHAN Sun On 因范圍內,尋找認該品系小鼠腦和人類腦衰老變化 同時相的同源基因。2. 通過生物信息學分析,在 2003-04 Is Abnormal Sacral Neural Crest Cell 確認的同源基因中尋找 3~5 個最有可能與腦衰老 Migration to the Gut Involved in 有關的決定基因。3. 在体內和体外通過基因藥物 Aganglionosis : An Investigation Using (AVV/Lentivirous 介導的基因超表達技術或 RNA an Animal Model for Hirschsprung's 干擾技術)對籂選的決定性基因(Mrna)進行干預調 Disease (CU03418) 控,研究其與腦衰老的直接關系,評價基因孳物的 CHAN Wood 療效。 Yee Alan J. BURNS* 本研究將推動對老年病特別是大腦衰老病變的分 子機理的闡明及腦衰老相關基因藥物的研發。人鼠 2004-05 The Role of DOC-2 / Dab2 in the 腦衰老同源靶點基因的建立可提供一個腦衰老相 Prenatal Development of the Neocortex 關的基因治療或藥物治療的評價体系;該体系也可 (CU04262) 作為雲南省天然抗衰老藥物的可靠的基因調控水 CHAN Wood Yee 平籂選平台;利用該靶點基因建立起來的基因藥物 YEW Tai Wai David MOK Chi Ho Samuel* 治療方案有望進一步發展到臨床應用。 (BL05458) 2005-06 S100 Proteins and Brain Development (CU05421) Please refer to previous issues of this publication CHAN Wood Yee for more details of the following ongoing research HEIZMANN C W* YEW Tai Wai David at the department: 2005-06 The Origin, Lineage and Distribution of Edition Title/Investigators Microglial Progenitor Cells in the Prenatal Mouse (BL05804) 2005-06 Role of ERRs in the Development of CHAN Prostate Cancer (MD05888) Wood Yee REZAIE Payam* CHAN Leung Franky 2003-04 Does Deletion of Male Accessory Sex Glands Produce Heritable Changes in Spermatozoa? (CU03419) 189 Faculty of Medicine Dept of Anatomy CHOW Pak Ham Patricia Proliferation ANNE and Differentiation (MD05617) Ferguson-Smith* O Wai Sum* LEE Ka Ho Kenneth 2005-06 A Role for Mammalian Male Accessory CAI Dong Qing* Sex Glands on Uterine Receptivity (CU05422) 2004-05 Sources, CHOW Pak Ham Patricia Health O Wai Fates, Environmental Effects of Persistent and Toxic Substances from E-waste Recycling in Sum* Southeast China (BL03916) LIU Wing Keung Ken WONG Tze 2003-04 The Role of a Novel TNF-a Modulator Gene (BRE) in Acute Hepatitis Wai (Community (CU03421) Medicine) LEE Ka Ho Kenneth CHAN John* WANG Youfa* CHUI Yiu Loon (Clinical Immunology Unit) 2004-05 Proteomic Analysis of Differentially Death in CHAN Pui Ha* LUK John* ZHANG Ren Ji* Howan* Bruneau YU Linda W L* WU Mouse 2003-04 The (CU04265) Mechanism Susceptibility YUNG Kin Lam Tangchun* DU Ping* Embryonic Limb Interdigital Tissues LEE Ka Ho Kenneth Christian* Expressed Proteins during the Onset of Cell WONG M. H.* MAK Nai Ki* LEUNG Programmed Family Ken* WONG Ngok Shun Ricky* CHING Kar Keung (Anatomical & Cellular Pathology) and to of Increased Retinoic Acid Teratogenicity in Diabetic Pregnancy CAI Dong (CU03397) Qing* SHUM Sau Wun Alisa COPP A J* 2005-06 Cardiac Vascular Specific Peptide H1 Mediate Functional Angiogenesis in Gynaecology) Ischemic Heart (MD05533) LEE Ka Ho Kenneth Qing* CAI Dong LI Ming (Epithelial Cell Biology Research Centre) 2005-06 Role of Cyclin I, An Atypical Cyclin, in the Regulation Faculty of Medicine of WANG Chi Chiu (Obstetrics & Cardiomyocyte 190 Dept of Biochemistry (Medicine) experiments will be performed to assess the expression RESEARCH PROJECTS of GHR and PRLR in seabream tissues under various osmotic conditions, hi addition, the promoters of these Osmoregulatory Control of Growth Hormone genes will be cloned and studied in cultured fish cell Receptor and Prolactin Receptor Expression in lines to correlate with the gene expression data. These Seabream: studies will lead to the elucidation of responsive Gene Promoter Studies and elements on the gene promoters responsible for Identification of Cis-and Trans-acting Elements controlling the expression of these genes during CHENG Hon Ki Christopher osmoregulation in fish. Results obtained in the present CHAN Chi Bun study would shed Light on the participation of GHR and (Biochemistry (Science))# PRLR in this vital physiological process in teleost. 1 January 2007 (CU06418) Research Grants Council (Earmarked Grants) Osmoregulation is an important physiological process in The Presence of a Novel Prolactin Receptor in aquatic organisms. In fish, mechanisms have been Teleosts-functional Characterization and Gene evolved to cope with changes in the osmolarity of the Regulation of the Two Teleostean Prolactin aquatic environment. Receptors Among them growth hormone (GH) and prolactin (PRL) secreted from the pituitary play important roles. Changes in the expression levels CHENG Hon Ki Christopher of these pituitary hormones have been demonstrated in 1 March 2007 response to osmotic changes. CUHK Research Committee Funding (Direct These hormones elicit their biological actions via their respective receptors Grants) located on the target tissues. However, changes in the expression level of growth hormone receptor (GHR) and Prolactin (PRL) is a polypeptide hormone secreted prolactin receptor (PRLR) during osmotic changes in from the anterior pituitary of vertebrates. fish tissues have not been systematically studied. Our receptor (PRLR), a member of the cytokine receptor initial experimental data show that the expression of family, is present on the cell surface of target tissues GHR and PRLR in fish is concomitantly controlled for ligand recognition and signal transduction. during osmotic challenge. We hypothesize that this addition to the existing PRLR found in vertebrates, coordinate control of both the hormones and their we have discovered another novel PRLR in teleost receptors is part of the animal’s physiological response fish encoded by a separate gene. This phenomenon to salinity changes in the environment. This project of having two independent PRLRs encoded by two attempts to study the regulatory mechanisms in the separate genes was substantiated in different fish control of GHR and PRLR expression during osmotic species, namely Nile tilapia, black seabream, fugu challenge in black seabream. This fish species, widely and zebrafish. cultured in Hong Kong and nearby regions, is a good PRLRs in fish, amphibian, bird and mammals model for such studies because of its ability to tolerate demonstrated that two PRLRs co-existing in a single a wide range of salinities. species is a unique phenomenon for teleost. These In vitro and in vivo PRL In Phylogenetic tree constructed with two PRLR subtypes (the conventional one named as 191 Faculty of Medicine Dept of Biochemistry (Medicine) PRLR1, the novel one as PRLR2) feature the typical debilitating diseases. There are currently 19 long form of mammalian PRLRs, especially in their FDA-approved therapeutic antibodies on the market, extracellular regions and the conserved motifs in the more than 150 are being critically evaluated by intracellular regions. However, despite their overall companies located worldwide [Nature Biotechnology structural similarity, the two PRLR subtypes share 23 (2005): 1073]. very low amino acid similarities (about 30%), mainly reengineering technologies such as chimerization and due to several deletions in the intracellular region of humanization are considered crucial for the clinical PRLR2. A tissue distribution study by real-time success of therapeutic antibodies. However, these PCR in black seabream exhibited that both receptors technologies are extensively patent-protected, making (sbPRLRl and sbPRLR2) were widely expressed in the entry barrier prohibitive for biotech start-ups. different tissues. In gill, the expression level of Based on a novel technology developed in our group sbPRLR2 is much higher than sbPRLRl. However, (US Patent Application Number 10/880238), we have in heart and spleen, sbPRLR2 was not detected at all. derived a novel and improved approach in reducing In this project we plan to functionally express the the immunogenicity of murine antibodies. cloned sbPRLRl and sbPRLR2 cDNA sequences in successful establishment of the platform will allow cultured eukaryotic cells and to study their signal HK and China-based companies to enter the global transduction mechanisms. Their regulation of gene antibody industry with competitive technologies. A expression in vitro and in vivo will also be China-based investigated. Also, we have already cloned the interested in the technology and agrees to sponsor the promoter regions of these two PRLRs and a detailed research with the provision of a well-characterized, characterization of their promoter activities will be proprietary chimeric therapeutic antibody targeting performed in response to various hormonal stimuli. TNFalppha for proof of concept studies. (MD06460) therefore aim to: (1) generate a clinically useful The advent of antibody therapeutic antibody company The is We anti-TNFalpha antibody with substantially reduced Antibody immunogenicities that eventually will go into clinics; Reengineering Platform Technology (Framework (2) establish a platform comparable to existing Casting) for Reducing the Immunogenicity of antibody Therapeutic Antibodies dissemination to industries located locally, in China, Establishment of an Improved humanization technologies for or globally CHEUNG Wing Tai (BL06395) LEE Sau Tuen Susanna (Biochemistry (Science)) YY1-and 1 March 2007 ATF4-mediated Control of Apolipoprotein E Gene Transcription ITF - Guangdong-Hong Kong Technology Cooperation Funding Scheme (Platform HO Yuanyuan WONG Kam Bo (Biochemistry Research Scheme) Lonn Ryonn Pharma Ltd (Science)) Sino Mab BioScience Ltd 30 June 2007 Therapeutic antibodies have constituted one-third of biologics approved for treating cancers and other Faculty of Medicine 192 Dept of Biochemistry (Medicine) 30 June 2007 CUHK Research Committee Funding (Direct Grants) CUHK Research Committee Funding (Direct Grants) Altered plasma apoE protein level is a risk factor for coronary heart disease (CHD) and Alzheimer’s The intent of the proposed research is to isolate and disease (AD). characterize In addition, single nucleotide laccases from wild mushrooms. polymorphisms (SNPs), i.e. -491A/T and -219 G/T in Mushrooms have proven to be rich sources of the APOE gene promoter have been shown to modify important natural products and are often dietary the risk of AD and CHD. These observations lead components in the Chinese population. to the speculation that the association between APOE mushroom species selected are wild mushrooms that promoter SNPs and disease risks is related to changes have been claimed to have health promoting effects. of APOE gene transcription activity and the They are available at affordable prices and have subsequent protein expression level. Our overall started to become popular. Laccases are enzymes objective is to understand the control mechanism of responsible for lignin degradation and thus important APOE gene transcription. By yeast one-hybrid to the saprophytic mode of life of fungi and are screening of the human brain cDNA library using the potentially useful for biotechnological applications polymorphic DNA sequences spanning APOE e.g. for biocatalytic purposes such as delignification promoter -491 polymorphic site as the ‘baits’, we of have identified ATF4 and YY1 being the interacting polysaccharides, for bioremediation such as waste transcription factors at this region. We have detoxification and textile dye transformation, for use demonstrated the active role of ATF4 in regulating in food technological, for personal and medical care APOE gene transcription. In this proposed project, applications and for biosensor and analytical we plan to achieve three specific aims: 1. To confirm purposes. the physical interaction between APOE promoter and subject YY1; 2. To confirm the functional effects of YY1 on extensively studied before and the wild mushroom APOE promoter activity and endogenous APOE gene species that we propose to work on are essentially expression; and 3. To study the interactive effect of unexplored. The YY1 and ATF4 on apoE gene expression. Based on lipid-lowering drug the reported association between APOE promoter immunoenhancing polysaccharopeptide from the SNPs mushroom Coriolus versicolor are but a few examples with human diseases, elucidating the lignocellulosics and The cross-linking of The mushroom proteins that are the of this investigation antibiotic have not been penicillin, lovastatin, and the the mechanism of transcription control of the APOE of fungal products beneficial to man. gene may inspire new ways to neutralize disease that novel and useful compounds for therapeutic and risks by normalizing plasma apoE level. industrial applications can arise from this proposed (MD06653) investigation on wild mushrooms. It is hoped (MD06720) Isolation and Characterization of Mushroom Laccases Molecular Epidemiology of HIV in Hong Kong NG Tzi Bun 193 Faculty of Medicine Dept of Biochemistry (Medicine) TSUI Kwok Wing (Medicine & Therapeutics) (Stanley Ho CEID) TSUI Kwok Wing SUNG Joseph Jao Yiu (Biochemistry (Science)) LEE Shui Shan TSANG Suk Ying CHIM Siu Chung Stephen (Obstetrics & Gynaecology) CHAN Kay Sheung Paul (Microbiology) YU Chun Ho Simon* 1 June 2007 1 October 2006 CUHK Research Committee Funding (Direct Council for the AIDS Trust Fund Grants) Molecular epidemiology is an important aspect of In the course of postnatal myocardial development, public health HTV medicine. The determination of cardiac myocytes convert from hyperplastic to the subtype, mutation patterns and their evolution hypertrophic growth. In the rat, myocytes lose their could inform public health authorities of the ways capacity to replicate after about two weeks, and different HTV strains are originated and spreading in myocardial growth from this point forward is a population. Therefore, molecular epidemiological primarily due to hypertrophy of existing myocytes. investigation is expected to provide information In contrast to the relatively well characterized critical for the prevention of local HIV spread. To possess date, no full-length genome of HTV isolates from investigations Hong Kong has been sequenced for reference, nor that control myocyte hypertrophy, focused on determining mechanisms regulating the has molecular virology been examined to plot the proliferation during path of virus dissemination. With the increasing development are limited. We previously identified interaction between the populations in Hong Kong a pool of differentially expressed genes in rat and Mainland, HIV epidemiology would likely neonatal hearts. evolve along new paths, a phenomenon different in DNA methylation and chromatin remodeling from that of importing virus from South East Asia processes. and western countries in the eighties and nineties. methylation-sensitive-representational The aim of this project is to study the molecular analysis method, we have performed a genome-wide epidemiology of HIV infection by analyzing the search for differentially methylated genes between full-length genome sequences of HIV isolates day 1 and day 14 neonatal rat hearts. In this project, collected in Hong Kong. At least 30 samples in more candidate genes will be isolated from the different categories according to the routes of subtractive cDNA library and the methylation status transmission will be analyzed. These sequences of candidate genes during neonatal heart development may serve as an important reference for the future will be validated by bisulfite sequencing technique molecular epidemiological study of HIV in Hong and 5-azacytidine treatment. We believe the genes Kong. identified in this project are important candidates for (MD06661) future studies on the terminal differentiation of loss postnatal of the myocyte myocardial Many of these genes are involved Using the difference cardiomyocytes. (MD06923) Identification of Methylated Genes Involved in the Terminal Differentiation of Cardiomyocytes A Proteomic and DNA Microarray Analysis on Serum Proteins and Heart Muscle after Chronic Faculty of Medicine 194 Dept of Biochemistry (Medicine) Infusion of a TCM Formula (Cenqi Fuzheng Injection 參芪扶正注射液) in an Ischemic Animal Edition Title/Investigators Model 2004-05 Molecular Mechanism of Prolactin Gene WAN Chi Cheong David (Biochemistry (Science)) Regulation in Fish (CU04410) SHAW Pang Chui FUNG Kwok Pui CHAN King Ming KWAN Yiu Wa (Pharmacology) CHENG Hon Ki Christopher 1 September 2006 2005-06 Regulation Livzon Pharmaceutical Group Inc of Metallothionein Gene Expression in Zebrafish (MD05355) CHAN King Ming The project objectives have two specific aims: 1. 2. To provide a comprehensive and global analysis of the protein expression profiles of serum 1990-91 Comparative Endocrinology of Prolactin, proteins in an ischemic animal model after TCM Growth Hormone, and Their Receptors infusion. (BP88031) To identify target gene candidates for the effect CHENG Hon Ki Christopher of TCM by the analysis of a differential RNA Tzi Bun expression profile through DNA microarray. (Physiology) NG WONG Chun Cheung (MD06841) 2002-03 Identification and Development Oxidase Inhibitors of Biochemical Analysis of Chinese Medicine : Xanthine from Establishment of Quality Assurance Chinese Medicinal Natural Products with Therapeutic Potentials (CU02269) CHENG Hon Ki Christopher WAN Chi Cheong David FUNG Kwok Pui 1 February 2007 偉信(香港)貿易有限公司 2005-06 Regulation of Growth Hormone Receptor This project aims at the establishment of quality and Prolactin Receptor Gene Expression assurance of TCM formula manufactured and traded during Osmolarity Changes in Seabream from Wilson Trading Ltd. We will use an array of (MD05638) biochemical and chromatographic techniques to CHENG Hon Ki Christopher identify key constituents from the herbs as indicated 2005-06 Construction and Evaluation of A ScFv from the specifications of the TCMs. Antibody-Based (BL06690) Immunotoxin Tumour-Activated for Cancer Please refer to previous issues of this publication (MD05691) for more details of the following ongoing research CHEUNG Wing Tai Therapy at the department: 195 Faculty of Medicine Dept of Biochemistry (Medicine) 2003-04 Bioassay-Guided Apolipoprotein E Gene Transcription Isolation, Characterization, and Mechanistic Study (BL05979) of the Bioactive Components from HO Yuanyuan Paeonia Lactiflora, Sophora Flavescens, Oldenlandia Diffusa and 2004-05 Riboregulator Scutellaria Modulation of Drug Barbata for the Anti-Proliferative Effect Resistance in Human Cancer Cells on Human Hepatoma Cells In Vitro (CU04270) (CU03399) KWOK Tim Tak FUNG Kwok Pui (Biochemistry (Science)) MAK Thomas Chung Wai (Chemistry) TSUI Kwok Wing KONG Siu Kai (Biochemistry (Science)) KONG Siu Kai 2005-06 Regulation of Therapeutics Induced Apoptosis in Human Cancer Cells by an WAYE Mary Apoptotic Factor on Chromosome 1q Miu Yee (CU05428) KWOK Tim Tak 2004-05 Immunomodulatory Activities of Herbal Formulate 'Kwan Du Bu Fei Dang' in Healthy Subjects: A KONG Siu Kai (Biochemistry (Science)) Randomized Double-Blind Placebo-Controlled Study 2004-05 Biological Characterization of Recently (MD04432) Reported New Classes of Ribosome FUNG Kwok Pui Chung (Institute Medicine) LEUNG Ping Inactivating Proteins (CU04272) of NG Tzi Bun WANG Hexiang* Chinese TSUI Kwok Wing WAN Chi Cheong David Mary Miu Yee Pathology) Christopher AU 2005-06 Isolation WAYE Human LAM of Immunodeficiency Virus NG Tzi Bun Ngor Shannon (Biochemistry (Science)) Characterization Enzymes from Edible Fungi (MD05977) (Chemical Wing and Compound(s) with Inhibitory Effects on WONG Chun Kwok (Chemical Pathology) Wai Kei 2005-06 The Role of Four and a Half LIM LAU Bik San Clara (School of Domain Protein 2 in the Regulation of Pharmacy) Interleukin-6 Expression in Cardiac and Skeletal Myocytes (MD05775) 2005-06 Treatment of Breast Tumors by Arsenic TSUI Kwok Wing Trioxide (MD05324) FUNG Kwok Pui 2003-04 Promoter Polymorphism-Mediated WAN Chi Cheong David Nucleotide Control of Wah-keung (Science))# Faculty of Medicine of Chicken Acetylcholinesterase Gene (CU03311) 2005-06 Dissecting the Molecular Mechanism of Single Analysis 196 Karl TSIM (Biochemistry Dept of Biochemistry (Medicine) WAN Chi Cheong David 2005-06 Molecular and Crystallographic Characterization of a Novel Orange 2005-06 To Study the Mechanism of Action of the Fluorescent Protein from Cerianthus sp. RhoC in Metastasis of Liver Cancer Cells (CU05571) (BL05383) WAN Chi Cheong David WAYE Mary Miu Yee WONG Kam Bo (Biochemistry (Science)) 2005-06 Biochemical Medicine: Analysis Establishment of of Chinese Quality Assurance (BL05378) 197 Faculty of Medicine Dept of Chemical Pathology work to further explore the biological and molecular RESEARCH PROJECTS characteristics of circulating placental-expressed mRNA transcripts which may have both biological Biological and Molecular Characterisation of and practical implications on the field. The Placental-expressed mRNA in Maternal Plasma characteristics to explore include the effects of different centrifugation speeds on the recovery and the differential distribution of both particle- and CHIU Wai Kwun Rossa LO Yuk Ming Dennis LAU Tze Kin (Obstetrics & Gynaecology) non-particle-associated placental expressed mRNA in maternal plasma; to develop genotyping methods to TSUI Bo Yin Nancy confirm 1 October 2006 the fetal origin of the placental-expressed transcripts in maternal plasma; Research Grants Council (Earmarked Grants) and to investigate if placental gene expression is The quest for methods for non-invasive prenatal affected by allele-specific gene expression. diagnosis and pregnancy monitoring has been a (CU06433) long-sought goal in obstetrical care. detected Prenatal diagnostic methods in current use rely on the Whole-Genome Linkage Analysis for Mapping a sampling of genetic material from the baby via means New such as amniocentesis or chorionic villus sampling. Hypocalcemia By virtue of their invasive nature, these methods are Single-Nucleotide Polymorphism Microarray Locus for Autosomal Using Dominant High-Density associated with a risk of spontaneous miscarriage. The recent discovery of the presence of fetal DNA in LAM Ching Wan the maternal circulation offers exciting opportunities 1 January 2007 for the development of safe methods for prenatal Research Grants Council (Earmarked Grants) assessment based solely on the collection of a blood sample from the mother. The However, as fetal DNA is system governing extracellular calcium mixed with a high background of maternal DNA in homeostasis maintains a stable extracellular calcium maternal plasma, the number of fetal-specific DNA concentration so as to ensure continual availability of markers available has been limited. Thus, the calcium ions for their numerous physiological roles. alternative use of fetal RNA markers was explored. The calcium-sensing receptor (CASR) functions as a In this regard, our group has demonstrated that genes sensor for parathyroid and kidney to determine the expressed by the placenta are detectable in maternal extracellular calcium concentration and thus helps to plasma and are pregnancy-specific. maintain a stable calcium concentration. To fully Patients appreciate the clinical utility and potential practical with activating CASR mutations present with limitation autosomal of the use of circulating dominant hypocalcemia (ADH; placental-expressed mRNA for prenatal assessment, OMIM#601198). Through our continuing interests we have previously studied a number of basic in studying the molecular basis of genetic diseases in biological characteristics of such markers. In the Hong Kong Chinese, we have identified a Chinese present study, we propose to extend on the promising family with 11 family members with ADH but without CASR mutation and without linkage to the Faculty of Medicine 198 Dept of Chemical Pathology CASR locus. (1) adhesion of human mast cells onto human The clinical features and biochemical BEAS-2B bronchial epithelial cells; findings of this family are identical to caused by We suggest that ADH in this (2) expression of chemokines RANTES, MIG, MCP, family is caused by mutation of a novel gene. IL-8, IP-10, MDC and TARC in co-cultures of Based on our experience in using high-density mast cells and BEAS-2B cells; and CASR mutations. in (3) release of cysteinyl leukotrienes, prostaglandin mapping disease loci, we propose to perform a E2 from mast cells, and cell surface expression of whole-genome linkage analysis for mapping the trait adhesion molecule ICAM-1, -3 on mast cells and locus of this ADH family. Identification of this BEAS-2B gene will improve our understanding of the molecular co-culture. single-nucleotide basis for polymorphism regulation of microarrays extracellular calcium 2. cells Relationship upon between their interaction in the activation of concentration; the insights gained will provide new intracellular signaling molecules ERK, JNK, p38 leads for finding drugs for clinical disorders related to MAPK, JAK-STAT, PI3K-AKT and NF-ΚB with calcium metabolism. the adhesion and expression of ICAM-1, -3, and (CU06435) release of chemokines, cysteinyl leukotrienes and prostaglandin E2 in co-cultures of mast cells and BEAS-2B cells. Adhesion between Mast Cells and Epithelial Cells: 3. Regulatory Mechanisms for the Release of Chemokines, Cysteinyl Leukotrienes Specific inhibitors of ERK, JNK, p38 MAPK, JAK-STAT, PI3K-AKT and NF-KB on adhesion, and expression of ICAM-1, -3, and the release of Prostaglandin in Allergic Inflammation chemokines, LAM Wai Kei Christopher cysteinyl leukotrienes and prostaglandin E2 in co-cultures of mast cells and WONG Chun BEAS-2B cells. Kwok This basic study should advance our knowledge on 1 January 2007 the immunopathogenesis of mast cell- mediated Research Grants Council (Earmarked Grants) allergic inflammation, and provide a biochemical Allergic diseases such as allergic asthma have been basis for the development of a new treatment strategy prevalent and increasing in Hong Kong and of interrupting mast cell-epithelial cell interaction in worldwide. allergy. Mast cells are the principal effector cells of IgE-mediated hypersensitivity. (CU06434) Activated airway epithelial cells are potent sources of cytokines and chemokines. The interaction of human mast Activation of Human Eosinophils by Mast cells with lung fibroblasts can induce the release of Cell-derived Chymase: Implication in Allergic inflammatory cytokines and chemokines in co-culture. Inflammation This project proposes to study the following using LAM Wai Kei Christopher co-culture of human mast cells and bronchial epithelial cells: 1. WONG Chun Kwok Effects of mast cell activators SCF and TNF-α 1 March 2007 on: 199 Faculty of Medicine Dept of Chemical Pathology CUHK Research Committee Funding (Direct Study of Patterns of Drugs of Abuse in New Grants) Territories East Cluster Drug of Abuse Clinic Using Conventional and New Technologies Allergic diseases such as allergic rhinitis, asthma and atopic dermatitis are associated degranulation of mast cells. with the LAM Wai Kei Christopher Release of different TANG Alan* cytokines, chemokines and other inflammatory upon The degranulation. particular, eosinophils: ( 1 ) (i) apoptosis; (ii) induction of youngsters. (iii) cell surface expression of adhesion molecules urine (CD54) and leukocyte function-associated antigen young population. Traditionally, psychiatrists rely very samples monitoring. eosinophil for diagnosis and therapeutic However, existing methods using immunoassay degranulation for the release of eosinophilic cationic and high-performance liquid chromatography with ultraviolet detector (HPLC-UV) protein (ECP) and superoxides. (2) Relationship for the detection of abused drugs have many between chymase mediated activation of intracellular limitations including lack of sensitivity, specificity, signaling molecules extracellular signal-regulated and the requirement of a known drug library or pure protein kinase (ERK), c-Jun amino-terminal kinase standards (JNK), p38 mitogen activated protein kinase (p38 for investigation, MAPK), Janus kinase-signal transducer and activator (JAK-STAT) our much on the detection of these substances in patients’ such as intercellular adhesion molecule (ICAM)-1 factor amongst contaminants that impose additional health hazards to (GRO)-α, monocyte chemoattractant protein (MCP)-l; transcription increasing manufacturing practice may introduce impurities or and chemokines IL-8, growth related oncogene of and Manufacture of the abused drugs without good inflammatory cytokines IL-1β, IL-6, IL-10, TNF-α (iv) pattern control, and clinical management of this problem, in following effects of mast cell-derived chymase on and changing in a community-wide concern for better detection, The project will study the CD1la/CD18); rapidly psychotropic substances in Hong Kong have resulted between mast cells and eosinophils have not been (LFA, HO Chung prevalence of abusing conventional and novel Immunological mechanisms for the interaction elucidated clearly. Beat Drugs Fund mast cell granules, which plays certain roles in inflammation TSUI Kam Chi 1 May 2007 Mast-cell specific protease chymase is a major component in allergic CHAN Ho Ming Shun LAW Lap Kay mediators by mast cells activates other immune effector cells to elicit allergic symptoms. novel drugs leading to ultra-performance phosphoinositide 3-kinase (PI3K)-AKT, and nuclear time-of-flight factor-κB (NF-κB) with apoptosis, degranulation, (UPLC-TOF/MS) expression of cytokines, chemokines and adhesion and chromatography spectrometric allow the Recent advances in liquid mass hinders mis-diagnosis under-reporting of the problem. and that target technique screening and confirmation of conventional as well as novel drugs molecules of eosinophils. without the need of pure standard as well as (MD06690) improved sensitivity and specificity. These advantages will greatly enhance the detection rate of conventional and novel drugs. Faculty of Medicine 200 Dept of Chemical Pathology (MD06983) Development of an Accurate Blood Test for the Detection and Monitoring of Hepatocellular Carcinoma Investigation into the Possible Passage of DNA from Plasma into Urine Using a Sex-Mismatched LO Yuk Ming Dennis Bone Marrow Transplantation Model CHAN Kwan Chee DING Chunming (Stanley Ho CEID) LO Yuk Ming Dennis CHAN Lik Yuen Henry (Medicine & Therapeutics) CHIK Ki Wai (Paediatrics) LAI Bo San Paul (Surgery) MOK Shu Kam Tony (Clinical Oncology) 1 August 2006 1 September 2006 Research Grants Council (Earmarked Grants) Innovation and Technology Support Programme, Recently much interest has been focused on the ITF, Innovation & Technology Commission biology and diagnostic applications of cell-free DNA in plasma. One group of investigators (Botezatu et Hepatocellular carcinoma (HCC) is particularly al) have made an interesting suggestion that a prevalent in Hong Kong and China because of the proportion of plasma DNA might pass through the high chronic hepatitis carrier rate in our locality. kidney barrier and may become detectable in the Unfortunately only a small proportion of the HCC urine, the so-called transrenal DNA hypothesis. In patients are qualified for curative intent therapies at particular, these investigators have presented data presentation because HCC is typically asymptomatic showing that fetal DNA can be detected in the urine until an advanced stage. of pregnant women and oncogene mutations from strong clinical demand for an accurate marker for the colorectal cancer can be detected in the urine of such early detection of HCC. cancer patients. While some investigators were able extensively to replicate these findings, controversy starts to arise fetoprotein, is only raised in half of the HCC patients. when other researchers were unable to reproduce In this project, we propose to develop a new marker these results. The potential importance of transrenal for the detection and monitoring of HCC based on the DNA with regard to development of non-invasive detection of tumor-derived aberrantly methylated molecular diagnostics and its biological implications DNA. Furthermore, the proposed technology can has prompted us to further explore this phenomenon. be applied for the detection of virtually all types of In a previous study, our group has shown that in cancers. sex-mismatched bone marrow transplantation (BMT), pioneered researches on the diagnostic applications the recipient’s plasma takes on the ‘gender’ of the of circulating nucleic acids for cancer detection and donor. prenatal diagnosis. This observation suggests that used HCC Therefore, there is a However, the most marker, serum alpha Over the last decade, our group has This project would further haematopoietic cells are the predominant source of consolidate the position of Hong Kong in the arena of plasma DNA in this model. We hypothesize that biotechnology research. this BMT system would be a powerful system for (MD06754) studying transrenal DNA. (CU06436) Development of Placental-specific Reference Transcripts in Maternal Plasma 201 Faculty of Medicine Dept of Chemical Pathology LO Yuk Ming Dennis (Obstetrics & Gynaecology) TANG Leung Sang Nelson LAU Tze Kin HO CHAN LEUNG Tse Suzanne (Community and Family Medicine) Ngong (Obstetrics & Gynaecology) CHIU Wai TO Ka Fai (Anatomical & Cellular Pathology) Kwun Rossa TSUI Bo Yin Nancy YEO Winnie (Clinical Oncology) CHU Chiu Wing Winnie (Diagnostic Radiology & Organ 29 June 2007 Imaging) CUHK Research Committee Funding (Direct WOO Jean (Medicine & Therapeutics) Grants) 1 January 2007 Non-invasive prenatal detection of fetal trisomy 21 Research Grants Council (Earmarked Grants) could potentially be achieved by measuring the maternal plasma concentration of a Blood level of IGF1 is influenced by both genetic and placental expressed mRNA which is pregnancy-specific and environmental factors. transcribed from chromosome 21. Theoretically, an reduces blood IGF1 concentration. elevation of the chromosome-21 derived mRNA hand, expression of IGF1 is also genetically would be expected in trisomic pregnancies due to programmed. transcription of the extra copy of the gene. However, (up to 70%) of IGF-1 between sibs and twins had this method has been shown to demonstrate large been demonstrated. degrees of overlap in the plasma placental mRNA bioactivity of IGF1 is determined by some, yet to concentrations between the trisomic and the euploid define, functional polymorphisms in the IGF1 pregnancies. We hypothesized that this overlap was promoter, which affects the expression of IGF1 gene due to a wide distribution in the transcript and in turn, its production and blood concentration, concentration as a result of the biological variation in and related intermediate phenotypes. plasma RNA abundance among different individuals. As the roles of regulatory elements (such as To improve the performance of the test, we propose to transcription factor binding sites) and sequence control for such individual variation by normalizing polymorphisms in promoter of IGF1 in regulation of the level of the chromosome-21 derived mRNA with blood IGF1 level was not fully understood. a reference transcript. In this study, we plan to Therefore, we proposed (A) To define the functional study three potential placental-specific reference polymorphisms in the human IGF1 promoters (B) To transcripts in maternal plasma. correlate the functional polymorphisms with two We also plan to For example, malnutrition On the other A remarkable degree of heritability Therefore, we hypothesize that investigate the chromosome-21 derived transcript clinical endophenotypes levels in maternal plasma of the trisomy 21 and the (CU06437) euploid pregnancies with our normalisation strategy. (MD06485) Activation of Human Eosinophils by a Novel T Helper Type 2 Cytokine IL-33: Implication in Search for Functional Polymorphisms in IGF1 Allergic Inflammation Promoters and the Link with Intermediate WONG Phenotypes of Breast Cancer in a Cohort of 800 Christopher Women Faculty of Medicine Chun 202 Kwok LAM Wai Kei Dept of Chemical Pathology 25 June 2007 intervention for the treatment of Th2 mediated allergic CUHK Research Committee Funding (Direct diseases such as allergic asthma. (MD06371) Grants) Allergic diseases such as allergic asthma and allergic Please refer to previous issues of this publication rhinitis are prevalent and have been increasing in for more details of the following ongoing research Hong Kong. Allergic asthma is characterized by the at the department: activation, accumulation and degranulation eosinophils in inflammatory sites. of Interleukin Edition Title/Investigators (IL)-33 is the most recently discovered T helper (Th)2 cytokine which cause severe pathological changes in 2004-05 Serial Analysis of the Molecular Size of the lungs and gastrointestinal tract, including Plasma Epstein-Barr Virus and Genomic eosinophilic and mononuclear infiltrates, increased DNA mucus production, and epithelial cell hyperplasia and Nasopharyngeal hypertrophy. We plan to study the following: (1) (CU04276) Effect of IL-33 on (i) apoptosis; (ii) induction of CHAN Kwan Chee during Radiotherapy Carcinoma inflammatory cytokines IL-1β, IL-6, IL-10, TNF-α Dennis and chemokine IL-8, growth related oncogene Cheung (Clinical (GRO)-α, monocyte chemoattractant protein (MCP)-l LEUNG Sing and Oncology) regulated upon activation normal T-cell in Patients LO Yuk Ming CHAN Anthony Tak Oncology) Fai (Clinical expressed and secreted (RANTES); (iii) cell surface expression of adhesion molecules such as intercellular 2005-06 Investigation of the Integrity of adhesion molecule (ICAM)-l (CD54) and leukocyte Circulating Cell-Free RNA in the Plasma function-associated antigen (LFA, CDlla/CD18); and of Pregnant Women (MD05648) (iv) cell migration of human eosinophils. (2) CHAN Kwan Chee LO Yuk Ming Relationship between IL-33-mediated activation of Dennis intracellular (Obstetrics & Gynaecology) signaling signal-regulated protein molecules kinase extracellular (ERK), c-Jun LEUNG Tse Ngong LAU Tze Kin (Obstetrics & Gynaecology) amino-terminal kinase (JNK), p38 mitogen activated protein kinase (p38 MAPK), Janus kinase-signal 2003-04 Non-Invasive Prenatal Diagnosis of β transducer and activator of transcription factor -thalassaemia through Maternal Plasma (JAK-STAT), Analysis: A Multi-Centre Collaborative phosphoinositide 3-kinase (PI3K)-AKT, and nuclear factor (NF)-ΚB with Study (CU03395) apoptosis, cell migration, expression of cytokines, CHIU Wai Kwun Rossa chemokines and adhesion molecules of eosinophils. Chong* This study will advance our knowledge on the LAU immunopathogenesis upon the interaction of IL-33 Gynaecology) CHAN Li CHUI David H.K.* Tze Kin (Obstetrics & LEUNG Tse Ngong and eosinophils in allergic inflammation and provide a biochemical basis for the development of therapeutic 203 Faculty of Medicine Dept of Chemical Pathology (Obstetrics & Gynaecology) 2005-06 Adhesion LO between Mast Cells and Epithelial Cells: Regulatory Mechanisms Yuk Ming Dennis for the Release of Chemokines and Cysteinyl 2004-05 Quantitative Aberrations in Circulating Leukotrienes in Allergic RNA in Maternal Plasma: Clinical and Inflammation (MD05806) Biological Implications in Preeclampsia LAM Wai Kei Christopher WONG (CU04277) Chun Kwok CHIU Wai Kwun Rossa Ming Dennis (Obstetrics LO Yuk 2001-02 Development of Genomic Strategies for LAU Tze Kin & Gynaecology) the Non-Invasive Detection of Down LEUNG Tse Ngong (Obstetrics & Syndrome (MD01862) Gynaecology) LO Yuk Ming Dennis Kwun Rossa 2005-06 Investigation Relationship of the between Quantitative Fetal LAU Tze Kin Nucleic 2003-04 A Centre for the Study of Fetal Nucleic Growth (CU05434) Acids in Maternal Plasma (MD03672) CHIU Wai Kwun Rossa Ming Dennis LO Yuk Ming Dennis LO Yuk Gynaecology) Gynaecology) (Obstetrics Michelle TSUI Hang Yuet (Obstetrics LEUNG Tse Ngong (Obstetrics & Gynaecology) LAU Tze Kin (Obstetrics & Gynaecology) LAU Tze Kin & LEUNG Tse Ngong (Obstetrics & & WONG Hing Nam & Gynaecology)# CANTOR Charles* Gynaecology) HUANG H M Tim* CHIU Wai Kwun Rossa 2004-05 Global Gene-Expression Analysis and Functional CHIU Wai (Obstetrics & Gynaecology) Acids in Maternal Plasma and Fetal (Obstetrics Clustering in 2004-05 Development of Maspin as an Epigenetic Sporadic Fetal DNA Marker in Maternal Plasma Basal-Cell Carcinoma of the Skin in for All Pregnancies (CU04279) Chinese LO Yuk Ming Dennis Using High-Density Oligonucleotide Arrays (CU04278) Kwun Rossa LAM Ching Wan (Obstetrics & CHIU Wai LAU Tze Kin Gynaecology) LEUNG Tse Ngong (Obstetrics & 2005-06 Whole Genome Scan of Genetics Gynaecology) Susceptibility for Hepatitis B Carriers CHIM Siu Chung Stephen (Obstetrics & Gynaecology) (MD05482) LAM Ching Wan 2004-05 Investigation on the Origin, Molecular CHAN Kay Characteristics and Clearance of Plasma Sheung Paul (Microbiology) Nucleic Acids in Nasopharyngeal Carcinoma Patients (MD04617) Faculty of Medicine 204 Dept of Chemical Pathology LO Yuk Ming Dennis Kwan Chee Cheung Activity CHAN (Clinical Oncology) Lymphocytes PANESAR Nirmal Singh LEUNG Sing Fai (Clinical Oncology) Mouse (MD05931) CHAN Anthony Tak in CHAN Kam Wing LO Kwok Wai (Anatomical & 2005-06 Genetic Cellular Pathology) Studies of Tuberculosis: Analysis of Tuberculosis Susceptibility 2005-06 Methylation Analysis of the RASSF1A Genes in the Chemokine-Genes Cluster Gene in the Placenta and in the Plasma of Region of Chromosome 17 in Chinese Pregnant Women (CU05437) (MD05978) LO Yuk Ming Dennis Chung Stephen Gynaecology) Rossa TANG Leung Sang Nelson CHIM Siu (Obstetrics & Jenefer M. Blackwell* LEUNG Tse Ngong (Obstetrics & Gynaecology) 2005-06 Molecular LO Epidemiology Kwok Wai (Anatomical & Cellular 5a-reductase Pathology) Metabolic WONG Hing Nam LEUNG Chi Chiu* TAM Cheuk Ming* LAU Tze Kin (Obstetrics & Gynaecology) CHAN Chiu Yeung Raphael (Microbiology) CHIU Wai Kwun and of Other Genes in Steroid Androgen Hepatocellular Carcinoma among Chinese Male Patients (Obstetrics & Gynaecology)# (CU05439) TANG Leung Sang Nelson 2005-06 Centre for Research into Circulating CHAN Fetal Nucleic Acids (MD05394) Ka Leung Francis (Medicine & LO Yuk Ming Dennis Therapeutics) Kwun Rossa CHIU Wai MicroRNAs of in 2005-06 The Association of Pharmacogenetics Plasma and Chemotherapy-Induced Toxicities in (MD05440) Breast LO Yuk Ming Dennis Chung Rossa Cancer Patients Receiving Chemotherapy (MD05817) CHIM Siu & TANG Leung Sang Nelson CHIU Wai Kwun Winnie (Clinical Oncology) Stephen Gynaecology) LAI Bo San Paul (Surgery) Fetal-Specific Maternal CHAN Lik Yuen Henry (Medicine & Therapeutics) LAU Tze Kin (Obstetrics & Gynaecology) 2005-06 Identification (Obstetrics YEO Eosinophils and LAU Tze Kin (Obstetrics & Gynaecology) 2004-05 Adhesion DING Chunming (Stanley Ho CEID) Epithelial LEUNG Tse between Cells: Its Regulatory Mechanism for Eosinophil Degranulation Ngong (Obstetrics & Gynaecology) and the Expression of Cytokines and Leukotrienes in Allergic Inflammation 2005-06 Effects of Glucocorticoids and Stress on Telomere Length and (CU04281) Telomerase 205 Faculty of Medicine Dept of Chemical Pathology WONG Chun Kwok Immune Response and Exacerbation of LAM Wai Allergic Inflammation (MD05721) Kei Christopher WONG Chun Kwok 2005-06 Intracellular Mechanisms Signal Transduction Regulating Receptor-Mediated Kei Christopher Toll-Like Activation of Eosinophils: A Link between Innate Faculty of Medicine 206 LAM Wai Dept of Clinical Oncology inducible factor-1 inhibitors) in NPC; (2) the effect of RESEARCH PROJECTS combining hypoxia targeting agent with radiation in NPC; and (3) the molecular interactions of hypoxia Targeting Hypoxia and the Epidermal Growth and anti-EGFR agents in NPC. Eventually, we aim Factor to: (a) develop novel strategies of combining agents Receptor (EGFR) Pathways in targeting hypoxia /EGFR pathways with radiation in Nasopharyngeal Cancer NPC; CHAN Anthony Tak Cheung HUI Pun MA Buig Yue Brigette (b) identify tissue biomarkers as pharmacodynamic endpoints for future clinical study. (CU06442) SUNG Lan (Hong Kong Cancer Institute) TAO Qian and HARRIS [An Adrian L* Open-label Study of Bevacizumab (AVASTIN®) Plus Taxane Monotherapy or in 1 January 2007 Combination for the First-line Treatment of Research Grants Council (Earmarked Grants) Patients with Locally Recurrent or Metastatic Nasopharyngeal cancer (NPC) is the most common Breast Cancer (ATHENA-Avastin THErapy) for head and neck cancer in Hong Kong and southern Advanced Breast Cancer] China. Our group has previously demonstrated HO Wing Ming improved survival when cisplatin is combined with YEO Winnie CHAN Tung Ching* concurrent radiation in the primary treatment of NPC. We have studied the expression of hypoxia markers 15 January 2007 in NPC biopsies and established the clinical Roche Hong Kong Limited significance of tumor hypoxia in relation to treatment outcomes after radiotherapy in NPC. This study is a multi-center study with 400 centres We further the from worldwide. The primary objective is to assess mechanisms of hypoxia induced gene expressions in the safety profile and efficacy of bevacizumab when NPC cell lines. combined characterized the hypoxia pathways and We have studied the prognostic with taxane monotherapy or in significance of epidermal growth factor receptor combination as first line treatment of patients with (EGFR) expression in NPC, and established the locally recurrent or metastatic breast cancer. anti-tumor effect of cetuximab, a monoclonal (MD06742) antibody against EGFR, in NPC cell lines and in a phase 2 clinical study in NPC patients. Targeted Based on our ground work on hypoxia and EGFR, we Downregulation propose that both the hypoxia and EGFR pathways Tyrosine are important molecular targets for development of Treatment novel therapeutic strategies in NPC. Carcinoma (NPC) In this Inhibition of Kinase, of of Another EGFR: Metastatic c-Met Induced Key Receptor Implication for Nasopharyngeal proposal, we will study: (1) the activity and changes LUI Wai Yan Vivian in underlying molecular biomarkers of novel hypoxia CHAN Anthony Tak Cheung targeting agents (including tirapazamine and hypoxia 207 Faculty of Medicine Dept of Clinical Oncology 1 June 2007 treatment of NPC (and potentially other malignancies CUHK Research Committee Funding (Direct also). (MD06621) Grants) Nasopharyngeal carcinoma (NPC) is prevalent in A Randomized, Open-label Phase II Study Southeast Asia and Hong Kong. Although it is Evaluating the Efficacy and Safety of FOLFOX-4 rather curable at early stages, the highly invasive and plus Cetuximab versus UFOX plus Cetuximab as metastatic nature of NPC contributes to metastasis First-line Therapy in Subject with Metastatic and recurrence with high fatality rate. Colorectal Cancer Mechanisms contributing to NPC metastasis are largely unknown. Studies indicate that c-Met and epidermal growth MA Buig Yue Brigette HO Wing Ming* factor receptor (EGFR), two important receptor HUI Edwin P* tyrosine kinases, may be involved. Linda* CHAN Anthony Tak Cheung These two proto-oncogenes can cause dysregulated growth, invasion and metastasis. CHAN Lam* LEUNG 1 June 2007 In NPC, c-Met and EGFR Merck KGaA are frequently overexpressed, clinically associated with advanced disease and poor survival in patients. Oxaliplatin-based chemotherapy regimens such as Activation of c-Met or EGFR can induce NPC FOLFOX proliferation and invasion in vitro. Recently, we Oxaliplatin & leucovorin) & UFOX (contains oral demonstrated that targeted c-Met inhibition (by c-Met UFT & oxaliplatin) have proven activity in metastatic siRNA) resulted in significant EGFR downregulation colorectal cancer (mCRC), & Cetuximab is a (70-80%), accompanied by dramatic inhibition of molecular-targeted agent that may enhance the effect NPC proliferation and invasiveness in vitro. This of chemotherapy. novel finding indicates that EGFR expression is for the treatment of mCRC in Hong Kong. potentially regulated by c-Met in NPC and the study evaluates the effect of combining cetuxmab subsequent EGFR downregulation may represent an with either FOLFOX or UFOX, the use of oral UFT additional potentially may avoid the inconvenience of using mechanism contributing to the (contains infusional 5-Fluorouracil, Most of these drugs are approved This effectiveness of c-Met targeting in NPC. Here, we intravenous infusion of 5-Fluorouracil. propose to: 1) study the mechanism of EGFR who had previous treatment with chemotherapy or regulation (transcriptional or post-transcriptional agents similar to cetuximab are excluded. levels) by c-Met in NPC; 2) examine the effects of industry-sponsored international randomized phase II c-Met NPC study will enrol a target of approximately 400 proliferation and metastasis; and 3) compare the patients with previously untreated mCRC. Subjects efficacy of c-Met and EGFR targeting in NPC cells. will be randomized in a ratio of 1:1 to 1 of 2 possible We EGFR study arm: Group A: FOLFOX + cetuximab; Group expression in NPC and c-Met targeting results in the B: UFOX + cetuximab. Both efficacy and safety inhibition of EGFR-mediated biological processes in data will be collected. NPC. treatment targeting hypothesize on that EGFR-mediated c-Met regulates This study has important mechanistic and clinical implication on tumorigenesis, metastasis and Faculty of Medicine is Patients This Radiological response to evaluated every 8 weeks. Randomization will be stratified into low, medium 208 Dept of Clinical Oncology and high risk groups, & treatment will continue until located upstream to Raf such as the EGFR. if Therefore, Raf/ MEK proteins represent novel targets patients experience intolerable toxicity. disease progression or After study completion, in NPC that warrant evaluation. AZD6244 is a subjects will be followed-up every 3 months for non-competitive MEK inhibitor that is currently progression and survival. under phase I clinical evaluation in solid tumors Tissue samples may be obtained for pharmacodynamic studies. outside Hong Kong, and the aim of this proposal is to (MD06478) evaluate MEK as a new therapeutic target for NPC and introduce this new therapy for local patients. Effect of AZD6244 Alone or in Combination with This study will determine the anti-cancer properties Cytotoxic Chemotherapy or Epidermal Growth of this MEK inhibitor in NPC cell lines, and its effect Factor Receptor Tyrosine Kinase Inhibitor in on NPC cell growth when combined with cytotoxic Nasopharyngeal Cell Lines chemotherapy or EGFR inhibitors in vitro. The longterm goal of this project is to provide the basis for future clinical studies using this new class of MA Buig Yue Brigette LUI Wai Yan Vivian drugs in NPC. (Note: AZD6244 is provided as part HUI Pun CHAN Anthony Tak Cheung of an unfunded project initiated by the Cancer 30 June 2007 Therapy CUHK Research Committee Funding (Direct Evaluation Program, National Cancer Institute, Bethesda, USA.) Grants) (MD06867) Nasopharyngeal carcinoma (NPC) is a common cancer in Hong Kong, and new therapeutic target is A Phase 3 Randomized Study to Evaluate Survival needed for patients with recurrent or metastatic of Patients Treated with Talaporifin Sodium disease that often progress despite conventional (LS11) and Interstitial Light Emitting Diodes chemotherapy due to drug resistance. Our previous (LED) as Compared to the Standard of Care studies have shown that inhibition of the epidermal Therapies in the Treatment of Unresectable growth factor receptor (EGFR) signaling pathway is a Hepatocellular Carcinoma promising strategy against NPC. However, research MOK Shu Kam Tony have shown that targeting the EGFR pathway alone LEE Sing Fun Paul may not be sufficient due to cross-talk with other (Diagnostic Radiology & Organ Imaging) signaling pathways, such that co-inhibition of EGFR Bo San Paul (Surgery) and other signaling pathways may augment growth CHAN Lam* inhibitory effects on cancer cells. The LAI DU Yingchun* 1 November 2006 mitogen-activated protein kinase kinase (MEK) Light Sciences Oncology Inc signaling protein is a key downstream protein of the RAS/RAF pathway, which is involved in the The study is a multi-center study with a total target regulation of cell growth and survival. The number of 200. The aim of the study is to assess the Ras/Raf/MEK pathway is deregulated in cancers due survival of patients treated with Litx versus standard to the presence of activating Ras or Raf gene of cancer therapies in the treatment of unresectable mutation, or overexpression of signaling proteins 209 Faculty of Medicine Dept of Clinical Oncology Hepatocellular Carcinoma and demonstrate the safety help to identify more biomarkers for its diagnosis of Litz therapy. and molecular targets for better therapeutics. 3p21 (MD06898) alteration is one of the most frequently detected genetic alterations in NPC, indicating the presence of Double-Blind, critical tumor suppressor genes (TSGs). Previously, Multi-Centre Parallel-Group Study to Assess the we identified a novel 3p21.3 gene, ZMYND10, as a A Phase Efficacy III, of Randomised, ZD6474 (ZACTIMA TM ) candidate TSG being frequently inactivated by both Versus Erlotinib (TARCEVA®) in Patients With Locally epigenetic Advanced or Metastatic (Stage IIIB – IV) ZMYND10 belongs to a group of proteins containing Non-Small Cell Lung Cancer (NSCLC) after the Failure domain which are involved in transcriptional of at Least One Prior Cytotoxic and genetic highly-conserved mechanisms MYND-type in zinc NPC. finger regulation and implicated in tumorigenesis, including Chemotherapy BS69/ZMYND11 which interacts with EBV proteins MOK Shu Kam Tony LAM Kwok Chi EBNA2 and LMPI. In this proposal, we intend to further characterize the LEUNG Kam Suet Linda molecular functions of this novel protein in the 10 January 2007 pathogenesis of NPC. I will use artificial expression AstraZeneca Hong Kong Limited of ZMYND10 in NPC tumor cells through It is a Phase III multi-centered study. The primary transfection to study the impact of ZMYND10 objective of this study is to evaluate progression free expression on NPC cell growth, proliferation, cell survival for ZD6474 in patients with locally cycle and apoptosis, colony formation and migration. advanced or metastatic (Stage IIIB - IV) Non-Small It is expected that this study will provide more insight Cell Lung Cancer. into the molecular functions of ZMYND10 in normal (MD06416) cell physiology and the tumorigenesis of NPC as well as other carcinomas with alterations of this novel Function Characterization of an Epigenetically TSG. Inactivated Tumor Suppressor Gene ZMYND10 (MD06403) in the Pathogenesis of Nasopharyngeal Carcinoma Value of CK20 mRNA and CEA mRNA in the TAO Qian CHAN Anthony Tak Cheung Non-Plasma Portion of the Blood for Diagnosis and Monitoring of Colorectal Cancer POON Fan Fong# 1 March 2007 WONG Sze Chuen Cesar CHAN Anthony Tak CUHK Research Committee Funding (Direct Cheung MA Buig Yue Brigette Grants) 1 August 2006 Nasopharyngeal carcinoma (NPC) is one of the The Hong Kong Anti-Cancer Society - Cancer leading cancers in Hong Kong, and strongly associated with Epstein-Barr virus Research Grant (EBV). Molecular studies on its pathogenic mechanisms will Faculty of Medicine 210 Dept of Clinical Oncology Colorectal cancer (CRC) is the second most common have successfully opened up a new circulating cancer in Hong Kong.1 The incidence rate of CRC in mRNA scenario for detection and monitoring of CRC the young population (<46 years of age at diagnosis) by detecting mRNA in non-plasma portion of the is 4 times the rate in other countries such as the blood samples. 1 This study plans to evaluate the United States, Scotland and Japan. As detection and clinical applications of CEA mRNA and CK20 treatment of this cancer at an early stage can mRNA in the non-plasma portion of the peripheral dramatically improve survival, there has been urgent blood in 4 cohorts and the quantity of blood taken is demand in developing population-based screening for 8 ml only. CRC.2 Many methods have been evaluated, such as (pre-OT) and 50 colorectal adenoma patients fecal occult blood testing, flexible sigmoidoscopy, (pre-endoscopy and on first follow-up). screening colonoscopy, virtual colonoscopy, and cohort continues to follow-up the above CRC patients. barium enema, but they have limited sensitivity, The 1st follow-up is before home leave, around 5-7 3 days after surgery; the 2nd follow-up should be specificity, or are invasive procedures. The 1st cohort includes 50 CRC patients The 2nd Quantification of tumor-derived mRNA in the blood around 3-4 weeks after surgery at the outpatient clinic; of subsequent follow-up visits, around 3 times a year, cancer patients opportunities 4-5 prognosis. for has opened non-invasive up immense diagnosis for the period of 2 years after surgery, and thereafter and if there is suspicious of relapse. However, the sensitivity of detection for consists of other benign colorectal diseases including carcinoembryonic antigen (CEA) mRNA and CK20 6 The 3rd cohort 7 mRNA in CRC patients were only 21% and 27% , 20 patients each for colitis, piles, colorectal ulcers respectively and the mononuclear fraction of the and hyperplastic polyps. peripheral blood was mainly used for mRNA other non-colorectal cancers, with 20 patients each of detection.6-9 In order to improve the sensitivity of breast liver cancer, detection of CEA mRNA and CK20 mRNA in CRC pancreaticobiliary cancer and lung cancer. mRNA patients, we assayed the CEA mRNA and CK20 is mRNA in non-plasma portion using quantitative centrifugation, reverse transcribed to cDNA, and reverse transcriptase PCR as we recently discovered assayed for CEA mRNA and CK20 mRNA level that there were much higher concentration of CEA using quantitative PCR molecular technique. mRNA (3-fold more) and CK20 mRNA (4-fold more) (MD06865) cancer, extracted prostate from the The 4th cohort includes cancer, blood samples after in the red blood cell than those in the mononuclear fraction after centrifugation. Our preliminary Prognostic Significance of Plasma b-catenin results from 35 CRC patients demonstrated that the mRNA in Patients with Colorectal Cancer sensitivity of CRC detection can be raised to 75% for CEA mRNA (median copy numbers: 23180) and WONG Sze Chuen Cesar MA Buig Yue 82% for CK20 mRNA (median copy numbers: 31840) Brigette whereas both transcripts were not found in 15 Fung Yee Janet (Surgery) CHAN Anthony Tak apparently healthy subjects. Our results, with much Cheung higher sensitivity of detection for both CEA mRNA LAI Bo San Paul (Surgery) LEE 1 January 2007 and CK20 mRNA, not only appears to be a promising Research Grants Council (Earmarked Grants) marker for CRC detection and monitoring, but also 211 Faculty of Medicine Dept of Clinical Oncology CUHK Research Committee Funding (Direct Most existing prognostic biomarkers of colorectal cancer (CRC) are limited by their accuracy, Grants) inefficiency and impracticality for routine use. Our As detection and treatment of colorectal cancer (CRC) recent discovery of circulating β-catenin mRNA in at an early stage can dramatically improve survival, the plasma of CRC patients has opened up a new there has been urgent demand in developing frontier for non-invasive detection and therapeutic monitoring of this common cancer. non-invasive test for CRC detection and monitoring. This discovery Quantification of tumor-derived mRNA in the blood is made possible through our pioneering work on a of novel extraction protocol for non-viral plasma mRNA, patients opportunities and enhanced processing with quantitative reverse transcriptase polymerase chain reaction method. cancer for has opened non-invasive up immense diagnosis and prognosis. However, the sensitivity of detection for As carcinoembryonic antigen (CEA) mRNA and CK20 CRC patients with stage IIb-III CRC are at higher mRNA in CRC patients were only 21% and 27%, risk of post-operative recurrence for which salvage respectively in the mononuclear fraction of the blood. treatment may improve prognosis, our new marker In order to improve the sensitivity of detection, we may improve early detection of disease relapse and assayed the CEA mRNA and CK20 mRNA in help streamlining patient selection for post-operative non-plasma portion of the blood using quantitative therapy. Our pilot study has shown that β-catenin reverse transcriptase PCR. Our preliminary results mRNA can clearly discriminate between patients from 35 CRC patients demonstrated that the with CRC, adenoma and normal subjects. In this sensitivity of CRC detection can be raised to 75% for study, we plan to expand our pilot study and establish CEA mRNA and 82% for CK20 mRNA whereas threshold values for determining positive and both transcripts were not found in 15 apparently negative predictive values of β-catenin mRNA. We healthy subjects. will also prospectively investigate the value of This study plans to analyze CEA mRNA and CK20 mRNA in the non-plasma portion plasma β-catenin mRNA in predicting disease in 3 cohorts. recurrence and shorter survival in patients with stage The 1st cohort includes 40 CRC patients (pre-OT). IIb-III CRC following primary resection and post- The 2nd cohort continues to follow-up the CRC patients. operative adjunct therapy, as well as in monitoring The 1st follow-up is before home leave, around 5-7 days after surgery; the response to chemotherapy in patients with metastatic 2nd follow-up should be around 3-4 weeks after or recurrent CRC. surgery; subsequent follow-up visits around 3 times a (CU06448) year, for the period of 2 years after surgery. The 3rd cohort includes non-colorectal cancers, with 20 Effectiveness of CEA mRNA and CK20 mRNA in patients each of breast cancer, liver cancer and lung the Non-Plasma Portion of the Blood for Diagnosis cancer. and Monitoring of Colorectal Cancer The information got is important for us to understand their potential in clinical applications. (MD06434) WONG Sze Chuen Cesar CHAN Anthony Tak Cheung MA Buig Yue Brigette An Open Label International Multi-Center Phase 1 May 2007 Faculty of Medicine 2 Activity and Safety Study of SU011248 in 212 Dept of Clinical Oncology Patients with Unresectable Pfizer Corporation Hong Kong Limited Hepatocellular Carcinoma This is an open label, phase 2 multi-center international study to be conducted in Asia and YEO Winnie CHAN Lam HUI Pun Europe. 5 July 2006 The primary objective is to evaluate SU011248 anti-tumor activity in gastric cancer. Pfizer Corporation Hong Kong Limited Sample size is 63 patients. (MD06915) SU011248 is an investigational drug that inhibits the RTKs of the VEGFR, PDGFR, FLT-3, and KIT. A HCC is a highly vascular tumor, in which vascular The expression of III, Multicenter, Randomized, Double-Blind, Active Controlled, Parallel Group recruitment and invasion greatly contribute to pathogenesis. Phase Study of vascular the Safety and Efficacy of the Intravenous and Oral Formulations of the endothelial growth factor (VEGF) and its receptors, Neurokinin-1 Receptor Antagonist, Casopitant and of other RTKs like the Platelet-Derived Growth (GW679769) in Combination with Ondansetron Factor Receptor-®, which are thought to have an and Dexamethasone for the Prevention of Nausea important role in HCC angiogenesis, has been and Vomiting Induced by Moderately Emetogenic confirmed in this disease. Agents that inhibit the Chemotherapy. NKV102549 cell signaling pathways may increase the therapeutic options for patients with HCC in patients with altered YEO Winnie HO Wing Ming* SUEN Joyce* liver function, and offer a potential better safety profile in comparison to chemotherapy agents. CHAN Lam* KWAN Wing Hong* LIEM Giok Siong There is therefore the rationale for testing the multi-targeted tyrosine kinase inhibitor SU011248 in 7 February 2007 patients with unresectable HCC. GlaxoSmithKline Limited This is an open-label, uncontrolled, multi-center, This Phase III clinical study will assess whether the Phase 2 clinical trial evaluating the activity, and safety of single-agent SU011248 in administration of casopitant (intravenous and oral) patients will improve the control of CINV following the unresectable HCC. administration (MD06489) Advanced/Metastatic emetogenic chemotherapeutic (MEC) regimens. The primary achieve a complete response (no vomiting/retching 2 Activity and Safety Study of SU011248 in with moderately endpoint will be the proportion of subjects who An Open Label International Multi-Center Phase Patients of and no use of rescue therapy) over the first 120 hours Gastric following the initiation of the first cycle of MEC Cancer Progressing or Recurring after One Prior regimen. Chemotherapy (MD06553) YEO Winnie LAM Kwok Chi A Randomized, Double-Blind, Parallel-Group 5 July 2006 Study 213 Conducted under In-house Blinding Faculty of Medicine Dept of Clinical Oncology Conditions to Determine Efficacy and Tolerability randomly assigned to 1 of 2 treatment regimens. For of of control arm which patients will take Aprepitant Chemotherapy-induced Nausea and Vomiting placebos, will receive Ondansetron 8mg as the Associated standard antiemetic therapy. Also, patients will be Aprepitant for the Prevention Moderately Emetogenic allowed to take “rescue therapy” throughout the study Chemotherapy for nausea or vomiting. YEO Winnie CHAN Lam* HO Wing Ming* LIEM GS* KWAN Wing Hong* (MD06910) SUEN Joyce* POON Annette* Please refer to previous issues of this publication 1 March 2007 for more details of the following ongoing research Merck Sharp & Dohme (Asia) Ltd at the department: The study will focus on patients receiving an initial Edition Title/Investigators cycle of Moderately Emetogenic Chemotherapy. Patients may participate in the study for a total of two cycles. 2004-05 MVA-EBNA1/LMP2 Vaccine: Phase I Patient is receiving chemotherapy for more Trial in Patients with EBV-Positive than one cycle may opt to participate in an optional Nasopharyngeal second cycle during which the patient will receive (MD04307) the same antiemetic regimen as per Cycle 1, except CHAN Anthony Tak Cheung Carcinoma that fosaprepitant (IV prodrug of aprepitant) will be Pun* substituted for oral aprepitant on Day 1. Yue Brigette TAO Qian The CHAN Lam* (MTA) HUI MA Buig substitution of fosaprepitant in the optional second cycle will allow for the collection of additional data 2004-05 EMR 62 202-013, Open, Randomized, in the Chemotherapy-Induced Nausea and Vomiting Controlled, Multicenter Phase III Study (CINV) patient population. Preparation of IV Comparing 5FU/FA plus Cetuximab vs fosaprepitant will be done by an unblinded 5FU/FA plus Irinotecan as First-Line pharmacist at each study site. Treatment for Epidermal Growth Factor Study drug administration on treatment Days 2 and 3 will be Receptor-Expressing given orally as in Cycle 1. Colorectal Cancer (MD04747) Approximately 610 patients worldwide will be CHAN Anthony Tak Cheung randomized into the study. About 12 months is Buig Yue Brigette allotted for enrollment of all patients. The duration Metastatic MA HO Wing Ming CHAN Lam of the study, from enrollment of the first patient into the study (Cycle 1 Prestudy Visit) to exit of the last 2004-05 A Randomized, Three Arm Multinational patient from the study (Cycle 2 Follow-Up Visit), Phase will be around 1 year. Bevacizumab Patients will be stratified by gender, provided Combination with Either Intermittent inclusion and exclusion criteria are fulfilled, each Capecitabine patient will be given a single allocation number and Faculty of Medicine 214 III Study to Investigate (q3w or q2w) plus in Oxapliplatin Dept of Clinical Oncology (XELOX)(q3w) or Fluouracil/Leucovorin 2005-06 A with Oxaliplatin (FOLFOX-4) versus Phase II Study of Concurrent FOLFOX-f Regimen Alone as Adjuvant Cetuximab-Cisplatin and Radiotherapy in Chemotherapy the in Colon Carcinoma of CHAN Anthony Tak Cheung Buig Yue Brigette CHAN Anthony Tak Cheung MA HO Wing Ming CHAN Lam III Trial of HUI Edwin P* LAM Kwok C* CHAN Lam* LEUNG Sing Fai CHIU K W* XU Wei* Tirapazamine FONG Tik Pui Daniel* versus Chun* Patients with Advanced Head and Neck TAO Qian Cancer (MD05556) ZEE Kwok Hung HUI Pun YUAN WONG Sze Chuen Cesar Joh, Sung Wook* Chung Ying Benny MA Buig Yue LAM Kwok Chi (Community and Family Medicine) YU 2005-06 A Multi-Center Prospective Randomized Brigette KAM Koon Ming Michael KAM K Michael* Concomitant Radiation and Cisplatin in CHAN Anthony Tak Cheung KWAN Wing H* Concomitant Radiation, Cisplatin, and (SR259075) MA Randomized Buig Yue Brigette LIN Marie MC* 2005-06 Phase Advanced Nasopharyngeal Carcinoma (MD05709) (MD04635) Treatment Phase II Trial to Determine the Benefit of Adjuvant CHAN Lam Chemotherapy Gemcitabine and Using Cisplatin in 2005-06 A Single Arm Phase IV Study to Assess Nasopharyngeal Carcinoma Patients with Efficacy and Safety of Bevacizumab in Residual EBV DNA Following Primary Combination Radiotherapy with or without Concurrent with Irinotecan and Infusional 5-Fluorouracil/Folinic Acid Cisplatin (MD05706) Regimens as First Line Treatment for CHAN Anthony Tak Cheung Patients with Meatastatic Colorectal Buig Yue Brigette Cancer (MD05590) LEUNG Sing Fai CHAN Anthony Tak Cheung Buig Yue Brigette MA HUI Pun* LEE Albert* CHAN V* HO Wing Ming* MA HO Wing Ming 2005-06 Cancer WONG Herman* LI Wa Patients with Fever and Neutropenia: A Prospective Evaluation of 2005-06 Novel Epigenetic Nasopharyngeal Demethylation Therapy towards Carcinoma Using Agents and Risk Assessment Tools and Infectious Etiology in Hong Kong (MD05773) HUI Pun Histone CHAN Anthony Tak Deacetylase Inhibitors (CU05443) Cheung CHAN Anthony Tak Cheung TAO YEO Winnie Qian HUI Pun Brigette MA Buig Yue Brigette MOK Shu Kam Tony MA Buig Yue LAI Ming Po (Centre for Clinical Trials) 215 ZEE Chung Ying Faculty of Medicine Dept of Clinical Oncology Benny (Community and Hepatocellular Carcinoma Cell Lines Family (MD04636) Medicine) MAK So Shan* MA Buig Yue Brigette 2000-01 Phase III Randomized Multicenter Comparatives Study of Peginterferon TAO Qian CHAN Anthony Tak Cheung YEO Winnie MOK Shu Kam Tony alpha2a vs. Roferon-A for the Treatment of Patients with Recently Diagnosed 2005-06 Therapeutic Targeting of Epidermal Chronic Phase Chronic Myelogenous Growth Factor Receptor Leukemia (CML) not Previously Treated Tyrosine Kinase with with Interferon (MD20042) Nasopharyngeal Carcinoma –Evaluation LEI Ieng Kit Kenny of LEUNG Wai Molecular (EGFR) Gefitinib in Biomarkers of Gefitinib-sensitivity in Cell Lines and Tong Thomas# HUI Pun Tumor Biopsies (CU05445) MA Buig Yue Brigette 2005-06 Evaluation of Novel Epigenetic Markers for Nasopharyngeal Carcinoma Sze Chuen Cesar (MD05316) TAO Qian TAO Qian HUI Pun* TO Ka Fai CHAN Anthony Tak Cheung 2005-06 Molecular Targeting of STAT3 for Nasopharyngeal Carcinoma 2005-06 Effect of the Novel Histone Deacetylase (NPC) Inhibitor (MD05813) PXD101 on Cellular Proliferation and Viral Gene Expression LUI Wai Yan Vivian NGAI in Hepatitis B Virus (HBV)-Carrying CHAN Anthony Tak Hepatocellular Carcinoma Cell Lines (MD05955) Cheung MA Buig Yue Brigette 2003-04 A Phase 1/2 Open-Label Study to Assess the WONG (Anatomical & Cellular Pathology) LEUNG Sing Fai Jenny* Safety, Tolerability, Xiaorong and (Hong Cancer Institute) of YEO Winnie in Subjects LIN Cancer Institute)# SUNG Lan (Hong Kong Pharmacokinetics of Intravenous Infusion MB07133 Kong with Unresectable Hepatocellular Carcinoma TAO Qian CHAN Anthony Tak Cheung and Child-Pugh Class a Liver Function (MD03679) 2002-03 A Phase II/III, Muliticenter, Randomized, MA Buig Yue Brigette Anthony Tak Cheung CHAN Controlled, MOK Shu Intravenous Open T138067-sodium Chemotherapy-Naïve, Deacetylase Faculty of Medicine Activities Inhibitor of Study of versus Intravenous Doxorubicin in Subjects with Kam Tony YEO Winnie 2004-05 Antitumor Label Hepatocellular Carcinoma (MD02843) Histone PDX101 Unresectable in 216 Dept of Clinical Oncology MOK Shu Kam Tony Yue Brigette MA Buig Selected Patients with Advanced (Stage ZEE Chung Ying IIIB or IV) Non-Small Cell Lung Cancer Benny (Community and (NSCLC) in Asia (MD05387) Family MOK Shu Kam Tony Medicine) CHAN Lam* 2004-05 A Randomized, Double-Blind Mulitcentre 2-Stage Phase III Study of Bevacizumab with Dose Finding Study of RO0503821 in versus Anemic Patients with Stage IIIB or IV Placebo, Cisplatin and Gemcitabine in Non-Small Cell Lung Cancer Receiving Patients First Cisplatin in and with Combination 2005-06 A Multicenter, Randomized, Open-Label Gemcitabine Advanced Recurrent Line Myelosuppressive Non-Squamous Non-Small Cell Lung Chemotherapy (MD05876) Cancer, Who Have Not Received Prior MOK Shu Kam Tony Chemotherapy (MD04411) MOK Shu Kam Tony POON Annette* LAM Kwok 2005-06 A Chi CHAN Lam Randomised, Double-Blind Placebo-Controlled, Phase II Study of of Sequential Administration of Tarceva with (Erlotinib) or Placebo in Combination Advanced Stage IIIB/IV Non-Small Cell with Gemcitabine/Platinum as First-Line Lung Cancer (MD05993) in Patients with Stage IIIB/IV Non-Small 2005-06 An Expanded TM Access (ERlotinib) Tarceva in Program Patients MOK Shu Kam Tony Cell Lung Cancer (NSCLC) (MD05790) LIN Marie MOK Shu Kam Tony MC* LAM Kwok Chi LEUNG Kam Suet Linda 2005-06 An Open-Label, Phase II Trial of Patupilone (EPO906) as Monotherapy to Evaluate Activity of Patupilone 2004-05 Identification in Suppressor of Novel Genes at Tumor 16q in Patients with Advanced Unresectable Nasopharyngeal Carcinoma through a and/or Combination of Genetic and Epigenetic Metastatic Hepatocellular Carcinoma (HCC) (MD05609) MOK Shu Kam Tony Approaches (MD04376) TAO Qian LEUNG Wai Ming Franky* 2005-06 Identification of Novel Suppressor Genes as Tumor Makers for 2005-06 An Open Label, Randomized, Parallel Group, Multicentre, Phase III Study to Lung Assess Efficacy, Safety and Tolerability Analysis (MD05649) of TAO Qian Gefitinib Carboplatin / (IRESSA) Versus Paclitaxel Doublet Tumor Cancer through Methylation CHAN Anthony Tak Cheung CUI Yan# Chemotherapy as First-Line Treatment in 217 Faculty of Medicine Dept of Clinical Oncology 2005-06 Prognostic Significance β-Catenin mRNA in of nd YONDELIS with DOXIL /CAELYX Plasma Patients with Alone Colorectal Cancer (MD05346) Subjects with Advanced Relapsed Ovarian Cancer (MD05350) WONG Sze Chuen Cesar Anthony Tak Cheung in YEO Winnie LIN Marie MC* CHAN MA Buig 2005-06 Randomised Phase II Study of the Yue Brigette Combination of Oral Vinorelbine with Capecitabine versus Peripheral Stem Cell Transplant for High Regimen Oral Risk Capecitabien versus the Combination of 1997-98 High Dose Adjuvant Chemotherapy and Breast Cancer Patients YEO Winnie Vinorelbine and with Metastatic Breast Cancer Previously KWAN Wing Hong TEO Man Lung Peter Wai Tong Thomas# Ming Sequential Docetaxel and Capecitabine in Patients (MD95266) of a Michael YEO Winnie SUEN Wang (Anatomical Cellular Pathology) Treated with Anthracyclines (MD05703) LEUNG & TANG Ben Zhong* POON Annette* KING Wing 2005-06 A Randomized, Double-Blind Phase 2 Keung Walter (Surgery) Study of Anastrozole plus Lonafarnib (SCH 2004-05 A Phase II Multi-center, Randomized, Double-Blind, Placebo Active-Controlled, 66336) with Dose-Ranging, Advanced (MD05395) Efficacy YEO Winnie the Oral Anastrozole Plus Placebo for the Treatment of Subjects and Parallel Group Study of the Safety and of or Neurokinin-1 Receptor Antagonist, GW679769 when Breast Cancer KWAN Wing Hong SUEN Joy See Joyce Administered at Daily Doses of 50 mg, 100 mg, and 150 mg Oral Tablets in Combination with 2005-06 Epigenetic Changes in RASSF1A, p16, Ondanstron p15 and GSTP1 in the Presence of Hydrochloride and Dexamethasome for Histone the Prevention of Chemotherapy-Induced Hepatocellular Carcinoma (MD05637) Nausea and Vomiting in Cancer Subjects YEO Winnie CHAN Lam* Receiving Highly Cisplatin-Based Emetogenic Chemotherapy (MD04547) YEO Winnie CHAN Lam POON Annette Ngar Ying 2005-06 An Open-Label, Multi-center, Randomized Phase 3 Study Comparing the Combination of DOXIL /CAELYX Faculty of Medicine 218 Deacetylase Inhibition in Dept of Community & Family Medicine similar studies to be conducted in other Chinese cities RESEARCH PROJECTS as part of the multi-staged study. (MD06761) Heat Wave Impact in China Unintentional Home Injury in Hong Kong : A JAFFE Cross-sectional Pilot Study on Prevalence, Risk Harold* GRIFFITHS Sian Meryl GOGGINS Factors, Health Seeking Behaviors, Public Health III William Bernard (The Nethersole School of Policy and Economic Implication CHAN Ying Yang Emily LI Liping* Nursing) CHAN Ying Yang Emily 1 June 2007 KIM Jean Hee LAU Tak Fai Joseph (Centre for Epidemiology Oxford - Li Ka Shing Foundation Collaborative and Biostatistics) Research Programme GRIFFITHS Sian Meryl CHOW Chun Bong* NG Queeni Tse Kay Epidemiological research in western countries have (School of Public Health) shown mortality and hospital admission increases (School of Public Health) CHEUNG Yu Kiu during heat waves attacks. Although recent reported 20 June 2007 health wave episodes in China have led to public CUHK Research Committee Funding (Direct health emergency, human impact of heat waves in Grants) China has not been studied systematically. This project is the pilot phase of the first multi-staged Purpose: To conduct a pilot cross-sectional study on project in China to analyze how climate change has home injury in Hong Kong. affected population mortality and morbidity. Objectives: 1) To determine the prevalence and 3 main research questions: 1) Do heat waves affect incidence of unintentional home injuries in Hong mortality patterns in China? 2) If so, who is at Kong; 2) To characterize the cause, nature, setting greatest risk? 3) Based on evidence, what would be and temporal patterns of these injuries; 3) To some potential actions for public health preparedness determine the burden of these injuries at individual, for extreme temperature? household and societal level; 4) To analyze health Data collection and analysis: This project involves seeking behaviors and health service utilization of data collection from various site and sources in China. Hong Kong residents after home injuries; 5) To In Hong Kong 1996-2006 for daily levels of identify risk factors and high risk groups in relations meteorological variables, air pollutants and mortality to unintentional home injury; and 6) To obtain of China SAR HK would be collected and analyzed. information about knowledge of injury prevention, Generalized additive Poisson regression models presence of safety equipment or safety measures adjusted for non-tmperature related seasonal factors taken to prevent unintentional injuries in the home. will be used to analyze daily mortality counts for Hypothesis: selected causes. worldwide show incidence rates for unintentional Outcome: Assessment of the impact of heat wave on injuries ranging from 16.1/1000 to 57/1000 persons the mortality in Hong Kong will serve as the pilot for with as many as 41% of households reporting an Various population-based surveys injury that required medical attention in 2005. 2004 219 Faculty of Medicine Dept of Community & Family Medicine HK population survey reported incident of home implications of home injury in Hong Kong. injury to be about 14.3% and literature review yield Findings will help shape effective interventions. limited information on risk factors and health (MD06664) seeking behavior after these injuries. Given the unique living conditions of Hong Kong, that is Traditional Chinese Medicine in Hong Kong: characterized by small and densely inhabited living Utilization Pattern and Its Role in the Future quarters, a detailed study on home injury should Health Care System yield a different picture and draw attention to important public health policy implication. Design and Subjects: A GRIFFITHS Sian Meryl LAU Janice* WOO population-based, Jean (Medicine & Therapeutics) LO Su Vui* cross-sectional, random telephone survey, stratified WONG Ming Chung (School of Public Health) by the 3 regions will be conducted using last birthday 30 September 2006 method. The study population is to be comprised of Public Policy Research Funding Scheme land-based non-institutional population of all ages, including foreign/local domestic helpers residing in Background: Traditional Chinese medicine (TCM) Hong Kong. started its rapid development in Hong Kong since the Study for reunification. Its importance was reemphasized by Conducting Community Surveys on Injuries and the latest policy address by the Chief Executive, but Violence (WHO 2004), a modified questionnarie that its role in the future health care system were not tailored for HK living arrangement will be developed. identified in the discussion paper “Building Healthy Information on health seeking practices (e.g. the use Tomorrow”. Updated data on local TCM utilization of traditional Chinese medicine) and cost incurred pattern and the characteristics of TCM users are from home injury will also be solicited. A pilot essential in formulating TCM development policies. study will be conducted to ensure validity and We explored the issue by performing a systematic reliability of the modified instrument. review on past literature and we found paucity in Analysis: Descriptive statistics, stratified by age, such data. gender and district area, will be reported on territory wide, population representative census scale prevalence and incidence of various types of injury. investigation commissioned by the Census and A two staged analysis will be conducted: I) An Statistic Department. univariate analysis to examine and to identify utilization, demographics, health condition and health significant independent related lifestyle data which has the potential to variables with unintentional home injuries; and II) A establish the basis of TCM policy formulation. stepwise multivariate logistic regression to analysis Aims: To describe local TCM use and its relevance to significant variable identified during 1st stage. planning future healthcare by: a. Systematic review Health seeking behavior, economic and public health on policy implication will also be explored. Describing the utilization of TCM in the local Main instrument: Based associations outcome: Major on Guidelines between will literature It contains unanalyzed TCM concerning local TCM use; b. include: population, using data from the Thematic Household Epidemiological profile of associated risk factors; Survey (THS); c. Performing a longitudinal analysis health seeking behaviors pattern and economic of the changes in utilization pattern, using previous Faculty of Medicine findings Thematic Household Survey (THS) is a 220 Dept of Community & Family Medicine and future THS results; d. Undertaking qualitative Determine if needs are being met: What proportion of research regarding the patients’ view on the children who need glasses have them? utilization and effectiveness of TCM; and e. Identify barriers: What prevents children from Establishing a platform for future regional and accessing good-quality spectacles, such as those international comparative analysis and researches. provided by our local vision centre in Xichang? Methods: We propose to perform cross section and Test a solution: Train teachers to screen students, and longitudinal analysis on the existing dataset from provide education to teachers, children and parents on THS 99-04, in addition to the new data from the the ability of glasses to correct poor vision, and the forthcoming THS 05, which we have contributed new availability of good-quality, affordable spectacles questions on lifetime utilization and perceived quality locally at Xichang eye center. of TCM consultation. The focus of analysis will be: The pilot study produced startling results: even I rural a. Descriptive statistic on TCM utilization and its Xichang, over half of the 1800 children examined sequential trend; b. Health condition, lifestyle factors were myopic, and more than half of these and TCM use; and c. Patient satisfaction level on near-sighted TCM services, with comparison to western outpatient inaccurately-prescribed glasses or none at all. Lack of services. knowledge, concern over cost and fears that glasses (MD06929) may harm the eyes appear to be major barriers among children either had parents and children. Educational efforts at the Evaluating Health Interventions for Children in schools to increase uptake of spectacles are now Rural China on-going and have been well-received. Having identified a major rural health problem and CONGDON Nathan piloted a solution, we are eager to scale up the Greenleaf (Ophthalmology and Visual Sciences) Xichang program to combat poor vision in other LAM Shun Chiu Dennis (Ophthalmology and schools in the Chaoshan area, and to develop and GRIFFITHS Sian Meryl Visual Sciences) JAFFE Harold* evaluate effective programme interventions. We SHARMA propose to use the opportunity provided by eye Abhishek* testing to add other health interventions in such 1 June 2007 critical areas as obesity and smoking, both growing Oxford - Li Ka Shing Foundation Collaborative problems in China, in selected schools. The goal is to Research Programme provide programs for rural Chinese children which In response to local concerns about the growing build on good vision to promote other healthy prevalence of myopia (near-sightedness) and poor behaviours. We will evaluate the interventions using access to glasses, Caring is Hip, CUHK, Shantou qualitative. Other interventions such as school-based University and Joint Shantou/International Eye provision of spectacles and pharmacologic treatments Centre recently launched a pilot project in the village to reduce myopia will be studied. of Xichang (Chaoshan Region) with the following (MD06584) goals: Assess the problems: What is the prevalence of Incentives and Barriers to Adopting the Family myopia in rural middle-schools? Doctor Model in Hong Kong – An In-depth 221 Faculty of Medicine Dept of Community & Family Medicine (MD06829) Qualitative Study of the Views, Knowledge and Attitudes of Patients A Population-based Survery on Internet Use GRIFFITHS Sian Meryl Cindy* LEE Albert LAM Lo Kuen PHILIP David* Patterns, Pathological Internet Use, Internet LAM Addictions Tai Pong* JONES Roger* WONG Chi Wai and Associated Adverse Health Outcomes Among Hong Kong Residents : A Pilot Study 1 June 2007 Food and Health Bureau - Studies in Health GRIFFITHS Sian Meryl KIM Jean Hee LAU Services Tak Fai Joseph (Centre for Epidemiology and Improving the use and effectiveness of primary care Biostatistics) services in Hong Kong is a key policy priority, (The Nethersole School of Nursing) particularly Kwai Wing (School of Public Health) in management. the area of chronic disease Fundamental to any programme of GOGGINS III William Bernard CHOW CHEUNG Yu Kiu (School of Public Health) change is an in-depth understanding of the views, 30 June 2007 knowledge, and attitudes of those who receive the services. CUHK Research Committee Funding (Direct The family doctor model has been Grants) proposed as one solution. The aim of the present study is to explore the Background: Despite the fact that Hong Kong ranks incentives and barriers to adopting the family doctor 9th globally in per capita internet access and that there model in Hong Kong from the viewpoint of patients is an ever increasing number of individuals using with chronic disease. computers, there has never been a population-based purposively from a Patients will be sampled large quantitative survey survey of internet use and its health outcomes in this conducted by Hong Kong University. 3 groups of region. patients will be interviewed: a) those with a family small-scale doctor; b) those with a primary care provider (GP or convenience sample-based studies, studies limited to TCM Practitioner); and c) those with no primary care student populations, or other specific risk-groups that provider. are not generalizable to the entire population of Hong In-depth qualitative methods will: a) explore views Kong. A systematic analysis of this phenomenon in on primary care as it currently exists; b) examine the general population of Hong Kong is long knowledge and understanding of the family doctor overdue. model; c) elucidate attitudes towards health, self-care, Objectives: The aims of this study are to examine the and the role of primary care; and d) delineate the prevalence of internet use, pathological internet use, incentives and barriers to adopting the family doctor internet addiction by sociodemographic factors and to model. The study will provide a rich understanding examine the effects of internet use on physical health of patients’ views on primary care, and the incentives and mental health factors such as depression and and barriers to adopting a family doctor model, with decreased physical activity. important implications for the further development of obtain a preliminary prevalence estimate of risky primary care in Hong Kong. internet behaviours such as meeting strangers from Faculty of Medicine 222 The local data on internet use are limited to consumer marketing surveys, The study will also Dept of Community & Family Medicine cyberspace in the population. knowledge and skills. The study also seeks to validate measures of pathological internet use in a Methods: A doctor and a nurse accompanied by Hong Kong Chinese sample. outreach team will consult at (1) AFRO drop-in Methods: An anonymous, random telephone survey clinic or (2) at FSW work places. will be used stratifying the sampling frame by 3 services will include HIV and, common and geographic areas (Hong Kong, Kowloon and New important Territories) A structured questionnaire with validated chlamdydia, hepatitis B as well as Pap smears. instruments for Quality of Life (Short Form-12), Treatment or referrals will be given for positive STI. Depression, Anxiety and Stress (DASS-21), Internet All positive HIV will be referred to the DH Kowloon Addiction (Young’s Internet Addiction Scale) will be Bay Clinic for assessment while this clinic will used to survey Chinese adults in Hong Kong between continue to look after non-HAART therapy related the ages of 18-65. medical needs of these HIV positive patients. First birthday method of STI including syphilis, Screening gonorrhoea, The respondent selection will be used. clinical Results: Pending education on safe sex and negotiation techniques on Conclusions: Pending condom use at the same time. (SS06403) Output and Deliverables : The output criteria staff will also provide opportunistic includes new attendance of 300 FSW, 150 returnees Outreach and 50 FSW presented with symptoms in a year’s Service for Sex Workers to Prevent and Manage period. Another criteria will be that 90% or more of HIV/STI in Hong Kong FSW will take up voluntary HIV testing and it is To Establish a Community-based expected over 90% of those diagnosed with STI will GRIFFITHS Sian Meryl YIM Kit Sum* receive treatment. A fourth output criterion will be that at least 50% of FSW will return at the end of the Eleanor Holoryd* HO King Man* two year period for repeated tests. 1 July 2007 Access and service output satisfaction will be assessed and sound Council for the AIDS Trust Fund satisfaction criteria will be that 80% of attendees will Aims: To reduce HIV infection by actively seeking score most (1) or very (2) satisfied with the service. and treating STI and HIV amongst FSW in Hong Further assessment will be that of HIV safe sexual Kong. knowledge, attitudes and behaviours (condom usage) Objectives as indicated by an improvement of 20%, 10% and 1. 2. 3. affordable, 5-10% (for local and non-local FSW respectively) non-stigmatising medical outreach service that between the baseline and those returned one year specifically targets Hong Kong’s FSW for later. screening of HIV/ STI and treatment of STI; (MD07815) To provide an accessible, To diagnose and treat FSW presented with STI symptoms or had a likely exposure to HIV (case Effects of Soy Protein or Isoflavones on Glycemic finding); and Control, Insulin Resistance and Cardiovascular To provide opportunistic education and equip Risks - A Six-month Randomized Double-blind, FSW with relevant and practical safe sex 223 Faculty of Medicine Dept of Community & Family Medicine Placebo-controlled Trial in The result from this study will yield valuable Post-Menopausal information on the effects of soy on the primary Women prevention of diabetes in susceptible subjects. This HO CHAN Suzanne WOO proposed study will form part of a larger research HO Yee Ping effort, including cross-sectional and longitudinal LAM Wai Kei studies and clinical trials on the potential benefits of CHEN Yuming Jean (Medicine & Therapeutics) (School of Pharmacy) soy on bone mass/loss, calcium retention, cognitive Christopher (Chemical Pathology) function, and lipid profiles. 1 January 2007 (CU06450) Research Grants Council (Earmarked Grants) Several animal studies and small scale human trials Evaluation of a School-based Empowerment showed that soy intervention improved glycemic Programme “School NutriAgent Project” (SNAP) control and diabetic complications in diabetic animals for the Promotion of Healthy Eating in Primary and humans. No study has reported if soy protein or School in Hong Kong isoflavones could prevent the progress of developing diabetes in individuals with impaired fasting glucose (IFG). LEE Albert HO Man (Centre for Health Ed. & Moreover, it is unclear whether the Health Promotion) beneficial effect is due to isoflavones alone, or 1 January 2007 isoflavones contained in soy protein. Department of Health, Hong Kong SAR We propose to perform a double-blind, randomized placebo-controlled trial to examine the hypothesis The project aims to evaluate whether “School that soy protein with isoflavones could improve NutriAgent Project” conducted by the Department of glycemic control, insulin sensitivity and decrease Health is effective in encouraging local primary cardiovascular risk factors in middle-aged women schools to comply with the nutritional guidelines on with IFG (5.6-7.0 mmol/l), and that the soy effects school lunch and snacks issued by DH in 2006. The might be more pronounced in post- than in effect of compliance is to increase the provision of premenopausal women. 180 eligible subjects (90 fruit and vegetables in school lunch and snacks, as pre- and 90 post-menopausal) will be randomly well as decrease the provision of unhealthy food assigned to receive one of three treatments with a items in school lunch and snacks during the 2006/07 daily dose of:. 20 g soy protein + 120 mg isoflavones; school year. 120 mg isoflavones + 20 g casein, or 20 g casein (ED06696) (placebo) for 24 weeks. Fasting and post-load plasma glucose, the primary outcome measures, and Organization insulin resistance, C-peptide, and cardiovascular risk Promoting School on January 22-26, Including factors (lipids, oxidized LDL, homocysteine, C Facilitation of Attendance by Cook Islands and reactive protein, fibrinogen, blood pressure and body Nauru fat) will be examined at baseline, 12 and 24 weeks post treatment. Faculty of Medicine LEE Albert 224 of Short Course on Health Dept of Community & Family Medicine 22 January 2007 - To enhance social adjustment and build up the capacity of ethnic minorities and Chinese new World Health Organization immigrants to achieve self-help and mutual help; 1. To conduct a 4-day curriculum development and - regional teachers training short course in Hong immigrants with personal life skills that develops Kong on health promoting schools with 2 their capacity and potentials; representatives each (1 from Health & 1 from 2. - 4. To promote social inclusion between ethnic Education) from Cook Islands and Nauru minorities, Chinese new immigrants and local including travel, meals and accommodation; people by enhancing mutual understanding and To organize a study tour for participants to visit a facilitating direct interaction; health education resources centre in Hong Kong 3. To equip ethnic minorities and Chinese new - To collaborate with other sectors/organizations and interact with other stakeholders in health to provide better support to ethnic minorities promoting schools such as community leaders, and Chinese new immigrants. school administrators, teachers and children; The project will build up the capacity of the ethnic To develop and maintain an interactive website minorities and Chinese new immigrants to integrate on an on-going basis for participants in the short into the local community. course to enable its use for continuing dialogue facilitation, and interaction as the regional teachers’ training self-image and self-confidence of ethnic minorities course is adopted at country level; and and Chinese new immigrants are enhanced. Equip To compile and submit a detailed final technical with these life skills, they will be capable to working report on the training and a financial report. with people from different age group, race and (MD06524) personal life Through the project’s skills, self-esteem, disciplinary so as to achieve “complementary” ad interlocking matching. At the same time, these Capacity Building for the Ethnic Minorities and skills will benefit their career development to enable the Chinese New Immigrants Towards Social them to serve community. This is also conducive to Inclusion social inclusion and racial harmony in the community. Mutual supportive network among ethnic minorities LEE Albert CHENG YAM FK Frances and Chinese new immigrants as well as the local (Centre for Health Ed. & Health Promotion) community can this be developed. (MD06683) 15 February 2007 Community Investment and Inclusion Fund, Development of Learning and Teaching Resource HKSAR Government Series for the New Senior Secondary Health The project aims at engaging the most marginalized groups (ethnic minorities and Chinese Management and Social Care Curriculum new immigrants) in Hong Kong to achieve the following LEE Albert objectives: CHENG YAM FK Frances (Centre for Health Ed. & Health Promotion) 1 March 2007 225 Faculty of Medicine Dept of Community & Family Medicine Education and Manpower Bureau, HKSAR providing a supportive home and school environment to nurture healthy lifestyles in school children. It Government emphasis a sustainable and consistent environmental To offer teaching and learning materials to Hong changes at home and school and the change of Kong Secondary School teachers who would teach knowledge or attitude in individual children as well. the New Senior Secondary HMSC Curriculum (the The project adopts the model of empowerment and “teachers”) in September 2009 by a variety of audiovisual firms. multi-disciplinary approach to address the complex It is expected that the teachers problem of childhood obesity. would acquire comprehensive understanding of the It also encourages active participation of parents to act as a health major objectives, key concepts, core knowledge and promoter at home and as volunteers for school to gain teaching skills of the curriculum, and be competent a better understanding about school policies and to with full confidence in teaching this subject to a share the workload of teachers on the one hand, and reasonably high standard. work in hand with school and health professionals to The service provider would develop one set of foster a supportive school and home environment on Learning and Teaching Resource Series, both in the other hand. It is an 18-month project adopts the English and Chinese respectively, for the HMSC home-school joint venture approach to foster a Curriculum covering both the student’s study texts holistic supportive home and school environment to and teacher’s teaching notes in both compulsory and help school children to learn proper weight elective parts. management skills, to develop healthy lifestyle, and (ED06909) to build up self-confidence and self-efficacy. 6 primary schools will be recruited to join the project. Home-School Joint Venture to Combat Childhood 20 obese students from each school will be invited to Obesity join the programme with their parents. (SS06838) LEE Albert HO Man (Centre for Health Ed. & Health Promotion) KWONG Chi Ming Amy (Centre for Health Ed. & Health Promotion) Utilization Pattern of Primary Care Services in Hong Kong-Does Having a Family Doctor Make YUNG Ka Chun (School of Public Health) Any Difference 1 June 2007 MERCER Stewart William Health Care and Promotion Fund Similar to other parts of the world, the problem of childhood obesity is increasingly prevalent in Hong LEUNG Gabriel* Daniel* LEE Albert LAM Lo Kuen FONG Yee Tak LAM Tai Pong* LO Yvonne* Kong school children. Obesity can pose immediate 1 June 2007 health problem to children as well as long-term health Health and Health Services Research Fund risks. This pioneer fitness programme fully make use of the positive family influence together with a Background: Primary health care in Hong Kong is close collaboration with school and healthcare provided by a variety of Western and Chinese professionals to combat childhood obesity through Faculty of Medicine Cindy* medicine practitioners, a recent survey found that 226 Dept of Community & Family Medicine 55% adults in Hong Kong said that they had a regular complete the diaries by themselves. All diaries will primary care doctor but only 10% thought that they be returned with the written consent form in a had a family doctor. It is not known how effective pre-paid self-addressed envolope to the investigators primary care services in Hong Kong are and whether Outcome Measures and Data Analysis: The primary having a family doctor or regular doctor make any outcomes are monthly consultation rate, patient difference to the care received. reported Effectiveness of a outcomes measured by the Patient consultation can be measured by the process and Enablement Instrument (PEI) score, and rates of patient reported outcomes of care. Aims and non-drug management. The outcomes will be Objectives: To find out the utilization rate, process analysed for the general population and compared and outcomes of primary health care services between people who report to have a family doctor, a provided by different types of practitioners in Hong regular primary care doctor and no regular primary Kong, and the effect of having a family doctor on care doctor for any difference. service utilization rate and pattern, heatlh promotion longitudinal study will be used to cross-validate and practice, and process and outcomes of consultations. adjust for any possible recall errors of the results Design and Subjects: A cross-sectional survey of a from the cross-sectional study. Conclusions: This is random sample of 3000 subjects from general the first study to evaluate the process and outcome of population in Hong Kong followed by a prospective primary care consultations for the general population study of 600 subjects recruited from the general in Hong Kong and to collect prospective data on population survey. Methods: Households will be primary care service utlization rates and pattern. It contacted by random digital dialing and a member of will also provide information whether people with a the household will be recruited randomly to answer a family doctor receive more effective primary health structured questionnaire on the usual type of primary care or not. health care provider and utilization pattern, illness (MD06952) behaviour including self-medication The data from the and consultations for the last episode of illness, process Will Hong Kong Experience an Epidemic of and last Mesothelioma? – Exploring the Evidence through to a Systematic Review and an Ecological Study on patient consultation.All reported subjects outcomes who are of the willing participate in a longitudinal study will be asked to Asbestos, Asbestosis, and Mesothelioma complete a diary on all illness episodes and consultations for 12 weeks. All subects will be TSE Lap Ah contacted by telephone within the week before the YU Tak Sun Ignatius AU Siu Kie* diary starting date to confirm receipt of the diaries, to 29 June 2007 give instructions on how to complete the diary and to CUHK Research Committee Funding (Direct identify those who require interviewer administration. Grants) Weekly telephone or SMS will be made to the subjects to remind them to complete the diary. The Worldwide, malignant mesothelioma was considered diaries will be self-completed by subjects (or carers to be a rare neoplasm before 1950s but the incidence of minors) who are able to do it, and by weekly rates have been increasing steeply since 1970s in telephone interviews for subjects who are not able to many parts of the world, and is predicted to go on 227 Faculty of Medicine Dept of Community & Family Medicine rising into the next decade with a peak between 2011 Kwok (Chemical Pathology) and 2015. CHAN Wan Kin Hong Kong may experience a similar epidemic of mesothelioma as a consequence of the extensive use of asbestos in the past. LEE Albert 1 August 2006 The Research Fund for the Control of Infectious occurrence of malignant mesothelioma has been very Diseases closely linked to asbestos exposure and asbestosis. However, not enough is known whether excessive risk Objective: There is now substantial literature of malignant mesothelioma occurs exclusively among showing that psychological stress can down-regulate workers who already have developed asbestosis various aspects of the cellular and humoral immune (fibrosis of the lungs). Moreover, evidence on a responses. In this study, the role of chronic stress possible link between chrysotile asbestos and on modulating immune response to influenza specific malignant mesothelioma remains unclear. immunity in community dwelling elderly in Hong The present study will systematically review the evidence Kong will be evaluated for the first time. from the published literature (1966-July 2007) on Design: A case-control study. whether asbestosis is a prerequisite for the link Setting: Baseline screening and interviewing of between asbestos exposure and mesothelioma, and subjects will be conducted at a community clinic. whether exposure to chrysotile asbestos alone Participants and intervention: 50 spousal caregivers increases the risk for mesothelioma. A time trend (cases) of patients with chronic diseases (COAD, analysis will also be conducted to estimate the age, stroke and Parkinson’s diseases) will be recruited period and/or cohort effects on the secular trend of from the Psycho-geriatric Day Hospital of the Shatin mesothelioma incidence rate in Hong Kong and shed Hospital where their partners have attended. lights on the underlying reasons. controls will be recruited from community health By relating 50 mesothelioma incidence to the local consumptions of centre. different types of asbestos and taking into account a matched on sex, age, family income and rates of lag time of 30-40 years, we shall be able to understand chronic diseases. the possible factors associated with the changes in the that were shown to influenze vaccine response will be time trend of mesothelioma incidence and predict the measured incidence of mesothelioma in the future decades. physical exams at baseline. (MD06521) vaccination will be given to all subjects in the fall of 2006. Caregivers and control subjects will be by Perceived stress and co-variates standardized questionnaires and Trivalent influenza Blood samples will be drawn before Chronic Psychosocial Stress: Does it Modulate inoculation, and at 6 weeks and 12 weeks post Immunity to Influenza Vaccine in Hong Kong vaccination. Chinese Elderly? Main outcome measures and analysis: The main outcome measures will be antibody titres and serum WOO Jean concentration and ex vivo production of cytokines in LAM Wai Kei both controls and cases in response to the influenza WONG Yeung Shan Samuel (Medicine & Therapeutics) Christopher (Chemical Pathology) Sheung Paul (Microbiology) CHAN Kay vaccination. Univariate and multivariate anlyses of WONG Chun variance will be used to assess differences between caregivers and controls in antibody titres and cytokine Faculty of Medicine 228 Dept of Community & Family Medicine concentration. Differences in the percentage of responders between the two groups will be compared ZEE Chung Ying Benny by chi-squared tests. 11 September 2006 (MD06855) Aegera Therapeutics Inc. A Pilot Study to Investigate the Efficacy and Develop a synopsis for Phase I/II trial of AEG35156 in Safety of IMD-1041 in Patients with Type II hepatocellular carcinoma patients. Diabetes Mellitus and budget for the full data management services for Provide timeline the above study. (MD06839) ZEE Chung Ying Benny 11 September 2006 Statistical Analysis Related to the Clinical Study Institute of Medicinal Molecular Design Inc. Entitled “A Pilot Study to Investigate the Centre for Clinical Trials will be responsible for Response of IMD-0354 Ointment in Patients with providing study administrative and data management Atopic Dermatitis” services for a clinical study entitled “A Pilot Study to Investigate the Efficacy and Safety of IMD-1041 in ZEE Chung Ying Benny Patients with Type II Diabetes Mellitus”. 10 December 2006 (MD06324) Institute of Medicinal Molecular Design Inc. A Pilot Study to Investigate the Response of Centre for Clinical Trials will be responsible for IMD-0354 Ointment in Patients with Atopic providing statistical analysis related to the clinical Dermatitis study entitled “A pilot study to investigate the response of IMD-0354 ointment in patients with ZEE Chung Ying Benny atopic dermatitis”. 11 September 2006 (MD06363) Institute of Medicinal Molecular Design Inc. Statistical Analysis Related to the Clinical Study Centre for Clinical Trials will be responsible for Entitled “A Pilot to Investigate the Efficacy and providing study administrative and data management Safety of IMD-1041 in Patients with Type II services for a clinical study entitled “A pilot study to Diabetes Mellitus” investigate the response of IMD-0354 ointment in patients with atopic dermatitis”. ZEE Chung Ying Benny (MD06375) 10 December 2006 Institute of Medicinal Molecular Design Inc. Development of Synopsis and Study Planning for “Phase I/II Trial of AEG35156 in Hepatocellular Centre for Clinical Trials will be responsible for Carcinoma Patients” providing statistical analysis related to the clinical study entitled “A Pilot Study to Investigate the 229 Faculty of Medicine Dept of Community & Family Medicine Efficacy and Safety of IMD-1041 in Patients with ZEE Chung Ying Benny LAI Ming Po (Centre Type II Diabetes Mellitus”. (MD06540) for Clinical Trials) 28 May 2007 The Hong Kong Emesis Registry 2006 (Quality of AstraZeneca (WuXi) Trading Company Limited Life Study for Moderate Emetogenic Patients) – Provides training and education for clinical research Manuscript Writing & Patient Recruitment personnel in hospitals. (MD06740) ZEE Chung Ying Benny 13 December 2006 Please refer to previous issues of this publication Merck Sharp & Dohme (Asia) Ltd for more details of the following ongoing research Professor Zee will be responsible for carrying out quality at the department: of life assessment from previous Hong Kong Emesis Registry Study plus 80 patients from the study entitled “A Edition Title/Investigators Phase III randomized, double-blind study to determine the efficacy and tolerability of aprepitant for the 2005-06 Non-Communicable Disease Prevention prevention of chemotherapy-induced nausea and and vomiting Developing and Public Health Training associated with Control Strategic adriamycin-cyclophosphamide adjuvant chemotherapy Support Services (MD05514) in Chinese breast cancer patients” and complete a GRIFFITHS Sian Meryl Framework manuscript writing for the captioned project. (MD06323) 2005-06 Public Health Research (MD05505) GRIFFITHS Sian Meryl YEOH Development for Otsuka Phase I Trial in Multiple Eng Kiong (School of Public Health) Myeloma and Lymphoma ZEE Chung Ying Benny TANG Jinling 2005-06 Provision of Economic Input into Research Studies Undertaken by the 9 May 2007 Research Office of the Health, Welfare Otsuka Beijing Research Institute and Food Bureau (MD05874) Protocol development and consent form development GRIFFITHS Sian Meryl YEOH for clinical trial in patients with multiple myeloma and Eng Kiong (School of Public Health) lymphoma. (MD06888) (School of Public Health) Clinical Research Professional Workshops in Beijing and Guangzhou Faculty of Medicine 230 LEUNG Chi Ming Michael Dept of Community & Family Medicine & Organ Imaging) 2003-04 Adolescent and Adult Soy Intake and Breast Cancer Risk in YU Ho Yan (School of Public Health) Chinese Pre-Menopausal Women (MD03666) HO CHAN Suzanne (Medicine & Therapeutics) Chiu Wing Winnie 2004-05 Health Promoting School Programme WOO Jean (MD04696) CHU LEE Albert (Diagnostic CHENG YAM FK Radiology & Organ Imaging) YEO Frances (Centre for Health Ed. & Winnie (Clinical Health Promotion) TANG Leung Oncology) Sang (Chemical Pathology) Nelson Kwan (Centre for Health Ed. & Health Promotion) LAU Tak YUEN Suk Fai Joseph (Centre for Epidemiology 2004-05 General and Biostatistics) Practice Management of Osteoarthritis (MD04469) LEE Albert 2005-06 Effects of Isoflavone in Patients with Watchful Waiting Benign Prostate 2004-05 Community Development Approach to Create Better Health of our Young WOO Jean (Medicine & Therapeutics) WONG CHAN Lung (School of Pharmacy) TSANG Kwong Ka Wai (Surgery) YOU Hoi Sze Joyce Albert WONG Chi Wai WONG Yeung Shan Samuel Hyperplasia (CU05453) HO CHAN Suzanne LEE Generation within the Settings of Their Shan Daily Life (MD04356) Yeung LEE Albert Samuel CHENG YAM FK Frances (Centre for Health Ed. & 2005-06 A Three-Year Progression of Followup Study Common of Health Promotion) Carotid HO Man (Centre for Health Ed. & Health Atherosclerosis and the Associated Risk Promotion) Factors in a Population-Based Cohort of (University Health Postmenopausal YUEN Suk Kwan (Centre for Health Chinese Women (MD05895) YUEN Wing Ki Service)# Ed. & Health Promotion) HO CHAN Suzanne WOO Jean 2005-06 A Phase III, Multicenter, Open-Label, (Medicine & Therapeutics) HO Sin Yee Stella (Diagnostic Radiology & Dose-Titrating, Organ Imaging) TANG Leung Evaluating the Efficacy, Tolerability and Sang Nelson (Chemical Pathology) Safety of Olmesartan Medoxomil 20 mg GOGGINS III William Bernard (The and 40 mg Alone or in Combination with Nethersole School of Nursing) 12.5 mg to 25 mg of Hydrochlorothiazide Christopher in Subjects with Mild to Moderate LAM Wai Kei (Chemical Pathology) 16-week Study Essential Hypertension (MD05959) AHUJA Anil Tejbhan (Diagnostic Radiology 231 Faculty of Medicine Dept of Community & Family Medicine LEE Albert WONG Chi Sang CHAN Wan Kin Target Early School Leavers in Hong Kong (MD05463) LAU LEUNG WONG Chi Wai Choi Har Louisa Eleanor 2005-06 Capacity Building for Pre-School Anne HOLROYD (The School of Nursing)# Nethersole LEE Albert Children: Health Promoting Kindergarten WONG Yeung Shan Samuel (SS05466) NGAI Sze Wan Emily (Educational LEE Albert Administration & Policy)# CHENG YAM FK Frances (Centre for Health Ed. & Health Promotion) 2005-06 To Determine the Prevalence and Risk CHYE Mee Factors for STDs/HIV for Female Street Len* and Brothel Sex Workers in HK (MD05560) 2005-06 Evaluation of Home Modification for the WONG Chi Wai Elderly Program in Wong Tai Sin and LEUNG Tse Kowloon City Districts (MD05374) Ngong (Obstetrics & Gynaecology) LEE Albert CHENG YAM FK LIANG Mei* Frances (Centre for Health Ed. & Health Promotion) Sang WONG Chi 2005-06 Evaluation Studies on Sexual Abuse NG Yiu Pan (Centre for Prevention Programs for Upper Primary and Junior Secondary School Studies Health Ed. & Health Promotion)# (SS05409) WONG Chi Wai 2005-06 Survey on Occupational Safety and Health Situation of Private Clinics in Catherine Hong Kong (MD05431) Gynaecology) LEE Albert TANG So Kum (Obstetrics & CHENG YAM FK 2004-05 Genitourinary Frances (Centre for Health Ed. & Problems and Mood Disorders in Elderly Chinese Men - A Health Promotion) First Epidemiological Cohort Study in Hong Kong (MD04760) 2005-06 Preparation of a Thematic Paper for the WONG Yeung Shan Samuel WOO Knowledge Network on Urban Settings (KNUS), WHO Commission on Social Jean (Medicine & Therapeutics) Determinants of Health on "Improving LYNN Sui Heng Henry (School of Health and Building Human Capital" Public Health)# (MD05488) LEE Albert 2004-05 Pearl-Postmenopausal Risk-Reduction 2005-06 Involving Developing and Lasofoxifene the "Hard-to Reach": (MD04831) and Evaluating a WONG Yeung Shan Samuel WOO Peer Education Sexual Health Programme to Faculty of Medicine with Evaluation Jean (Medicine & Therapeutics) 232 Dept of Community & Family Medicine 2004-05 Quality LEUNG Ping Chung (Institute of Chinese Medicine) Non-Ignorable GRIFFITH of Life Analysis Missing Data with Using James Francis (Diagnostic Radiology Pattern-Mixture Models with Generalized & Organ Imaging) Estimating Equation (GEE) and Multiple Imputation (MI) (CU04291) ZEE Chung Ying Benny 2005-06 A Randomized, Controlled Clinical Trial: The Effect of Mindfulness-Based Stress MOK Shu Kam Tony (Clinical Oncology) Reduction Programme on Pain, as well as Quality of Life in Chronic Pain Sufferers 2005-06 Safety Testing and Protocol Development (MD05983) for Bone Rescuer (MD05740) WONG Yeung Shan Samuel ZEE Chung Ying Benny LEE Albert 2005-06 Phase I Study on the Safety and 2003-04 Male Lung Exposures Cancer, and Pharmacokinetics of Single and Repeated Occupational Smoking - Application of IMD-0354 in Healthy A Case-Control Study in Hong Kong Male Volunteers (MD05520) (CU03460) ZEE Chung Ying Benny YU Tak Sun Ignatius TSE Lap Ah 2005-06 Feasibility Tests for Measuring the WONG Tze Wai Concentrations of IL-6 and 8-Isoprostane from Exhaled Breathe Condensate of 2005-06 Mortality Experience of Register II Silicotic Patients in Hong Kong - An COPD Patients (MD05835) Extended (1981-2006) ZEE Chung Ying Benny TSE Lap Ah 2005-06 Collaboration with Bridgetech Medical Follow-Up (MD05495) YU Tak Sun Ignatius Technologies Research & Development KO Mo Lin, Regina* (BMT 2004-05 Data Management "Randomized Phase Services II Study R&D) for Clinical Trials Operations in China (MD05782) for ZEE Chung Ying Benny to Investigate the Effects of Recombinant 2005-06 Prediction of Population Risk of Chronic Intestinal Trefoil Factor (ITF) on Oral Mucositis in Patients Diseases Receiving by Generating PIN-ER-t Radiation Therapy for Nasopharyngeal Numbers for Hong Kong (MD05587) Cancer ZHANG Xin-Hua with Protocol Number 2004-ITF-004" (MD04927) (Medicine ZEE Chung Ying Benny GRIFFITHS Sian Meryl 233 & WOO Jean Therapeutics) Faculty of Medicine Dept of Diagnostic Radiology & Organ Imaging motions in AIS were not compromised when RESEARCH PROJECTS compared with the normal controls. In the present study, the main Objective is to evaluate of the effect of corrective surgery on AIS patients. As Pulmonary Functional Change in Adolescent we have obtained the pre-operative MR study and Idiopathic Scoliosis before and after Corrective lung function tests on a group of 30 AIS patients, we Surgery are going evaluate the post operative changes on lung Dynamic Magnetic Resonance Imaging functions two years after the surgery. We will look CHU Chiu Wing Winnie Martin (Paediatrics) LI Man Chim Albert into the absolute change of lung volume movement NG Kin Wah Bobby amplitude of chest wall and diaphragm on both convex (Orthopaedics & Traumatology) Ping (Orthopaedics & Traumatology) and concave side of the scoliotic curve and the LAM Tsz compare CHENG clinical CUHK Research Committee Funding (Direct and indices for better surgical planning, prognostication and also lay the foundation for Grants) establishing more evidence-based management of Idiopathic Scoliosis (AIS) is scoliotic patients a (MD06374) three-dimensional torsion deformity of the spine. than pre-operatively Significance of the study should provide useful 1 June 2007 Other difference post-operatively. Chun Yiu Jack (Orthopaedics & Traumatology) Adolescent the important cosmetic (and hence psychological) effect, the major medical implications Detection of Nasopharyngeal Carcinoma (NPC) of AIS are related to the adverse impact on using Magnetic Resonance Imaging (MRI) respiratory function, which includes reduced exercise KING Ann Dorothy tolerance, increased risk of developing respiratory VLANTIS Alexander failure and in extreme cases, premature morbidity. Chris (Otorhinolaryngology, Head and Neck S) Despite extensive research, there are controversies TSANG about the exact etiology of respiratory impairment in (Otorhinolaryngology, Head and Neck S) AIS. Chung Ying Benny (Community and Family The effects of surgical treatment on dynamic King Yin Raymond ZEE lung function changes have not been adequately studied. Medicine) In our recently published study, we have employed Cellular Pathology) dynamic breath-hold Magnetic Resonance (MR) Andrew (Otorhinolaryngology, Head and Neck S) imaging to elucidate the respiratory mechanism in TSE Man Kit Gary (Anatomical & VAN HASSELT Charles AHUJA Anil Tejbhan patients with AIS compared with healthy individuals. 1 January 2007 Significant reduction in inspiratory, expiratory lung Research Grants Council (Earmarked Grants) volume and diaphragmatic heights in AIS patients with severe curve but the change in lung volume was Nasopharyngeal carcinoma (NPC) is endemic in not affected. Hong Kong. Many patients are refereed to hospital The chest wall and diaphragmatic for investigation of suspected NPC because they have symptoms from the head and neck, or they have had a Faculty of Medicine 234 Dept of Diagnostic Radiology & Organ Imaging positive result from a blood test used to screen for the Therapeutics) disease. Fortunately, only a small number of these Therapeutics) patients turn out to have NPC. However, in order to YU Cheuk Man (Medicine & 1 October 2006 exclude NPC, patients undergo endoscopy to inspect Research Grants Council (Earmarked Grants) the nasopharynx, followed by an endoscopic guided biopsy (removal of small tissue samples). Even in Ischaemic heart disease caused significant coronary cases where no cancer is identified on inspection, artery biopsy is essential to sample various sites within the morbidity in our society. It is also the second killer nasopharynx in an attempt to detect small cancers just after cancer in our locality. below the surface of the nasopharynx. present with non-specific symptoms and cardiogenic guided biopsy is invasive, Endoscopic unpleasant, stenosis is associated with significant Patients very often time chest pain could be difficult to be differentiated from consuming, associated with a risk of haemorrhage non-cardiogenic chest pain. Cardiac catheterisation and sometimes may require a general anesthetic. delineating the anatomy of coronary artery has long Even after taking several biopsies small cancers may been accepted as the gold standard for documentation be missed. High resolution MRI (magnetic of coronary artery disease. Early intervention might resonance imaging) is a non-invasive technique that decrease the mortality and morbidity and might produces exquisite pictures of the nasopharynx in improve the quality of life. Cardiac catheterisation, 10-15 minutes. MRI is already used in patients with however, is an invasive test and the patients have to biopsy proven NPC to assess the local spread of the be admitted into hospital causing economic burden cancer. However, because its accuracy in finding on the society. small cancers is unknown, it has not been used to try non-invasive imaging modalities including state of to detect cancer in patients with suspected NPC. the art magnetic resonance imaging and computed The aim of the study is determine whether high tomography can now be employed in the evaluation resolution MRI can be used in patients with suspected of ischaemic heart disease. NPC to (1) screen out those normal patients who do imaging might evaluate the perfusion of myocardium not require an invasive endoscopic guided biopsy (2) and ischaemia during rest and stress could be aid in directing the site of biopsy in those patients detected. with small cancers that cannot be seen through the allows endoscope and may be missed by sampling biopsies. morphological assessment of coronary artery can be (CU06457) performed. With advances in technology, Magnetic resonance Multi-detector computed tomography sub-millimeter spatial resolution and The degree of stenosis, length of stenosis and site of stenosis could be demonstrated Prediction of Coronary Artery Intervention by the and intervention could be planned accordingly. In State of Art Imaging: Magnetic Resonance this study, we are assessing the predictability of Perfusion intervention by both magnetic resonance perfusion and 64 Detector Computed and computed tomography angiography and assess Tomography Angiography the feasibility of replacement of diagnostic cardiac LAM Wai Man Wynnie catheterisation CHAN Wai Man Wilson (Medicine & Therapeutics) WONG Ka modalities. Tak Jeffrey (CU06458) CHAN Kin Yin (Medicine & 235 by these non-invasive imaging Faculty of Medicine Dept of Diagnostic Radiology & Organ Imaging Man Kit Gary (Anatomical & Cellular Pathology) Please refer to previous issues of this publication for more details of the following ongoing research 2004-05 Remodeling and Plaque Composition of at the department: Middle Cerebral Artery: Its Significance Edition in Development of Thrombotic and Title/Investigators Embolic Stroke in Patients with Middle 2005-06 Longitudinal Cerebral Artery Stenosis (MD04753) Contrast-Enhanced Sonographic Study Lymphadenopathy of LAM Wai Man Wynnie Superficial in Ka Sing Lawrence (Medicine & Lymphoma Patients on Chemotherapy (MD05727) Therapeutics) AHUJA Anil Tejbhan Winnie Augustine* LAM Tsan CHU Chiu Wing LEI Ieng Kit Kenny (Clinical Oncology) Gregory WONG 2003-04 Radio-Frequency Ablation for Better ANTONIO LEE Yolanda Y.P.* Quality of Life (MD03435) LEE Sing Fun Paul CHAN T.C. Ricky* Simon HO Sze Ming LEUNG Sing Fai (Clinical Oncology) 2004-05 Kinematics of the Osteoporotic Spine CHAN Lung Wai (Surgery) (EE04301) GRIFFITH James Francis YEUNG 2003-04 Prevention and Treatment of Ischaemic Siu Wing* Stroke by Endovascular Stenting of 2004-05 Squamous Cell Carcinoma of the Head Intracranial and Neck: Can In Vivo Proton Magnetic (MD03571) Resonance YU Chun Ho Predict Spectroscopy and (1H-MRS) Monitor Tejbhan YUEN Hok Yuen# Faculty of Medicine YU Kwok Hung (Clinical Oncology) WONG Ka Sing LAM Wai Man Wynnie Wai Sang (Surgery) AHUJA Anil YEUNG Ka Wai Daivd Stenosis Lawrence (Medicine & Therapeutics) Therapeutic Response? (CU04300) KING Ann Dorothy Vascular TSE 236 POON Dept of Medicine & Therapeutics (MD06919) RESEARCH PROJECTS Do Apolipoprotein E Genotypes Affect the Risk of Stroke by Altering Cytokine Expression? DNAzymes for Treatment of Dengue Fever BAUM Lawrence William NGAI Jenny* BAUM Lawrence William CHAN Kay Sheung Paul (Microbiology) LAM (Biochemistry (Medicine)) Wai Yip (Microbiology) Timothy HO Yuanyuan KWOK Chi Yui 15 December 2006 1 April 2007 Research Fund for the Control of Infectious CUHK Research Committee Funding (Direct Grants) Diseases Purpose: To treat infections caused by single-strand Stroke is the fourth most serious disease worldwide RNA virus. as measured by disability adjusted life-years lost. It are is vital to understand stroke risk factors so that viruses, such Objectives/hypothesis: as dengue DNAzymes oligonucleotides shaped like the letter omega, with preventive measures may be developed. the horizontal portion complementary to a target We found that apolipoprotein E (apoE) isoforms E2, sequence and the loop containing a fixed sequence E3, and E4 affect inflammatory cytokine production which has the ability to catalyze cleavage of the in bound RNA. This cleavage ability may be used to expressing apoE2 or apoE4 expressed more TNF-α attack the RNA that encodes RNA viruses. We (18-65%, p<0.05) and IL-6 (54-101%, p<0.05) than propose to synthesize, test, and refine the design of did macrophages expressing apoE3. Inflammatory DNAzymes that could be used to treat dengue virus cytokines may cause atherosclerosis and increase the infection. risk of stroke. Design and subjects: We have already designed and affect stroke risk. Indeed, we and others have found synthesized DNAzymes against conserved regions of that the apoE alleles corresponding to E2, E3, or E4 the positive-strand RNA of dengue virus type 2 isoforms affect the risk of ischemic stroke. strains. We are now testing the ability of this first control studies, the frequencies of apoE ε2 and ε4 set of DNAzymes to cleave dengue RNA. alleles are generally increased in stroke patients. Study instruments: We detect cleavage activity by To help support or refute the hypothesis that apoE observing fragments of the viral RNA on gel genotypes affect the risk of stroke via an effect on electrophoresis. inflammatory cytokine expression, we propose to Interventions: Incubating purified viral RNA with a examine whether the association of apoE isoforms DNAzyme. with cytokine production that we observed in cultured Main outcome measures: Amount of cleaved and cells also occurs in humans. We will select 200 of intact RNA, as measured by intensity of bands on the participants in an ongoing longitudinal community Northern blots and by quantity of RNA by RT-PCR. study (the MrOs study) who had a stroke any time after Analysis: ANOVA enrollment, and an equal number who did not have a transfected, cultured cells. Macrophages Therefore, apoE genotypes might In case stroke. We will measure levels of apoE, IL-6, and 237 Faculty of Medicine Dept of Medicine & Therapeutics TNF-α in serum samples collected and frozen at In this proposal, we aim to investigate the association enrollment, genotype DNA of subjects for apoE between amylin gene mutations and islet amyloid in polymorphisms ε2/ε3/ε4 and promoter SNPs, and will type 2 diabetes using postmortem specimens. then compare cytokine levels among subjects with Human autopsy materials of 300 type 2 diabetic different apoE genotypes. patients and that of 200 nondiabetic control cases will (MD06643) be used to examine the following hypothesis. Increased islet amyloid was associated with reduced The Amylin Gene Mutations and Islet Amyloid in beta/apha cell ratio and increased clinical severity of Type 2 Diabetes Mellitus type 2 diabetes and that these associations were in part related to amylin gene mutations (S20G, CHAN Chung Ngor Juliana IAPP-132G/A, NG Ho Keung (Anatomical & Cellular Pathology) combination ZHAO -215T/G, of Q10R). molecular Using biology a and histopathological techniques, genomic DNA will be Hailu TONG Peter Chun Yip used to determine the amylin genotypes and their 1 January 2007 correlations with frequency and extension of islet Research Grants Council (Earmarked Grants) amyloid deposits, islet beta/apha cell ratio, and Type 2 diabetes mellitus is characterized by islet clinical severity of type 2 diabetes as reflected by a amyloid formation consisting predominantly of requirement of insulin therapy for glycaemic control amylin (islet amyloid polypeptide, IAPP), a 37-amino will be examined. acid polypeptide co-localized and co-secreted with important insights into the role of amylin and its insulin by islet beta-cells. There is accumulating genetic determinants in pancreatic beta- cell failure, data supporting the notion that amylin is central to now widely accepted as a critical factor in the overt the pathophysiology of Type 2 diabetes. manifestation of type 2 diabetes. Four These results should throw (CU06462) mutations (S20G, IAPP-132G/A, -215T/G, Q10R) of the amylin gene have been implicated in association with type 2 diabetes. Synthetic S20G amylin forms A amyloid more readily than wild-type amylin and Double-dummy, exerts The Comparative Efficacy and Safety Study of IAPP-132G/A mutation has been shown to enhance Esomeprazole 20mg qd Versus Ranitidine 150mg the transcription of the amylin gene and hence has the Bid in Patients with an NSAID-associated Gastric potential to increase the production of amylin. A Ulcer when Daily NSAID is Continued (Study pilot genetic-autopsy correlative study showed that Code : D9617L00001) greater biological cytotoxicity. Multicentre, Randomized, Double-blind, Parallel-group, 8-week 7% of type 2 diabetic patients with islet amyloid had CHAN Ka Leung Francis -132G/A mutation compared with 0% in those without islet amyloid. Yiu These data therefore suggest SUNG Joseph Jao WONG Wai Sun Vincent* Grace LH* LAI Larry H* that genetically-determined qualitative or quantitative changes in amylin can affect islet amyloid deposition 1 May 2007 with resultant toxicity to pancreatic insulin-producing AstraZeneca Hong Kong Limited cells. Faculty of Medicine 238 WONG Dept of Medicine & Therapeutics Research Fund for the Control of Infectious Millions of people worldwide take NSAIDs each day to treat inflammation and pain primarily due to Diseases arthritic conditions such as osteoarthritis and rheumatoid arthritis. Purpose: To investigate the relationship of serum However, NSAID use has hepatitis B virus (HBV) DNA levels with the been associated with a relatively high level of development adverse side effects, including the development of liver cirrhosis, cirrhotic complications and hepatocellular carcinoma (HCC). upper GI symptoms, gastric and duodenal ulcers, and Objective / Hypothesis: We aim to study the serial serious and fatal complications resulting from such HBV DNA levels in a longitiudinal cohort of chronic ulcers (e.g., hemorrhage and perforation). Newly introduced NSAIDs of HBV infected patients to determine a level that is that are selective associated inhibitors of COX-2 (i.e., celecoxib and rofecoxib) with increased risk of developing liver-related complications. We hypothesize that a appear to reduce the incidence of gastric and higher HBV DNA level is associated with higher risk duodenal ulcers and ulcer complications compared to of liver-related complications. those that are not selective for COX-2 (i.e., Design and subjects: We have recruited and nonselective NSAIDs, such as naproxen). However, prospectively followed up a cohort of 426 chronic the overall incidence of adverse events associated hepatitis B patients since 1997. with these agents remains high, and they may not be All patients are regularly followed up with biochemistry and virology appropriate as monotherapy in patients at risk of tests monitored. All patients are undergoing HCC thromboembolic events. surveillance program with regular alfa-fetoprotein Esomeprazole is the first PPI developed as an optical isomer which has the capacity to inhibit gastric H+, and ultrasound abdomen examination. K+-ATPase, the proton-transporting enzyme involved residual serum samples are stored in -80 degree freezer. in the production of hydrochloric acid in the stomach. Instruments: TaqMan real-time PCR assay will be The oral form of esomeprazole 20 mg and 40 mg is used to measure HBV DNA at a range of 100 to approved in the US, the European Union, China and a 1,000,000,000 copies/ml. number of countries in the rest of the world for Interventions: Serum HBV DNA will be measure at treatment of reflux disease and in combination with the baseline and yearly intervals. antibiotics for healing of duodenal ulcer and eradication of Helicobacter pylor. Serial Main Outcome Measures and Analysis: HBV DNA In US and the will be expressed as peak level, trough level, mean European Union Esomeprazole is also approved to level and area under curve for analysis. treat and prevent NSAID induced gastric ulcer. The association of HBV DNA levels with development of (MD06444) liver-related complications will be determined. Hepatitis B Virus DNA and Potential confounding variables including clinical Liver-related (age, gender, cirrhosis) and virological (genotype, Complications basal core promoter mutations) will be adjusted. To determine a HBV DNA cutoff level that has a CHAN Lik Yuen Henry CHEUNG Siu Tim* sensitivity of 90% with half width 95% confidence 1 January 2007 239 Faculty of Medicine Dept of Medicine & Therapeutics interval of 3%, 385 patients will have sufficient Idiopathic Thrombocytopenic Purpura (ITP), power for the study. Previously Enrolled in an Eltrombopag Study (MD06680) CHENG Gregory LAM Tai Pong* Targeting EZH2/Stathmin Signaling Cascade for 1 August 2006 Cancer Therapy GlaxoSmithKline Limited CHEN Yangchao Chronic ITP is primarily a disorder of adult.. KUNG Hsiang Fu (Stanley The disease is characterized by a chronically low platelet Ho CEID) count (<150,000/µl). 1 April 2007 Patients’ signs and symptoms are largely, though not exclusively, dependent on the CUHK Research Committee Funding (Direct platelet count. Patients may have few symptoms or Grants) may suffer bruising or purpura. The most serious Hepatocellular carcinoma (HCC) is a leading cause complication of ITP is bleeding, which includes of cancer morbidity and mortality in Hong Kong and catastrophic intracerebral or gastrointestinal bleeding. China. The enhancer of zeste homolog 2 (EZH2), a These are uncommon when the platelet count is member of polycomb-group (PcG) protein family, above 30,000/µl but it is well recognized that the has been shown to play a crucial role in embryonic natural history of ITP in adults is highly variable and development and cellular differentiation. We unpredictable in its natural history The main goal of recently shown the critic role of EZH2 and its therapy is the well-being of the patient and prevention signaling cascade in HCC tumorigenesis (Chen et al. of bleeding by elevating the platelet count to a “safe” Hepatology, 2007, in press). level. To date, the long-term treatment of ITP has Using proteomic technology, we showed that suppression of EZH2 been resulted corticosteroids, in the down-regulated (manuscript submitted). of stathminl unsatisfactory, and involves immunoglobulins, immunosuppressive In this proposal, we will treatment more chemotherapy, extend our study to further characterize the oncogenic splenectomy roles of EZH2/statminl signaling cascade and to antibodies targeted against B cell antigens. examine the therapeutic value of Lenti-shEZH2 and Patients often respond to first-line therapies but Lenti-Stathminl for the treatment of HCC. Finally, relapse soon after discontinuation, requiring second- we will validate additional downstream targets of and third-line therapies. EZH2. significant clinical management problem. Information gained from this study will and drugs, recently monoclonal Refractory disease is a All advance our knowledge and provide new therapeutic treatments to date are associated with significant targets for HCC. morbidity, and for some agents, mortality. (MD06890) administration of an oral agonist of The the thrombopoietin (TPO) receptor, such as eltrombopag Dosing olamine (SB-497115-GR), could reduce the severity Study): An Extension Study of Eltrombopag and duration of thrombocytopenia, reduce the Olamine requirement for steroids, The rationale for this EXTEND (Eltrombopag (SB-497115-GR) eXTENded in Adults, with proposed phase III study is two-fold: 1) to confirm the Faculty of Medicine 240 Dept of Medicine & Therapeutics short-term safety and efficacy profiles of eltrombopag; with previously treated chronic and 2) to evaluate the long-term 6 month safety and thrombocytopenic purpura (ITP). efficacy of eltrombopag in the treatment of previously (MD06836) idiopathic treated subjects with ITP. (MD06730) LENS – Long-term Eltrombopag ObservatioNal Study – A Long Term Observational Ocular A Randomized, Double-Blind, Placebo-Controlled Safety Follow-up Study in Adults Who Have Phase III Study, to Evaluate the Received Study Medication (SB-49711-GR / Efficacy, Safety Tolerability of Eltrombopag Eltrombopag Olamine or Placebe) in a Phase II or Olamine III Clinical Study Evaluating Eltrombopag (SB-497115-GR), a Thrombopoietin Receptor Agonist, Administered for 6 Months as CHENG Gregory Oral Tablets Once Daily in Adult Subjects with Previously Treated Chronic Idiopathic WONG Siu Ming Raymond CHENG Chak Kwan Arthur (Ophthalmology and Visual Sciences) Thrombocytopenic Purpura (ITP). 1 March 2007 CHENG Gregory WONG Raymond* GlaxoSmithKline Limited 1 November 2006 Idiopathic thrombocytopenic purpura is a very GlaxoSmithKline Limited common hematological condition. Patients have Idiopathic thrombocytopenic purpura is a very increased bleeding tendency and sometimes fatal common hematological condition. Patients have hemorrhage. High dose steroid is usually the first increased bleeding tendency and sometimes fatal line of treatment with response rate of 30-60%. For hemorrhage. High dose steroid is usually the first patients line of treatment with response rate of 30-60%. For splenectomy, anabolic steroids, cytotoxic drugs, patients intravenous not responding to steroid therapy, not responding to immunoglobulin, steroid are therapy, alternative splenectomy, anabolic steroids, cytotoxic drugs, treatment options. However, 10-15% of patients are intravenous alternative refractory despite the above treatment modalities. treatment options. However, 10-15% of patients are These patients have frequent admission to hospitals refractory despite the above treatment modalities. with uncontrolled bleeding. These patients have frequent admission to hospitals thrombopoietin receptor agonist had been shown to with uncontrolled bleeding. increase platelet counts in patients with refractory immunoglobulin, are SB 497115-GR, a SB 497115-GR, a thrombopoietin receptor agonist had been shown to immune thrombocytopenia in preliminary studies. increase platelet counts in patients with refractory In animal models, there may be increased risk of immune thrombocytopenia in preliminary studies. A cataract. randomized, double-blind, placebo-controlled phase study in adults who have received study medication III study, to evaluate the efficacy, safety tolerability (either active drug or placebo) in a phase II or phase of III clinical study evaluating eltrombopag. eltrombopag olamine (SB-497115-GR), a A long term observation ocular safety The thrombopoietin receptor agonist, administered for 6 study will follow subjects for 2.5 years since months as oral tablets once daily in adult subjects completion of previous eltrombopag studies. 241 Faculty of Medicine Dept of Medicine & Therapeutics The duration of patient's participation depends on (MD06429) whether the patient is enrolled at the beginning, Randomized, Multinational, Double-Blind, middle, or at the end of the study. Multicenter, Placebo-Controlled, The longest duration is expected to be 50 months (just over 4 Two-Arm Parallel Group Trial of Rimonabant 20 mg OD for years). Reducing the Risk of Major Cardiovascular (MD06778) Events in Abdominally Obese Patients with Inhaled Pre-Prandial Human Insulin with the Clustering Risk Factors AERx® iDMS versus s.c. Insulin Aspart in Type 2 CHOW Chun Chung Francis KONG Pik Shan Diabetes: A 104-Week, Open-Label, Multicentre, LEUNG Linda* LI Liping* ZHU Rong* Randomised Trial Followed by 12-Week Re-Randomised Extension to Investigate Safety 1 August 2006 and Efficacy (Trial ID: NN1998-2161 Trial Phase: Sanofi-Aventis Singapore Pte Ltd 3a) The purpose of this research study is to see whether CHOW Chun Chung Francis an experimental drug called rimonabant, at 20 mg a day, can help lower the chances of having a heart attack, a stroke, or of dying from a heart attack or Yuen Shan Angela# stroke. LAU Wing Yan Rimonabant, at this dose, has been given in several OZAKI Risa KONG Pik Shan YEUNG Chun Yip CHENG LUK On Yan Andrea 1 September 2006 studies already, to more than two thousand patients. Novo Nordisk Hong Kong Ltd It works on receptors (targets) in the brain and in the fat cells. It does not affect the way patient digest Subcutaneous insulin administration has been the food. only mode used in clinical practice in treatment of Rimonabant may decrease weight and waist diabetes for nearly eighty years. Despite the fact circumference (waist measurement), and it may, even that today’s devices, including plasma glucose without loss of weight or waist circumference, also monitors, have substantially improved compliance, improve other conditions that increase the risk of frequent injections remain an obstacle for many heart attack and stroke, such as diabetes and certain subjects. lipid (blood fat) abnormalities. treatment in type 2 diabetes leads to suboptimal Besides the current treatments, patient will have one glycaemic control. additional pill to take every day. Patient will have a The development of non-invasive insulin delivery 50:50 (1 in 2) chance of receiving rimonabant and an systems that mimic the physiological insulin profiles equal 50:50 chance of receiving placebo (an inactive is considered to improve compliance for subjects in or sugar pill). obtaining acceptable plasma glucose control by Neither the patient nor the study Poor compliance to intensive insulin doctor will know which treatment the patient are means of frequent insulin injections. receiving during the study. This study is also called a The AERx insulin Diabetes Management System “randomized” study. (AERx® iDMS), a breath actuated device for administration of liquid insulin by inhalation has been Faculty of Medicine 242 Dept of Medicine & Therapeutics developed for administration of insulin at mealtime to primary care setting, with two parallel treatment arms: closely mimic the endogenous release of insulin. standard clinical practice versus education on ® AERx iDMS is a registered trademark of Aradigm diabetes management using International Diabetes Corporation or its affiliates in the United States and Federation-Western other countries. It is generally believed that the deep “Type 2 diabetes (T2DM) practical targets and lung (alveolar, gas exchange region) is the site of treatments”. The study duration will be 12 months. maximum macromolecular absorption, and therefore General Practitioners (GPs) will be randomised to this area of the lungs is anticipated to be the optimal receive education on the IDF-WPR guidelines or to site for disposition of the insulin aerosol. AERx receive no trial-related education. 400 subjects will produces a fine particle aerosol and the device is be recruited from ten Asian countries (China, Hong constructed to optimise the amount of insulin Kong. delivered during a single breath and transport the Philippines, insulin to the desired parts of the lungs. The amount Vietnam). of insulin delivered during a single breath can be The primary objective is to evaluate whether precisely steps education about T2DM management using the comparable to one subcutaneous International Unit. IDF-WPR publication “Type 2 Diabetes Practical The subject’s inspiratory profile must be within Targets and Treatments, Fourth Edition” is more specified flow/volume parameters for the device to effective than standard practice in primary care extrude the insulin, ensuring optimal delivery. (general practice) for the management of T2DM. The AERx device contains a validated data capture (MD06616) controlled and increased in Pacific Indonesia, Region South Singapore, (IDF-WPR) Korea, Taiwan, Malaysia, Thailand and and downloading system enabling downloading of data stored in the device, providing information on Reduce Ventricular Pacing in Dual Chamber date, time, dose of inhaled human insulin, and the ICDs using AutoIntrinsic Conduction Search flow rate and volume, allowing monitoring of (REDUCE Study) adherence to therapy. (MD06830) FUNG Wing Hong CHAN Chi Kin Hanmish* CHAN Yat Sun Joseph CHAN Chin Pang GIANT : General Practitioner Implementation in LAM Yat Yin CHAN Wai Ling* Asia of Normoglycaemic Targets Man YU Cheuk 1 November 2006 COCKRAM Clive Stewart KONG Pik Shan St Jude Medical (Hong Kong) Ltd CHAN Chung Ngor Juliana TONG Peter Chun Yip An Implantable Cardioverter Defibrillator (ICD) is indicated for the treatment of ventricular tachycardia 1 March 2007 (VT) and ventricular fibrillation (VF). These two The International Diabetes Institute (IDI), types of fast irregular rhythms begin in the lower Melbourne, Australia chambers (ventricles) of the heart. In VT and VF This is a prospective multinational, multicentre, the heart beats too rapidly and cannot deliver cluster-randomised oxygen-rich blood to vital organs. If the supply of study conducted within the 243 Faculty of Medicine Dept of Medicine & Therapeutics oxygen-rich blood is reduced, loss of consciousness via and death may occur unless the blood supply is assessment restored. An electrical pulse or shock delivered ciprofloxacin, from the device through a lead (thin insulated wire) azithromycin, to the heart can stop the fast irregular heart rhythm ceftazidime, and restore normal function. piperacillin/tazobactam, The dual-chamber Minimum Inhibition with Concentration levofloxacin, moxifloxacin, amoxicillin/clavulanate, clarithromycin, cefuroxime, (MIC) cefepime, penicillin, ceftriaxone, imipenem, pacemaker in the ICD is needed when the heart’s trimethoprim/sulfamethoxazole, electrical system is not providing proper electrical panipenem (in China only) and cefotaxime (outside signals to the upper (atria) and lower (ventricles) China only) among clinical isolates of bacteria from chambers of the heart. patients with Acute Bacterial Exacerbation of The pacemaker delivers electrical impulses from the device through a lead to Chronic the heart as needed to copy the heart’s own natural (ABECOPD). rhythm. Several studies suggested that right distribution of the causative bacteria from ABECOPD ventricular apical pacing may have deleterious effects patients in the targeted Asian countries will be on cardiac function. investigated. One of the new features in the Obstructive amikacin, Pulmonary Disease Furthermore, the prevalence and Results of this study will help to ICD is called “AutoIntrinsic Conduction Search” develop evidence-based guidelines on the proper and (AlCS). optimal antibiotic recommendations of ABECOPD When this feature is turned on, the ICD allows natural heart rhythm to take over the suitable for the Asian region, based on contraction of the heart, which can lead to a longer microbiological data through clinical screening for battery life and may improve overall condition. The causative pathogens from ABECOPD patients in this primary purpose of this research is to evaluate the region and antimicrobial susceptibility testing of such effectiveness of AlCS on the heart to beat on its own pathogens in this study. more. (MD06500) (MD06767) Evaluation and Control of Allergic Rhinitis IN A Comparative Study of the In-Vitro Activity of Patients with Asthma (CARINA) Levofloxacin and 15 Other Antibiotics among Bacterial Isolates Causing Acute HUI Shu Cheong David Bacterial KO Wai San Fanny Exacerbation of Chronic Obstructive Pulmonary TO Kin Wang Disease (ABECOPD) in Selected Asian Countries Michael* NGAI Jenny* WONg Carrie* NG Susanna* CHAN 1 February 2007 HUI Shu Cheong David FOK Pui Chu Joan KO Wai San Fanny TO Kin Wang Merck Sharp & Dohme (Asia) Ltd CHAN Chio Ho Michael* 王迎軍* This is a descriptive study to evaluate the proportion of allergic rhinitis in patients with persistent asthma 1 August 2006 who visit clinics for asthma treatment. The patient Daiichi Pharmaceuticals Co Ltd who visits clinic during study period, aged 18 years This is a multi-center study involving an in-vitro and over, with and without allergic rhinitis and surveillance of antimicrobial resistance, determined eligible by inclusion criteria will be enrolled. Study Faculty of Medicine 244 Dept of Medicine & Therapeutics sample will include approximately 500 persistent demonstrated to reveal the full spectrum of aerosol asthma patients. dispersion (as marked with smoke particle), from a Two to three hospitals will participate in this study. high-fidelity human patient simulator during the About 100-200 patients who are eligible will be enrolled consecutively application without omission from the study commencement to (including oxygen masks and nebulisers). avoid detection bias in each clinic. simulator The number of of will common be respiratory programmed apparatus to The reproduce asthma patients with concomitant allergic rhinitis by conditions of mild, moderate and severe chest ISAAC questionnaire will be counted. The severity infections. Aerosol dispersion during non-invasive of asthma, allergic rhinitis, physicians’ therapeutic positive pressure ventilation and coughing bouts will class choice for asthma and allergic rhinitis, asthma also be examined. and allergic rhinitis related resource utilization such repeated in the ward with active scavenging system as OTC medication and visiting doctor will be and in an isolation room with negative pressure. recorded. The primary endpoint is the maximum aerosol (MD06502) (indicated by smoke) dispersion. These experiments will be This study will evaluate the interactions among the types of Aerosol Dispersion During Common Respiratory respiratory apparatus, oxygen flow, lung injury and Therapies : A Risk Assessment Model of room ventilation on the spread of infected aerosols. Nosocomial Infection to Healthcare Workers This study promotes safe practice in the healthcare workplace. HUI Shu Cheong David Potential application of results: The study will alert CHAN Matthew Tak Vai (Anaesthesia & Intensive Care) healthcare workers on the risk associated with aerosol Stephen generating procedures and facilitate clinicians to HALL* develop 1 February 2007 strategies for preventing nosocomial infection. The study will provide important data for Research Fund for the Control of Infectious engineers and architects to design a safe environment Diseases for the care of patients with chest infection. (MD99564) Purpose: Healthcare workers are concerned about the risk of acquiring contagious diseases such as SARS and avian influenza while providing respiratory A therapies to patients with severe chest infection. Double-Mask, Double-Dummy Study Comparing The purpose of this study is to assess the risk of the Efficacy and Safety of Peramivir Administered generation and extent of dispersion of potentially Intravenously Once Daily versus Oseltamivir infected respiratory Administered Orally Twice Daily in Adults with We also evaluate the effectiveness of Acute Serious or Potentially Life-Threatening therapies. aerosols during common scavenging devices and negative pressure room Phase II, Multicenter, Randomized, Influenza ventilation to minimize transmission of infectious HUI Shu Cheong David KO Wai San Fanny* aerosols. Study design: This study will employ a novel laser TO Kin Wang* NG Susanna* CHAN visualization method that has been successfully 245 Faculty of Medicine Dept of Medicine & Therapeutics Michael* NGAI Jenny* WONG Carrie* nasal congestion, headache, myalgia, feverishness, LEE Lai Shun Nelson LUI Grace* malaise or fatigue (these assessments will be recorded on each day that the subject's medical 1 April 2007 condition BioCryst Pharmaceuticals, Inc. allows for query by study staff). Participating subjects will be asked to provide a daily This is a multinational, randomized, double-mask, self assessment of ability to perform usual daily double-dummy study comparing the efficacy and activities (these assessments will be recorded on each safety of peramivir administered intravenously once day that the medical condition allows). daily for 5 days versus oseltamivir administered duration of hospitalization, indicators of possible orally twice daily for 5 days in adults hospitalized clinical relapse and incidence of mortality will also with acute serious or potentially life-threatening be assessed. influenza. (MD06351) The Subjects with signs and symptoms compatible with acute influenza infection and for whom a positive A Rapid Antigen Test (RAT) for influenza virus Placebo-Controlled, infection is present will be evaluated for participation. Assess Long Term (one-year) Efficacy and Safety Enrolled subjects will be randomized to receive one of of Tiotropium Inhalation Solution 5µg (2 puffs of three treatments: 2.5µg) Delivered by the Respimat® Inhaler in Treatment Gp 1: Peramivir (BCX-1812) 200 mg, Patients with Chronic Obstructive Pulmonary administered intravenously, once daily (q 24 hrs) for Disease (COPD) Randomized, Doubled-Blind, Parallel-Group Study to 5 days (5 doses). Treatment Gp 2: Peramivir BCX-1812) 400 mg, HUI Shu Cheong David KO Wai San Fanny* administered intravenously, once daily (q 24 hrs) for TO Kin Wang* 5 days (5 doses). Michael* NGAI Jenny* WONG Carrie* Treatment Gp 3: Oseltamivir 75 mg, (oral suspension) administered po, twice daily for 5 days (10 doses). NG Susanna* CHAN 1 April 2007 Boehringer Ingelheim Int'l Trading (Shanghai) Randomization will be stratified according to two Co Ltd strata: • Transcutaneous oxygen saturation<94% or This study is a one-year multicentre, multinational, =94%. randomised, • placebo-controlled study to evaluate the long-term Duration of illness =48 hr or >48 hr to =72 hr. double-blind, parallel-group Subjects will be evaluated at least twice daily while safety and efficacy of tiotropium inhalation solution hospitalized to assess the criteria for clinical stability 5µg. This study investigates the pulmonary effects (measurements of temperature, respiration rate, of tiotropium inhalation solution, a long-acting systolic blood pressure, heart rate and transcutaneous anticholinergic bronchodilator, administered by the oxygen saturation). newly At least once during each developed pocket-sized, multi-dose scheduled study visit day, subjects will be assessed Respimat® soft mist inhaler in patients with chronic by study staff for the presence and severity of each of obstructive pulmonary disease (COPD). seven symptoms of influenza- sore throat, cough, Respimat® inhaler is a novel, propellant-free inhaler, Faculty of Medicine 246 The Dept of Medicine & Therapeutics which is a new alternative to metered dose and dry improves patient's blood sugar, compared to taking powder inhalers. It has a unique delivery mechanism, rosiglitazone and metformin alone. which relies on a spring rather than a propellant or Patient who is aged from 18-78 with Type II DM is electrical energy to generate a slow-moving cloud eligible for participating in the study. The enrolled from a drug solution contained in a cartridge. This patient will be in the study about 77 weeks (about 1 study will take place in to 36 countries worldwide and year and 7 months). at least 3000 patients with either sex, 40 years or older, (MD06484) and with a diagnosis of moderate to server COPD will be invited to take part. Following an initial screening To visit, patients will be randomised into the one year, Rehabilitation on Exacerbations, Hospitalization double-blind treatment period of the study in which Rates and Quality of Life in Patients Admitted to they will receive either tiotropium 5µg or placebo. Hospital with Acute Exacerbation of Chronic This study consists of a screening period, a treatment Obstructive Pulmonary Disease Study the Effect of Early Pulmonary period and follow-up period and requires a total of 15 clinic visits or contacts over a period of approximately 14 months. A questionnaire (St. KO Wai San Fanny George’s HUI Shu Cheong David DAI Lok Kwan David LAU Herman* Respiratory Questionnaire) will be completed by 1 July 2006 patients at the randomisation visit and repeated after Hong Kong Lung Foundation 24 and 48 weeks of study treatment. Vital signs will be measure on breathing test days. Additional Chronic obstructive pulmonary disease (COPD) is a observations will include review of exacerbation disease state characterized by airflow limitation that status, adverse events, and concomitant therapies is not fully reversible. Acute exacerbation of COPD during the period of the study. (AECOPD) with increasing symptoms like dyspnea, (MD06815) cough and sputum is the natural history of the disease and incurs significant burden to our health care In Hong Kong, COPD was the 5th leading A Phase III Randomized, Placebo-Controlled system. Clinical Trial to Study the Safety and Efficacy of cause of death, and accounted for at least 4% of all the Addition of Sitagliptin (MK-0431) in Patients public hospital acute admissions in 2003. Previous with Type 2 Diabetes Mellitus Who Have studies have shown that pulmonary function and Inadequate Glycemic Control on Combination quality of life were adversely affected by frequent Therapy with Metformin and a PPARγ Agonist exacerbations. Strategies to decrease the heavy use of health care resources is urgently needed for the KO Tin Choi TONG Peter Chun Yip benefits of the patients and the society. 10 August 2006 Pulmonary rehabilitation programme (PRP) is a multidisciplinary programme of care for patients with Merck Sharp & Dohme (Asia) Ltd chronic respiratory impairment. In COPD patients, The purpose of the study is to test the safety of the the programme can be tailored individually and can research study drug, sitagliptin & test whether taking optimize sitagliptin, together with rosiglitazone and metformin performance and autonomy. 247 each patient’s physical and social Previous studies on Faculty of Medicine Dept of Medicine & Therapeutics KO Wai San Fanny patients with stable COPD found that a PRP HUI Shu Cheong David including education and physical training could lead LEUNG Ting Fan (Paediatrics) to statistically significant and clinically meaningful Kin Gary (Paediatrics) improvements in health related quality of life and WONG Wing 1 July 2007 exercise capacity. Hong Kong Lung Foundation COPD patients who just have experienced an episode of acute exacerbations are at high risk of developing Non-invasive assessment of airway inflammation has another been a hot research topic in recent years. attack. There has been only one There is a randomized controlled study looking at the effect of growing body of literature on the role of fractional out-patient PRP for patients immediately after an exhaled exacerbation. It has shown that PRP immediately measurement. after an exacerbation was safe and improved the significantly elevated in subjects with asthma when exercise capacity and the quality of life at 3 months. compared to controls a decade ago. However, the follow up duration of the study was asthmatics with inhaled corticosteroid (ICS) results short and thus the effect of rehabilitation on recurrent in improved disease control, which is also associated exacerbations and hospitalizations is not assessed and with a reduction of their FeNO. this information is important. suggested that FeNO might be used to guide asthma We would thus like perform a randomized controlled therapy, and asthma control was not compromised trial to assess if a short course (for 6 weeks) despite the fact that the maintenance doses of ICS out-patient PRP for patients admitted to acute were significantly reduced. hospital for AECOPD could have a positive impact Correct interpretation of the FeNO value is important on the patients by decreasing their health care when using it for assessment of airway inflammation. resources utilization (recurrent COPD exacerbations, The production of endogenous nitric oxide (NO) is hospitalizations dependent the enzyme NO synthase(NOS). and accident and emergency nitric oxide concentration (FeNO) FeNO was first demonstrated to be Treatment of A recent study has A department [AED] attendance) and improving the previous study has found that NOS3 missense quality of life of the patients over a period of 1 year. sequence variant in endothelial NOS gene (G894T) Patients will be randomized to either a control group was associated with elevated FeNO level in a US or PRP intervention group. cohort (TT genotype had a significantly higher FeNO It is hope that the information generated from this value than GT genotype). study will be able to give a guide to whether short polymorphism (SNP) C5266T in exon 29 of NOS1 course PRP is effective for the patient (in terms of was linked to asthma in Caucasians. Our group has quality of life) and the health care system (in terms of demonstrated that NOS1 C5266T and AAT repeats health care utilization). affected plasma IgE concentrations in Chinese (MD06801) children. The single nucleotide There is, however, no such information available for the Chinese adult population. As there Study of Exhaled Nitric Oxide Level and Nitric is considerable ethic difference in genetic makeup in Oxide Synthase Gene Polymorphisms in Normal different racial groups, assessment of the relationship Adults in Hong Kong of FeNO and NOS in our own population is Faculty of Medicine 248 Dept of Medicine & Therapeutics KONG Pik Shan CHAN Chung Ngor Juliana important. There is also a controversial relationship between FeNO and atopy. TONG Peter Chun Yip Previous studies on reference values of FeNO in the Angela# population are mainly limited to children. We have CHENG Yuen Shan 1 November 2006 compared the healthy school students of Chinese Roche Hong Kong Limited descent and the healthy school children of Caucasian descent in Hong Kong and found that FeNO were Type 2 diabetes mellitus (T2D) is a chronic, significantly higher in the former. The data on adult progressive and multisystem disorder affecting all reference FeNO values are even more limited as we ages and population groups. This is a condition that could only identify two studies in the literature. Both leads to an increased amount of a sugar called studies were limited by a small sample size (about glucose in blood. RO0728804 belongs to a class of 200 subjects( and none looked into other factors that drugs could affect FeNO, such as atopy and the genetic mulit-center phase 2 study is to learn how effective, make up of the subjects. safe and well tolerated the study drug is in treating The aim of this study is to establish the normal T2D. Additionally, RO0728804 may also improve reference value of FeNO in our adult population. In the level of lipids (fats) in patient’s blood. addition, the relationship between the FeNO in our RO0728804 has been studied in animals, and to date population with atopy and the NOS1 C5366T and it has been given to at least 183 people at various NOS3 G894T SNP will be assessed. FeNO, doses, for up to six weeks, without unexpected side spirometry, atopic status (by total IgE level and skin effects. prick test), and NOS1 C5366T and NOS3 G894T The main purpose of this study is to find a safe and SNP will be assessed in all subjects. well tolerated dose of the study drug that will FeNO is a promising non-invasive marker for improve control of glucose in T2D patients. assessment of airway inflammation, particularly effects of the study drug will be compared to those of asthma. By studying FeNO in our normal population a placebo (an inactive substance that resembles an and factors that may affect its levels (like NOS gene active drug, but has no medical value), and a 45 mg and atopy), it will advance our understanding of the dose of Actos®, a medication known to effectively potential role of FeNO in the clinical management of lower blood sugar levels and approved in many asthma. countries for the treatment of T2D. Patients who pass (MD07599) screening will undergo a 4-week run-in period known as insulin sensitizers. This The followed by a 16-week treatment period. During the A Randomized, Double-Blind, Parallel Group, run-in period, a diet and exercise program will be Placebo-Controlled reinforced to the patient. Treatment duration is 16 Comparator Arm), (with Open-Label Dose-Ranging Active Study weeks followed by a follow-up visit within 4 to 15 to Determine the Efficacy, Safety, Tolerability and days after the last dose of study medication. Pharmacokinetics of RO0728804 (Dual PPAR α/γ (MD06556) agonist) Therapy when Administered to Patients with Type 2 Diabetes Mellitus 249 Faculty of Medicine Dept of Medicine & Therapeutics Sleep Duration, Neurohormonal Dysregulation Results from this study will throw major insights into and Obesity in Hong Kong Children and the pathogenesis of this massive public health problem Adolescents of obesity, diabetes and cardiovascular diseases as well as provide rationale for testing of new intervention strategy. KONG Pik Shan CHAN Chung Ngor Juliana (CU06465) TONG Peter Chun Yip YANG Xilin LI Man Chim Albert Martin (Paediatrics) Wing Kin Gary (Paediatrics) Kwok (Psychiatry) WONG WING Yun A LAM Wai Kei Christopher Multi-Center, Double-Blind, Randomized, Placeo-Controlled, Does-Ranging Phase 2 Study to (Chemical Pathology) Investigate Pharmacodynamics, Safety, Tolerability and Pharmacokinetics of RO5073031 1 January 2007 in Patients with Type 2 Diabetes Mellitus Treated Research Grants Council (Earmarked Grants) with a Stable Dose of Metformin Rapid changes in technology, human behavior and KONG Pik Shan CHAN Chung Ngor Juliana lifestyle over the last few decades have resulted in a TONG Peter Chun Yip dramatic increase in the prevalence of obesity worldwide. There is also growing evidence showing 1 February 2007 that childhood obesity may herald adult obesity. Besides social stigmata and Roche Hong Kong Limited psychological consequences, obesity is associated with increased This risks of type 2 diabetes mellitus, hypertension, parallel-controlled, multi-centre study that consists of hyperlipidemia, sleep apnoea, cardiovascular disease, three phases; screening phase of up to 3 weeks, 8 cancer and arthritis. Accompanying this global rising weeks of treatment period and up to 4 weeks of trend of childhood and adolescent obesity, there is follow-up period. amassing evidence suggesting associations between The target population for this study consists of type 2 sleep deprivation, endocrine and metabolic changes, diabetic patients, treated with an individual maximum notably obesity. tolerated daily dose of metformin monotherapy Understanding the nature of these associations will (metformin daily dose of at least 1.5g, maximum not add new dimensions to our current body of knowledge higher than recommended in the label) for at least 3 relating to behavior and disease states. It will also months prior to screening. help identifying at risk individuals for surveillance and There are six arms in the study. Patients will be testing of new treatment strategies such as the effects randomly allocated to the injected doses of of improving sleep behavior on obesity and metabolic RO5073031 5 mg, 10 mg or 20 mg every week.; 10 consequences. mg or 20 mg every two weeks; or placebo every Given the potential inter-relationships between obesity, week. Due to the double-blind nature of this study, metabolic syndrome and sleep disorders, we aim to patients randomized to the every two weeks dosage conduct a study to examine the relationships between will obesity, neurohormonal dysregulation and sleep RO5073031 or placebo. glucose intolerance and disturbance in Hong Kong children and adolescents. Faculty of Medicine 250 study receive is a randomized, alternate weekly double-blind, injections of Dept of Medicine & Therapeutics Primary Objective: To determine the efficacy, with respect 6 June 2007 to glycemic control, of multiple doses and regimens of Pfizer Corporation RO5073031 which, when added to metformin, are safe and tolerable compared with placebo in patients with type It is increasingly recognised that patients with 2 diabetes. epilepsy may have a range of comorbid conditions Secondary Objective : To compare the effects of that can exert negative impact on their quality of life, RO5073031 with placebo, when both are added to including metformin, on body weight and additional parameters of disturbances. This cross-sectional survey will help glycemic and lipid control. document the prevalence of anxiety and sleep (MD06595) disturbances among a cohort of Chinese epilepsy psychological problems and sleep patients. Prevalence findings will be correlated with A Randomized, Double-Blind, Placebo-Controlled, quality of life scores and other clinical factors related Parallel-Group, Multicenter Study to Evaluate the to epilepsy. Efficacy, Safety and Tolerability of RWJ-333369 (MD06811) as Adjunctive Therapy in Subjects with Partial Onset Seizures Followed by an Open-Label Genetics and Expression of P-glycoprotein and Extension Study Other Drug Transporters in Pharmacoresistant Epilepsy KWAN Kwok Leung Patrick Lawrence WONG Ka Sing HUI Andrew CF* KWAN LEUNG & Cellular Pathology) 24 November 2006 (Surgery) Johnson & Johnson (Hong Kong) Limited is Leung Patrick BAUM Lawrence William NG Ho Keung (Anatomical Howan* This Kwok a randomised, placebo-controlled, POON Wai Sang WONG Ka Sing Lawrence O'BRIEN Terence* 25 June 2007 double-blind, parallel-group, multi-centre Research Grants Council (Earmarked Grants) study to determine the efficacy, safety, at tolerability of RWJ-333369 as adjunctive treatment to partial Despite antiepileptic drug (AED) treatment, one third onset seizures. of patients with epilepsy continue to have seizures. AED resistance is believed to be multifactorial. (MD06774) One of the hypothesised mechanisms is the limitation Anxiety, Sleep Disturbance, and Quality of Life in of drug access to the seizure focus by a range of Chinese Adults with Epilepsy efflux transporters. These proteins extrude a wide range of foreign substances, including drugs, out of cells as a physiological host defence mechanism. KWAN Kwok Leung Patrick LEUNG Ho Wan LEUNG Wai Hong Thomas Chung Edward SOO Oi Yan WONG Ho Some of these transporters are present in the NG Ping Wing blood-brain barrier where they act as “gatekeepers” to limit the accumulation of drugs in the brain by HUI K.F.* “pumping” them back to the blood stream. 251 Faculty of Medicine Dept of Medicine & Therapeutics CUHK Research Committee Funding (Direct P-glycoprotein (P-gp) is the most studied drug transporter. Grant It has been found to be upregulated within certain epileptic brain lesions. Short-term in Angiotensin converting enzyme (ACE) inhibitor vivo animal studies suggest that some antiepileptic drugs are substrates of these transporters. use was associated with higher bone mineral There are density (BMD) in Chinese people. This conflicting data from Caucasian populations that suggested that the renin-angiotensin system (RAS) variants of the P-gp gene (ABCB1 or MDR1) are associated with drug resistant may have a significant influence in bone epilepsy. metabolism, but the exact mechanisms require Discrepancies between studies might have resulted further investigations. There is some from the heterogeneity of the study populations and experimental evidence that Angiotensin II differences in phenotype definition. The pattern and promotes osteoclastic activities. Angiotensin II frequency of genetic polymorphisms vary widely between different ethnic groups. may also reduce perfusion of bone vasculature Whether this which has been associated with osteoporosis. association can be demonstrated in the Chinese We therefore hypothesize that angiotensin II population is unknown. receptor blocker (ARB) has a significant We aim to examine the genetics and expression of beneficial effect in male osteoporosis. We also P-gp and other drug transporters in pharmacoresistant hypothesize that ARB increases perfusion in epilepsy in greater details: (1) by searching for bone vasculature. genetic variants of P-gp in patients with drug resistant epilepsy among Chinese patients; and (2) by A male osteoporosis model will be made by measuring the level and pattern of expression of P-gp orchidectomy and other drug transporters in brain tissues removed in six-month old spontaneously hypertensive rats (SHR) and the wistar Kyoto (WKY) from patients during epilepsy surgery, and correlating rats. The SHR rats and WKY rats will be randomly them with genotype and other host factors. assigned to have ARB or placebo orally once daily (CU06466) for twelve weeks. The outcome measurements include in -vivo BMD of proximal femur by pQCT, The Effect of Angiotensin II Type I Receptor Blocker on Bone Architecture and biochemical bone markers, in-vitro bone architecture Bone of femur by micro CT and histomorphology, and bone Vasculature Perfusion in Orchidectomized Male strength of femur by mechanical tests. The changes Rats in perfusion rates of vasculature in vertebrae will also be measured in-vivo by dynamic MRI at baseline and KWOK Chi Yui Timothy (Orthopaedics & Traumatology) Yafeng* QIN Ling 4 weeks after the initiation of medication. ZHANG (MD06989) ZHANG Ge (Orthopaedics & Traumatology) WANG Yixiang (Diagnostic Radiology & Organ Imaging) Influenza Virus Load in Hospitalized Patients SHENG Hui (Orthopaedics & Traumatology)# LEE Lai Shun Nelson 30 June 2007 Faculty of Medicine CHAN Kay Sheung Paul (Microbiology) HUI Shu Cheong David 252 Dept of Medicine & Therapeutics CHOI Kin Wing* COCKRAM Clive Stewart supplemental oxygen or ZHANG Mingdong (Stanley Ho CEID)# prolonged hospitalization). ventilatory support, Viral kinetics after admission/treatment will also be described and 1 January 2007 compared Research Fund for the Control of Infectious between patients with different characteristics and disease severities. Diseases (MD06326) Introduction: It is uncertain whether a higher influenza viral load is present among sicker, Identification of Proteins Forming the Gastric hospitalized patients, who are usually of advanced Cancer-Specific Serum Proteomic Fingerprint age and have co-morbid illnesses. The relationship between virus load and disease severity or LEUNG Wai Keung influenza-related complication is unclear. POON Chuen Wai SUNG Joseph Jao Yiu Objectives: (1) to determine the initial, pre-treatment 1 March 2007 influenza virus loads among hospitalized patients, CUHK Research Committee Funding (Direct and to study the relationship between initial virus Grants) load and disease severity; and (2) to describe the viral kinetics and duration of viral shedding in hospitalized, Recently we have explored the potential of oseltamivir-treated patients. non-invasive diagnosis of gastric cancer by using the Design: prospective, observational study for 12 latest serum proteomic technology. With the use of months (2 influenza seasons). very stringent criteria, we identified five proteomics Setting: a regional, university hospital. features that are differentially expressed in the sera of Subjects and sampling: all laboratory-confirmed gastric cancer patients. The individual ROC curve influenza cases admitted to the medical unit. area of the five proteomic features ranged from Clinical information and serial pooled nasal and 0.64-0.87 in the discovery set and 0.71-0.84 in the throat swabs will be collected daily for 6 days or after validation set. completion of oseltamivir treatment. combined to generate a diagnostic index, the best Laboratory studies: immunofluorescence assay for sensitivity and specificity of this panel of proteomic influenza A and B will be used for the initial markers was 83 and 95%, respectively. diagnosis of influenza infection; virus isolation will proposed study, we will purify these diagnostic be conducted using MDCK cell line; influenza virus proteomic features, and uncover their protein load in all ‘pooled swabs’ collected will be assessed identities by mass spectrometric approaches. by real-time PCR technique. We have established a findings protocol for measuring the copy number of M-gene immunoassays. from clinical specimens. (MD06928) Data analysis: we plan to will When the five markers were be subsequently In this validated The by compare initial/pre-treatment influenza virus loads (adjusting An for baseline characteristics) between patients with Parallel Group Study to Demonstrate Treatment ‘mild’ and ‘severe’ illnesses (e.g. development of of Anemia using Intravenous Injections of Open-Label, Randomized, Multi-Center, complications, high symptom-score, requirement of 253 Faculty of Medicine Dept of Medicine & Therapeutics RO0503821 in Patients with Chronic Kidney treated according to individual center practice. A Disease Who are on Dialysis – ML20680 follow-up (final) visit will be performed for all patients at study end (week 53) or at any time during LI Kam Tao Philip CHOW Kai Ming the study in case of premature withdrawal. 9 January 2007 Thereafter patients should be treated according to individual center practice. Roche Hong Kong Limited (MD06872) This is an open-label, randomized, multi-center, parallel group study to demonstrate treatment of A Randomized, Double-Blind, Placebo-Controlled, anemia using intravenous injections of RO0503821 Four-Arm, in patients with chronic kidney disease who are on Multinational Safety and Efficacy Trial of 100mg, dialysis. 300mg and 900mg of Abetimus Sodium in The purpose of the study is to investigate Systemic Lupus Erthematosus (SLE) Patients with RO0503821, an experimental new drug being a History of Renal Disease Parallel-Group, Multicenter, studied by F Hoffmann-La Roche AG for treating patients with anemia caused by chronic kidney LI Kwok Ming Edmund disease. We will study the efficacy and safety of 15 December 2006 i.v. RO0503821 treatment of anemia in patients with La Jolla Pharmaceutical Company chronic kidney disease who are on dialysis. This study is being conducted throughout mainland China The primary objective is to determine whether and HongKong, and is expected to last for at least abetimus is more effective than placebo in delaying 2.5 years. the time to renal flare in SLE patients with a history Approximately 360 patients will take part in this of SLE renal disease and who have high -affinity study. 180 patients in the RO0503821 group, 180 abtibodies to the oligonucleotide epitope of abetimus patients in the Epoetin Beta reference group. After at baseline. written informed consent is obtained, the patients The safety and efficacy of abetimus in SLE patients will be screened for eligibility over a period of 1 to 2 will be evaluated at weekly doses of 100 mg, 300 mg, weeks. and 900 mg weekly over the intended 52-week All patients must receive iv iron supplementation during the correction/evaluation periods. screening and exposure period. The study consists The secondary objectives of the trial are to determine of a correction (dose titration) period of 16 weeks whether treatment with abetimus is more effective and an evaluation period of 8 weeks, followed by an than placebo in delaying the time to Major SLE flare extension and to determine whether treatment with abetimus is period of up documentation of safety. to 28 weeks for At week 25 (after 24 more effective than placebo in reducing proteinuria. weeks of treatment), the responders of both the (MD06750) RO0503821 group and the epoetin reference group will be kept on this treatment regimen for the Activation of Intracellular Mitogen Activated subsequent 28 weeks. Protein Kinases in T, B Lymphocytes and Non-responders in both groups will be withdrawn from the study and will be Faculty of Medicine 254 Dept of Medicine & Therapeutics Macrophages in Patients with Systemic Lupus IL-18; and (3) relationship between the activation of Erythematosus ERK, JNK and p38 activity with SLE disease activity index score. Analysis of abnormal intracellular LI Kwok Ming Edmund TAM Lai Shan signaling molecules in SLE patients may provide a WONG Chun Kwok (Chemical Pathology) biochemical basis for the development of therapeutic (Chemical strategy and surrogate makers for monitoring disease LAM Wai Kei Christopher Pathology) severity. (MD06711) 1 March 2007 CUHK Research Committee Funding (Direct A Grants) 24-Weeks Prospective, Multicentre, Randomised, Double-Blind, Placebo-Controlled Systemic lupus erythematosus (SLE) is a prototypic Study of Dysport Injection for the Treatment of systemic autoimmune disease characterized by Upper Limb Spasticity in Early Stroke dysregulated activation of both T and B lymphocytes and subsequent polyclonal activation of circulating B lymphocytes to produce autoreactive antibodies. a large quantity MOK Chung Tong Vincent of mechanism T helper cell cytokines for lymphocyte WONG Ka Sing Lawrence 1 December 2006 response in SLE is very complex and the intracellular signaling Beaufour Ipsen International and macrophages activation requires further investigation. ABCDE-S Previous studies of intracellular signaling molecules multicentre, in SLE indicated the abnormal nuclear factor (NF)-κB, placebo-controlled trial to evaluate the efficacy and protein tyrosine kinase, protein kinase A, Src kinases safety of one botulinum toxin injection (DYSPORT® activity and defect of protein kinase C in T cells in 500 U) in early post-stroke spasticity. The primary SLE patients. object Another study showed the B cell is trial is a 24-weeks randomised, to evaluate the prospective, double-blind, efficacy of BTA kinase lyn deficiency in SLE patients. This project (DYSPORT®) injection in the reduction of excessive will investigate the following aspects of peripheral muscle tone of upper limb muscles. blood mononuclear cells (PBMC) from SLE patients: objective is to (i) improve neurologic outcome by (1) of improving mobility and function; (ii) alleviate painful phospho-extracellular signal-regulated kinase (ERK), muscular spasm; (iii) assess the safety profile of BTA. phospho-c-Jun NH2-terminal protein kinase (JNK) Male or female patients with moderate to severe and phospho-p38 mitogen activated protein kinase spasticity 2-12 weeks after stroke will be recruited. A (MAPK) in different leukocyte subsets including total of 162 male and female stroke patients will be CD4+ T helper (Th) cells, CD8+ T suppressor (Ts) included from Hong Kong, Malaysia, Singapore, plus cytotoxic T (Tc) cells, CD19+ B cells and Thailand, and Philippines. CD14+ macrophages; (2) the activation of ERK, JNK (MD06955) assessing the differential expression The second and p38 MAPK activity in Th, Ts, B cells and macrophages and ex vivo production of Thl/2 A Phase 2, 12-Week, Double-Blind, Dose-Finding, cytokines from PBMC upon the ex vivo activation by Placebo-Controlled Study to Assess the Efficacy 255 Faculty of Medicine Dept of Medicine & Therapeutics and Safety of a Range of SCH 420814 Doses (1 mg Therapy to Acetylcholinesterase Inhibitors on BID, 2 mg BID, 5 mg BID, and Possibly 10 mg Cognition and Overall Clinical Response in BID) in Subjects with Moderate to Severe APOEε4-Stratified Parkinson’s Moderate Alzheimer’s Disease (REFLECT-3) Disease Experiencing Motor Subjects with Mild to Fluctuations and Dyskinesias MOK Chung Tong Vincent MOK Chung Tong Vincent HO Wan Sze Wency WONG Ka Sing Lawrence YEUNG Hon Ming Jonas LEUNG 31 December 2006 Ho Wan GlaxoSmithKline Limited 1 December 2006 Study AVA102670 is a Phase III, multi-national, Schering-Plough Research Institute multicenter, randomized, double-blind, placebo This is an 18-week research study for patients diagnosed -controlled, parallel-group study designed to assess with Moderate to Severe Parkinson’s disease and also the efficacy and safety of Rosiglitazone extended experiencing difficulty in voluntary movements. release The (RSG XR) as adjunctive therapy in purpose of the study is to assess the efficacy and safety of a mild-to-moderate Alzheimer’s disease (AD) patients. range of doses of SCH 420814 when used together with a Eligible subjects who are taking a stable dose of an stable dose of L-dopa/dopa decarboxylase inhibitor to approved Acetylcholinesterase inhibitor (AchEl) will treat Parkinson’s disease. SCH 420814 is a drug that be genotypes, then assigned to one of the 2 groups may prove to be effective in treating Parkinson’s disease, based on APOE e4 status: those who carry at least and therefore the sponsor is currently gathering data to one copy of the APOEe4 allele and those who do not. allow us to gain approval from the FDA and/or other Subjects will be randomized equally to each Health Authorities, so that SCH 420814 can be used to treatment group relevant to their APOE e4 status and treat patients in the future. In this study, we will be will receive 8mg RSG XR, 2mg RSG XR, or comparing 3 doses (1 mg, 2mg, and 5 mg taken twice a matching placebo (daily). Study participation will day) of SCH 420814 with placebo (sugar pill). last a total of 58 weeks, consisting of a 4-week Approximately 160 subjects will be randomized in this screening phase, a 48-week double-blind treatment study in approximately 22 study centers worldwide for the phase, and a 6-week single blind treatment phase. first part of this study. Following the Interim Analysis, All subjects completing the double-blind treatment we may add 40 new patients, for a total of 200 patients. phase will enter the single-blind treatment phase and The study is double blind, which means neither the patient receive placebo once daily while maintaing their nor the study doctor will know whether the patient is AchEl regime. receiving the study medication or placebo. will be measured clinically using the clinical (MD06993) dementia rating scale, and psychometrically using the Primary efficacy of the study drug Alzheimer’s Disease Assessment Scale - Cognition AVA102670 – A 54-week, (ADAS-cog). Cognitive, health, activities of daily Double-Blind, Randomized, Placebo-Controlled, Parallel-Group living, Study to Investigate the Effects of Rosiglitazone pharmacology, (Extended pharmcogenomics are taken as secondary endpoints Release Faculty of Medicine Tablets) as Adjunctive 256 resource utilization, quality pharmacogenetics of life, and Dept of Medicine & Therapeutics impairment and 40 healthy controls without cognitive (MD06469) impairment will be recruited. Validity of Chinese Clinical Utility of Chinese Version of the Montreal MOCA (CMOCA) and VCA will be determined via Cognitive Assessment and Vascular Cognitive comparison with their performances on formal Assessment neuropsychological tests. Discriminant ability, inter Among Chinese Patients with and intra-rater reliability, and internal consistency of Vascular Cognitive Impairment the 2 tests will be determined. Technical properties MOK Chung Tong Vincent WONG Ka Sing Lawrence Wynnie (Diagnostic Imaging) WONG Adrian of these 2 tests will be compared against that of MMSE. LAM Wai Man Radiology NYENHUIS, & David cognitive test that can be applicable in evaluation of Organ Lee* This project aims to generate a brief vascular cognitive impairment among our ethnic group. NASEREDDINE, Ziad S* (MD06666) 1 April 2007 CUHK Research Committee Funding (Direct Validation of Genes Affecting Type 2 Diabetes in Grants) Chinese Population Ischemic white matter change (WMC) is endemic among elderly. Cognitive decline is a common sequel of WMC. With an ageing population, NG Chor Yin CHAN Chung Ngor Juliana SO Wing Yee TONG Peter Chun Yip cognitive burden of WMC will escalate. However, Ching Wan Ronald a brief cognitive test that is valid to evaluate vascular Valgerdur* cognitive impairment for daily management is KONG, lacking. Gudmar* YAU Wai Ip Ellis* The traditional mini-mental state examination is valid for evaluation of dementia of MA STEINTHORSDOTTIR, THORSTEINSDOTTIR,Unnur* Augustine* THORLEIFSSON, 15 November 2006 the Alzheimer’s type and is insensitive to mild deCODE Genetics ehf cognitive impairment or executive dysfunction that characterizes vascular cognitive impairment. Type 2 diabetes (T2D) is characterized by Montreal Cognitive Assessment (MOCA) was hyperglycemia which can occur through mechanisms recently adopted by the Neuropsychology Working such as impaired insulin secretion, insulin resistance Group of die National Institute of Neurological in peripheral tissues and increased glucose output by Disorders and Stroke as the cognitive screening test the liver. for vascular cognitive impairment. Based on our complications of chronic hyperglycemia including experiences and studies, we had constructed a new nephropathy, neuropathy, retinopathy and accelerated brief development cognitive test — Vascular Cognitive Most T2D patients suffer serious of cardiovascular disease. The Assessment (VCA). The objectives of this study are prevalence of T2D worldwide is currently 6% but is to examine the validity of MOCA and VCA in the projected to rise over the next decade. This increase evaluation of vascular cognitive impairment among in T2D is attributed to the increasing age of the Chinese. Eighty stroke patients with confluent population and rise in the prevalence of obesity. WMC and varying severity levels of cognitive Family and twin studies show that there is a 257 Faculty of Medicine Dept of Medicine & Therapeutics significant genetic component to T2D. Therefore, a epidemiology study hypothesis-independent genetics approach to find anthropometric and metabolic phenotypes. The genes with common variants contributing to T2D risk identification their may be one way to attain this goal. This project independent and interacting effects with lifestyle aims to study the T2D genes found from European factors for obesity and related metabolic disorders in populations and validate in our Chinese population. Hong Kong adolescents will provide important (MD06892) information on the pathogenesis of related diseases. of consisting genetic markers of detailed and This will enable early diagnosis and exploration of Candidate Gene Study for Adiposity in Hong novel therapeutics measures. Kong Chinese Adolescents (MD06601) NG Chor Yin Deciphering the Membrane Proteome of Rat Liver WAYE Mary Miu Yee (Biochemistry (Medicine)) GULDAN Georgia POON Chuen Wai Sue (Biochemistry (Science)) KONG Pik Shan CHAN Chung Ngor Juliana 1 March 2007 1 March 2007 CUHK Research Committee Funding (Direct CUHK Research Committee Funding (Direct Grants) Grants) Liver is one of the vital organs in mammals. There is now an epidemic of obesity and associated Deciphering the proteome (global expression pattern metabolic disorders affecting an increasingly young of proteins) of liver will lead to a better understanding population in Hong Kong. At the onset of puberty, of the function of liver. there is a rise in growth hormone (GH) level, which proteins are receptors regulating the cell proliferation promotes growth and reproductive adaptation in signals, detail analysis of liver cancer-specific adolescents, via the insulin-like growth factor (IGFl) membrane proteins may lead to identification of pathways. novel therapeutic targets. Both GH and IGFl have been reported to As many of membrane However, owing to the be related with body composition and insulin actions. unique physicochemical properties of membrane We hypothesize that genetic variations in the genes proteins, comprehensive analysis of membrane encoding the GH-IGF1 axis are associated with the proteome has been being a difficult task. susceptibility for obesity and related disorders. In proposed study, we plan to establish a reliable addition, genes that regulate food intake and energy methodology for deciphering the membrane proteome expenditure are good candidates for obesity, with of liver by using the rat as the animal model. The lifestyle factors such as dietary pattern that may outcome of this study will form the technology modify the genetic effect. In this study, we aim to platform for subsequently comparative analysis of investigate the association of these genes with membrane proteomes between normal liver and liver obesity and related metabolic traits, as well as the cancer tissues. interaction between genetic variants and lifestyle in (MD06810) modulating adiposity in 500 Hong Kong Chinese adolescents randomly selected from our previous Faculty of Medicine 258 In this Dept of Medicine & Therapeutics Early Diagnosis of Gastrointestinal Cancer: another Key Laboratory in Gastrointestinal Endoscopic and Molecular Approach Cancer in China. 3. SUNG Joseph Jao Yiu YU Jun LEUNG Wai Keung POON Chuen Wai Our ongoing research on the development of novel non-invasive gastrointestinal NG Kai On diagnostic cancer tests including for proteomic CHAN Lik markers for gastric and liver cancer and stool Yuen Henry NG Enders Kwok-wai (Surgery) markers for colorectal cancer will lead the way CHIU Wai Yan Philip (Surgery) NG Siu Man towards important medical discoveries. We are TO Ka Fai (Anatomical & applying for a patent in viral marker for HCC. (Institute of Digestive Disease) Simon (Surgery) Licensing of the marker is under negotiation with Cellular Pathology) a biotech company. We will also consider filing 1 July 2006 a patent on our proteomic markers the future. Focused Investments Scheme - Major Area of 4. Biomedical Sciences The Institute of Digestive Disease has established a working group with over 10 Asian Overall Goals and Deliverables in 6 Years countries on the study of colorectal cancer in 1. To establish the use of endoscopic diagnostic Asia. We are alos forming a working party on tool (e.g. narrow band imaging) on early gastric cancer screening. These establishments diagnosis of gastric and colorectal cancers. will put Hong Kong at the forefront of GI cancer To identify serum biomarkers for early diagnosis research and screening. 2. (MD06436) and monitoring of gastrointestinal cancer. 3. 4. To identify stool markers for screening of colorectal cancer. Collaboration with Evivar on Hepatitis B Virus Through the above, we will recommend Drug Resistance Mutation Detection authorities in healthcare services to promote SUNG Joseph Jao Yiu CHAN Lik Yuen Henry prevention and early cancer detection. 11 December 2006 Long-term Vision 1. 2. Evivar Medical Pty Limited In collaboration with our colleagues in Clinical Oncology, Chemical Pathology, and Anatomical We will collaborate with Evivar on the use the & establish SeqHepB in the determination of drug resistance partnership with Zhongshan University on the mutations among patients on anti-viral drugs in Hong development of a Key Laboratory in Cancer Kong. Research. HBV DNA extraction and sequencing of HBV Our close ties and partnership with Xijing polymerase gene. Clinical and HBV genomic data Hospital of the Fourth Military University in will be sent to Evivar and the HBV mutations will be Xian-the top center in Gastroenterology and the determined from the SeqHepB database. A cost will Peking University School of Oncology will be charged by CUHK and Evivar from the patients for further strengthen our position in Greater China this service. Cellular Pathology, we will CUHK will provide laboratory service of Our collaboration also agrees on the and will put us in a better position to apply for 259 Faculty of Medicine Dept of Medicine & Therapeutics sharing of database as well as patent in case new identify the effects of dosing on various subgroups of mutations are found under this project. dialysis patients. (MD06789) Design: Open-label randomized controlled, multicentre study. A Study on the Current Practice of Physicians Setting: A multicentre study in Hong Kong. Treating Hepatitis in Asia Pacific Region Participants: Peritoneal dialysis patients recruited from three dialysis units, all of them being SUNG Joseph Jao Yiu serologically negative for hepatitis B surface antigen 1 May 2007 (HBsAg) and antibody to hepatitis core antigen (anti-HBc) with no history of receiving hepatitis B Unrestricted Grant from SOL Limited (Hong vaccination . Kong Branch) Interventions: Half of subjects randomly assigned to The objective of the project is to further the receive 80 microgram Engerix-B intramuscularly in a awareness and understanding of the current treatment three-dose schedule at 0, 1, and 6 months, and of hepatitis in Hong Kong and round the Asia Pacific another half assigned to 40 microgram each in an region. otherwise identical manner. The project would entail developing a current treatment survey, distributing the survey via Main outcome measures: seroconversion, defined as electronic means to colleagues in Hong Kong and the hepatitis B surface antibody anti-HBs level ≥ 10 Asia Pacific and analyzing the results. IU/L 3 months after completion of the third dose, (MD06391) and the persistence of protective anti-HBs 12 months after completion of the third dose. (MD06858) Does Extra-High Dose Hepatitis B Vaccination Confer Longer Serological Protection in Detection of Circulating Endothelial Cells by Peritoneal Dialysis Patients? Peripheral Blood Endothelium-Specific Gene Expression Study in Renal Failure Patients SZETO Cheuk Chun CHOW Kai Ming 18 August 2006 SZETO Cheuk Chun Research Fund for the Control of Infectious 1 March 2007 Diseases CUHK Research Committee Funding (Direct Objective: To determine the optimum strategy of recombinant hepatitis B vaccination in Grants) the maintenance of protective anti-HBs antibody among Cardiovascular disease is the major cause of end-stage renal disease patients on peritoneal dialysis. mortality in renal failure patients. First, this study is designed to establish whether show that circulating endothelial cells (CECs) is a three-dose schedule of 80 microgram Engerix-B sensitive and specific measure of endothelial injury. vaccine could maintain protective antibody response However, enumeration of CEC requires flow among dialysis patients. cytometry and secondary staining, which are labor Secondary aim is to Recent studies intensive. We hypothesize that the peripheral blood Faculty of Medicine 260 Dept of Medicine & Therapeutics messenger RNA (mRNA) expression of The investigator (NT) led the discovery of OCTN2 as endothelium-specific genes by real time quantitative the causative gene in Primary Carnitine Deficiency polymerase chain reaction (RT-QPCR) represents a and revealed ancestral haplotypes and common convenient surrogate of CECs and a useful measure mutations in this gene in Chinese in 1999 and 2002 of endothelial injury. We plan to study 30 chronic (Tang et al. 1999; Tang et al. 2002)#. hemodialysis patients. The peripheral blood mRNA hypothesize that a different haplolype background expression of a panel of endothelium-specific gene across ethnic group accounts for the inconsistent will be measured by RT-QPCR, and the result will be findings and the true functional genetic variations compared to the degree of arterial stiffness as predisposing to AID is yet to be identified. quantified by pulse wave velocity study as well as Therefore, we propose to carry out a genetic other serologic markers of endothelial dysfunction. association study in 2 patients groups, SLE and RA (MD06714) to clarify the genetic predisposition in We this OCTN1-OCTN2 locus. One Gene Many Disease – Study of the (# The research in OCTN2 has been named OCTN1-OCTN2 Loci in Chinese Patients with Outstanding Research of the Faculty 2001/2002.) Autoimmune Disease (AID) (MD06560) TAM Lai Shan A Pilot Study of a New Device for the Diagnosis of TANG Leung Sang Nelson (Chemical Pathology) WOO Jean LI Kwok Obstructive Sleep Apnoea in High Risk Chinese Ming Edmund Patient Population in Hong Kong 1 June 2007 TO Kin Wang HUI Shu Cheong David CUHK Research Committee Funding (Direct 6 March 2007 Grants) Hong Kong Lung Foundation Genetic factors play a major role in predisposing people to autoimmune diseases including Purpose: A pilot study to validate a new portable Rheumatoid arthritis (RA) and systemic lupus sleep diagnostic device. erythematosus (SLE) (van der Helm-van Mil et al. Hypothesis: New home sleep study device provides 2005). These autoimmune diseases may share some an alternative for inpatient sleep study. common Design: Prospective randomized study. genetic predisposition dysregulation of immune system. leading to A predisposition Subject: Patients suspected of OSAS patients referred locus in 5q31 was first found in inflammatory bowel to a tertiary center. disease, located to the gene cluster of OCTN1-OCTN2 Study instruments: Home sleep study: a portable (SLC22A4-SLC22A5). Recently, haplotypes of this sleep apnea risk evaluation system(ARES) and an locus has been associated with RA and SLE in inpatient sleep monitoring system. Japanese patients but the association has been Interventions: Patients with scheduled appointment controversial as it was not replicated in other ethnic for inpatient polysomnographic sleep study (PSG) group. would be invited to use the ARES concurrently for the validation of the system. 261 This portable device is Faculty of Medicine Dept of Medicine & Therapeutics chosen because it is feasible, to perform PSG and concentration, which is thought to be the major ARES concurrently for validation. determinant Concurrent of the cardiovascular outcome. sleep study as such for validation has the advantage Optimising this response in individuals by predicting of eliminating the potential effect of night to night the best dose of the best statin to use, or whether variation in parameters of sleep studies. Patients other drugs such as cholesterol absorption inhibitors also do not have to repeat sleep studies in different like ezetimibe should be added or substituted is likely time and places. This is a pilot study for the to have a major effect in preventing cardiovascular validation of the portable device, and a subsequent disease events. The variation between individuals is cost utility assessment of the 3 models of algorithm due to a variety of lifestyle factors including diet and will be performed: 1) the conventional inpatient PSG compliance with drug therapy and a number of sleep study followed by autoCPAP titration in genetic factors. hospital; 2) empirical application of home autoCPAP different effects on different statins, because of for treatment and then inpatient PSG sleep study; and differences in metabolism and disposition resulting in 3) home sleep study with the ARES followed by differences home autoCPAP titration. This subsequent study (pharmacokinetics), but the drug concentrations in aims to assess the cost utility benefit of different the systemic circulation do not always reflect the algorithms for diagnosing and treatment of OSAS, lipid lowering efficacy. after validating the device. related to the effects of the drug (pharmacodynamics) Main outcome measures: The primary outcome is the may be similar for all the drugs in the class. validity of the ARES compared to inpatient PSG Identification of genetic factors influencing the sleep study. response to 3 of the statins in current usage in Hong (MD06662) Kong Some genetic factors may have in plasma using concentrations Other genetic factors a combined pharmacokinetic-pharmacodynamic approach should Pharmacogenetics of HMG Co-A Reductase provide information to help predict the most safe and Inhibitors with effective drug for individual patients and whether Combined drugs working though other mechanisms such as in Chinese Hyperlipidaemia: a Patients inhibition of cholesterol absorption might also be Pharmacodynamic-pharmacokinetic Approach needed. TOMLINSON Brian (CU06472) WAYE Mary Miu Yee (Biochemistry (Medicine)) Randomized, 1 September 2006 Double-Blind, Research Grants Council (Earmarked Grants) Multinational, Placebo-Controlled, Multicenter, Two-Arm Parallel Group Trial of Rimonabant 20 mg OD for The statins are known to be safe and effective and are Reducing the Risk of Major Cardiovascular indicated for the prevention of cardiovascular events Events in Abdominally Obese Patients with in a large proportion of the population in developed Clustering Risk Factors countries. However, there is a considerable TOMLINSON Brian variation between individuals in the response to these drugs in the reduction in plasma LDL-cholesterol Faculty of Medicine 262 Dept of Medicine & Therapeutics Institute of Medicinal Molecular Design Inc. 1 September 2006 Sanofi-Aventis Singapore Pte Ltd The purpose of this pilot study is to evaluate the The purpose of this study is to investigate an effectiveness and safety of an investigational product, experimental drug, rimonabant, to determine whether IMD-1041 in patients with type 2 diabetes mellitus. it can help to lower the chances of having heart attack IMD-1041 is developed by Institute of Medicinal or stroke, or dying from heart attack or stroke. Molecular Design, Inc. (IMMD), Japan, for the The primary objective of this trial is to demonstrate treatment of type 2 diabetes mellitus. The safety of the efficacy of rimonabant versus placebo for IMD-1041 has been tested in two phase I clinical reducing the risk of myocardial infarction, stroke, or studies conducted in Hong Kong and United cardiovascular death in patients with abdominal Kingdom. obesity at increased risk for such cardiovascular and well tolerated in both studies. events. A total of 20 patients with type 2 diabetes mellitus The secondary objective is to demonstrate IMD-1041 has been shown to be safe the efficacy of rimonabant versus placebo for will be recruited. reducing the risk of myocardial infarction, stroke, IMD-1041 (2xl00mg capsule) twice daily for 12 cardiovascular weeks and will be asked to come back for follow up 4 death, or hospitalization for They will receive a fixed dose of cardiovascular cause (unstable angina, transient weeks after the 12-week of treatment. The ischemic attack, cardiac rhythm disorder, congestive effectiveness of IMD-1041 will be evaluated by heart failure, syncope, or urgent revascularization measuring the blood glucose and insulin levels in procedure) in patients with abdominal obesity at patients while the safety of IMD-1041 will be learned increased risk for such cardiovascular events. by routine clinical examination, laboratory safety test Moreover, this study aims to demonstrate the effect as well as by patient’s reporting of abnormal of rimonabant versus placebo on all-cause mortality, symptoms. and to assess the safety of rimonabant in the study (MD06968) population over the duration of the study. After starting study medication, patients will be asked A Multi-Center, to see the study doctor at 1 month, 3 months, 6 Placebo Controlled, Dose-Ranging Phase 2 Study months, and then every 6 months to the last visit at to the end of the study, a total of 50 months. The Tolerability and Pharmacokinetics of RO5073031 laboratory parameters will be measured from the in Patients with Type 2 Diabetes Mellitus Treated blood samples of the patients. with a Stable Dose of Metformin Investigate Double-Blind, Randomized Pharmacodynamics, Safety, (MD06682) TOMLINSON Brian A Pilot Study to Investigate the Efficacy and 15 February 2007 Safety of IMD-1041 in Patients with Diabetes Roche Hong Kong Limited Mellitus Type 2 diabetes is a disorder characterized by elevated blood glucose (sugar) levels. Onset usually occurs TOMLINSON Brian after 35 years of age and it is associated with obesity in 11 September 2006 263 Faculty of Medicine Dept of Medicine & Therapeutics more than 80% of those afflicted. The purpose of this of these two formulations will be assessed and study is to evaluate the safety, tolerability and efficacy concluded of multiple doses of RO5073031 (a new injection bioequivalence studies. medication) in which when added to metformin (a (MD06308) based on WHO guideline for diabetic medication) comparing with placebo (with no active ingredient) in patients with type 2 diabetes. Pharmacokinetics of Single and Repeated Oral The treatment will last 8 weeks. Suitable patients Administration of S33138 20mg Daily in Chinese will be randomly allocated into six groups to injected Healthy Male and Female Volunteers doses of RO5073031 5 mg, 10 mg or 20 mg every week.; 10 mg or 20 mg every two weeks; or placebo every week. TOMLINSON Brian During the study, the efficacy of CHAN Chung Ngor Juliana WONG Raymond SM* RO5073031 will be determined regularly by measuring 1 June 2007 the patients HbAlc value (a index for blood sugar Servier (Beijing) Pharmaceutical Research and control), and patients’ safety will be monitored by Development Company Limited changes in: ECG, blood pressure, body weight and clinical laboratory tests. The purpose of this study is to characterize the (MD06562) pharmacokinetic parameters of S 33138 (concentration, time for which the concentration is Clinical Bioequivalence Study on Two Acarbose maximal and time for which the compound is no Formulations longer present in the blood) in plasma at the dose of 20 mg in healthy young male and female Asian volunteers TOMLINSON Brian after single and repeated administration. The dose of 1 June 2007 20 mg was chosen as the maximal therapeutic dose. Up to now, all clinical and phase I studies on S 33138 Vickmans Laboratories Limited development have been performed in Caucasian The objective of the study is to compare the healthy volunteers or schizophrenic patients. Prior to bioequivalence of two acarbose formulations in performing worldwide clinical trials (phases III healthy studies in patients) involving Asia, it is needed to subjects pharmacodynamic by effects standardized test meal. single-dose, assessment when of a explore how S 33138 is metabolised by Asian people. The study design is a The study is to be conducted in 24 healthy young two-treatment, taken their with three-period, Asian volunteers known to be intermediate or three-sequence crossover with washout periods of 1 extensive metabolisers for CYP 2D6 (12 males and week. Subjects will be randomly assigned to three 12 females), between 18 and 45 years of age. groups corresponding to three dosing sequences. (MD06871) During each study session, the subjects will be administered a single oral dose of acarbose or no Mechanism of Statin-induced Myopothies in medication to be taken with a standardized test meal Rodent Skeletal Muscle: the Possible Protective after an overnight fast. Efficacy parameters will be Role of Isoprenoids generated and the bioequivalence or bioinequivalence Faculty of Medicine 264 Dept of Medicine & Therapeutics TOMLINSON Brian JAMES Anthony Edward (Laboratory These include geranylgeranol and farnesol. The Animal Services Centre) proposed study thus intends to investigate the Dewi Kenneth (Laboratory molecular mechanisms of statin-induced myopathy in ROWLANDS Animal Services Centre) order to elucidate whether coenzyme Q10 deficiency or other intermediates in cholesterol synthesis are 30 June 2007 involved. CUHK Research Committee Funding (Direct (MD06424) Grants) The high incidence of atherosclerotic vascular A Phase III Randomized, Placebo-Controlled diseases in developed nations as well as increasing Clinical Trial to Study the Safety and Efficacy of prevalence in developing nations is a serious cause the Addition of Sitagliptin (MK-0431) in Patients for concern. Lipid lowering agents are believed to with Type 2 Diabetes Mellitus Who Have particularly useful in both primary and secondary Inadequate Glycemic Control on Combination prevention Therapy with Metformin and A PPARγ Agonist of CVD, with 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (HMGRIs), TONG Peter Chun Yip CHAN Chung Ngor commonly referred to as “statins” currently being the Juliana treatment of choice for hypercholesterolaemia. CHENG Yuen Shan Angela# LI Liping* MA Although statins are reasonably well tolerated, there Ronald* have however been reports of severe liver and CHAU Foo Tim* CHINNAIYAN, Arul* skeletal muscle damage as a result of high statin KONG Pik Shan YIP Chi Wai* OZAKI Risa YIP Wing Kin* 1 August 2006 concentrations reaching the skeletal muscle, in the Merck Sharp & Dohme (Asia) Ltd worst cases leading to rhabdomyolysis and acute renal failure. The precise molecular mechanisms of About the study drug(s) statin-induced myopothies however are still not Sitagliptin is part of a new class of drugs to treat clearly considerable diabetes. About 3250 people have taken either one controversy over whether deficiencies of cholesterol dose or daily doses of sitagliptin for up to about 24 pathway since months. Studies are still ongoing. Sitagliptin has HMG-CoA reductase inhibition results in the removal been generally well tolerated at the dose used in this of a number of essential metabolites from the study and at higher doses. cholesterol pathway. One of the prime deficiencies Therapies that enhance the incretin axis, including suspected of leading to the statin-induced myopathy DPP-4 inhibitors such as sitagliptin, have several appears to be coenzyme Q10 or ubiquinone, an end potential advantages over drugs that stimulate the product of one of the side pathways of cholesterol release of insulin. synthesis, although this remains unproven. A more insulin release and suppression of glucagon occur in a likely explanation however is that the mechanism is blood glucose-dependent manner. For this reason, through some other intermediates in cholesterol the risk of low blood sugar event was expected to be synthesis, which are involved in prenylation of low low—and this was observed in Phase II and Phase III molecular weight proteins in the muscles cells. studies of sitagliptin in patients with type 2 diabetes understood, intermediates with are some responsible, 265 First, incretin stimulation of Faculty of Medicine Dept of Medicine & Therapeutics mellitus. Second, incretins appear to have a role in CHENG Yuen Shan Angela# LI Liping* MA appetite regulation, with weight loss observed in Ching Wan Ronald preclinical and clinical studies treatments, and Ling Linda resistance to weight gain observed in animal studies. Sze Vanessa Consistent with this expectation, Phase II and Phase YIP Chi Wai* LUK On Yan Andrea YU Wai NG Wan 1 August 2006 III studies of sitagliptin showed a neutral effect on Merck Sharp & Dohme (Asia) Ltd weight, compared to weight gain with a sulfonylurea comparator agent. This is an open label, multi-center 13 week study to The purpose of this study is to: (adapted from main evaluate the efficacy of switching to losartan/HCTZ informed consent form and protocol) combination in patients with essential hypertension ‧ test the safety of the research study drug, whose blood pressure was not at the BP goal (BP sitagliptin. goal is defined as trough SiDBP <90 mmHg in non-diabetics; <80 mmHg in diabetics) with previous ‧ test whether taking sitagliptin, together with rosiglitazone and metformin improves your blood monotherapy sugar, compared to taking rosiglitazone and antihypertensive medications (angiotensin II receptor metformin alone. antagonists or ACE inhibitors). Patients not at BP with submaximal doses of About 300 people will be recruited in the study. goal at the screening visit and baseline visit one week Patients will be in the study for about 77 weeks later will be discontinued from their current (about 1 year and 7 months). There will be 14 visits antihypertensive and patients will be required to monitor blood losartan/HCTZ combination. After 4 and 8 weeks glucose at home during the study. All patients will of treatment, if the BP goal is not reached then the receive rosiglitazone (4 mg, once or twice a day) and dose of the combination will be titrated upwards metformin (500/1000 mg, two or three times per day). according to the following scheme: HYZAAR Patients will be randomised to receive either 50/12.5 → HYZAAR 50/12.5 + COZAAR 50 → sitagliptin (100 mg, once per day) or placebo in a HYZAAR FORTE 100/25. double-blinded manner. In cases where the blood (MD06935) medication and switched to sugar level becomes very high, patients will be given glipizide, a known treatment for diabetes to control Association the blood sugar. Polymorphisms of Aldose Reductase and ApoE (MD06579) Genes for Nephropathy in Type 2 Diabetes of Glomerulopathy with the Mellitus An Open Label Study to Assess the Efficacy of TONG Peter Chun Yip Losartan/HCTZ Combination Therapy in Patients with Essential Inadequately Hypertension Controlled Who on MAC-MOUNE LAI Fernand (Anatomical & Cellular Pathology) Were ZHAO Hailu CHAN Chung Ngor Juliana Current Antihypertensive Monotherapy 1 April 2007 CUHK Research Committee Funding (Direct TONG Peter Chun Yip Juliana CHAN Chung Ngor KONG Pik Shan Faculty of Medicine OZAKI Risa Grants) 266 Dept of Medicine & Therapeutics Diabetes mellitus is the most common cause of renal Prevention failure in developed countries. The heterogeneous Cardiovascular Events of Ischaemic Origin with nature of renal histopathologies in type 2 diabetes is teRutroban in Patients with a History of determined by multiple risk factors and polygenic Ischaemic Stroke or tRansient IschaeMic Attack. components. The PERFORM Study. Hyperglycaemia, hypertension, and of Cerebrocascular and An International, dyslipidaemia are the major modifiable risk factors Randomised, Double-Blind, Two Parallel Group for diabetic nephropathy. The polymorphisms in the Study Comparing Terutroban 30mg O.D. versus hyperglycaemia-related Aspirin 100mg O.D. Administered Orally for a aldose reductase, and dyslipidaemia-related apolipoprotein E genes confer 3-Year Mean Duration (Event Driven Trial) a considerable risk for diabetic nephropathy. In this proposal, we aim to investigate the correlations WONG Ka Sing Lawrence MOK Chung Tong between clinical characteristics, glomerulopathy, the Vincent LEUNG Wai Hong Thomas SOO Oi polymorphisms of these two genes, and their protein Yan immunolocalization in type 2 diabetes. We will use Edward consecutive autopsy materials from 100 patients with 1 July 2006 type 2 diabetes and 70 non-diabetic control subjects. stratified into glomerulosclerosis; 5 2) groups: 1) non-nodular MAN Bik Ling WONG Ho Chung Institut De Recherches Internationales Based on histopathological assessment, the cases will be Servier/Servier (Beijing) Pharmaceutical nodular Research & Development Co Ltd diabetic glomerulopathy; 3) near normal glomeruli with type The primary objective is to demonstrate the 2 diabetes; 4) non-diabetics with glomerulopathy; or superiority of S 18886 30mg o.d. over aspirin 100mg 5) non-diabetics with near normal renal structure. o.d., in reducing cerebrovascular and cardiovascular Kidney for event (primary efficacy endpoint: composite of The frequency, ischaemic stroke [fatal or non-fatal], myocardial distribution and intensity of positive immunoreactivity infarction [fatal or non-fatal], other vascular death) in will be examined. Genomic DNA will be extracted patients with a history of ischaemic stroke (IS) or from archival paraffin blocks from the spleen. The transient ischaemic attack (TIA). polymorphisms be The secondary objectives are to assess the effect of S determined by polymerase chain reaction (PCR). 18886 on the other efficacy endpoints and its safety, as The frequency of alleles and genotypes will be well as on prevention of cognitive decline and compared in the 5 groups in relation to the dementia. immunohistochemical staining, glomerulopathy, and Methodology: Randomised, double-blind, two-parallel clinical characteristics. groups, controlled study versus aspirin. tissue sections will immunohistochemical staining. of these four be genes used will This investigation will provide a model to characterize disease genes by Estimated total: 18,000 patients (9,000 per treatment systematically correlating among genotype, protein group), to be adapted according to the number of observed expression, histopathology, and clinical phenotype. events. (MD06594) Mean duration: 3 years - Minimum durations 2 years, Maximum duration 4 years (could be extended up to 5 Years). 267 Faculty of Medicine Dept of Medicine & Therapeutics The duration of patient’s participation depends on (MD06577) whether the patient is enrolled at the beginning, middle, Randomized, Multinational, Double-Blind, Placebo-Controlled, or at the end of the study. The longest duration is Multicenter, expected to be 50 months (just over 4 years). Two-Arm Parallel Group Trial of Rimonabant 20 mg OD for At the first study visit, the doctor will collect information Reducing the Risk of Major Cardiovascular about medical history, especially about nervous system Events in Abdominally Obese Patients with and moods. A physical exam will be done. Patient’s Clustering Risk Factors height, weight, waist circumference, heart rate, and blood pressure will be measured. Patient will have an ECG WONG Ka Sing Lawrence LEUNG Wai Hong (also called an EKG, electrocardiogram, or heart tracing) Thomas MOK Chung Tong Vincent LEUNG done, and about 1 tablespoon of blood will be taken for a Ho Wan WONG Ho Chung Edward SOO Oi blood count, and for liver and kidney tests. Yan MAN Bik Ling woman of childbearing potential, a urine pregnancy For test must be negative for patient to participate. 1 September 2006 After starting study medication, patient will be asked Sanofi-Aventis Singapore Pte Ltd to see study doctor at 1 month, 3 months, 6 months, The purpose of this research study is to see whether and then every 6 months to the last visit at the end of the an experimental drug called rimonabant, at 20 mg a study. At each visit, general condition will be checked, day, can help lower the chances of having a heart attack, including nervous system and moods, heart rate and a stroke, or of dying from a heart attack or stroke. blood pressure will be measured while lying down, Rimonabant, at this dose, has been given in several and a record will be made of the medications taking, studies already, to more than two thousand patients. including study medication. At the visits occurring It works on receptors (targets) in the brain and in the fat every 6 months and at the last visit, about 1 cells. It does not affect the way patient digest food. tablespoon of blood will be taken for the blood cell Rimonabant waist count and liver and kidney tests, weight and waist circumference (waist measurement), and it may, even circumference will be measured, and will have a physical without loss of weight or waist circumference, also exam. improve other conditions that increase the risk of heart another ECG (heart tracing) done. attack and stroke, such as diabetes and certain lipid month until the end of the study, patient will also be (blood fat) abnormalities. called by phone between each 6-month visit by either Besides the current treatments, patient will have one the study doctor or the study nurse. additional pill to take every day. Patient will have a (MD06315) may decrease weight and At the next to last visit, patient will have From the ninth 50:50 (1 in 2) chance of receiving rimonabant and an equal 50:50 chance of receiving placebo (an inactive or A sugar pill). Neither the patient nor the study doctor Double-Blind, Placebo-Controlled, Parallel-Group will know which treatment the patient are receiving Study to Evaluate the Efficacy, Safety and during the study. Tolerability of Pregabalin (150-600 mg/day) Using This study is also called a “randomized” study. Faculty of Medicine 13-Week, Randomized, Multi-Center, a Flexible Dosing Schedule in the Treatment of 268 Dept of Medicine & Therapeutics Subjects with Central Post-Stroke Pain (CPSP) #A0081063 CADENZA WONG Ka Sing Lawrence LEUNG Wai Hong WOO Jean Thomas MOK Chung Tong Vincent LEUNG KWOK Chi Yui Timothy LAU YL Alexander* CHAN Tan, Jessica* Ho Wan WONG Ho Chung Edward 10 August 2006 1 September 2006 The Hong Kong Jockey Club Charities Trust Pfizer Corporation Hong Kong Limited The purpose of the project is to revolutionise the way The study is designed to explore the effectiveness and society views its elders, the current mode of care for tolerability of pregabalin on the central nerve pain the elderly, existing services and facilities, and the patients are experiencing after stroke. The study excessive reliance on the medical model of care. will also evaluate the occurrence of any side effects The attitude and mindset of the general public have to whether or not they might be related to pregabalin. be changed. The study will also assess whether patients will summarized below: experience improvement in sleep, general health, and The objectives of the project are to train different levels of professionals and on symptoms of anxiety and depression. front-line workers involved in elderly work, not This is a 13-week, randomized, multi-center, only in terms of skills, but also in the way they double-blind, placebo-controlled, parallel-group trial view and treat the people they serve; of pregabalin in adult subjects (18 years and over) with central post-stroke pain (CPSP). Subjects who rather than a “social problem”; meet all of the eligibility criteria will enter the trial which consist of 4 phases: 2-week screening and washout phase; 2. 4-week double-blind, placebo to devise new services in response to changing needs; controlled flexible dose adjustment phase, to plan for a generation of soon-to-be-old whilst during which subjects start on 150 mg/day enhancing skills and services for the existing pregabalin (or matching placebo) and may elderly population; and increase to a maximum of 600 mg/day pregabalin (or matching placebo); 3. to encourage and promote inter-generational accommodation and understanding; 1. randomized, to look at the elderly trend as “social growth” 8-week randomized, to cultivate and nurture academic leadership in social gerontology so as to bolster the standard double-blind, and image of the profession of dealing with the placebo-controlled treatment maintenance phase aged and all ageing-related services. (dose of pregabalin remains constant at 150 (MD06911) mg/day, 300 mg/day, or 600 mg /day or 4. matching placebo); and Ageing and Utilisation of Hospital Services in 1-week taper double-blind, placebo-controlled Hong Kong: Retrospective Cohort Study treatment phase (either pregabalin 150 mg/day or matching placebo). WOO Jean (MD06880) GOGGINS III William Bernard (The Nethersole School of Nursing) 269 ZHANG Faculty of Medicine Dept of Medicine & Therapeutics Xin-Hua (Community and Family Medicine) GRIFFITHS Sian Meryl Pantoprazole Sodium 40 mg o.d. over 8 Weeks (Community and (BY1023/M3-341) Family Medicine) WU Che Yuen Justin WONG Lai Hung 1 November 2006 Hin Health & Health Services Research Fund 任兵* LEUNG Wai Keung LAI LEE Yuk Tong Objectives: The increasing of life expectancy in Hong 1 July 2006 Kong inevitably increase the number of elderly ALTANA Pharma AG Regional Office-Asia patients because of the exponential relation of ageing and morbidity from common diseases. We aim to Aim: Identification of factors (e.g. symptom patterns use the days spent in hospital and the number of and symptom scores) determining the response to admissions to hospital services during the last 12 treatment with pantoprazole 40 mg o.d. as measured month, 24 months and 36 months of life to estimate by different methods (e.g. ReQuest™ questionnaire, the burden of health care service by each age group; to patient and investigator assessment). take the health care service used as a surrogate of Study Design: Treatment, Non-Randomized, Open Label, morbidity from severe diseases amongest the birth Uncontrolled, Single Group Assignment. cohorts and time periods to exam if the prolonged life Title: expectancy was due to the compression of morbidity Symptoms Due to Gastroesophageal Reflux Disease (prolonged healthy life expectency) in elderly Either With or Without Esophagitis Treated With population, indirectly evaluate the effect of health Pantoprazole Sodium 40 Mg o.d. Over 8 Weeks. promotion measures in Hong Kong population. Primary Outcomes: Response to treatment with Design: Retrospective cohort study analysis of Hong pantoprazole at week 8, as measured by the Kong Hospital Authority CMS data base. questionnaire ReQuest™. Setting: HA hospitals. Secondary Outcomes: Response to treatment with Data se: All deaths occurred in HA hospitals during pantoprazole at week 4, as measured by the 1999 and 2005 and the health care services used questionnaire ReQuest™; investigator assessment; within the Hospital Authority system by the decedents safety and efficacy. during the previous three years. Participating countries: Argentina, Australia, Austria, Outcome measures: The accumulated bed-days spent Belgium, Brazil, Canada, France, Germany, Hong in hospitals and the number of.admissions to health Kong, India, Italy, Malaysia, Mexico, Poland, care services within the Hospital Authority system Portugal, Singapore, South Africa, South Korea, during the last three years of life, by age at death, year Spain, Switzerland, Taiwan, United Kingdom. of death and the birth cohorts. Expected total enrollment: 2000. (MD06931) Ages eligible for study: 18 and above. Treatment Response in Patients With Criteria: Treatment Response in Patients with Symptoms Main Inclusion Criteria due to Gastroesophageal Reflux Disease Either Written informed consent. with Outpatients of at least 18 years (21 years in or without Esophagitis Treated with Argentina). Faculty of Medicine 270 Dept of Medicine & Therapeutics and other cells. Patient considered to have GERD symptoms. Transient receptor potential Main Exclusion Criteria vanilioid receptor 1 (TRPVl) is a TRP channel which Acute peptic ulcer and/or ulcer complications. is highly expressed in primary sensory neurons of the Systemic non-steroidal vagal and dorsal root ganglia of the nervous system anti-inflammatory drugs (NSAIDs) including and epithelial cells of gastrointestinal tract. TRPVl COX-2-inhibitors (> 5 days on demand but not is sensitive to vanilioid molecules such as capsaicin, more than 3 consecutive days) during the last 28 the hot ingredient contained in chili and pepper. days before study start (except regular intake of TRPVl also mediates visceral pain caused by acetylsalicylic acid at a dose up to 163 mg/day). mechanical stimulation. Intake of proton pump inhibitors during the last 10 TRPVl in pathogenesis of IBS is still unclear. days before study start. The objective of this study is to evaluate the activity Female patients of childbearing potential not using and responsiveness of TRPVl to visceral noxious adequate means of birth control. stimulation in a rat model of irritable bowel Pregnant or breast-feeding females. syndrome. The findings of this project will promote glucocorticoids or (MD06863) However, the role of understanding of the potential role of TRPVl as an important mediator of visceral hypersensitivity in Effects of Colorectal Noxious Stimulation on development of IBS. Modulation of TRPVl activity Activity of TRPV1 and c-Fos Protein in a Rat may have major implications on the development of Model of Irritable Bowel Syndrome novel effective treatment of IBS and other functional gastrointestinal disorder. (MD06563) WU Che Yuen Justin 1 March 2007 Prospective Randomized Evaluation of Celecoxib CUHK Research Committee Funding (Direct Integrated Safety vs. Ibuprofen Or Naproxen Grants) YIP Wai Kwok Gabriel Irritable bowel syndrome (IBS) is a common YU Cheuk Man LI gastrointestinal disorder that is associated with Kwok Ming Edmund TAM Lai Shan KWOK significant morbidity and creates huge burden on Lai Wa CHAN Chi Yuen healthcare resource. Unfortunately, treatment of 1 June 2007 IBS has been far from satisfactory and its mechanism Pfizer Corporation is still poorly understood. It is generally considered abnormal increase in sensation of internal organs This phase IV, international multicenter, randomized, (visceral hypersensitivity) plays an important role in double-blind, active control, parallel assignment, pathogenesis of IBS. safety study aims to assess overall benefit and risk of In recent years, the transient receptor potential (TRP) celecoxib when compared to two most commonly family of proteins has been recognized as an prescribed traditional (non-selective) nonsteroidal important sensor of chemical and physical stimuli of anti-inflammatory drags (NSAIDs) in the treatment various tissues and organs. This is a group of ion of arthritis pain. A target of 20,000 patients aged channels located at plasma membranes of neurons ≥18 years with osteoarthritis or rheumatoid arthritis 271 Faculty of Medicine Dept of Medicine & Therapeutics with or at risk of developing cardiovascular disease, YU Cheuk Man LEE Pui Wai LAM Yat Yin who require for chronic, daily NSAID therapy, will be recruited. The cardiovascular, gastrointestinal and renal safety and symptomatic benefit in each CHAN Chin Pang 5 July 2006 treatment group will be assessed accordingly. Sanofi-Aventis Singapore Pte Ltd Subjects are excluded if they: 1) have had a recent cardiovascular event, unstable cardiovascular This study is a prospective multi-center, randomized, conditions, or any major surgery (cardiac or double-blind, active-controlled parallel-group, dose non-cardiac) within 3 months prior to randomization; ranging study with 5 treatment groups (AVE7688 AT 2) with medical or laboratory abnormality that would 4 different dosages, and losartan-potassium 100 mg). make the subject inappropriate for trial entry; and 3) There will be 3 study phases: placebo lead-in require aspirin treatment >325mg /day; and 4) known treatment, and follow-up. hypersensitivity to celecoxib, ibuprofen, naproxen, During the placebo lead-in phase (duration 3 to 4 aspirin or esomeprazole. weeks), The primary end-point of patients will discontinue concomitant the study is the first occurrence of cardiovascular treatment with any antihypertensive or vasodilating death (including hemorrhagic death), non-fatal agents and will receive single-blind placebo until myocardial infarction, or non-fatal stroke (APTC randomization. Patients who meet the inclusion and composite endpoint). The secondary outcome exclusion criteria will be randomized to receive measures are: l)The first occurrence of a MACE once-daily oral doses of either 2.5, 10, 35 or 50 mg defined as the composite of cardiovascular death AVE7688, or 100 mg losartan-potassium. (including Ml, The treatment phase will consist of two parts: an non-fatal stroke, hospitalization for unstable angina, efficacy evaluation period, with a week titration revascularization or hospitalization for transient period (from randomization to week 2, visit Tl to visit ischemic attack; 2) The occurrence of Clinical T3) up to 12 weeks, followed by a long-term safety Significant Gastrointestinal Events (CSGIEs); and 3) evaluation period until the end of week 52. Patient’s Assessment of Arthritis Pain (VAS). The Antihypertensive treatment such as diuretics, beta trial will continue until the planned 762 APTC blockers or calcium channel blockers can be composite endpoints have been reached and all introduced or re-introduced if indicated during the subjects long term safety evaluation period but angiotensin hemorrhagic have had death), non-fatal follow-ups ≥18 months. (ClmicalTrials.gov identifier NCT00346216) converting enzyme inhibitors (ACE-I) or angiotensin (MD06668) receptor blockers (ARBs) are not permitted. An additional visit (visit Fl) will occur two weeks Double-Blind, Randomized, Parallel-Group, Dose after the last dose of study medication. During this Ranging, Multi-Centre Study to Evaluate the follow-up phase, patients will be evaluated to assess Efficacy and Safety of 2.5, 10, 35 and 50mg the effect of study drug withdrawal on blood AVE7688 pressure. Once Daily, Using 100mg (MD06882) Losartan-Potassium Once Daily as Calibrator, for 12 Months Treatment, in Patients with Mild to Moderate Hypertension Faculty of Medicine 272 Dept of Medicine & Therapeutics A Multicenter, Double-Blind, Randomized Study Randomized, to Establish the Clinical Benefit and Safety of Double-Blind, Vytorin vs. Parallel Group Trial of Rimonabant 20 mg OD for Simvastatin Monotherapy in High-Risk Subjects Reducing the Risk of Major Cardiovascular Presenting Events in Abdominally Obese Patients with (Ezetimibe/Simvastatin with Acute Tablet) Coronary Syndrome (Improved Reduction of Outcomes: Vytorin Multinational, Multicenter, Placebo-Controlled, Two-Arm Clustering Risk Factors Efficacy International Trial – IMPROVE IT) YU Cheuk Man YU Cheuk Man KUM Chi Chiu Leo WONG LAM Yat Yin YIP Wai Kwok Gabriel CHAN Chin Pang CHAN Kin Man Lok Edmond# CHAN Wai Man Wilson Yin 18 July 2006 1 August 2006 Schering-Plough Research Institute Sanofi-Aventis Singapore Pte Ltd The primary objective of this study is to evaluate the Primary Objective: To demonstrate the efficacy of clinical Ezetimibe/Simvastatin rimonabant versus placebo for reducing the risk of Combination (single tablet containing ezetimibe and myocardial infarction, stroke, or cardiovascular death simvastatin) compared with simvastatin in stabilized in patients with abdominal obesity at increased risk acute coronary syndrome (ACS) subjects - either for such events. acute myocardial infarction (MI) or unstable angina. Secondary Objective: To demonstrate the efficacy of Clinical benefit will be defined as the reduction in the rimonabant versus placebo for reducing the risk of risk of the occurrence of the composite endpoint of myocardial infarction, stroke, cardiovascular death, CV death, major coronary events, and non-fatal or hospitalization for cardiovascular death, or stroke. CV death, major coronary events, and hospitalization for cardiovascular cause (unstable non-fatal stroke are designated primary endpoint angina, transient ischaemic attack, cardiac rhythm events. Major coronary events include non-fatal MI, disorder, congestive heart failure, syncope, or urgent documented unstable angina that requires admission revascularization into a hospital, and all coronary revascularization abdominal obesity at increased risk of such events. with either percutaneous coronary intervention (PCI) Study Design: The present study is designed as a or coronary artery bypass grafting (CABG) occurring multicentre, multi-national, randomized, double-blind, at placebo-controlled, 2-arm parallel-group trial. All subjects for least benefit 30 assignment. days of after randomized treatment Only revascularization events that must procedure), meet in patients eligibility criteria with occur after the first 30 days of treatment will be CRESCENDO study and must give written informed considered as clinical endpoint events, in order to consent. focus on revascularization events that can be mg daily or placebo and they would be followed up reasonably expected to be affected by treatment and for cardiovascular outcomes. are unrelated to the initial ACS event. end date, which is estimated to occur when the last (MD06410) randomized patients has been followed for 33 months, Subjects would be given rimonabant 20 The common study based on a 17-month recruitment period. (MD06532) 273 Faculty of Medicine Dept of Medicine & Therapeutics by a prospective, follow up study of at least 150 Serial Echocardiographic Assessment of Early patients with different severity of COPD. The latter Right Ventricular Dysfunction by Tissue Doppler prospective study will permit serial echocardiography Echocardiography and lung function test that help to delineate the & its Impact on Left degree of progression of cardiac dysfunction over the Ventricular Function time course of 1 year. The study will provide YU Cheuk Man HUI Shu Cheong David information reference data for the relationship between COPD and cardiac dysfunction, and be LEE Pui Wai KO Wai San Fanny potentially helpful to provide a comprehensive plan 1 October 2006 of patient management. Research Grants Council (Earmarked Grants) (CU06475) Chronic obstructive pulmonary disease (COPD) is one of the leading causes of hospitalization in Hong The Effect of Eplerenone versus Placebo on Kong resulting in disability and high mortality as a Cardiovascular Mortality and Heart Failure result Hospitalisation in Subjects with HYHA Class II of progressive loss of lung function. Management of this condition has long been focusing Chronic Systolic Heart Failure (EMPHASIS-HF) on the treatment strategies that improve symptoms YU Cheuk Man and defer deterioration of lung function. However, as YIP Wai Kwok Gabriel COPD progresses, function of the heart, in particular CHAN Anna* the right-sided chambers, can be adversely affected in Wah* which clinical information has been very limited. CHAN YEUNG Yuk Ching DONG Ming This study examined the deleterious effect of COPD KUM Chi Chiu* WU Eugene Brian* KWOK Lai LAM Yat Yin* 17 November 2006 on heart failure, which include both systolic Pfizer Corporation Hong Kong Limited (contractile) and diastolic (relaxation) function on the right ventricle (RV). Furthermore, in these patients, Patients with heart disease will be asked to take part RV dysfunction and COPD itself may also affect left in this study. The drug is called eplerenone. This ventricular (LV) systolic and diastolic function which drug is approved in the U.S. and countries in Europe will also be systematically studied. The main tool for for the treatment of a certain type of heart attack; cardiac assessment is by advanced echocardiographic however, this drug is not approved for the disease technology (ultrasound of the heart) that is equipped treated in this study. The overall purpose of this with tissue Doppler imaging (TDI) and 3-dimensional trial is to evaluate the efficacy and safety of echocardiography (3DE) capabilities. This new tools eplerenone (plus “standard care”) versus placebo are sensitive enough to allow cardiologists to perform (plus “standard care”) in subjects with NYHA II detailed quantitative assessment of cardiac systolic chronic systolic heart failure (HF). and diastolic function, and to assess uncoordinated therapy includes angiotensin converting enzyme contraction and relaxation of the heart that might (ACE) inhibitors and/or angiotensin receptor blockers develop over the course of COPD, in the presence (ARBs) and β-blockers at the optimal target or and absence of pulmonary hypertension. The research maximally tolerated doses (unless contraindicated), proposal will contain a cross-sectional study followed Faculty of Medicine 274 Standard HF Dept of Medicine & Therapeutics and diuretics, if clinically indicated to minimize fluid Secondary Objective: To assess the safety and retention. tolerability of AZD6140 compared with clopidogrel. The trial is a multinational (approximately 30 The primary safety endpoint is the time to first countries), occurrence of any total major bleeding event. randomized, placebo-controlled, double-blind parallel-group (MD06523) trial. Approximately 2,584 subjects will be randomized to receive eplerenone 25 mg once daily (OD) or Novel Effect of Lipoprotein Lipase Activator in matching placebo. Placebo is a pill that does not the Severity of Nutritional Steatohepatitis contain any drug. Patients have an equal chance of getting eplerenone or placebo. Both the patient and YU Jun CHAN Lik Yuen Henry the study doctor will not know if they get placebo or 1 June 2007 drug. At four weeks, the dose of study drug may be CUHK Research Committee Funding (Direct increased to 50 mg OD (two 25mg tablets of Grants) eplerenone or 2 matching placebo tablets once daily) based on serum potassium level. The trial will Due to the rapid change in lifestyle, there is an continue until 813 primary endpoints are reached. increasing trend of metabolic syndrome in Hong The anticipated trial duration is 48 months. Kong. Non-alcoholic fatty liver disease (NAFLD), (MD06705) a common compliment to the metabolic disorders, is increasingly an important cause of liver diseases. A Randomised, Double-blind, Parallel Group, Nonalcoholic steatohepatitis (NASH) is a subset of Phase 3, Efficacy and Safety Study of AZD6140 NAFLD characterised by histological changes of Compared with Clopidogrel for Prevention of necroinflammation. The inflammation may further Vascular Events in Patients with Non-ST or ST lead to fibrosis and cirrhosis. Elevation Acute Coronary Syndromes (ACS) with NASH may progress into liver cirrhosis, there is [PLATO-A Study of PLATelet Inhibition and no effective therapy for NASH. Patient Outcomes.] novel compound that Although patients has NO-1886 is a recently shown encouraging results with improvement in serum lipid YU Cheuk Man profile and in fat accumulation in animals through increasing lipoprotein lipase (LPL) activity. These KUM Chi Chiu Leo WU E B* LAM Yat Yin findings indicate that NO-1886 could be a potential YIP Wai Kwok Gabriel CHAN Yat Sun Joseph CHAN Kin Yin CHAN Chin Pang therapeutic agent for NASH. In the present project, we will first clarify the potential biological effects 14 December 2006 and mechanisms of NO-1886 on prevention of AstraZeneca Hong Kong Limited steatohepatitis in mice, and extend study to the Primary Objective: This study is to test the regression effect of NO-1886 to characterise more hypothesis that AstraZeneca 6140 is superior to fully the influence of this compound on evolution of clopidogrel for the vascular events in patients with steatohepatitis. non-ST or ST elevation Acute Coronary Syndromes. provide the new insight into the pathogenesis of 275 The results of this research will Faculty of Medicine Dept of Medicine & Therapeutics 2002-03 A Multicentre, Randomised Study to steatohepatitis and the potential value of lipoprotein lipase activation for intervention of NASH. Examine (MD06422) Management on Clinical Outcomes in Type the 2 Effects Diabetic of Disease Patients with Please refer to previous issues of this publication Nephropathy (MD02610) for more details of the following ongoing research CHAN Chung Ngor Juliana TONG Peter Chun Yip at the department: Stewart Edition COCKRAM Clive ZHANG Xuejie (Community and Family Medicine)# Title/Investigators LEUNG Y S Wilson* 2004-05 Mechanisms of Action of Potential 2003-04 Olmesartan Alzheimer's Disease Drug Curcumin, an Reduces Incidence of Extract of Geung Wong (CU04302) Endstage Renal Disease in Patients with BAUM Lawrence William NG Ho Type 2 Diabetic Nephrophathy Trial Cellular (ORIENT) (MD03356) Keung (Anatomical Pathology) & CHUI Yiu CHAN Chung Ngor Juliana TONG Loon Peter Chun Yip (Clinical Immunology Unit) Chun SZETO Cheuk TOMLINSON Brian COCKRAM Clive Stewart OZAKI 2005-06 A Pilot Study of Curcumin for Treating Alzheimer's Disease (MD05563) R* SO Wing Yee* CHOW Chun BAUM Lawrence William KWOK Chung Francis Chi Yui Timothy 2004-05 A Multicenter, Randomized, 2005-06 Screening Potential Alzheimer's Disease Double-Blind Study to Evaluate the Drugs by Amyloid Disaggregation Assay Safety of MK-0431 Monotherapy in and In Vivo Testing (MD05873) Patients with Type 2 Diabetes Mellitus BAUM Lawrence William Ho Yin Edwin and Chronic Renal Insufficiency Who CHAN Have (Biochemistry Inadequate Glycemic Control (MD04795) (Science)) CHAN Chung Ngor Juliana KONG Pik Shan CHAN W. B.* 2005-06 A Novel Cancer Screening Method Using Mismatch Binding Proteins to Detect 2004-05 A Phase III, 18 Month, Multicenter, Mutant, Tumor-Derived DNA in Body Randomized, Fluids (MD06861) BAUM Lawrence William Active-Controlled Double-Blind, Clinical Trial to Compare Rosiglitazone versus Glipizide LEUNG Wai Keung on the Progression of Atherosclerosis in Subjects with Type 2 Diabetes Mellitus and Cardiovascular Disease (MD04363) Faculty of Medicine 276 Dept of Medicine & Therapeutics CHAN Chung Ngor Juliana TONG CHAN Chung Ngor Juliana CHAN W. B.* KONG Pik Shan Cheuk Man Peter Chun Yip KONG Pik Shan YU CHAN Wai Man 2005-06 An Wilson Open-Label, Multicentre and Long-Term Extension Study to Evaluate 2004-05 A Multidisciplinary Project to Identify the Safety and Tolerability of Oral Major Genes for Diabetes and Metabolic Tesaglitazar 1 mg in Patients with Type 2 Syndrome in Chinese and to Assess Its Diabetes Functional Significance (MD04484) (MD05844) CHAN Chung Ngor Juliana TONG CHAN Chung Ngor Juliana TONG Peter Chun Yip (Clinical Oncology)* Sing (Physiology) WAYE Mary 2005-06 Diabetes, Metabolic Syndrome and Cardio-Renal Complications in Hong Kong (MD05927) SO Wing Yee CHAN 2005-06 International 1 LEUNG Po Miu Yee (Biochemistry (Medicine)) GALLEX Peter Chun Yip KONG Pik Shan ZEE Benny Mellitus Diabetes Management Chung Ngor KONG Pik Shan Practices Study, The "IDMPS" HOE Juliana TONG Peter Chun Yip 901/9010 (MD05511) CHAN Chung Ngor Juliana 2005-06 The Effect of Sulodexide in Overt Type 2 Diabetic Nephropathy (MD05702) 2005-06 A Long-Term, Post Treatment, Safety CHAN Chung Ngor Juliana TONG Follow-up, Multicentre Study in Patients Peter Chun Yip KONG Pik Shan with Type 2 Diabetes Mellitus from the LEE K. F.* GALLANT, GALLEX or ARMOR Studies G-PLUS (GALLANT, GALLEX and ARMOR Long-Term - Post Treatment Follow-up Study) 2005-06 Type 2 Diabetes Gene Discovery Project (MD05341) CHAN Chung Ngor Juliana NG (MD05610) Chor Yin SO Wing Yee* TONG CHAN Chung Ngor Juliana TONG Peter Chun Yip Peter Chun Yip KONG Pik Shan 2005-06 Immunopathological 2005-06 A Parallel-Group, Mechanisms of Inflammatory Reaction in Chinese Type Multicentre, Active-Controlled (Glibenclamide) Long 2 Term Extension Study to Evaluate the Nephropathy (MD05354) Safety Oral CHAN Chung Ngor Juliana Tesaglitazar Therapy in Patients with WONG Chun Kwok (Chemical Type 2 Diabetes Mellitus (GALLEX 4) Pathology) and Tolerability of Diabetic Patients with Diabetic TONG Peter Chun Yip (MD05623) 277 Faculty of Medicine Dept of Medicine & Therapeutics KONG Pik Shan LAM Wai Kei 2005-06 Double-Blind, Christopher (Chemical Pathology) Triple Dummy, Parallel-Group, Randomized, Six-Month Study to Compare Celecoxib (200 mg 2005-06 The International 1q Type 2 Diabetes BID) with Diclofenac SR (75 mg BID) Consortium (MD05654) Plus Omeprazole (20 mg QD) for CHAN Chung Ngor Juliana Gastrointestinal Events in Subjects with NG Osteoarthritis and Rheumatoid Arthritis Chor Yin at High-Risk of Gastrointestinal Adverse Events (MD05466) 2005-06 To Evaluate the In Vivo Effects of CHAN Ka Leung Francis Chinese Medicine (CM) on Metabolic Syndrome and Diabetic Complications Nafees Begum* using Animal Models (MD05863) Lutz* CHAN Chung Ngor Juliana TONG Yuk Tong Peter Chun Yip ZHAO Hailu NG KATZSCHNER LEUNG Wai Keung Baig LEE WU Che Yuen Justin LI Chi Hong Felix* Ho Keung (Anatomical & Cellular Pathology) LAM Wai Intereron-Beta-1a for the Treatment of Edward Chronic Hepatitis C in Asian Patients Christopher (Chemical Pathology) JAMES Anthony 2002-03 A Multicentre Phase III Study of Kei (MD02926) (Laboratory Animal Services Centre) CHAN Lik Yuen Henry CHAN Ka 2001-02 Cyclooxygenase and Trefoil Peptides in Leung Francis Stomach - Biology & Clinical Diseases Nancy* (MD01711) Jao Yiu CHAN Ka Leung Francis LEUNG Wai Yee HUI Y* SUNG Joseph LEUNG SUNG 2003-04 A Randomized, Double-Blind Trial of NG Enders Telbivudine (LdT) versus Lamivudine in CHUNG Adults with Decompensated Chronic Sheung Chee Sydney (Surgery) TO Hepatitis B and Evidence of Cirrhosis Ka Fai (Anatomical & Cellular (MD03850) Pathology) CHAN Lik Yuen Henry Wai Keung YU Jun Joseph Jao Yiu Kwok-wai (Surgery) CHEN M H* HU P J* 2003-04 Preventing NSAID-Associated Ulcer 2004-05 Cytokine Gene Polymorphism and Liver Fibrosis Cyclooxygenase-2 (CU04304) Therapeutics in Chronic Joseph Jao Yiu LEUNG Wai Keung SUNG Joseph Jao Yiu Tsek 278 (Anatomical Pathology)# Faculty of Medicine Hepatitis CHAN Lik Yuen Henry (CU03455) CHAN Ka Leung Francis HUI Yui# WONG Wai Sun Bleeding for High-Risk Patients: From to B SUNG LIEW Choong & Cellular Dept of Medicine & Therapeutics Cellular (LdT) versus SUNG Joseph Jao Yiu 2004-05 A Randomized, Open Label Trial of Telbivudine Pathology)# Adefovir 2005-06 A Phase I, Multicentre, Randomized, Dipivoxil in Adults with Compensated Chronic Hepatitis B (MD04746) Placebo-Controlled CHAN Lik Yuen Henry HUI Yui# Study to Assess the Local and Systemic SUNG Joseph Tolerability of the Therapeutic DNA WONG Wai Sun by Hepatocellular Delivery Carcinoma CHAN Lik Yuen Henry Wing (Medicine)) Subjects Hepatitis B with Infection WONG Wai Sun WONG Lai Hung MOK Shu Kam Tony in CHAN Lik Yuen Henry (Biochemistry (Clinical Oncology) Epidermal (MD05887) TSUI Medicated System Chronic (MD04701) Kwok Particle Delivery Using the PowerJect ND10 2004-05 Serum Genomic Markers of Hepatitis B for Escalation Plasmid pdpSC18 Vaccine Administered Jao Yiu Virus Dose SUNG Joseph 2005-06 An Open Label Trial of Telbivudine Jao Yiu (LdT) in Adults with Chronic Hepatitis B Previously Treated in Idenix-Sponsored 2004-05 A Randomized, Blinded, Phase IIB Trial of Telbivudine Combination (LdT) of versus Telbivudine the Telbivudine Studies (MD06368) and CHAN Lik Yuen Henry Valtorcitabine (val-LdC) in Patients with LI Chi Hong Felix* Baig Nafees Begum* Chronic Hepatitis B (MD04646) CHAN Lik Yuen Henry WONG Wai Sun 2004-05 A HUI Yui# Prospective, Randomised, Double-Blind, Placebo Controlled, Dose SUNG Joseph Ranging, Multicentre Study of the Safety Jao Yiu and Efficacy of Three Days Continuous 2005-06 Role of Hepatitis B Virus Covalently Intravenous Infusion of GR270773 in the Closed Circular DNA in Determination Treatment of Suspected or Confirmed of Treatment Outcome (MD05619) Gram-Negative Severe Sepsis in Adults CHAN Lik Yuen Henry (EMD20001) (MD04466) HUI Yui# CHENG SUNG Joseph Jao Yiu Gregory WONG Raymond* 2005-06 Proteomic Profiling of Liver Fibrosis in Chronic Hepatitis B (CU05466) CHAN Lik Yuen Henry Chuen Wai Choong Tsek HUI Yui# 2004-05 A Double-Blind, Randomized, POON Placebo-Controlled, Parallel Group Study LIEW to (Anatomical Investigate Tolerability, & the Efficacy, Pharmacokinetics Safety and Pharmacodynamics of SB 497115-GR, A 279 Faculty of Medicine Dept of Medicine & Therapeutics Thrombopoietin Receptor Agoinst in 2005-06 A 2-Year Study to Assess the Efficacy, Adult Male and Female Subjects with Safety, and Tolerability of L-000899055 Refractory, in Obese Patients (MD05518) Chronic Immune CHOW Chun Chung Francis Thrombocytopenia (MD04780) CHENG Gregory KONG Pik Shan WONG Raymond* OZAKI Risa CHENG Yuen Shan Angela# LUK On Yan Andrea 2002-03 A Multinational, Double-Blind, Randomized, CHINNAIYAN, Arul* Placebo-Controlled, Forced-Titration, 2 x 2 Factorial Design 2005-06 Liraglutide Effect and Action in Diabetes Study of the Efficacy and Safety of Long (LEAD-1): Effect on Glycaemic Control Term Administration of Nateglinide and after Once Daily Administration of Valsartan in the Prevention of Diabetes Liraglutide and Cardiovascular Outcomes in Subjects Glimepiride with Impaired Glucose Tolerance (IGT) Monotherapy versus Glimepiride and (MD02454) Rosiglitazone Combination Therapy in CHOW Chun Chung Francis in versus with Glimepiride Subjects with Type 2 Diabetes. COCKRAM Clive Stewart FUNG Six-Month Wing Hong CHAN W* CHAN Double-Dummy, Wing Bun SO Wing Yee CHAN Control, Combination Double-Blind, Randomised, Parallel-Group, Active Multicentre, Multi-National Trial (MD05897) N* MA R* CHOW Chun Chung Francis 2004-05 A A Multicenter, Randomized, KONG Pik Shan Double-Blind, Active Controlled Study CHENG Yuen Shan Angela# to Compare the Long-Term Effect (up to 5 Years) of Treatment with LAF237 50 2005-06 Risk Stratification for Active Pulmonary mg bid to Glimepiride up to 6 mg Daily Tuberculosis as Add-On Therapy in Patients with Type Interferon-y Assay (MD05547) 2 Diabetes Inadequately Controlled with COCKRAM Clive Stewart Using Whole Blood Metformin Monotherapy (MD04418) CHOW Chun Chung Francis Wing Yee CHAN Wing Bun LAU Wing Yan Andrea 2003-04 Atrial Fibrillation Clopidogrel Trial with SO KONG Pik Shan OZAKI Risa Irbesartan for Prevention of Vascular Events - A Parallel, Randomized, Controlled Evaluation of LUK On Yan YU Wai Ling Linda (ACTIVE) Copidogrel plus Aspirin, with Factorial Evaluation CHENG Yuen Shan Angela# of Irbesartan, for the Prevention of Vascular Events in Patients with Atrial Fibrillation (MD03400) Faculty of Medicine 280 Dept of Medicine & Therapeutics FUNG Wing Hong John Elsby# Joseph SANDERSON WONG Tai Hung John# 2005-06 Effects of Growth Hormone on Body Fat Distribution, Yin* Insulin Cardiovascular 2002-03 A Randomized, Middle-Aged Double-Blind, Men Assessing the Rate of Decline of Lung KONG Pik Shan Inhalation Patients Tiotropium Capsule with Once 18 mcg Daily Chronic Ngor Juliana in Michael* 2005-06 A CHAN Chung TONG Peter Chun Multicenter, Comparative, Parallel-Group, Monotherapy, Study of Pregabalin (Lyrica) and Lamotrigine CHAN Chio Ho CHAN Pui Shan# Randomized, Double-Blind, KO Wai FOK Pui Chu Joan* TONG Mabel* Metabolic Obstructive HUI Shu Cheong David in Yip Pulmonary Disease (COPD) (MD02758) San Fanny* and Factors with Syndrome (MD05408) with Action Risk Placebo-Controlled, Parallel Group Trial Function YU LAM Yat (Science)) Cheuk Man CHAN Yat Sun KUM Chi Chiu Leo (Biochemistry (Lamictal) HO in Patients with Newly Diagnosed Partial Seizures (MD05809) Wai Mun# KWAN Kwok Leung Patrick 2005-06 A 12-Week, Double-Blind, Randomized WONG Ka Sing Lawrence Study to Investigate the Effect of 500μg HUI Andrew Che Fai LEUNG Ho Wan Roflumilast Tablets Once Daily versus Placebo on Pulmonary Function in Patients with Chronic 2004-05 Can Oral Vitamin B12 and Folate Obstructive Supplementation Pulmonary Disease (MD05356) HUI Shu Cheong David San Fanny Chun Li TO Kin Wang Preserve Cognitive Function of Patients with Early Dementia? (CU04307) KO Wai KWOK Chi Yui Timothy NGAI FOK Pui Chu Joan Chiu Wa (Psychiatry) CHAN Chio Ho LAM WOO Kam Sang (Biochemistry (Science)) ZEE 2005-06 A Randomized Controlled Study of the Chung Ying Benny (Community and Family Medicine) Long-Term Effects of Nasal CPAP on Systemic Blood Pressure, Coagulability, 2005-06 A Case Management Model of and Carotid Intima-Media Thickness in Interdisciplinary Care to Improve Quality Obstructive Sleep Apnoea Syndrome of Life of Older People with Early (MD05819) Dementia and to Reduce Their Caregiver HUI Shu Cheong David Gregory WOO Burden (MD05970) CHENG Kam Sang 281 Faculty of Medicine Dept of Medicine & Therapeutics KWOK Chi Yui Timothy LEUNG Wai Keung LAM TO Ka Fai Linda* LEUNG Chi Ming Michael (Anatomical & Cellular Pathology) (School of Public Health) NG Enders Kwok-wai (Surgery) 2005-06 ACE Gene I/D Polymorphism and 2005-06 Development of an in Vitro Cell Culture Testosterone in Older Men (MD05494) Model for Human Noroviruses and Its KWOK Chi Yui Timothy Clinical Application (MD05729) Leung Sang Nelson TANG LEUNG Wai Keung (Chemical Pathology) HO C S* CHAN Kay Sheung Paul (Microbiology) Lai Shun Nelson 2005-06 A Pilot Study on Influenza Viral Kinetics LEE SUNG Joseph Jao Yiu (MD05670) LEE Lai Shun Nelson 2005-06 Colorectal Cancer in Chinese Families Risk of Colorectal Adenoma in Cancer 2005-06 Establishment of a Public Norovirus Genome Database in Hong Relatives and the Search for New Cancer Kong Susceptibility Genes (MD05714) LEUNG Wai Keung (MD05734) LEUNG Wai Keung (Anatomical & Cellular Pathology) CHAN Lik Yuen Henry LAI Wai Man (Microbiology) SUNG Joseph Jao TO Ka Fai LAU Yun Wong James (Surgery) SUNG Joseph Jao Yiu Yiu 2004-05 A Multinational, Randomised, 2005-06 Colonoscopic Screening in First-Degree Double-Blind, Relatives of Hong Kong Chinese Patients Double-Dummy, with Controlled Sporadic Colorectal Cancer Stratified, Parallel LEUNG Wai Keung (Surgery) Group Study JONES Intravenous Zoledronic Acid, 5 mg Once LEE Fung Yee Janet Yearly, and Oral Risedronate, 5 mg Daily, TO Ka Fai (Anatomical in the Prevention and Treatment of & Cellular Pathology) Corticosteroid SUNG Induced Osteoporosis (MD04790) Joseph Jao Yiu LI Kwok Ming Edmund 2005-06 Epigenetic Active Comparing the Efficacy and Safety of (MD05631) Roger* Multi-Centre, Inactivation of Secreted TAM Lai Shan Frizzled-related Protein Gene Family in Gastric Cancer: Functional Significance and Potential Clinical 2004-05 A Randomized, Double-Blind, Parallel Application Group Study of the Safety and Reduction (CU05473) of Signs and Symptoms during Treatment with MRA versus Placebo, in Placebo, in Combination Faculty of Medicine 282 with Methotrexate, in Dept of Medicine & Therapeutics POON Chuen Wai Patients with Moderate to Severe Active Rheumatoid Arthritis (MD04763) Yuen Henry LI Kwok Ming Edmund Joseph Jao Yiu TAM Lai CHAN Lik HUI Yui# SUNG Shan* 2005-06 Deciphering the Proteins Secreted by Hepatocellular 2005-06 Long-Term Extension Study of Safety Tocilizumab (MD05315) (MRA) in Patients Completing Treatment POON during Treatment with in WA 17822 (MD05442) Chuen Wai Cells WONG Nathalie (Anatomical & Cellular LI Kwok Ming Edmund Pathology) TAM Lai Shan* 2005-06 A Carcinoma LAI Bo San Paul (Surgery) SUNG Joseph Jao Yiu Randomized, Parallel Group, 2004-05 A Multicenter, Randomized, Placebo-Controlled, Double-Blind Study Double-Blind, Placebo-Controlled Study to Assess the Safety and Tolerability of to Evaluate the Safety and Efficacy of the SB-681323 at 7.5 mg Daily Dose for 28 Addition of MK-0431 to Patients with Days and Its Effect on the Levels of Type 2 Diabetes Mellitus Who Have Serum C-Reactive Protein (CRP) in Inadequate Subjects with Rheumatoid Arthritis (RA) Glimepiride Alone or in Combination (MD06843) with Metformin (MD04403) LI Kwok Ming Edmund SO Wing Yee CHAN Chung Ngor Glycemic Control on Juliana KONG Pik Shan OZAKI 2004-05 Characterization of Serum Proteomic Risa LUK On Yan Andrea Signatures of Hepatocellular Carcinomas (MD04724) 2002-03 Acid Suppression by Proton Pump POON Chuen Wai Inhibitor PANG Ting Kai Ronald (Stanley Ho CEID)# Wai Keung CHAN Anthony Tak Francis Sheung Chee Sydney B Infection by Differential Lectin Affinity and CHAN Ka Leung (Surgery) Chromatography LEUNG LAU Yun Wong James (Surgery) Glycoforms of Serum Proteins from Hepatitis CHUNG Chronic Bleeding WU Che Yuen Justin 2005-06 Identification of Liver Cirrhosis-Specific with Ulcer SUNG Joseph Jao Yiu Cheung (Clinical Oncology) Patients Peptic (MD02996) MOK Shu Kam Tony (Clinical Oncology) in 2003-04 Screening of Colorectal Neoplasm in Quantitative Chinese (MD03767) SUNG Joseph Jao Yiu Proteomic Profiling (MD05322) Wai Keung TO LEUNG Ka Fai (Anatomical & Cellular Pathology) 283 Faculty of Medicine Dept of Medicine & Therapeutics HUI Shu Cheong David LAM Wai Man Wynnie (Diagnostic Radiology & Organ Imaging) Kwok CHAN Ka Leung Francis Wing (Medicine)) YEUNG Deacons* (Biochemistry TANG Leung Sang Nelson (Chemical Pathology) Margaret (Microbiology) 2003-04 Genotypes of Pro-Inflammatory Chuen Wai Cytokines (IL-1b, TNF-a and IL-10) TSUI IP POON CHEUNG Fanny Mui Ching (Psychology) Associated with Pre-Malignant Gastric Lesions (CU03436) 2003-04 A SUNG Joseph Jao Yiu Leung Francis Double-Blind, CHAN Ka Randomised, Parallel Group, Placebo-Controlled Trial on Safety and CHUNG Sheung Chee Sydney (Surgery) Multicentre, Efficacy LEUNG of Activated Recombinant Wai Keung NG Enders Kwok-wai Factor VII (rFVIIa/ NovoSeven®) in the (Surgery) TO Ka Fai (Anatomical Treatment of Active Variceal Bleeding in Patients & Cellular Pathology) with Advanced Cirrhosis (MD03518) SUNG Joseph Jao Yiu 2003-04 The Role of Cyclooxygenase (COX)-2 Overexpression in Gastric LAU Yun Wong James (Surgery) Carcinogenesis: A Transgenic Mouse Model (MD03968) 2004-05 Chinese Herbal Medicine for Irritable SUNG Joseph Jao Yiu Wai Keung Bowel LEUNG CHUN Wu Kai* From Basic Mechanism to Clinical Cure (MD04788) CHENG Sze Lok SUNG Joseph Jao Yiu (Institute of Digestive Disease) FU Yuangen# Syndrome: WU Che Yuen Justin LEUNG Wai Keung XU Li* WANG Xin* 2003-04 The Role of Cyclooxygenase-2 in Liver CHAN Ka Leung Francis BIAN Zhaoxiang* ZHAO LIU Liang* Zhongzhen* JIANG Zhi-hong* Fibrosis and the Potential of Misoprostol as an Anti-Fibrotic Agent (CU03446) SUNG Joseph Jao Yiu Yuen Henry 2004-05 Functional Bowel Disorders in Chinese Medicine (MD03458) CHAN Lik SUNG Joseph Jao Yiu CHENG Sze Lok (Institute of Digestive Disease) Tao (School of Chinese Medicine) LEUNG Wai Keung LEUNG Wai Keung Keung Ken (Anatomy) 2003-04 Commissioned Projects - Research on the Control of Infectious Yuen Justin Diseases (Anatomy) (MD03896) SUNG Joseph Jao Yiu LO Yuk Ming Dennis (Chemical Pathology) Faculty of Medicine CHE Chun 284 LIU Wing WU Che YEW Tai Wai David Dept of Medicine & Therapeutics 2004-05 Genomic Study of Viral Hepatitis B to Lik Yuen Henry WU Che Yuen Predict Development of Liver Cancer in Justin Asian Patients (MD04467) Nafees Begum* SUNG Joseph Jao Yiu Lutz* WU Eugene Brian* 2005-06 Functional Bowel Disorders in Chinese 2005-06 Research Medicine (MD05831) Baig KATZSCHNER Digestive SUNG Joseph Jao Yiu WU Che Disease (School of Chinese Medicine) CHAN Ka Leung Francis LEUNG Wai Keung CHE Chun Tao into (MD05770) SUNG Joseph Jao Yiu Yuen Justin LI Chi Hong Felix* CHAN Lik Yuen Henry LEE LEUNG Wai Keung YEW Tai Yuk Tong Wai David (Anatomy) LIU Wing YU Jun NG Enders Kwok-wai HU Shiu (Surgery) LAU Yun Wong James Ying (School of Chinese Medicine) (Surgery) Keung Ken (Anatomy) ZIEA Tat Chi ZHENG RP* YEUNG Chun Yip* Annie Nga Yin* & Organ Imaging) Yee WALTHER Beverly* YU Chun Ho (Diagnostic Radiology & Organ LAW Sin XIAO Zhuangwei* LAM Wai Man Wynnie (Diagnostic Radiology TO Ka Fai (Anatomical William, Gray Argust* Angelina* LEE Fung Yee Janet & Cellular Pathology) ES Debnam* CHAN SO Chan Ying Peggy* CHEUNG (Surgery) WU Che Yuen Justin Imaging) (Clinical XIE Xinhui* TSE Sui Wah Betty* MOK Shu Kam Tony Oncology) ZHANG Mingdong (Stanley Ho CEID)# HE Mingliang (Stanley Ho CEID) 2005-06 A Randomized, Double-Blind, Parallel-Group, Placebo Controlled Study 2005-06 Clinical Research on HIV/AIDS of Esomeprazole I.V. (Bolus Infusion of Management (MD05994) 80 mg Followed by a Continuous SUNG Joseph Jao Yiu Infusion of 8 mg per Hour) Administered Shan (Stanley Ho CEID) for 72 Hours to Assess Prevention of Shun Nelson Rebleeding in Undergone Subjects That Successful LEE Shui LEE Lai Have Primary 2005-06 Novel HBV Mutations as Early Endoscopic Haemostasis of a Bleeding Diagnostic Markers for HCC (MD05973) Peptic SUNG Joseph Jao Yiu Ulcer - The PUB Study (MD05822) CHAN Hin Lee Henry (Paediatrics) SUNG Joseph Jao Yiu LAU Yun Wong James (Surgery) CHAN Ka Leung NG Francis Kwok-wai (Surgery) Keung 2005-06 Administration of High-Dose Intravenous Proton Enders Inhibitor for Upper Gastrointestinal Bleeding (MD05603) LEUNG Wai LEE Yuk Tong Pump CHAN 285 Faculty of Medicine Dept of Medicine & Therapeutics SUNG Joseph Jao Yiu CHAN Ka 2005-06 Open Label Extension Study Evaluating Leung Francis LEUNG Wai Keung the Long Term Safety, Tolerability and WU Che Yuen Justin Efficacy of an Iron Maintenance Dosing LAU Yun Strategy Utilizing Intravenous VIT-45 in Wong James (Surgery) the Treatment of Anemia in Non-Dialysis 2005-06 A Dependent Randomized, Open Label Study (NDD) Chronic Kidney Evaluating the Efficacy and Safety of Disease (CKD) Protocol: 1VIT05005 Peginterferon Alfa-2a (PEGASYS) or (MD05845) Adefovir Dipivoxil (ADV) in Patients SZETO Cheuk Chun with Lamivudine Resistant HBeAg CHOW Kai Ming Positive Chronic Hepatitis B (MD06733) SUNG Joseph Jao Yiu Yuen Henry 2003-04 A Sibling-Based Study of the Molecular CHAN Lik LI Chi Hong Felix* Genetics of Hypertension-Application of Microarray-Based Baig Nafees Begum* DNA Chip Technology (CU03438) TOMLINSON Brian 2003-04 Treatment of Early Immunoglobulin a THOMAS Nephropathy by Angiotensin Converting Neil G (School of Pharmacy)# Enzyme Inhibitor - A Randomized YANG Michael* Controlled Trial (MD04749) SZETO Cheuk Chun 2005-06 Pharmacokinetics of Single and Repeated LI Kam Tao Oral Administration of S 18886 30 mg Philip* YU Wai Yin Alex* Daily in Chinese Healthy RNA Expression of Volunteers (MD05889) Podocyte-Associated Molecules in TOMLINSON Brian 2005-06 Messenger Urinary Sediment - A Non-Invasive Male FOK Siu Pong Prognostic Marker of Chronic Kidney Diseases? (MD05946) 2005-06 Single- SZETO Cheuk Chun and Multiple-Dose, Tolerability and Pharmacokinetic Study of 2005-06 Comparison of the Safety and Efficacy of Oral Rivoglitazone Subjects (MD05338) (VIT-45) TOMLINSON Brian Oral Iron in (CS-011) in Healthy Chinese Male and Female a Unique Intravenous Iron Preparation versus Safety, the Treatment of Anemia in Non-Dialysis Dependent Chronic Kidney Disease 2005-06 Expert Report on the Safety and Efficacy (Protocol: 1VIT04004) (MD05657) of "Trimix" (MD05566) SZETO Cheuk Chun TOMLINSON Brian CHOW Kai Ming 2005-06 Phase I Study on the Safety and Pharmacokinetics of Single and Repeated Faculty of Medicine 286 Dept of Medicine & Therapeutics Application of IMD-0354 in Healthy Diabetes Who Have Inadequate Male Volunteers (MD05644) Glycemic Control on Metformin Therapy TOMLINSON Brian Alone (MD04461) TONG Peter Chun Yip 2005-06 Reduced Factorial Design, Randomized, Double Blind Trial Chung Ngor Juliana Comparing CHAN SO Wing Yee WONG Siu Man* Combinations of Telmisartan 20 or 80 mg and Simvastatin 20 or 40 mg with 2005-06 The Effect of Sulodexide in Patients with Single Component Therapies in the Type 2 Diabetes and Microalbuminuria Treatment (MD05379) of Hypertension and Dyslipidemia (MD06332) TONG Peter Chun Yip TOMLINSON Brian Chung Ngor Juliana Shan 2002-03 The Participation of the Cytoskeleton in KONG Pik CHAN Wing Bun* CHAN MA Ronald* Insulin Action in Human Skeletal Muscle (CU02124) TONG 2005-06 Synthesis of Recombinant Insulin-Like Peter Chun Yip Growth Factor-I and Insulin-Like Growth Factor Binding Protein-3 in Transgenic COCKRAM Clive Stewart Rice (MD05915) TONG Peter Chun Yip 2003-04 Oxidative Stress and Insulin Resistance in Hong Kong Chinese with Ming Samuel (Biology) Thalassaemia Minor (CU03439) TONG Peter Chun Yip Chung Ngor Juliana Leung (Anatomical Pathology) Kei Christopher Pathology) 2005-06 #CV181-040A NG - CHAN Multicenter, Randomized, Cellular Double-Blind, Placebo-Controlled Phase 3 Trial to HO Chung Shun (Chemical Pathology) CHAN & SUN Sai Chung Ngor Juliana CHAN Yu LAM Wai Evaluate the Efficacy and Safety of (Chemical Saxagliptin Heung in Combination with Glyburide in Subjects with Type 2 Ling Margaret (Anatomical & Cellular Diabetes Who Have Inadequate Pathology) Glycemic Control on Glyburide Alone. (MD05502) TONG Peter Chun Yip 2004-05 A Phase-3 Randomized, Three Arm, Double-Blind, Active Controlled, Parallel Chung Ngor Juliana Group, Multicenter Trial to Evaluate the Shan Safety and Efficacy of Muraglitazar in Combination with Metformin Compared Arul* CHAN KONG Pik CHENG Yuen Shan Angela# MA Ronald* CHINNAIYAN, to Glimepiride in Combination with Metformin in Subjects with Type 2 287 Faculty of Medicine Dept of Medicine & Therapeutics 2003-04 The Significance of with Moderate to Severe Leukoaraiosis Microembolic Signals and New Cerebral Infarcts on the (CU04317) Progression of Neurological Deficit in WONG Ka Sing Lawrence Acute Stroke Patients with Middle Chung Tong Vincent Cerebral Artery Stenosis (CU03440) Leung WONG Ka Sing Lawrence Pathology) CHAN MOK CHAN Yu (Anatomical & LAM Cellular Wai Man Yu Leung (Anatomical & Cellular Wynnie (Diagnostic Radiology & Pathology) Organ Imaging) LAM Wai Man WOO Kam Sang Wynnie (Diagnostic Radiology & (Biochemistry (Science)) Organ Imaging) Wai Kwong (Psychiatry) 2003-04 A Randomized, Double-Blind, TANG Multicenter, 2004-05 PRoFESS - COG Sub-Study Effects of Placebo-Controlled, BP Lowering with Micardis®, and 18-Month Study of the Efficacy of Anti-Platelet Xaliproden with Aggenox® or Clopidogrel, on Cognitive the Function and Dementia Following Acute in Mild-to-Moderate Patients Dementia of Alzheimer's Type (MD03610) with either Ischaemic Stroke (MD04379) WONG Ka Sing Lawrence Chung Tong Vincent Therapy WONG Ka Sing Lawrence MOK Chung Tong Vincent DAI Lok Kwan David Che Fai Patrick 2004-05 PRoFESS - Prevention Regimen For Thomas MOK HUI Andrew KWAN Kwok Leung LEUNG Wai SOO Oi Yan Hong WONG Effectively Avoiding Second Strokes: A Ho Chung Edward Double-Blind, Shing Eric# LEUNG Howan* Active and Placebo LIANG Ka Controlled Study of Aggrenox® vs. Clopidogrel Aspirin, with and without 2005-06 A Pilot Study of Enhanced External Micardis® (MD04510) Counterpulsation for Cerebral Blood WONG Ka Sing Lawrence Chung Tong Vincent Kwok Leung Patrick Hong Thomas Eric# MOK Flow Augmentation in Chinese Ischemic KWAN Stroke Patients with MCA Stenosis (MD05308) LEUNG Wai WONG Ka Sing Lawrence LIANG Ka Shing WONG H C Edward* Wai Man Wynnie LAM (Diagnostic Radiology & Organ Imaging) LEUNG Howan* LAM Tsan Augustine* 2004-05 Effect of Multivitamins Supplementation on the Progression of Cerebral White Matter Changes and 2005-06 A Cognitive Double-Blind, Placebo-Controlled, Impairment in Chinese Stroke Patients Randomized, Parallel Group, Multicenter, Phase IIb/III Study to Assess the Efficacy and Safety of Inravenous Faculty of Medicine 288 Dept of Medicine & Therapeutics Stoke 2005-06 Influenza-like Illness in Residential Care SAINT II (Stroke - Acute Ischemic - Homes: A Study of the Incidence, NXY Treatment) (MD05881) Aetiological Agents, Natural History, and NXY-059in Acute WONG Ka Ischemic Sing Lawrence LEUNG Thomas WH* Andrew CF* Vincent* WOO Jean HUI Duqin* (Microbiology) SHARMA Abhishek* FONG W.F. David* IP Margaret HUI Shu Cheong David KWOK Chi Yui Timothy GRAHAM C A (Accident 2005-06 Non-Erosive Gastroesophageal Reflux and Emergency Medicine Academic Disease (NERD): A Disease of Excessive Unit) Acid Stroke: (DIAS) A Double-Blind, Placebo-Controlled, Multinational, Single Bolus, Multi-Center, Parallel Dose Ranging Study Visceral Hypersensitivity? WU Che Yuen Justin Prospective, Randomized, or (MD05497) 2005-06 Desmoteplase (INN) in Acute Ischemic Group, CHAN Kay Sheung Paul (Microbiology) MOK Chung Tong WANG Health Resource Utilization (MD05849) Joseph Jao Yiu SUNG CHAN Ka Leung Francis LEUNG Wai Keung of 2005-06 A Triple-Blinded, Randomized, Desmoteplase (INN) in the Indication of Placebo-Controlled Trial to Examine the Acute Stroke (MD05358) Efficacy and Safety of ViNeuro in WONG Ka Sing Lawrence LEUNG Thomas WH* Patients Parkinson's Disease (MD05950) MOK YEUNG Hon Ming Jonas Chung Tong Vincent* LIANG K S Eric* with Ka Sing Lawrence GRAHAM C A (Accident and Emergency Medicine Academic WONG MOK Chung Tong Vincent Unit) 2002-03 A Multicentre, Multinational, Long-Term, 2005-06 A Placebo-Controlled Double-Blind, Extension Study to Assess the Safety and Parallel Arm Trial to Assess the Efficacy Toleration of Dronedarone 400mg Bid for the Treatment Regimens of Oral Sildenafil Prevention Cardiovascular for Pulmonary Arterial Hypertension in Hospitalization or Death from Any Cause Subjects Who Have Completed Study in Patients with Atrial Fibrillation/Atrial A1481140 (MD02489) Flutter YU Cheuk Man of (AF/AL) (ATHENA-Study) EFC5555 (MD05403) WONG Ka Sing Lawrence Ling# of Subject Chung Tong Vincent* KONG Shun MA Wing Yan# Kwok Gabriel MOK Optimised (Ophthalmology Sciences)# YIP Wai WANG Zheng and Visual WONG Wing Cheong (Ophthalmology and Visual Sciences) 289 Faculty of Medicine Dept of Medicine & Therapeutics WONG Tai Hung John# Chi Chiu Leo YU Cheuk Man KUM John LAI Hong Yee Connie* Elsby# (Physiology) SANDERSON HUANG Yu LUNG Wai Ming Raymond (Anatomical & Cellular 2003-04 Predictors of Response To Cardiac Pathology) Resynchronization Therapy (PROSPECT) 2004-05 CONTAKTM RENEWAL ® 4 AVY (MD03718) YU Cheuk Man System Field Following (MD04679) FUNG Wing YU Cheuk Man Hong ZHANG Qing* Hong 2004-05 A Multicentre, Multinational, Long-Term FUNG Wing SANDERSON John Elsby# CHAN Yat Sun Joseph CHAN Extension Study to Assess the Safety and Chi Kin Hamish Toleration Ping Alice# KONG Shun Ling# of Subject Optimised CHEUNG Siu Treatment Regimens of Oral Sildenafil for Pulmonary Arterial Hypertension in 2004-05 Consultant Agree with Guidant Inc. Subjects Who Have Completed Study (MD04303) A1481140 (MD02736) YU Cheuk Man YU Cheuk Man Gabriel YIP Wai Kwok TAM Lai Shan Chi Chiu Leo LEE Pui Wai 2004-05 Cardiac Contractility Modulation for the KUM Treatment of Heart Failure - Impact of Haemodynamic Optimization of Lead LAM Yat Yin Position (MD04842) 2004-05 Assessment of Remodeling with Echocardiography Imaging Left in Tissue and Doppler Strain Patients YU Cheuk Man Ventricular after FUNG W. H.* CHAN Yat Sun Joseph CHAN Chi Rate Kin Hamish Acute Myocardial Infarction Compared with 2004-05 Sensitivity of the InSync Sentry OptiVol Contrast-Enhanced Magnetic Resonance Feature for the Prediction of Heart Imaging (CU04312) Failure (MD04370) YU Cheuk Man Gabriel YU Cheuk Man YIP Wai Kwok Grace* LAM Wai Man Wynnie (Diagnostic Radiology & Organ CHAN MC FUNG Wing Hong* KUM Chi Chiu* DUAN Delin* Imaging) ZHANG Yan 2005-06 FAST (Fluid Accumulation Status Trial) 2004-05 The Application of Baicalein (MD05932) and YU Cheuk Man ZHONG Yuzhuo* Wogonin (Traditional Chinese Medicine) for the Treatment of Pathological Myocardial Fibrosis in an Animal Model of Hypertension (CU04318) Faculty of Medicine 290 LUKE Kit Ling* Dept of Medicine & Therapeutics Edmond# 2005-06 Early Glycoprotein IIb/IIIa Inhibition in Non-ST-segment Elevation FUNG Wing Hong CHAN Wai Man Wilson Acute Coronary Syndrome: A Randomized, 2005-06 A Phase III, 18-month, Multicenter, Placebo-Controlled Trial Evaluating the Clinical Benefits of Early Front-loaded Randomized, Eptifibatide in the Treatment of Patients Active-Controlled with Non-ST-segment Elevation Acute Compare Rosiglitazone versus Glipizide Coronary Syndrome (EARLY ACS) on the Progression of Atherosclerosis in (MD05967) Subjects with Type 2 Diabetes Mellitus YU Cheuk Man Wilson WONG Man Lok YEUNG Leata Y.C.* Edmond# Clinical Trial to and Cardiovascular Disease (MD05464) CHAN Wai Man KUM Chi Chiu Leo Double-Blind, YU Cheuk Man Wilson* YUEN Hui Leung* KWOK Lai Wah* WU Eugene Brian* CHAN Wai Man HUANG Ying Ying* CHAN YEUNG Yuk Ching 2005-06 Vascular Medicine (Clinical Research) 2005-06 Randomized Evaluation of Long Term (MD05941) Anticoagulant YU Cheuk Man ZHANG Qing YIP Gabriel* (RE-LY) Comparing the Efficacy and Safety of Two CHAN Yat Sun Therapy Blinded Doses of Dabigatran KUM Etexilate with Open Label Warfarin for Chi Chiu Leo LAM Yat Yin LEE the Prevention of Stroke and Systemic Pui Wai Embolism in Patients with Non-Valvular Joseph CHAN Kin Yin Atrial Fibrillation: Multi-Centre, 2005-06 Assessment of the Effect of Dual Prospective, Parallel-Group, Chamber Pacing on Left Ventricular Non-Inferiority Trial (RE-LY STUDY) Diastolic Function in Patients With and (MD05753) Without YU Cheuk Man Pre-existing Diastolic Dysfunction (CU05485) YU Cheuk Man Joseph CHAN Yat Sun CHAN Chin Pang WONG Man Lok Edmond# FUNG Wing Hong Pui Wai LEE CHAN YEUNG Yuk Ching CHAN Hoi Man# 2005-06 A Study on the Epidemiology, Management and Outcome of Chinese 2005-06 A Placebo-Controlled, Double-Blind, Patients with Acute Coronary Syndrome Parallel Arm Trial to Assess the Efficacy (ACS Registry HK) (MD05344) of Dronedarone 400mg Bid for the YU Cheuk Man Prevention Leo KUM Chi Chiu Cardiovascular CHAN Hospitalization or Death from any Cause WONG Man Lok in Patients with Atrial Fibrillation/Atrial CHAN Chin Pang Lip Kiong of 291 Faculty of Medicine Dept of Medicine & Therapeutics Flutter (AF/AFL) Registry of Hospitalized Heart Failure (ATHENA-Study) (MD05332) (MD05625) YU Cheuk Man Lawrence YU Cheuk Man WONG Ka Sing CHAN MC Grace* Leung* FUNG Wing Hong* CHAN Anna* KWOK Lai Wah* Richard* Angela* Vincent* Yat Yin* YUEN Hui WILLIS Richard* LAM KWOK Lai Wah* CHAN Anna* WILLIS YIP Wai Kwok Gabriel* LEUNG Yee Man MOK Chung Tong FONG W.F. David* WANG Duqin* 2005-06 Influence of Heme Oxygenase Nutritional Steatohepatitis (MD05639) YU Jun SUNG Joseph Jao Yiu (An International Decompensated Heart Failure Registry) - Faculty of Medicine 1 Modulation on the Progression of Murine CHEUNG Chi Chiu Chris* 2005-06 ADHERE 292 Dept of Microbiology of specimen collection and information regarding RESEARCH PROJECTS their treatment status will be analysed alongside data generated by spoligotyping and a new RAPD Epidemiological Analysis and Establishment of a approach, so as to delineate whether these resistant DNA of isolates share some degree of genetic relatedness. Mycobacterium The results shall therefore reveal whether each Fingerprinting Database Multiple-Drug-Resistant MDR-MTB strain developed independently through Tuberculosis Clinical Isolates in Hong Kong drug selection, or emerged through dissemination of established or parent MDR-MTB strains through the CHAN Chiu Yeung Raphael CHAN Wai Chi community. A database of DNA fingerprints of all KAM Kai Man* YIP Chi Wai* resistant strains will also be set up so as to serve as a 1 January 2007 reference library for matching the genetic identities Research Fund for the Control of Infectious of future MDR-MTB isolates and for tracing the Diseases routes of transmission of such strains in the Effective treatment of Mycobacterium tuberculosis community. (MTB) infections has been compromised by the (MD06698) emergence of multi-drug resistant strains of this organism (MDR-MTB) in the past Assessment decade. of Structural Diversity and Although MDR-MTB strains account for only a small Transposition Efficiency of Two Variant Forms of proportion (<10%) of all local MTB isolates, results a Tn4001-like Transposon that Confers High-level from our recent study involving over 200 MDR-MTB Gentamicin-Resistance in Clinical Streptococcus clinical isolates showed that they exhibit a diversity Pasteurianus Isolates of resistance patterns, and that isolates resistant to 3 or more anti-tuberculosis drugs were common. CHAN Chiu Yeung Raphael CHAN Wai Chi In AU Tai Kong FUNG Ka Chun# addition, a wide spectrum of chromosomal mutations were also recovered from the known resistance genes, 30 June 2007 with strains harboring four or more mutations being a CUHK Research Committee Funding (Direct common finding. We hypothesize that these highly Grants) mutated resistant bacteria did not acquire all mutations during the course of selection in one Bacterial transposable genetic elements play a major patient, and that an organism needs several selection role in dissemination of resistance determinants among rounds, which probably involve several patients, to bacterial pathogens, especially in clinical or hospital accumulate settings. enough mutations to achieve the We recently isolated seven clinical To test this hypothesis, we Streptococcus pasteurianus strains which exhibited propose to perform epidemiological analysis of our high level resistance to gentamicin (MICs. ≥ 512 collection of MDR-MTB which encompasses the vast µg/ml). majority of such strains isolated in Hong Kong in the phenotype was attributable to the chromosomal past 10 years. Epidemiological data such as the date integration of a Tn4001-like transposon bearing the MDR-MTB status. We have shown that this resistance aac(6')Ie-aph(2")Ia 293 bi-functional aminoglycoside Faculty of Medicine Dept of Microbiology modifying enzyme gene. Our results also showed 1. Target at an HPV type relevant to Chinese and that there were at least two variant forms of Asian women: The first generation vaccines target Tn4001-like transposon in these isolates. The at HPV 16 and 18 which are the two most proposed project aims to probe the difference common types worldwide. However, in China between the molecular structures of the two forms of and Asia, other types also cause a significant Tn4001-like transposons and test their transposition proportion of cervical cancers. This study will efficiency in a bacterial host. target at HPV52 which is one of the priority HPV The results of this study should provide valuable information about the types for China as well as Asia. structural diversity and possibly reveal whether the 2. Focus on cellular immunity and therapeutic two variant forms of this important mobile genetic vaccine element exhibit differential efficiencies in promoting vaccines induce a good humoral immune response, horizontal transfer of aminoglycoside resistance and thus are effective as prophylactic (i.e. among Gram-positive clinical isolates. preventative) vaccines. (MD06783) already been infected with HPV and with development: The first generation Women who have established cervical lesions require another form Identification of Viral Peptide Candidates for the of vaccine that can achieve therapeutic effect. Development of Second Generation Cervical This study aims at identifying viral peptides that Cancer Vaccines Tailored for Chinese Women can elicit cellular immunity, so as to provide essential data for the design of therapeutic vaccines that can be used to treat pre-cancers. CHAN Kay Sheung Paul CHEUNG Tak Hong (Obstetrics & Gynaecology) MAN Stephen* These have a potential to established invasive cervical cancer. 1 January 2007 (CU06483) Research Grants Council (Earmarked Grants) Goal: also supplement the existing treatment modes for TANG Julian Wei Tze Ultimate vaccines Decrease cervical A Comparative Study on Host Cellular Gene cancer-associated deaths, particularly in China Transcription and Asia. Viruses with Different Pathogenicity Response to Avian Influenza Background: Cervical cancer kills more than 250,000 women every year CHAN Kay Sheung Paul worldwide. LAM Ching Wan Vaccines targeting the causative agent human (Chemical Pathology) papillomavirus (HPV) will soon be available. & Cellular Pathology) TANG Julian Wei Tze While these first generation vaccines show LAM Wai Yip promising results in clinical trials, there are 1 January 2007 inadequacies that need to be addressed. Our TO Ka Fai (Anatomical Research Fund for the Control of Infectious study aims at providing essential data for the Diseases development of second generation cervical cancer vaccines. Background: Influenza pandemic remains a serious Objectives & Impact: threat to human health. In addition to H5N1, H7 Faculty of Medicine 294 Dept of Microbiology and H9 have occasionally succeeded in crossing the 15 June 2007 species barrier. CUHK Research Committee Funding (Direct It is clear that H5, H7, H9 and perhaps other subtypes also have pandemic potential. Grants) The consequence of human infection with avian influenza viruses varies markedly with the subtype. The In addition to viral factors, the difference in host dysregulation (e.g. TNF-alpha, IP-10) observed in cellular response is likely to play a critical role. human H5N1 infection is thought to play a key role Aims: This study aims at improving our understanding leading to the severe clinical outcome. on the pathogenesis of avian influenza infection in are major mediators of human immune responses. humans, and with a long term goal leading to the However, dysregulation of cytokine production may identification result in unwanted inflammation and indirect cell of novel intervention targets to inflammatory/proinflammatory cytokine Cytokines ameliorate the outcome of such infection. damage. Specific objectives: both at the transcriptional and post-transcriptional 1. levels. 2. 3. To compare the host cellular response to Cytokine synthesis is tightly regulated Imbalance between the stability and infections with highly pathogenic avian influenza degradation viruses versus low pathogenic avian influenza cytokine viruses and usual human influenza viruses. inflammatory Cytokine To delineate and characterize the repertorie of of inflammatory/proinflammatory mRNAs can responses mRNAs result or contain in even uncontrolled cell death. adenylate-uridine host cellular response to infections with highly (AU)-rich element (AREs) in the 3’ untranslated pathogenic avian infleunza viruses. regions (UTR) which enables them to be targeted for stabilization or rapid degradation by a variety of To identify critical host cellular responses that ARE-binding proteins. account for increased pathogenicity. Study design : This is a comparative study The genome of influenza A virus is segmented, comprising the H5, H7, and H9 avian subtypes that consisting of eight single-stranded, negative-sense have caused human infections, and the H1 and H3 RNA molecules, which encode 11 proteins. circulating human subtypes; using an in-vitro lung found that there is a class I ARE (AUUUA) sequence cell derived model. Post-infection effects on host in the 3’ UTR of the NS1 gene but not in the other cell gene expression of each influenza subtype will be viral genes. Since mRNA turnover plays a major examined initially by the broad-catching technique role in regulating cellular function, it is possible that based on a well-characterized microarray assay that viruses may utilize this route to regulate cellular gene covers 3,300 human genes. The screening results expression will be confirmed by gene-specific assays at the Therefore, we hypothesize that influenza A virus transcription and translation levels. infection will directly or indirectly cause an (MD06903) imbalance between the stability and degradation of to enhance its own It is replication. the mRNAs of early inflammatory/proinflammatory Effect of Influenza A H5N1 Infection on the cytokines, and result in abnormal cytokine Turnover of TNF-Alpha mRNA of Host Cell production, especially in H5N1 infection. We propose to study the effect of infection with different subtypes of influenza A viruses on the stability of CHAN Kay Sheung Paul LAM Wai Yip 295 Faculty of Medicine Dept of Microbiology TNF-alpha mRNA in an in-vitro human lung cell characteristics of local MDR-MTB isolates, and model. should help identify any deleterious physiological (MD06522) and metabolic changes that may render the resistant organisms less growth-competitive as compared to Assessment of Physiological Fitness of Drug their drug-sensitive counterparts. In addition, since Resistant Mycobacterium Tuberculosis Clinical we identified a sub-set of MDR-MTB strains which Isolates in Hong Kong harbour no detectable chromosomal mutations in the corresponding resistance genes, we propose here to CHAN Wai Chi CHAN Chiu Yeung Raphael further characterize them by the proteomic approach, AU Tai Kong CHEUNG Wai Tsoi Frankie* and hope the results may lead to a better understanding of the drug resistance mechanism in 1 January 2007 this category of MDR-MTB isolates. Research Fund for the Control of Infectious (MD06525) Diseases Mycobacterium tuberculosis (MTB) infections Urethritis in Male Patients – Study on the remain an important infectious disease in Hong Kong. Molecular Basis of Fluoroquinolone Resistance in In 2004 there were 6295 recorded cases of MTB, Neiserria Gonorrhoea, and Preliminary Study on corresponding to a rate of 91.46 per 100,000 people. the Family Mycoplasmataceae in Non-gocococcal Our current efforts to contain this disease has been Urethritis complicated by the emergence of multi-drug resistant strains of this organism (MDR-MTB). HUI Mamie Results from LUK Nai Ming Tommy our recent analysis of over 200 MDR-MTB clinical (Medicine & Therapeutics) isolates showed that the resistance patterns were very Yeung Raphael diverse, and that strains exhibiting resistance to 3 or CHAN Chiu 30 June 2007 more anti-tuberculosis drugs were common. Each CUHK Research Committee Funding (Direct of the drug resistance phenotypes was also found to Grants) be associated with a wide spectrum of chromosomal mutations in the corresponding resistance gene. In Urethritis is a common presentation for male patients order to evaluate the potential threat of these attending the sexually transmitted diseases clinic. MDR-MTB strains in Hong Kong, we propose here The diseases are clinically divided into gonococcal to assess the physiological fitness of these organisms urethritis and non-gonococcal urethritis. and determine whether major resistance phenotypes gonorrhoeae, developed at a physiological cost. Experiments are gonococcal urethritis, can be treated with a single designed to measure their growth rates and dose of empiric antibiotic. However, emergence of characterise the virulence and proteomic profiles of resistance selected strains, followed by comparison to those of Fluoroquinolones, was once the antibiotic of choice, the drug-sensitive organisms. Information obtained but its resistance has been reported. In particular, from this study shall complement our current our collaborative study with Jiangsu Province, China, knowledge had reported fluoroquinolone resistance of nearly on the Faculty of Medicine genotypic and phenotypic 296 the is pathogen observed Nesseria responsible for world-wide. Dept of Microbiology 100%. Fluoroquinolone resistance is associated classified according to their viral nucleic acid with point mutations in the quinolone resistance sequence similarity. determining region (QRDR), especially in gyrA and In Hong Kong, previous studies have shown that parC. Accumulation of multiple point mutations in HCV genotypes l b and 6a are the commonest, these sites, not only lead to a cumulative increase in though other genotypes (la, 2a, 3a, and 4) are also MIC levels, but also signify its path down the present. Whilst HCV genotype l b can be found evolutionary such worldwide and responds least well to treatment, HCV information is still scarcely available. At the same 6a is relatively unique to Southeast Asia and has an time, the other clinical entity: non-gonococcal intermediate response to treatment. urethritis, are still minimally understood. It is The different HCV genotypes may have been believed to be caused by Chlamydia trachomatis and introduced into Hong Kong at different times by the (including different populations (e.g. intravenous drug-users, Mycoplasma hominis, Mycoplasma genitalium, and blood donors), and spread amongst these different Ureaplasma these populations by different routes (e.g. intravenous via organisms, especially the group Mycoplasmataceae, drug abuse or blood transfusion, or more rarely, are difficult to cultivate in vitro. sexual and vertical transmission). family stream. of In Hong Mycoplasmataceae urealyticum). Kong, However, Thus information on their prevalence and antibiotic resistance are We propose to sequence full-length HCV 6a limited. Often, the treatment of which is based on genomes (approximately 9.4 kb in length) and apply empirical ground and response to treatment. With phylogenetic analysis to both the whole genome as the advent of molecular techniques and microculture well as the individual genes to determine the epidemic techniques, it would allow studies to understand the history and evolution of HCV 6a in Hong Kong. prevalence and drug susceptibilities of these genital The presence of any recombination will investigated, mycoplasmas. particularly within the putative interferon-sensitivity (MD06497) determining region (ISDR) within the NS5A gene. This will further characterize the behaviour of HCV The Molecular Epidemiology of Hepatitis C 6a infections in Hong Kong, which may be useful in Genotype 6a in Hong Kong the future management of this disease. Presently, there are few HCV 6a sequences available on public TANG Julian Wei Tze databases, CHAN Kay Sheung to which this project will add significantly. Paul NGAI Lei Ka (MD06981) 1 June 2007 CUHK Research Committee Funding (Direct Please refer to previous issues of this publication Grants) for more details of the following ongoing research Hepatitis C virus (HCV) infects approximately 3% of at the department: the world’s population (about 170 million people) and is one of the leading causes for liver Edition Title/Investigators transplantation in developed countries. It exists in several subtypes called ‘genotypes’ which are 297 Faculty of Medicine Dept of Microbiology 2003-04 Development of Oligonucleotide Probe 2005-06 Development of Antiviral Compound for Microarrays for Molecular Detection of Drug Resistance in Avian Influenza H5N1 (MD05824) Mycobacterium CHAN Kay Sheung Paul Tuberculosis (CU03430) CHAN Chiu Yeung Raphael 2005-06 Differential Gene Expression Analysis of CHENG Fun Bun Augustine# HUI Bacterial Stress Responses to Antibiotic Mamie Induction and Selection (MD05376) CHAN Wai Chi 2004-05 Mechanisms of Lymphocyte Loss in SARS-CoV Infection (MD04850) CHAN Kay Sheung Paul CHAN Chiu Yeung Raphael CHEN 2004-05 Hospital Gong George (Surgery) Surveillance of Childhood Respiratory Infections in Hong Kong (MD04526) 2005-06 Identification of T-cell Epitopes in Oncogenic Human Papillomavirus to IP Margaret Provide a Foundation for Developing Anthony Peptide-based SUNG Yn Tz Rita (Paediatrics) Prophylactic and Therapeutic Vaccines against Cervical NELSON Edmund Severn (Paediatrics) CHAN Kay Sheung Paul Cancer (CU05487) CHAN Kay Sheung Paul 2004-05 Rapid Detection of Food-Borne CHEUNG Tak Hong (Obstetrics & Pathogens in Clinical Specimens, Foods Gynaecology) and Environmental Samples (MD04353) NGAI Sai Ming LING Mei Lun Julia (Biology) Stephen MAN* 2005-06 Development 2005-06 Identification of T-Cell Epitopes of SARS-Coronavirus: Provision Methods of of for Rapid the Molecular Detection and Investigation of Fundamental Data for the Design of Epidemiological Peptide-Based Food-Borne Outbreaks (MD05710) Vaccines and the LING Mei Lun Julia Development of Peptide-Based Cellular Immunity Assessment Methods 2005-06 Sequencing and Phylogenetic Analysis of (MD05912) CHAN Kay Sheung Paul Sai Ming (Biology) NGAI Influenza A Isolates Collected Over the Stephen Past 15 Years at the Prince of Wales Hospital, Hong Kong (MD05636) MAN* TANG Julian Wei Tze CHAN Kay 2005-06 Development and Validation for a Sheung Paul Low-Cost HIV Viral Load Monitoring Assay (MD05877) CHAN Kay Sheung Paul Faculty of Medicine 298 The Nethersole School of Nursing (CU06531) RESEARCH PROJECTS Establishing Psychometric Properties of the Labor Second Primary Malignancies Associated with Agentry Scale (LAS) among Chinese Post-partum Nasopharyngeal Carcinoma in Hong Kong Women GOGGINS III William Bernard IP Wan Yim CHIEN Wai Tong YU Tak Sun Ignatius (Community and Family Medicine) 30 June 2007 1 January 2007 CUHK Research Committee Funding (Direct Grants) Research Grants Council (Earmarked Grants) This project is a pilot study designed to determine the The purpose of this study is to establish the feasibility of conducting a large scale retrospective psychometric properties of the Chinese version of cohort study to determine the risk of second primary Labour Agentry Scale (Hodnett, 1982) among Hong malignancies among survivors of nasopharyngeal Kong Chinese postpartum women. carcinoma (NPC) in Hong Kong. Such a study is The study comprises two phases. In the first phase desirable since the question of whether or not NPC of the study, the English version of LAS will first be survivors have an excess risk of second primaries has translated not been satisfactorily addressed by previous studies independently back translated, according to the and survivors of NPC are both numerous in Hong translation procedure suggested by Brislin (1986). Kong and relatively young. The pilot study will A focus group interview with a 6-8 postpartum retrospectively collect data for a few hundred NPC women will be conducted to strengthen the cultural patients, including age at and date of diagnosis of NPC, equivalence of the translated tool. An expert panel gender, date of death or last follow-up, date of will be invited to establish the content validity index development of any second primaries, and type of of the translated version. After that, the research treatment from the records of hospital oncology assistant will recruit 20 postpartum women to test the departments. semantic equivalence of the Chinese and English The Hong Kong ID numbers of these into Chinese language and then patients will then be used to perform searches of versions. The second phase will examine the databases from the Hong Kong Cancer Registry, the internal consistency and construct validity of the Hospital Authority, and the Mortality database of the Chinese version of the LAS in a convenience sample Hong Kong Census and Statistics Department in of 290 eligible postpartum women within 48 hours order to ascertain and/or verify second cancer cases after delivery. The participants will be asked to fill and deaths. The results of the pilot study will be used in the translated LAS and the Visual Analogue Scale to determine whether or not completeness of patient for Pain and Anxiety during labour. follow-up and ascertainment and verification of A pilot study on 5 eligible subjects will be carried out second cancer cases are sufficient to allow an to assess the feasibility of the study. unbiased assessment of second cancer risk in Hone will help develop a reliable and valid measure of Kong NPC patients at this time. Chinese LAS which is the cornerstone in a currently This findings planned study that evaluate the effectiveness of a 299 Faculty of Medicine The Nethersole School of Nursing training program to promote Chinese pregnant social care professionals to identify and evaluate women’s sense of control over childbirth. appropriate interventions to promote the care of older (MD06747) people with CHF; and ii) provide a Chinese cultural perspective to understanding Adjusting to Living with Chronic Heart Failure: adjustment to living with CHF. A Culturally Relevant Framework for Chinese (CU06658) older people’s Elders The Effectiveness of Compression Bandaging on LEE Tze Fan Diana THOMPSON David Wound Healing and Psychosocial Outcomes in Robert (School of Public Health) YU Sau Fung Older People with Venous Ulcers-A Randomized Doris WOO Jean (Medicine & Therapeutics) Controlled Trial 1 November 2006 WONG Kit Yee Irene Research Grants Council (Earmarked Grants) LEE Tze Fan Diana THOMPSON David Robert (School of Public The incidence and mortality rate of chronic heart Health) failure (CHF) is increasing sharply in the older KWONG Kwok Hung (Surgery) population in Hong Kong. While a large body of Wai Lin* research reveals that this condition causes immense LAU Yun Wong James (Surgery) TSANG AU 1 May 2007 loss in many areas of an older person’s life and Health and Health Services Research Fund requires tremendous changes in many aspects of daily living, little is known of the dynamic process Purpose: Examine over time the health outcomes through which the older person adjusts to living with among three groups of older people with venous this illness. Still less is known of this process in ulcers in the community: those recieving either older Chinese people with CHF. four-layer This study is to develop a culturally relevant compression bandage; or usual care. theoretical framework to explain older Chinese Objectives: Compare the time to healing, wound size, people’s CHF. ulcer related pain, functional status, and quality of Approximately 80 older CHF patients from an life among patients receiving either four-layer out-patient department of the medical unit of a compression bandage; short stretch compression regional hospital will be invited to participate in an bandage; or usual care before treament, at 12 and 24 in-depth weeks after treatment. adjustment interview to to living identify with the problems, compression bandage; short stretch challenges, strategies and tactics older people use to Design and subjects: A randomized controlled trial live with CHF. The chief emphasis is to discover that involves two experimental groups and one the process by which older people re-order the control group will be employed. patterns and priorities of their lives as they go about venous ulcer patients (107 in each group) with ankle living with CHF. brachial pressure index equal or greater than 0.8 will Specific cultural beliefs that A total of 321 contribute to the understanding of these experiences be recruited. will also be explored. Results of this study will i) Instruments: Modified Parkside Health Trust Leg produce a sound theoretical basis for health and Ulcer Record, VeV VERGe Videometer, Brief Pain Faculty of Medicine 300 The Nethersole School of Nursing Inventory, Frenchay Activities Index, Short of a subacute hospital and a community-based Form-12item Health Survey, Charing Cross Venous program for focus group interview. Ulcer Questionnaire, Treatment record. Chinese heart failure patients will be recruited from Interventions: the medical out-patient clinic of a regional hospital for Control group - usual care. testing the psychometric properties of the SCHFI Experimental group 1 - usual care plus four-layer (Chinese version). compression bandage. Data collection and main outcome measures: Focus Experimental group 2- usual care plus short stretch group interviews exploring the symptom experience compression bandage. and the associated self-care of the patients will be Outcome measures analysis:Descriptive conducted “to inform and improve the cultural statistics such as frequency count, percentage, and relevancy and contextual appropriateness of the central Chinese versions of SCHFI and EHFScBS. tendency and Another 150 will demographic data. be used to analyze After Time to healing will be completing the cross-cultural adaptation of the SCHFI compared using the Kaplan-Meier survival curves. and the EHFScBS, the Chinese versions of the SCHFI Repeated measures analysis of variance will be used and EHFScBS, the Hospital Anxiety and Depression to examine differences among the means of ulcer Scale (HADS), and the Medical Outcomes Study related pain, functional status, and quality of life Social Support Survey (MOS-SSS-C) will be across the study period. administered to the heart failure patients attending the (MD06916) Out-patient Department, for establishing the validity and reliability of the Chinese versions of the SCHFI Assessing Self-Care Behavior of Heart Failure and the EHFScBS. Patients: Cross-Cultural Adaptation of Two Heart Data analysis: Systematic coding via content analysis Failure Self-Care Instruments will be used to analyse the data of focus group interview. The construct validity of the Chinese THOMPSON David versions of SCHFI and EHFScBS will be determined Robert (School of Public Health) LEE Tze Fan by their respective correlations with the HADS and the Diana WOO Jean (Medicine & Therapeutics) MOSSSS-C. The factorial validity of the Chinese YU Sau Fung Doris version of the SCHFI (Chinese version) will be 1 October 2006 examined by using confirmatory factor analysis. Health & Health Services Research Fund The internal consistency of the Chinese versions of Objectives: The aim of this study is to adapt the SCHFI and EHFScBS will be determined by using Self-Care Heart Failure Index (SCHFI) and the Cronbach’s alpha coefficient and item analysis. European Heart Failure Self-care Behavioral Scale Conclusion: Effective self-care behavior of heart (EHFScBS) for use in the Chinese population, and to failure patients plays a vital role in preventing establish its validity and reliability. avodable hospital readmissions. Design: Methodological research with descriptive SCHFI and the EHFScBS for use in the Chinese correlational and focus group methods. population with heart failure in Hong Kong is timely Setting and subjects: A total of 20 Chinese heart and important. It can enhance our understanding of failure patients will be recruited from the medical unit the self-care needs of the Chinese HF patients and 301 Adapting the Faculty of Medicine The Nethersole School of Nursing give directions to disease 2005-06 "Doing the Month" An Exploratory Study It also serves as an of Three Generations of Chinese Women develop management intervention. effective important outcome measure of the existing heart (CU05676) failure-related health care services and interventions. CHAN Wai Chi Sally (MD06561) Eleanor Anne# HOLROYD LOPEZ Violeta (School of Public Health)# Please refer to previous issues of this publication 2005-06 Assessing Sexual Functioning Amongst for more details of the following ongoing research Hong at the department: Kong Chinese Women with Gynecological Cancer: The Validation of Edition Disease-Specific Title/Investigators Sexual Functioning Instruments (MD05658) 2005-06 The Effectiveness Multidisciplinary Cardiac of A CHAN YIP Carmen Wing Han Structured Weight Reduction Rehabilitation Program TWINN Sheila Frances Kin Fong Karis CHAIR Sek Ying MENG Hong* Tung Ching* Man SONG You Wing MOK Shu Kam Connie of the Oropharyngeal Learning in Mucositis-specific CHENG Kin Fong Karis LEUNG Sing Fai (Clinical Oncology) TWINN Sheila LEE Tze Fan Diana An with Cancer Therapy (MD05688) Nursing Education: A Pilot Project (MD05618) OMQoL: Measure of Quality of Life in Patients 2005-06 An Evaluation of Two Approaches to Frances (Clinical LAU Leo Woon 2005-06 Development CHAIR Sek Ying WONG Oncology) SHIU Tak Ying Ann CHAN Ming* Case-Based CHENG Tony (Clinical Oncology) (MD05906) Qiang* Wai Ming Josepha* TAI THOMPSON KEMBER David Richard (Centre for David Robert (School of Public Learning Health) DUAN En Kui* Enhancement and Research) 2005-06 Risk Factors for Oral Mucositis in Pediatric 2004-05 The Provision and Evaluation of a Patients Undergoing Suicide Prevention and Management Chemotherapy: A Matched Case-Control Programme by Frontline Nurses in Hong Study (MD05543) Kong (MD04733) CHENG Kin Fong Karis LEE Vincent (Paediatrics) THOMPSON CHAN Wai Chi Sally CHIEN Wai David Robert (School of Public Tong TSO Steve* Health) Faculty of Medicine 302 The Nethersole School of Nursing LEE Albert (Community and Family 2004-05 Privacy and Dignity in Residential Care Homes: Framework A Culturally for Medicine) Relevant Chinese Elders LAM Augustine (Community and Family Medicine)* (CU04161) LEE Tze Fan Diana LOW Lisa Pau (School of Public Health) Le THOMPSON David Robert CHENG YAM FK Frances (Centre for Health Ed. & Health Promotion) 2004-05 An Evaluation of the Effectiveness of Different Models of Health Care Delivery in the Primary Care Setting of General Outpatient Clinics in Hong Kong (MD04712) TWINN Sheila Frances LOPEZ Violeta (School of Public Health)# 303 Faculty of Medicine Dept of Obstetrics & Gynaecology the placenta has been shown to release its mRNA into RESEARCH PROJECTS maternal blood plasma. Furthermore, we hypothesise that a panel of aberrantly expressed Application of Functional Genomics in Human mRNA transcripts of the preterm placenta can be Placenta and Quantification of Placental mRNA in detected in maternal plasma and hence can serve as Maternal Plasma for Study of Term and Preterm non-invasive molecular markers for preterm labour. Partutition (CU06484) CHIM Siu Chung Stephen Dennis (Chemical Pathology) Ngong LO Yuk Ming Genetic and Development Defects of a Mouse LEUNG Tse Mutant Mcc with Microphthalmia, Cataract and Closed eyelid CHIU Wai Kwun Rossa (Chemical Pathology) LAU Tze Kin CHOY Kwong Wai SHAM Mai Har* SONG 1 January 2007 You Research Grants Council (Earmarked Grants) Qiang* PANG Chi Pui Calvin (Ophthalmology and Visual Sciences) Preterm birth, defined as delivery before 37 1 September 2006 completed weeks of gestation, is the leading cause of CUHK Research Committee Funding (Direct perinatal mortality and morbidity in modern Grants) obstetrics. Currently, the exact mechanism of preterm labour remain elusive, so widely-used prediction Congenital cataract is a leading cause of visual markers are unavailable and the treatment strategies disability have been hampered. Prior to labour onset, an identification of genetic mutations that cause cataract integrated series of changes occur within the is the first step in understanding the molecular myometrium, cervix, decidua, gestational membranes, mechanisms for cataract formation. Congenital although the main triggers have not been identified. cataract has a heterogeneous genetic basis, to date The placenta produces many substances implicated in about 15 causative genes have been identified in the labouring process and is known to have an cataract patients. Studies of mouse mutants, either important influence on triggering labour in primates. naturally occurring or generated by gene knockout However, there is currently no study addressing the technology, have greatly facilitated our understanding genome-wide gene expression profiling of placentas of the genetic basis of cataract and congenital eye from women undergoing (i) spontaneous labour at defects. Characterization of cataract mouse mutants term; (ii) elective caesarean section (no labour) at not only lead to the identification of a wider spectrum term; and (iii) preterm deliveries. In this proposed of cataract related genes, but also allow the study of study, we will fill in this gap by analysing the mRNA the cellular and molecular basis for normal eye and levels of over 33,000 genes in these 3 groups of lens development. In our laboratory we have placentas with the Affymetrix GeneChip microarrays. identified a spontaneously occurring mouse mutant We hypothesise that preterm parturition involves named Mcc, which displays combined features of aberrant gene expression in the placenta. Previously, microphthalmia (small eye), cataract and closed among children worldwide. The eyelid that transmit through generations as an Faculty of Medicine 304 Dept of Obstetrics & Gynaecology autosomal dominant trait. In our pilot study by performance genome-wide mapping and linkage analysis, we have identification located the susceptible region to mouse chromosome abnormalities in prenatal diagnostics has not yet 1. The aim of this project is to identify the Mcc been established. mutant gene locus by fine mapping and cloning, and ability to permits the simultaneous rapid high to characterize the abnormal eye phenotypes of Mcc resolution genome analysis and mapping of DNA during mouse development, in order to understand sequences, aCGH will become a routine cytogenetic how the defective gene function lead to the eye and testing procedure within the near future. However, lens defects. In this project, we shall identify a new there are many questions that need to be addressed gene/mutation involved in eye and lens development, before aCGH could be used routinely in perinatal which may be responsible for human congenital eye medicine. Among these issues, the one appear to defect. By examining the developmental defects of be most important is the accuracy and reliability of the Mcc mutant eye, novel mechanisms and pathways aCGH in perinatal medicine has not yet been for eye and lens developmental processes will be established. This proposal outlines a pilot study to discovered. It is possible that some of the genes investigate the accuracy, efficacy and clinical causing early onset cataract will be implicated in age advantages of cytogenetic prenatal diagnosis using related cataract which remains the most common high cause of blindness the world. Therefore, genomic hybridization as compared to standard identification of the Mcc gene will have an impact in conventional forms of cytogenetic analysis such as our understanding of human eye diseases. G-banded chromosome analysis and rapid FISH (MD06518) (fluorescence in situ hybridization). Notably, this in and of resolution potential for unbalance detection and chromosomal We anticipate that given its microarray-based comparative study could potentially lead to the identification of Development and Validation of Comparative new categorized micro-deletion or micro-duplication Genomic Hybridization based Microarray for syndromes. Prenatal Cytogenetic Diagnosis (MD06588) CHOY Kwong Wai WANG Chi Chiu LAU Genetic Association Study in Hong Kong Chinese Tze Kin Women with Pelvic Organ Prolapse 1 February 2007 CHOY Kwong Wai YIP Shing Kai Alexander Agilent Technologies Incorporation - Research 1 March 2007 Project Grant CUHK Research Committee Funding (Direct Microarray based hybridization technique comprehensive comparative (aCGH) discovery enables Grants) a chromosomal Pelvic organ prolapse (POP) is a common yet aberrations at a resolution unattainable by other distressing pelvic floor dysfunction affecting one-third molecular of cytogenetic of genomic techniques. Since its adult women worldwide. However, the development, aCGH has been applied mostly in the underlying pathophysiology is largely unknown. Its field of cancer cytogenetics. etiology is multifactorial, including direct mechanical However, its 305 Faculty of Medicine Dept of Obstetrics & Gynaecology injury, partial denervation of pelvic floor, and The introduction of intracytoplasmic sperm injection hormonal changes caused by pregnancy. Findings (ICSI), where an immobilized sperm is injected from epidemiologic studies suggest that occurrence directly into the cytoplasm of the oocyte, has of POP can be attributed to genetic factors. revolutionized the treatment of male sterility. ICSI The disease is an example of a complex trait, where the bypasses course of the disease could be influenced by a determining combination of common variation in an assemblage ultimately fertilize oocyte. of genes and the effect of a wide range of risk factors. DNA is essential for the accurate transmission of However, there is still lack of studies to investigate genetic material to offspring. the genetic association of female pelvic organ prolapse. always show oligozoospermia and thus had higher We hypothesized that genetic variants affecting genes risk of transmission genetic defects to offsprings. involved in the collagen and extracellular matrix Embryos fertilized with sperm samples with a higher metabolism may be involved in the pathogenesis of DNA damage had oligozoospermia had lower POP via modulating collagen and extracellular matrix implantation rate and live birth rate. protein contents in urogential tissues, and hence which still remains of the utmost importance for ICSI affect the biomechanical property of the pelvic floor is sperm DNA integrity. In this research, first, we tissues. In this study, we search for functionally will use biochemical methods to determine the DNA relevant genetic variants in genes involve in integrity of spermatozoa that do ICSI in our IVF regulating connective tissue structure (EDN1, TIMP, reproduction center, group the patients with their MMPs) or hormonal response (ESR1 and ESR2) to DNA integrity parameters and trace the output after investigate its prevalence among Hong Kong Chinese ICSI in different groups. Secondly, protein 2D-gel women with and without POP. The results will electrophoresis and mass spectrometry are used to enable us to establish a genetic basis for such disease reveal the differences between the DNA damaged and revealing genetic alterations unique to POP that and the normal spermatozoa in order to find protein shed light on disease pathophysiology. markers of DNA damaged spermatozoa. (MD06309) (MD06877) Studies on DNA Damages in Spermatozoa which Studies on DNA Damages in Spermatozoa from Have Failed to Fertilize Oocytes in Vitro and Men with Oligozoospermia and Possible Protein Potential Protein Markers of DNA Damage Markers for DNA Damages HAN Yibing HAINES Christopher John all natural which HAN Yibing LAM Po Mui CHIU Tak Yu Tony CHEUNG selection sperm will methods for penetrate and Good quality sperm Patients doing ICSI One factor HAINES Christopher John LAM Po Mui CHIU Tak Yu Tony Lai Ping 1 June 2007 13 February 2007 CUHK Research Committee Funding (Direct Hong Kong Obstetrical and Gynaecological Grants) Trust Fund The introduction of intracytoplasmic sperm injection (ICSI), where an immobilized sperm is injected Faculty of Medicine 306 Dept of Obstetrics & Gynaecology directly into the cytoplasm of the oocyte, has techniques. Since its development, array-CGH has revolutionized the treatment of male sterility. ICSI been applied mostly in the field of cancer bypasses all determining natural which selection sperm ultimately fertilize oocyte. methods for cytogenetics. penetrate and potential for detection and identification of unbalance Good quality sperm chromosomal abnormalities in prenatal diagnostics will However, its performance and DNA is essential for the accurate transmission of has not yet been established. genetic material to offspring. Patients doing ICSI given its ability to permits the simultaneous rapid always show oligozoospermia and thus had higher high resolution genome analysis and mapping of risk of transmission genetic defects to offsprings. DNA sequences, array-CGH will become a routine Embryos fertilized with sperm samples with a higher cytogenetic testing procedure within the near future. DNA damage had oligozoospermia had lower However, there are many questions that need to be implantation rate and live birth rate. addressed before aCGH could be used routinely in One factor We anticipate that which still remains of the utmost importance for ICSI perinatal medicine. is sperm DNA integrity. In this research, first, we appear to be most important. will use biochemical methods to determine the DNA and reliability of array-CGH in perinatal medicine integrity of spermatozoa that do ICSI in our IVF has not yet been established. Secondly, the clinical reproduction center, group the patients with their DNA implication of existence of copy number variation integrity parameters and trace the output after ICSI in (CNV) in the genomes of healthy individuals. different 2D-gel proposal outlines a pilot study to investigate the electrophoresis and mass spectrometry are used to accuracy, efficacy and clinical advantages of reveal the differences between the DNA damaged cytogenetic prenatal diagnosis using array-based and the normal spermatozoa in order to find protein comparative genomic hybridization as compared to markers of DNA damaged spermatozoa. standard conventional forms of cytogenetic analysis (MD06663) such as G-banded chromosome analysis and rapid groups. Secondly, protein Among these questions, two Firstly, the accuracy This FISH (fluorescence in situ hybridization). Notably, A Pilot Study on Microarray based Comparative this study could potentially lead to the identification Genomic Hybridization for Prenatal Cytogenetic of Diagnosis micro-duplication syndromes. new categorized micro-deletion or (MD06344) LAU Tze Kin WANG Chi Chiu CHOY Kwong Wai Role of Eicosanoid-related Enzymes in Murine 15 March 2007 Embryogenesis CUHK Research Committee Funding (Direct Grants) WANG Chi Chiu Kuhn Hartmut* Borchert Astrid* Microarray based comparative genomic hybridization technique (array-CGH) enables a comprehensive 1 January 2007 discovery of chromosomal aberrations at a resolution Germany/Hong Kong Joint Research Scheme unattainable by other molecular cytogenetic 307 Faculty of Medicine Dept of Obstetrics & Gynaecology Eicosanoids such as prostaglandins and leukotrienes There is no literature studying the physiological are important lipid mediators, which have been pattern recognition lectins during normal pregnancy. implicated in regulation of cell physiology but also in In this study, we proposed to use pregnant mice as the pathogenesis of various diseases with major control model to characterise the maternal and health political importance (cardiovascular diseases, placental lectins throughout the gestation. Dynamic inflammation, etc.). changes of lectin concentrations in maternal plasma, Unfortunately, little is know about the relevance of and temporal and spatial mRNA and protein eicosanoid metabolism for developmental processes expressions of lectins in uterus/decidua and placenta such embryonic from early to late gestation will be investigated. This collaborative research project The results of this study will not only provide the is aimed at investigating the developmental defects in physiological data of lectins in the feto-maternal murine embryogenesis, which can induced by interactions during normal pregnancy, but also siRNA-mediated expression silencing of eicosanoid provide background information to compare with the related gene products or selective enzyme inhibition. pathological change of lectins during abnormal (MD06677) pregnancy in animal models. as neurodegeneration, cell organogenesis. maturation and/or (MD06876) Characterisation of Pattern Recognition Lectins During Normal Pregnancy in Mouse Please refer to previous issues of this publication for more details of the following ongoing research WANG Chi Chiu CHOY Kwong Wai LAU at the department: Tze Kin ROGERS Michael Scott Edition 1 March 2007 Title/Investigators CUHK Research Committee Funding (Direct 2005-06 Feasibility Study on Using MicroRNAs Grants) as Fetal RNA Markers in Maternal Lectins are a type of pattern recognition receptor Plasma (MD05393) protein that interact with carbohydrate molecules in CHIM Siu Chung Stephen LO Yuk pathogens and involve in lectin-complement pathway Ming Dennis (Chemical Pathology) for innate immunity. We have identified the LEUNG Tse Ngong CHIU Wai abnormal changes of plasma lectins in pregnant Kwun Rossa (Chemical Pathology) women complicated with pre-eclampsia, an unknown LAU Tze Kin hypertensive disorder unique to pregnant women. The lectins were specifically bind to apoptotic 2005-06 A Pilot Study on Proteome Profiling of trophoblasts and participated in its clearance in Ligamentous Tissues and Peri-Urethral pre-eclamptic placentae. Skin in Patients with Pelvic Organ Local and systemic innate proinflammatory cytokines were then triggered and Prolapse (MD05836) clinical CHOY Kwong Wai YIP Shing Kai manifestation of pre-eclampsia was developed. Faculty of Medicine Alexander 308 WANG Chi Chiu Dept of Obstetrics & Gynaecology HAN Yibing HAINES Christopher POON Chuen Wai (Medicine & John LAM Po Mui Therapeutics) 2005-06 Postpartum Depression Among Hong 2003-04 Vaginal Birth after Caesarean Section - Kong Chinese Men (MD05581) Effect CHUNG Kwok Hung Tony Shing Kai Alexander on Maternal YIP Function (CU03423) LOK Hung LAU Tze Kin Ingrid Hung Tony Psychosocial CHUNG Kwok LEE Tak Shing Dominic (Centre of Research and 2005-06 A Multicenter, Double-Blind, Promotion of Women's Health) Randomized, Placebo Controlled Study on the Effect of Ultra-Low LEUNG Tse Ngong Dose Transdermal Estradiol (Menostar® 0.014 2003-04 Hyperglycamia and Adverse Pregnancy mg/day via weekly patch) on the Outcome Study (MD03946) Incidence and Severity of Hot Flushes, LI Chi Yin Other Menopausal Symptoms and on ROGERS Michael Scott NG Pak Cheung (Paediatrics) Well-Being in Postmenopausal Asian Women Over 12 Weeks (MD05692) HAINES Christopher John Siu Ping* 2004-05 An XIONG Zhuo* Chinese Women in LOK Hung Ingrid of of Hong Kong (MD04554) CHUNG Kwok Hung Tony 2005-06 Measurement Study Psychiatric Morbidity Among Infertile LAM Ethnoepidemiology Hormones and in LEE Tak Shing Dominic (Centre of Research and Exhaled Breath Condensate (MD05351) Promotion of Women's Health) HAINES Christopher John CHEUNG Lai Ping Wai San Fanny Therapeutics) KO (Medicine HAN Yibing & Christopher John HAINES CHAN Cheung Ming* HUI Shu Cheong David (Medicine & Therapeutics) 2005-06 3D Ultrasound Biometry of Pelvic Floor PANESAR Nirmal in Postpartum Women (MD05797) LEUNG Ting Fan (Paediatrics) SAHOTA Daljit Singh LAM Po Mui Singh (Chemical Pathology) LOK Hung Ingrid YIP Shing Kai Alexander CHEUNG Lai Ping 2005-06 Innate and Adaptive Immune Responses 2005-06 Studies of Protein Phosphatase in Pre-Eclamptic Women (MD05891) 1 WANG Chi Chiu Inhibitor 11 Expression in Mice Testis, Epididymis, Spermatozoa and Its LEUNG Tse Ngong ROGERS Michael Scott Functional Pathways (MD05763) 309 Faculty of Medicine Dept of Obstetrics & Gynaecology 2005-06 Identification Proteins of in Glycation Gestational Plasma 2004-05 Epigenetic Profiling of Cervical Cancer Diabetes Predisposed to Preeclampsia (MD05579) in Hong Kong Women Using CpG Island WANG Chi Chiu Microarray: A Pilot Study (MD04817) POON Chuen Wai (Medicine & Therapeutics) TAM Wing Hung LI Chi Yin WONG Yick Fu Hung Tony ROGERS Michael Scott Expression CHUNG Kwok LO Yuk Ming Dennis (Chemical Pathology) Tak Hong* 2003-04 Gene Profiling of CHEUNG YU Mei Yung May* LAU Winnie WY* Endometrioid Endometrial Carcinoma in Hong Kong Women and Correlation with 2005-06 A Randomized, Double-Blind, Clinico-pathological Features (CU03427) Placebo-Controlled Study on Treatment WONG of Yick Fu BIRRER, Nocturia with Desmopressin in Michael J.* CHEUNG Tak Hong Women (MD05325) CHUNG YIP Shing Kai Alexander CHEON Kwok Hung GARDNER, Ginger J.* Yung (Anatomical Tony & Cecilia* YU Mei Cellular Pathology) Faculty of Medicine 310 Dept of Ophthalmology and Visual Sciences specifically tackled. Photodynamic therapy (PDT) is RESEARCH PROJECTS a two-step procedure involving first, intravenous infusion of a photosensitizer and then the application The Safety and Efficacy of A Modified Regimen of of low-energy diode laser to activate the drug. This is Photodynamic Therapy with Verteporfin on regarded as an innovative and relatively safe Chronic Central Serous Chorioretinopathy - A procedure in ophthalmology in treating abnormal Randomized Controlled Trial choroidal neovascularization of various etiologies. The application of PDT on CSC requires a higher CHAN Wai Man LAM Shun Chiu Dennis safety threshold, in which this can be enhanced in our previous studies by a modified regimen with reduced LAI Wai Kwan Wico# LAI Yuk Yau Timothy verteporfin infusion dosage of 3mg/ m2 and earlier 1 July 2006 laser delivery at 10 minutes. Preliminary data from CUHK Departmental Funding our pilot series have demonstrated encouraging Central serous chorioretinopathy (CSC) is an clinical and angiographic responses in chronic CSC exudative macula, with rapid subretinal fluid absorption in a month in commonly affecting middle-aged adults. The patients 80% of cases, improving visual acuity, no recurrence may present with disturbing visual symptoms such as during distorted images, color desaturation, or central black electrophysiological response shortly after treatment. spot. Most of the macular detachment will resolve Our proposal is to further delineate the efficacy and spontaneously after weeks or months. However, safety of PDT on chronic CSC by a randomized many patients may still have persistent symptoms controlled trial of 1-year follow-up. We target 50 such as loss of contrast sensitivity, despite apparently cases to answer the efficacy in achieving better visual recovering of normal visual acuity. In addition, some improvement and faster subretinal fluid absorption (closer to 30%) may have recurrent attacks, and a and visual improvement. small proportion (5%) may develop a chronic disease (MD06992) retinal detachment of the the follow-up period, and safer with atrophy and decompensation of the retinal pigment epithelium and severe and irreversible visual Adeno-associated Viral Vector-mediated impairment. It is an ocular problem particularly Transgene Expression and Gene Silencing in common in Asian populations. In Hong Kong, with a Visual System Repair majority of Chinese people, about 300 chronic cases occur per year. Laser and pharmacologic agents have CUI Qi been tried but achieved only unsatisfactory results. 26 February 2007 These treatments have not been shown to improve the CUHK Research Committee Funding (Direct final visual outcome or the rate of recurrence. The Grants) lack of success of these treatments are not unexpected, as the underlying pathophysiological problems which In most area of the adult human central nervous include choroidal abnormalities, vascular congestion system and hyperpermeability leakage have not been spontaneous repair of fibre pathways after injury. including the eye there is minimal This failure is attributable to the loss of affected 311 Faculty of Medicine Dept of Ophthalmology and Visual Sciences axons and neurons, lack of neurotrphic factor supply, 7 June 2007 presence of axon growth inhibitory molecules Nogo, CUHK Research Committee Funding (Direct oligodendrocyte-myelin glycoprotein (OMgp), and glial scar formation at the injury site. Grants) In all neuropathological situations it is important to This study aims to assess the safety and efficacy of minimise the loss of compromised neurons and at the different doses of intravitreal bevacizumab in the same time promote the regrowth of axons within treatment damaged pathway. degeneration (AMD). The visual system has unique of neovascular age-related macular Bevacizumab is a drug The eye developed to bind to a chemical released by cells and optic nerve are readily accessible, the retinal known as Vascular Endothelial Growth Factor function (VEGF). advantages as a target for gene therapy. can be assessed using quantitative, Several studies have demonstrated that non-invasive techniques, the extent of retinal intravitreal bevacizumab appeared to be effective in ganglion cell (RGC) survival and the amount of improving the visual outcome in patients with CNV axonal regrowth after injury can readily be secondary to AMD or pathologic myopia. However, quantified. previous studies have used different dosages of A technology currently receiving a great deal of intravitreal bevacizumab ranging from 1mg to 2.5mg attention involves the us of viral vectors to introduce and therefore the optimal dosage remained uncertain. genes into cells, providing a method for the long-term The aim of this study is to evaluate the treatment but local and targeted supply of relevant molecules to response of patients to 1.25mg versus 2.5mg compromised cells. intravitreal bevacizumab in order to determine the recognition Gene silencing has also gained recently for optimal dose for usage in patients with neovascular counteracting disease-causing gene, and the discoverers have been AMD. Patients will be given three monthly awarded Nobel prize this year. In this study, we aim intravitreal injections of bevacizumab and followed to use adeno-associated viral vectors (AAV) to for 6 months to look at the treatment response. introduce both axon-growth promoting gene and axon Changes in the aqueous levels of growth factors such growth inhibitory molecule silencing genes into the as PEDF and VEGF will also be determined. eye in order to achieve enhanced axonal regeneration (MD06825) of injured retinal ganglion cell. Examination of 3-Dimensional Retinal Nerve (MD06737) Fiber Layer Profile for Early Detection of Glaucoma Effects of Different Dosages of Intravitreal Bevacizumab Age-related (Avastin) Macular for Neovascular Degeneration : LEUNG Kai Shun A CHEUNG Yim Lui PANG Chi Pui Calvin LAM Shun Chiu Dennis Randomized Controlled Trial 30 June 2007 LAI Yuk Yau Timothy Dennis LIU Tai Li David* LAM Shun Chiu CUHK Research Committee Funding (Direct CHAN Wai Man Grants) PANG Chi Pui Calvin Faculty of Medicine 312 Dept of Ophthalmology and Visual Sciences Glaucoma is characterized by progressive loss of Shaheeda retinal ganglion cells (RGC) with subsequent loss of CHEUNG Yim Lui LAM Shun Chiu Dennis vision. Early diagnosis is imperative to prevent visual loss through early interventions. The optic RAO Srinivas Kamalakara 1 July 2006 CUHK Departmental Funding disc and the retinal nerve fiber layer (RNFL) are important structural surrogates to evaluate the integrity Corneal thickness measurement is important in of RGC. refractive Using optical coherence tomography surgery and assessing the risk of (OCT), we have showed that measuring RNFL development of glaucoma in patients with ocular thickness is more sensitive than measuring the optic hypertension. Accurate measurement of corneal disc to detect glaucomatous damage. And yet, the thickness is therefore of primary importance. The current model of OCT is limited in measuring the purpose of this study is to compare corneal thickness RNFL only in a specific distance away from the optic measurement by three different methods, namely disc. Spatial relationship of RNFL profile around the Ultrasound Pachymetry, Orbscan II and Optical optic disc cannot be examined. This poses a major Coherence Tomography (OCT) and to assess problem in monitoring RNFL changes. The spectral correlation and agreement of measurements by these domain OCT is the latest OCT imaging technology three methods. recently introduced. (MD05317) of data, higher Because of its rapid acquisition resolution and sensitivity, three-dimensional topographic profiles of the RNFL Quality Control of Myocilin and Development of can be analyzed in detailed with the instrument. The Small objective of this study is to examine the 3-dimensional Glaucoma Molecule Chaperone Therapy for topography of the RNFL in normal and glaucomatous eyes and to evaluate the diagnostic sensitivity and PANG Chi Pui Calvin LAM Shun Chiu Dennis specificity of the 3-dimensional RNFL measures in detecting early glaucomatous damage. The in vivo Hin Fai 劉剛* topography of the retinal nerve fiber layer has never been examined. Quantitative analysis of the THAM Chee Yung Clement CUI Qi YAM 1 August 2006 CUHK Departmental Funding 3-dimensional RNFL profile could provide new insights to the pathophysiology of glaucoma and serve Primary open-angle glaucoma (POAG) is a major as a new paradigm for early detection and monitoring form of glaucoma and a leading cause of visual progression. defects and blindness. It is a progressive optic (MD06345) neuropathy characterized by obstructive aqueous humor outflow and elevated intraocular pressure. by Mutation of the myocilin (MYOC) gene is associated Ultrasound Pachmetry, Orbscan II and Optical with juvenile and adult-onset POAG. More than 70 Coherence Tomography glaucoma-causative MYOC mutations have been Measurements of Corneal Thickness identified. Elevated intraocular pressure due to LI Yuen Mei Emmy Arthur reduced CHENG Chak Kwan LEUNG Kai Shun aqueous outflow via the trabecular meshwork is a major risk factor for glaucoma. The MOHAMED 313 Faculty of Medicine Dept of Ophthalmology and Visual Sciences MYOC protein is a major component of trabecular 1 March 2007 extracellular matrix and is involved in aqueous CUHK Research Committee Funding (Direct outflow. Elevated MYOC expression is found in Grants) trabecular meshwork of patients with steroid-induced glaucoma, typified with increased outflow resistance. Limbal adult stem cells play an active role in corneal However, the failed expression of MYOC, per se, wound healing. They possess therapeutic potential for seems insufficient to cause glaucoma, as homozygous retinal or neural cell replacement due to their neural MYOC knockout mice display normal eye function. transdifferentiation capacity. It is likely that mutant MYOC acquires a identification marker is currently available rendering gain-of-function them difficult to isolate and study. by restricting normal MYOC However, no definite In most secretion. A number of MYOC mutations disrupt the laboratories, limbal stem cells can only be identified folding capacity of the polypeptide to become a after the use of a combination of protein markers. functional protein. The aberrantly folded protein is MicroRNAs have recently been implicated as key recognized by the quality control in the endoplasmic regulators of gene expression in different biological reticulum. We have obtained evidence that the processes, including cell growth, death, development aggregate formation leads to secretion deficiency of and differentiation. Alike protein markers, expression MYOC, ultimately resulting in cell death. So far, of stage-specific microRNAs have been shown to experimental evidence for such trafficking problem is involve in embryogenesis. limited. We propose a comprehensive cellular and investigate microRNA expression profile of limbal stem molecular study of the regulatory quality control of cells showing profound maintenance of self-renewal and naturally occurring and glaucoma-causing MYOC multipotency. Quiescent limbal and corneal basal cells variants to gain a mechanistic insight on the will be isolated from frozen sections of human cornea pathogenesis of glaucoma. Pharmacological rescue of by laser capture microdissection technique followed by conformation-defective MYOC protein variants by low molecular weight microRNA isolation. utilizing the chaperoning activities of specific small and enriched microRNAs will be analyzed by mirVana molecules will be investigated for stabilizing a more qRT-PCR miRNA Detection Kit (Ambion) and specific native conformation of malfolded protein and primer sets. Our study will isolate a subset of specific. promoting its exit from the endoplasmic reticulum. microRNAs which will operate key regulatory roles of Results of this study will contribute to understanding self-renewal and multipotency in limbal stem cells. of The identification of the associated genes will hold a glaucoma pathogenesis and devising new This work is aimed to Purified therapeutic intervention. basis for further study looking for true limbal stem cell (MD06794) markers, which will also serve as potent molecular markers for the undifferentiated adult stem cells in MicroRNA Expression Profiling of Ocular Limbal other tissues. Stem Cells (MD06468) PANG Chi Pui Calvin YAM Hin Fai Argon CHOY Laser Peripheral Iridoplasty (ALPI) Kwong Wai (Obstetrics & Gynaecology) LAM Versus Systemic Intraocular Pressure Lowering Shun Chiu Dennis Medications Faculty of Medicine 314 Dept of Ophthalmology and Visual Sciences As the Immediate Management for Acute This procedure may work as effectively in acute Phacomorphic Angle-closure (Phacomorphic phacomorphic angle-closure. Glaucoma) The aim of our study is to compare the efficacy and safety of argon laser peripheral iridoplasty (ALPI) to THAM Chee Yung Clement systemic LAM Shun Chiu intraocular pressure (IOP) lowering Dennis CHI Chung Chai LEUNG Yu Lung medications in the immediate management of acute YICK Wai Fong KWONG Yuen Ying Yolanda phacomorphic LI Chi Hong Felix LAI Shiu Ming Jimmy angle-closure by a prospective randomized controlled study. Forty CHAN Jonathan Cheuk Hung CHAN Hoi Yee (40) patients with acute phacomorphic angle-closure will be recruited for this study. 14 July 2006 Patients will be randomized into one of the following CUHK Departmental Funding groups : Aute phacomorphic angle-closure (phacomorphic Group 1 - patients will receive ALPI under topical glaucoma) is type of angle-closure condition resulting anesthesia. from a mature, swollen cataract, which causes closure Group 2 - patients will be given intravenous of the drainage channels (the 'angle') in the eye and acetazolamide as medical treatment. These patients hence elevation of eye pressure (intraocular pressure, will continue to take oral acetazolamide until the IOP IOP). Patients with this condition usually have is normalized. If intraocular pressure is higher than ocular pain and decreased vision. Treatment includes 60 mmHg at presentation, intravenous mannitol will lowering the intraocular pressure with medications also be administered. and subsequent removal of the cause by cataract For both groups of patients, the definitive treatment extraction. Time is important because persistent with cataract extraction is performed within 72 hours. high intraocular pressure can result in permanent We will compare the clinical outcome of the two closure of the angle as well as irreversible optic nerve groups of patients. damage. IOP profile before and after treatment; return of Medical treatment includes the use of systemic corneal clarity; symptoms, particularly pain, nausea carbonic anhydrase inhibitor and hyperosmolar agent, & vomiting; visual acuity; corneal endothelial cell which are well known to have many side effects. count; evidence of optic nerve damage at presentation Moreover, medical treatment may fail to effectively and follow-up; final visual outcome; final angle control the intraocular pressure. status; visual field loss, complications of treatment. Recently, argon The outcome measures include (MD06897) laser peripheral iridoplasty (ALPI) is being used to open up the drainage angle in acute primary angle-closure (APAC) by applying a number of burns Pharmacological Chaperone Therapy of Mutant on the peripheral iris to contract the iris near the Myocilin in Primary Open-Angle Glaucoma angle. This will widen the angle (i.e. to open up the drainage channels), thus lowering the intraocular YAM Hin Fai pressure at a much shorter time, and allow the eye to PANG Chi Pui Calvin LAM Shun Chiu Dennis THAM Chee Yung Clement become quiet before definitive treatment is performed. 1 March 2007 315 Faculty of Medicine Dept of Ophthalmology and Visual Sciences CUHK Research Committee Funding (Direct Please refer to previous issues of this publication Grants) for more details of the following ongoing research at the department: Primary open-angle glaucoma (POAG) with elevated intraocular pressure is a leading cause of blindness Edition worldwide. Mutations of the myocilin gene account for most of juvenile-onset POAG and 4% adult-onset POAG. Misfolded secretion-incompetent mutant myocilin intracellular 2005-06 Glaucoma Drainage Device with and forms without Adjunctive Intra-bleb Injection aggregates, of leading to apoptotic cell death. We have recently a Shiu Ming Jimmy LEUNG Yu Lung myocilin, reduced their intracellular retention and a possibility of CHAN Hoi Yee sodium we aim to perform with CHAN Wai Man Ho Emily diffusibility and toxicity of sodium 4-phenylbutyrate Our LEE Yau Wing, MOHAMED Shaheeda LAI Yuk Yau Timothy Chi Wai result will form a basis for further animal study. TSANG LI Kai Wang Kenneth LI Siu Hung LIU Ta Li Transgenic mice expressing POAG-causing mutant myocilin will be established and tested for the 2005-06 Evaluation of the Safety and Efficacy of efficacy of sodium 4-phenylbutyrate in correcting the High-density Silicone Oil (Oxane HD) as Its safety as well as a Tamponade Agent in Macular Hole tissue and cell permeable features will hold its Related Retinal Detachment in Patients potential as a topical drug for POAG patients. with High Myopia (MD04819) (MD06608) Faculty of Medicine LAI Wai Kwan Wico# TANG Wai pressure-associated POAG and to investigate the disease-associated phenotypes. LAM Shun Chiu Vincent LAM Shun Chiu Dennis intraocular in various ocular tissues of young male rats. Chorioretinopathy (MD04609) 4-phenylbutyrate on ten different myocilin mutants associated KWONG Yuen Verteporfin on Acute Central Serous a comprehensive screening of the effect of sodium frequently Regimen of Photodynamic Therapy with To demonstrate its application as a topical medication patients, THAM Chee Safety and Efficacy of A Modified on misfolded myocilin for the treatment of POAG. POAG LAI 2005-06 A Randomized Controlled Trial on the 4-phenylbutyrate as the first specific drug targeting for Dennis This highly using Trial Ying Yolanda LI Chi Hong Felix The treatment released the ER stress and significantly reduced the apoptosis of suggests A Yung Clement LEUNG Yu Lung POAG-causing C245Y, G364V, P370L and Y437H cells expressing mutant myocilin. Controlled CHAN Jonathan Cheuk Hung cell-permeable small-molecule chemical chaperone stabilized severe, restored their secretion. Acetonide. (MD04453) treatment on mutant myocilins in a cell culture model. 4-phenylbutyrate, Triamcinolone Randomized demonstrated a novel pharmacological chaperone Sodium Title/Investigators 316 Dept of Ophthalmology and Visual Sciences CHEUNG Tze On Benson Yin Fun LAI Yuk Yau Timothy LAI Wai Kwan Wico# Tak Hung Kai Shun Christopher LAM Shun Chiu Dennis 2005-06 Prospective LEUNG LAU Hoi Shan Flora YIP Wai Kuen WONG TSANG Chi Wai FAN Shu Ping Dorothy YUEN YU Bing On CHEUNG Yan Yan (Centre for Clinical Trials) Randomized Study of 2005-06 Screening of Visual Defects in Preschool Silicone Stent Intubation in Endoscopic Children (MD05827) Dacryocysto-Rhinostomy for Acquired FAN Shu Ping Dorothy LAM Nasolacrimal Duct Obstruction - SEND Shun Chiu Dennis Study (MD05974) Yan (Centre for Clinical Trials) CHONG Kam Lung Chiu Dennis CHEUNG Yan LAM Shun CHAN Wai Man CHAN Ding Nai 2005-06 The Use of Multifocal Electroretinography for the Detection and WONG Wing Monitoring Cheong of Drug-Related Retinal Toxicity (MD04388) 2005-06 Tear Lake Evaluation by LAI Yuk Yau Timothy LAM Shun Anterior Segment Optical Coherence Tomography Chiu Dennis (ASOCT) in Patients with Acquired Ricky LI Haitao Nasolacrimal Obstruction LAI Yiu Kwong (NLO) (MD05756) 2002-03 A Randomized, Controlled Pilot Study to CHONG Kam Lung Chiu Dennis Intravitreal Fluocinolone Acetonide (0.5 WONG Wing or 2 mg) Implants in Patients with WAT Sze Kee CHEUNG Yim Lui Evaluate the Safety and Efficacy of an LAM Shun YUEN Kwok Lai Clinically Significant Diabetic Macular CHENG Chak Kwan Arthur Edema (MD02973) Cheong LAM Shun Chiu Dennis CHAN Wai Man CHAN Wai Man CHAN Kar Mun Carmen 2005-06 Prevention of Myopia Development in Kindergarten Children by Early WONG Tak Hung Kenneth Shu Ping Dorothy FAN Shu Ping Dorothy CHONG Kam Lung Shun Chiu Dennis LAM LI Kai Wang TSANG Chi Wai Correction of Astigmatism (CU05498) FAN LI Siu Hung MOHAMED Shaheeda TANG Wai Ho Emily YU Bing On Christopher* FAN Hoi T Wong* 2003-04 A Prospective Randomized Comparative Study on the Efficacy and Safety of Early 2005-06 Retinal Nerve Fiber Layer Thickness and Macular Thickness in Children with Cataract Anisometropic Amblyopia or Refractive Development of Chronic Angle-Closure Error (MD05462) Glaucoma (CACG) after Aborting Acute 317 Removal in Preventing Faculty of Medicine Dept of Ophthalmology and Visual Sciences Attack of Primary Angle-Closure Glaucoma (PACG) (CU03350) 2005-06 Clinical Satisfaction Assessment Acrysof LAM Shun Chiu Dennis Yee Hang Thomas ReSTOR IOL (MD05643) CHIU LAM Tsze Ho Philip LAI Shiu Ming Jimmy LEUNG Yu Lung THAM Srinivas Kamalakara Chee Yung Clement Chiu Dennis YEUNG Yat Ming Barry YICK Wai Fong Arthur RAO LAM Shun CHENG Chak Kwan CHOW Wing See Vanissa HO Chuen Kwong Thomas 2005-06 A Six-Month, Phase 3, Multicenter, Masked, Randomized, Sham-Controlled Trial (with Six-Month 2005-06 A Open-label Prospective, Randomized Control Study Examining the Efficacy, Safety Extension) to Assess the Safety and and Efficacy 350μg Rimexolone 1% Versus Prednisolone Dexamethasone Posterior Segment Drug Acetate 1% Ophthalmic Solution in the Delivery Treatment of Severe Ocular Allergy in of 700μg System and (DEX PS DDS) Ocular Hypertensive Applicator System in the Treatment of Children (MD05596) Patients with Macular Edema Following LAW Wai Kee Central Retinal Branch Vein Retinal Occlusion Vein or 2005-06 Evaluation of Optic Nerve Morphology, Ping Dorothy FAN Shu Macular Thickness and Retinal Nerve LAI Wai Kwan Fiber Layer Thickness in Myopia Using CHONG Kam Lung Yau Wing, Vincent Wai LAM Shun Chiu Occlusion LAM Shun Chiu Dennis of Dennis (MD05920) Wico# Effect Optical LEE Tomography (MD05854) TSANG Chi MOHAMED Shaheeda Coherence LEUNG Kai Shun WONG Lee Lung LEUNG Yu YICK Wai Fong Hong Felix LI Chi KWONG Yuen Ying 2005-06 Twelve-Week, Double-Masked, Parallel Yolanda Group, Study of Travoprost 0.004% Clement Compared to Timolol 0.5% in Patients MOHAMED with Open-Angle Glaucoma or Ocular Srinivas Kamalakara Hypertension (MS-06-02) (MD05919) Chak Kwan Arthur LAM Shun LAM Shun Chiu Dennis Chiu Dennis Chee Yung Clement THAM THAM Chee Yung LI Yuen Mei Emmy Shaheeda RAO CHENG LEUNG King Sai (Faculty Office of Medicine) LEUNG Kai Shun MOHAMED Shaheeda HO Chuen Kwong Thomas Mei Emmy Yolanda 2005-06 Diagnostic Imaging Assessment in the LI Yuen Evaluation KWONG Yuen Ying LI Chi Hong Felix Glaucomatous Neuropathy (MD05567) CHI Chung Chai LEUNG Yu Lung Faculty of Medicine of 318 Optic Dept of Ophthalmology and Visual Sciences LEUNG Kai Shun LEUNG King Sai (Faculty Office of Medicine) Thomas Yolanda Tear Components between Normal Patients and Patients HO Chuen Kwong with Blepharitis, Ocular Allergies and KWONG Yuen Ying Dry Eyes Syndrome Using Liquid/Gas of MOHAMED LI Yuen Mei Emmy Shaheeda 2005-06 Comparison Chromatography THAM Chee Yung Mass Clement LAM Shun Chiu Dennis Spectrophotometry (LCMS/GCMS) and LI Chi Hong Felix ELISA (MD04718) LEUNG Yu PONG Chiu Fai Lung YICK Wai Fong Dennis 2005-06 Evalucation of Bleb Morphology with Anterior Segment Tomography and Optical Coherent Corneal Confocal 2004-05 A Microscopy (MD05722) LEUNG Kai Shun LAM Shun Chiu RAO Srinivas Kamalakara PANG Chi Pui Calvin Multi-Centered Controlled Randomized Interventional Trial to KWONG Yuen Compare Cataract Extraction Alone by Ying Yolanda LI Chi Hong Felix Phacoemulsification versus Combined LEUNG Yu Lung YICK Wai Fong Phaco-Trabeculectomy in the Treatment THAM Chee Yung Clement of Chronic Angle-Closure Glaucoma CHEUNG Yim Lui (CACG) LAM Shun with Coexisting Cataract (MD04706) Chiu Dennis 2005-06 Analysis of Clinical Profiles of Chinese THAM Chee Yung Clement CHAN Jonathan Cheuk Hung Patients with Normal Tension Glaucoma CHIU Yee Hang Thomas LAI Shiu (MD05531) Ming Jimmy LEUNG Yu Lung LAM Shun Chiu Dennis Dennis CHI Chung Chai Shiu Ming Jimmy Ming Barry Clement LAM Shun Chiu LAM Sze Wing Yu Lung LAI YICK Wai CHIU Yee Hang Thomas KWONG 2005-06 A Multicentered Randomized Controlled LI Chi Hong Yuen Interventional Trial to Compare Lens Ying Extraction Alone by Phacoemulsification versus Trabeculectomy 2005-06 Identification of Genes for Primary Open Adjunctive Angle Glaucoma (MD05621) Treatment of Chronic Angle-closure PANG Chi Pui Calvin Chee Yung Clement LEUNG Fong Yolanda LEUNG Kai Shun Shun POON Shuet Yan SHEN Yu Sunny# YEUNG Yat THAM Chee Yung YICK Wai Fong Felix THAM Chemotherapy) in (+/the Medically-uncontrolled Glaucoma (CACG) without Visually Significant LEUNG Kai FAN Shu Ping Dorothy Alone Cataract (MD04442) LAM Shun Chiu Dennis 319 Faculty of Medicine Dept of Ophthalmology and Visual Sciences THAM Chee Yung Clement Chung Chai Lung CHI CHAN Hoi Yee CHAN Jonathan Cheuk Hung CHI Chung Chai YEUNG Yat Ming Barry 2005-06 A KWONG Yuen Ying Yolanda LAI Double-Masked, and Parallel-Group, Shiu Ming Jimmy LAM Shun Chiu Efficacy Safety Dennis LEUNG Yu Lung LI Chi Brinzolamide Hong Felix YICK Wai Fong Therapy to Travoprost 0.004% in Patients 1.0% Study as of Adjunctive with Chronic Angle-Closure Glaucoma (MS-06-01) (MD05992) 2005-06 Phacoemulsification-trabeculectomy with THAM Chee Yung Clement in Intra-bleb Injection of Triamcinolone LAM Acetonide Versus Phaco-trabeculectomy Shun Chiu Dennis with Mitomycin C in Patients with Shun MOHAMED Shaheeda HO Co-existing Cataract and Glaucoma and Chuen Kwong Thomas Risk Factors for Filtration Failure - A Mei Emmy Randomized Yolanda Controlled Trial (MD04529) Shun Chiu Dennis Randomised Yuen Density Trial to Failed Trabeculectomy in Glaucoma Patients (MD05700) THAM Chee Yung Clement Yolanda KWONG LAM YICK Wai Yuen Ying CHIU Yee Hang Thomas LI Chi Hong Felix CHI Function LEUNG Kai Shun LEUNG Yu 320 RAO MOHAMED CHEUNG Yim Lui LAM Shun Chiu Dennis vs Repeat Trabeculectomy in Managing Visual Srinivas Kamalakara Controlled Shun Chiu Dennis and CHENG Chak Kwan Arthur Needle Revision of Trabeculectomy Bleb Faculty of Medicine LI Chi Hong Felix WONG Lee Ying Compare the Clinical Outcomes of KWONG Yuen Ying Assessment (MD05589) CHAN Jonathan Cheuk LI Chi Hong Felix Lens YICK Shaheeda Fong LI Yuen 2005-06 Quantitative Measurement of Cataractous CHAN Hoi Yee 2005-06 A LAM LAI Shiu Ming KWONG Yolanda LEUNG Yu Lung Wai Fong Hung LEUNG Kai Chung Chai THAM Chee Yung Clement Jimmy Dept of Orthopaedics & Traumatology and its ability to monitor supination torque in real RESEARCH PROJECTS time will be verified by biomechanics test. The developed sensing system provides real-time ankle Development of an In-Shoe Sensor System for torque measurement during running for further sprain Real-Time Ankle Supination Torque risk identification, and helps the decision to trigger corrective motion while sprain occurs in the final CHAN Kai Ming sprain-free sports shoe. HONG Youlian (Sports (MD06966) Science & Physical Education) HUI Kin Chuen (Mechanical and Automation Engineering) Wen Jung Engineering) (Mechanical and LI The Effect of Functional Inserts with Different Automation LUI Po Yee Pauline Posting Angles on Impact Force, Plantar Pressure KHOO Distribution and Foot Kinematics during Walking Lawrence* and Jogging 1 September 2006 Dr Kong Footcare Ltd Innovation and CHAN Kai Ming Technology Support Programme, ITF, FUNG Kwai Yau Po Yee Pauline Ankle sprain is the most common sports injury. 15 October 2006 Repeated Dr Kong Footcare Ltd causes ankle YUNG Shu Hang Patrick FONG Tik-Pui Daniel LUI Innovation & Technology Commission injury instability, proprioceptive and functional impairment, medical cost and economic loss. We propose to develop an This study investigates the effect of functional inserts innovative intelligent sprain-free shoe to prevent with different posting angles on impact force, plantar ankle sprain during running. The project consists of pressure distribution and foot kinematics during three parts: (1) Sensing; (2) Identification; and (3) walking and jogging. Correction. This proposal will concentrate on the recruited and divided into 3 groups according to their first part and will develop an in-shoe wireless sensor degree of pronation (Group A: 6 degree and above; system which can detect external forces and ankle Group B: 4-6 degree; Group C: 0-4 degree). motion, and estimate ankle supination torque during subject will perform heel-toe walking at 1.30 m/s in running. walking shoes, and jogging at 1.66 m/s in jogging Ankle torques, plantar pressure and shoe surface shoes on a 10-meter walkway. kinematics data will be obtained during running and conditions with inserts of four posting angles (X: flat, simulated sprain motion in 10 human subjects using A: 6 degrees, B: 4 degrees, C: 0 degrees) will be sports biomechanics analysis techniques. performed. Ankle Ninety subjects will be Each Barefoot and shod A pressure mat will be placed on top of torque estimation models will be constructed to a force plate in the middle of the walkway. determine the representative locations to install Kinematics and ground reaction force will be individual pressure and motion sensor. Then a pair obtained by motion capture system and force plate at of testing sports shoe with embedded sensors that 600 Hz. Ten valid trials (5 for each foot) with whole supports wireless data transfer will be manufactured foot stepping within the mat region will be recorded in each of the conditions. 321 Faculty of Medicine Dept of Orthopaedics & Traumatology Impact force and pressure distribution data will be improve obtained environment. by pressure mat. Ankle joint both the biological Bone and cement mechanical reduces the inversion/eversion data will be obtained by the micro-motion (“micro-interlocking”) and provides an motion be osteoconductive environment bridging the host bone time-normalized from foot strike to take off as 0% to and grafted tendon, suppress fibrous tissue formation, 100% stance, and will be extracted at every 5% whereas MSC provides a cell source to induce more stance. For impact force, the peak value and its time bone formation. occurrence will be retrieved. Plantar pressure will synergistic improvement in healing and mechanical be evaluated in ten regions. The change of impact strength of the tendon inside bone tunnel complex. force and plantar pressure will also be evaluated. Bilateral ACL reconstruction with free hamstring Ankle inversion/eversion limit and range will be tendon grafts will be performed with application of determined. either calcium phosphate bone cement or bone (MD06388) cement and MSC into tendon-bone tunnel interface. analysis system. Data will We expect that there will be The contralateral limb will serve as control. At 2, 6 Augmentation of Tendon Graft Healing within and 12 weeks after operation, the biological events at Bone Tunnel Using In-Situ Setting, Calcium the grafted tendon-bone tunnel interface will be Phosphate examined by general histology. Bone Cement Complement with Bone formation and remodeling at the interfacial area and new Autologous Mesenchymal Stem Cells bone/cement volume ratio will be assessed by histomorphometry and µCT. CHAN Kai Ming WONG Wan Nar Margaret The strength of QIN Ling LEE Kwong Man Simon (Lee Hysan tendon-bone tunnel complex will be evaluated by Clinical Research Laboratories) loading to failure via pull-out (tensile) testing. LUI Po Yee (CU06497) Pauline 1 January 2007 Joint Research Grants Council (Earmarked Grants) Universities Sports Medicine and Rehabilitation Centre Many surgical reconstructions require passing an autograft tendon through a bone tunnel. The site of CHAN Kai Ming CHAN Chetwyn* attachment of grafted tendon to bone is the weak link 1 January 2007 in the early tendon-bone tunnel healing and is critical Restructuring and Collaboration Fund (RCF) for to the stability of the bone-tendon junction. 2005-06 Slippage and micro-motion (both longitudinal and saggittal) between tendon and bone The which Centre supported by RCF focuses on compromises healing and insufficient oteogenic cells UGC-funded undergraduate teaching and research for bone formation are possible causes of poor postgraduate program. It is dedicated to equipping healing. We hypothesized that application of in-situ undergraduate setting and knowledge in the realms of sports medicine and autologous mesenchymal stem cell (MSC) into the rehabilitation in the management of sports injuries interface gap between tendon and bone tunnel can from prevention to rehabilitation, with sufficient calcium phosphate Faculty of Medicine bone cement 322 and postgraduate students with Dept of Orthopaedics & Traumatology clinical exposure and cross-disciplinary training to AIS girls is not only a matter of bone mineral status meet the demand for well-qualified sports health but also a problem in bone quality which would be an professionals in the Asia-Pacific region and to train important prognostic factor for the curve progression. research postgraduate students in researching the In the present study, we will investigate the systemic sciences of sports medicine and rehabilitation. problem of bone formation during the peri-pubertal (MD06906) growth of AIS girls compared with age-matched controls in term of areal BMD of hips, volumetric A Bone Quality-Based New Prognostic Factor in BMD of cortical bone, and trabecular bone micro- Predicting Curve Progression in Adolescent -architectural parameters. These parameters will be Idiopathic Scoliosis measured by duel-energy x-ray absorptiometry (DXA) at the bilateral hips, peripheral quantitative computed LEE tomography (pQCT) at the trabecular bone and Kwong Man Simon (Lee Hysan Clinical cortical bone dominant region of the radius and by Research Laboratories) YEUNG Hiu Yan the quantitative ultrasound (QUS) assessment at the CHENG Chun Yiu Jack QIN Ling calcaneum. 1 January 2007 The BMD measurement of hip by DXA, the QUS parameters, and the cortical bone BMD will Research Grants Council (Earmarked Grants) be used as a stand-alone parameter and also Adolescent idiopathic scoliosis (AIS) is a complex combined with other commonly accepted prognostic three-dimensional deformity of the spine occurring factor in AIS to generate a new and bone-quality commonly in girls at the peripubertal period between specific prognostic model for better prediction of 10-16 years of age. curve progression in AIS. The prevalence of AIS in Hong Kong is high at nearly 4%. The current treatment of The clinical significance of the present study is to AIS is unsatisfactory since the etiopathogenesis are provide for the first time a more comprehensive still not clear and precise quantitative prognostic understanding of the problem of both osteopenia and factors for predicting curve progression at the early quality of bone in AIS girls and its link to the stage of deformity is still lacking. progression Results of our of scoliosis. Further systematic previous RGC supported studies have revealed the research into the etiopathogenesis of AIS could lead presence of generalized osteopenia in 36-38% of AIS to new bone quality based novel approaches in the subjects. monitoring, prognostication and more evidence based bone Taller, longer arm span, and abnormal turnover were also found. treatment of AIS These (CU06498) characteristics clearly pointed to an abnormality in bone growth and bone mineralization in AIS manifested both in the abnormal peripheral An International Effort to Fine Map the IS Gene anthropometric measurements and bone mineral density (BMD). in a Critical Region on Chromosome 9q31-q34 Since mechanical stability of the CHENG Chun Yiu Jack bone is better determined by bone quality than its quantity (i.e. BMD) and the AIS is TANG Leung Sang Nelson (Chemical Pathology) a Miller, Nancy Hadley* three-dimensional structural deformity of the spine, we hypothesize that the systemic problem of bone in 323 Faculty of Medicine Dept of Orthopaedics & Traumatology AO Research Grant 1 January 2007 Cotrel Fondation Grant The stem cell therapy using technology of tissue Idiopathic scoliosis (IS) is a complex genetic disorder engineering is applied in spinal fusion research. In potentially our resulting from multiple genetic previous study, bone marrow derived interactions and variations. In order to elucidate the mesenchymal stem cells (MSCs) were isolated and genes responsible for this disorder, our laboratory has expanded in number ex vivo. The differentiation of pursued MSCs was directed to osteogenic cells in the a systematic approach of family identification, collection of genomic DNA from presence of osteogenic medium. blood samples, a genome-wide scan of a large sample cells were seeded on tricalcium phosphate ceramics. population, followed by linkage analysis and fine The cell-ceramics composite was implanted in mapping with the association of specific genomic loci well-established rabbit PSF model. with the observed phenotype. These results include that the cells-ceramics composite could enhance an area on chromosome 9, a region of 25 Mb (109 spinal fusion with decortication approach but not Mb to 134 Mb) including greater than 280 genes. under un-decortication approach. This proposal is directed to the refinement of this treatment is required to improve stem cell therapy locus through two complementary approaches at two after operation. centers utilizing single nucleotide polymorphisms ultrasound (LIPUS) is reported to enhance fracture (SNPs), association studies, the Haplotype map healing, non-union and distraction osteogenesis. In combined with statistical analyses. Both family and this population linkage disequilibrium (LD) information micromechanical stimulation is applied on ex-vivo will be incorporated into the study design. The goal and/or in-vivo stages in rabbit PSF model implanted of this work is to define a much higher resolution with tissue engineered composite. linkage map for FIS with a marked reduction in the the project are 1) to investigate the effect of LIPUS number of putative genes. on decorticated posterior spinal fusion implanted with (MD06463) tissue engineered osteogenic cell-calcium phosphate study, The osteogenic Result showed Thus additional Recently, low intensity pulsed LIPUS which is provided The objectives of ceramic composite; 2) to study the effective timing of Ultrasonic Therapy on Tissue Engineered Stem LIPUS treatment for enhancing posterior spinal Cell-Bioceramics Composite in Posterior Spinal fusion; and 3) to explore the possibility of Fusion undecortication approach in posterior spinal fusion surgery by application of LIPUS. CHENG Chun Yiu Jack HU Yun Yu* Simon (Lee Laboratories) QIN Ling The outcome of this study will shed light on our LEE Kwong Man knowledge of engineered stem cells in enhancing LEUNG Kwok Sui Research bone fusion of PSF, micromechanical stimulation of CHAN Chun Wai (Lee Hysan bone formation and the role of decortication. It will Hysan Clinical Clinical Research Laboratories) eliminate surgical procedure of autograft collection YIP Raymond and decortication and so as to reduce blood loss and Churk Lun shorten operation duration. 2 January 2007 Faculty of Medicine 324 It will provide Dept of Orthopaedics & Traumatology unlimited supply of bone substitute and reduce the development of a new diagnostic/prognostic strategy associated complications at the donor site. for AIS severity. (MD06901) (MD06571) Melatonin Signaling Pathway Malfunction in The Use of Antioxidants to Reduce Tendon Osteoblasts of Adolescent Idiopathic Scoliosis Adhesion CHENG Chun Yiu Jack HUNG Leung Kim NG Tzi Bun (Biochemistry (Medicine)) Simon Clinical (Lee Hysan CHAN Kai Ming WONG Wan Nar Margaret LEE Kwong Man Research Bruma Laboratories) YEUNG Hiu Yan (Lee Hysan FU Sai Chuen Clinical Research Laboratories) 1 June 2007 1 January 2007 CUHK Research Committee Funding (Direct Research Grants Council (Earmarked Grants) Grants) Adhesion formation is a frequent complication of Adolescent idiopathic scoliosis (AIS) is a complex tendon injury repair, especially in the local Chinese spinal deformity affecting mainly girls during their population who received surgical operation in hands. peripubertal period. The 4% prevalence of AIS in The postoperative outcome of hand flexor tendon Hong Kong is relatively high compared with other repair remains limited by tendon adhesions that countries. prevent normal range of motion, and hand dexterity The current treatment of AIS is unsatisfactory because its etiopathogenesis is still will unknown and precise prognostic factors for curve overwhelming inflammatory response has long been progression previous considered a cause of tendon adhesion, in which RGC-supported studies have revealed the presence of epitenon cells are activated to mediate an excessive generalized osteopenia in 36-38% of AIS subjects. fibrotic response. They clearly point to an abnormality in ossification of include the use of anti-fibrotic drugs, anti-adhesive AIS. Meanwhile, we have shown that the melatonin membranes, biophysical intervention and second receptor gene is associated with AIS. surgical operation. are lacking. Our Others be largely affected. Hemorrhage and Potential treatment strategies But tendon adhesion still showed dysfunction in the melatonin signaling presents a major clinical problem in hand surgery. pathway. Oxidative Hence, we hypothesize that stress is inevitably involved in malfunctioning of the melatonin signaling pathway inflammatory responses as well as tissues damages may be systemic and affects bone formation of AIS and haemorrhage. girls during puberty. This study aims to depict the (ROS) generated during oxidative stress are able to changes of the melatonin receptor in AIS and the activate fibrotic response. It is possible that tendon cellular responses of osteoblasts under the influence adhesion is caused by ROS produced in intra- and of melatonin. The clinical significance of the post-operative inflammation and haemorrhage, thus present study is to provide further understanding of antioxidants will have a great potential to be reduce the the extent of tendon adhesion. melatonin signaling pathway in the etiopathogenesis of AIS, and to shed light on the The reactive oxygen species In the present study, we propose to investigate the roles of oxidative stress 325 Faculty of Medicine Dept of Orthopaedics & Traumatology in epitenon cells and the formation of tendon International adhesion. High-Frequency Vibration Therapy for Training Then we will explore the potentials to use antioxidants to reduce tendon adhesion. Workshop on Low-Magnitude, Musculoskeletal Professionals (CU06500) LEUNG Kwok Sui CHEUNG Wing Hoi SZE Pan Ching NG Wai Kin Post-menopausal Women Walk towards a Healthy Life 1 July 2006 Applicant's contribution Asian Association for LEUNG Kwok Sui SZE Pan Ching LAU Dynamic Osteosynthesis Professional Services Yuen Wah Josephine* Development Assistance Scheme, Commerce, 1 May 2006 Industry and Technology Bureau, HKSAR Govt Health Care and Promotion Fund This Project aim to introduce the concept and As women approach menopause stage, they will face importance lots of changes in their lives, such as osteoporosis, vibration decrease in physical performance and emotional musculoskeletal disturbance. A program is specifically designed for neuro-muscular coordination, circulation of lower this group of women to promote bone health and limb arid bone quality for medical doctors, vibration physical their therapy scientists, mechanical engineers, occupational of therapists and related paramedical professionals in osteoporosis and reduce number of osteoporosis. It Hong Kong, Mainland China, and the Asia-Pacific includes an educational carnival for improving bone region. health and nutritional advice, with interactive games Moreover, this workshop can enhance the professional in booths, with brochures prescription, weekly Bone standard and update the latest knowledge of related health ten-combos classes taught by Tai Chi masters medical professionals on vibration therapy by and self-help groups are established to monitor the inviting famous researchers and speakers in this field, progress of balance exercise training. By increasing thus promoting the high quality healthcare service in their awareness towards healthy menopause and Hong Kong. The workshop also provides guidance continued exercise training, 3 promotional drama to participants who plan to apply vibration therapy performances for fitness awareness in menopause, towards preventive are shown to the increase measures public with of low-magnitude, therapy enhancing on functions high-frequency enhancing and musculoskeletal various diseases, functions e.g. and de-briefing sessions held by doctors after the shows. preventing osteoporosis and fractures in elderly It is hoped that rate of osteoporosis and degenerative population in Hong Kong. changes can be reduced among post-menopausal This Project can provide a platform for medical and women, and their family members in Women’s clubs paramedical professionals in Hong Kong and can be benefited. overseas experts to share experience, exchange (MD05521) scientific information in using vibration therapy and discuss for further research and development in related field Faculty of Medicine 326 Dept of Orthopaedics & Traumatology Finally, this project can consolidate our international Application of High-Frequency, Low-Magnitude reputation in the related fields and leading role in Vibration Therapy on the Healing of Normal and Asia-Pacific region, especially in using vibration Osteoporotic Femoral Fracture - An Experimental therapy for preventing osteoporosis and related Study Using Rat Model fractures and improving functional outcomes of the elderly. LEUNG Kwok Sui (MD06972) Wing Hoi Hysan QIN Ling CHEUNG LEE Kwong Man Simon (Lee Clinical Research Laboratories) LEUNG Lai Kwok (Biochemistry (Science)) Effect of Low Intensity Pulsed Ultrasound on Fracture Healing at Different Angles 1 October 2006 Research Grants Council (Earmarked Grants) LEUNG Kwok Sui QIN Ling CHEUNG Wing Hoi Fracture is a major medical challenge with increasing aged population. 1 August 2006 Fracture patients undergoing surgery usually suffer from severe pain, particularly Smith & Nephew UK Ltd patients with hip fracture. This will cause reduced Low-intensity pulsed ultrasound (LIPUS) has been mobility reported to increase the bone mineral density and stimulation is a critical factor to promote healing. accelerate fracture healing with 20-minute treatment Therefore, the period of bed occupancy for fracture every day. Several animal and clinical studies have cases is rather long. There is a pressing need to proven its beneficial effects on fracture healing. explore a method to accelerate fracture healing, Our previous clinical study on complex fracture also especially for osteoporotic fracture repair where the showed encouraging results by shortening 30% of patients are old and fragile. healing time. With its simple, convenient and Our previous in vitro, in vivo and clinical studies non-invasive characteristics, LIPUS may potentially have demonstrated that cyclic mechanical stimulation become a routine treatment for fracture healing was beneficial for bone formation. clinically. also showed cyclic compressive loadings provided by Most recent studies indicated that LIPUS has an actuator-driven fixator enhanced callus formation generated shearing effect at different angles, which in may help to further accelerate the fracture healing. vibration therapy is characterized with systemic 45Hz In the present proposal, with the support from Smith vibrational signals with subjects standing on the & Nephew Inc, we would like to testify this platform for 20 min/day. This will be a promising phenomenon. The objective of this study is to biophysical method for accelerating fracture repair as investigate the effects of LIPUS on fracture healing at it has been proven to be effective in increasing bone different angles using our established rat femoral mineral density and blood flow, and currently also fracture model. being used for treatment of osteoporosis. (MD06982) transmissibility up to spine has also been confirmed. and fractures. slow recovery High-frequency, as mechanical Another study low-magnitude Signal In the present study, we aim at applying vibration therapy on our established femoral fracture rat model 327 Faculty of Medicine Dept of Orthopaedics & Traumatology with intramedullary nail to investigate its effect to and caring of fragility fractures and it is the most accelerate fracture healing. Our hypothesis is that effective way to achieve better treatment outcome vibration therapy can provide mechanical stimulation and prevention of subsequent fractures. Department on bone and enhance circulation to accelerate of Orthopaedics and Traumatology of The Chinese fracture healing in both normal and osteoporotic University of Hong Kong is the pioneer institution to bones. The healing status of fractured rats treated adopt this approach to provide services to patients with vibration therapy will be monitored in terms of with fragility fractures in Asia Pacific region (Lam et blood radiography, al. Annual congress of Hong Kong Orthopaedics densitometry, histology and biomechanics compared Association, 2005). Our experience can be shared with the control. Normal and osteoporotic fracture with other expertise through the symposium, and healing responding to vibration therapy will also be hence the leading post of Hong Kong in high medical compared to investigate their different biological standard can be consolidated. responses to cyclic loading. Aims of this project are: (CU06502) 1) To introduce the new concept in comprehensive flow in femoral artery, caring and management of patients with fragility in fractures in enhancing treatment outcomes and Comprehensive Management of Patients with avoiding recurrent fractures for Asia Pacific and Fragility Fracture – from Hospital to Community overseas medical, healthcare and social work Program of Training Professionals professionals LEUNG Kwok Sui CHAN Tan Jessica through an international symposium. SZE 2) To update the latest knowledge in management Pan Ching NG Wai Kin CHEUNG Wing Hoi of fragility fractures for related professionals by 1 May 2007 inviting famous speakers in this field in order to Contribution from Applicant Professional enhance participants’ medical standard, thus Services Development Assistance Scheme, promoting our high quality healthcare service in Commerce, Industry and Technology Bureau, Hong Kong. HKSAR Govt 3) To propose a consensus workflow in Fragility fractures are the forth major cause of management of fragility fractures for related hospitalization among elderly in Hong Kong. The professionals in order to standardize and advance associated medical expenditure is also as high as 2 the medical and social welfare services for billion each year in Hong Kong. patients with fragility fractures in Hong Kong. Patients with (MD06372) fragility fracture have double the risk of suffering subsequent fractures. With increasing aging population, this issue will become very important and Validation of a Fall Risk Screening Test for attract professionals’ attention worldwide. Community-dwelling Elderly A multidisciplinary approach involving orthopaedic LEUNG Kwok Sui surgeons, geriatricians, allied health professionals CHEUNG Wing Hoi SZE Pan Ching LAW Sheung Wai* and social workers in hospital and community settings will be a trend worldwide in management Faculty of Medicine 328 Dept of Orthopaedics & Traumatology 1 June 2007 International Symposium on Comprehensive Care CUHK Research Committee Funding (Direct of the Fragility Fracture – from Hospital to Community Grants) Background: Development of an accurate fall risk LEUNG Kwok Sui screening test is key issue for a fall prevention program to be effective. CHAN Tan Jessica SZE Pan Ching NG Wai Kin CHEUNG Wing Hoi Although there are some 20 June 2007 assessment tools being used in Hong Kong, only one The Croucher Foundation or two fall risk factors are assessed in these tests, which is in contrast to the multifactorial cause of fall. Fragility fractures are the forth major cause of Furthermore, the predicting values of these tests on hospitalization among elderly in Hong Kong. fall risk need further investigation. associated medical expenditure is also as high as 2 A fall risk The screening tool is thus developed by our department billion each year in Hong Kong. and in our preliminary study, the tool shows fragility fracture have double the risk of suffering satisfactory construct validity. subsequent fractures. Objectives: To investigate and compare the accuracy population, this issue will become very important of the newly developed screening tool and that of the and attract professionals’ attention worldwide. other tools. multidisciplinary approach involving orthopaedic Significance: The result of the study will provide surgeons, geriatricians, allied health professionals essential evidence on the selection of the best fall and social workers in hospital and community risk assessment tool in order to improve the settings will be a trend worldwide in management effectiveness of fall prevention program. and caring of fragility fractures and it is the most Design: Prospective 9-months follow up. effective way to achieve better treatment outcome Setting: A district elderly community center. and prevention of subsequent fractures. Department Participants: 50 community-dwelling elderly. of Orthopaedics and Traumatology of The Chinese Assessment: The new developed screening test, Time University of Hong Kong is the pioneer institution to up and go test, and the Berg Balance Scale will be adopt this approach to provide services to patients done to all the subjects at the beginning of the study. with fragility fractures in Asia Pacific region (Lam et Outcome measure: fall incidence of the subjects will at Annual congress of Hong Kong Orthopaedics be recorded by the investigator biweekly in phone Association, 2005). throughout the follow up period. with other expertise through the symposium, and Statistics and calculation: accuracy in terms of hence the leading post of Hong Kong in high medical sensitivity, standard can be consolidated. specificity, positive and negative Patients with With increasing aging A Our experience can be shared predicting values of the three tests will be compared Aims of this project are: using Fishers exact probability test and Kaplan-Meier 1) To introduce the new concept in comprehensive hazard statistic is used to assess the likelihood of falls caring and management of patients with fragility in high- and low-risk patients for each of the tools. fractures in enhancing treatment outcomes and (MD06976) avoiding recurrent fractures for Asia Pacific and overseas medical, healthcare and social work 329 Faculty of Medicine Dept of Orthopaedics & Traumatology professionals through an international The investigators have carried out a pilot study and symposium; the preliminary findings suggested that 2) To update the latest knowledge in management phytoestrogenic fraction (PF) extracted from a of fragility fractures for related professionals by traditionally and safely used ‘Bone Strengthening’ inviting famous speakers in this field in order to Chinese enhance participants’ medical standard, thus steroid-induced ON via inhibiting both intravascular promoting our high quality healthcare service in thrombosis and extravascular lipid-deposit. In order Hong Kong; and to substantiate our preliminary findings, the proposed 3) To propose a consensus workflow herb Epimedium might prevent in research will systemically investigate PF using our management of fragility fractures for related established steroid-induced ON rabbit model through professionals in order to standardize and advance the following two specific aims: 1) to evaluate the the medical and social welfare services for efficacy profile in relation to PF dosage; 2) to study patients with fragility fractures in Hong Kong. the action mechanism profile in relation to PF (MD06816) dosage. The scientific findings to be confirmed from our R&D of Epimedium-derived-flavonoids-fraction proposed research will help establish a logic for Prevention of Steroid-induced Osteonecrosis relationship through a Unique Mechanism by Inhibiting both underlying mechanism for further commercial R&D Intravascular Thrombosis and Extravascular of PF for potential clinical investigations and Lipid-deposit applications for prevention of steroid-induced ON. between prevention efficacy and (MD06657) QIN Ling ZHANG Ge LEUNG Kwok Sui CHEUNG Wing Hoi LEUNG Ping Chung Sonomygraphy (Institute of Chinese Medicine) QIN Ling 1 September 2006 Innovation and Technology Support Programme, ZHENG RP* SO R* CHAN H* AU-YANG A* CHI ZR* 1 December 2006 ITF, Innovation & Technology Commission CUHK Research Committee Funding (Direct Steroid-induced osteonecrosis (ON) has a large Grants) impact on our health-care systems since steroid is frequently indicated for treating many infectious Electromyography (EMG) has been widely used for diseases. The underlying pathogenesis is known to the assessment of musculoskeletal functions and the be both intravascular thrombosis-induced occlusion control of electrical prostheses, which make use of and extravascular lipid-deposit-induced compression. the EMG signal generated by the contraction of the The residual prevention strategy shall therefore muscles. In spite of the successful simultaneously target on those two pathogenic applications of EMG in different fields, it has some pathways. Unfortunately, up to now there are no inherent limitations, such as the difficulty to candidates available to be used safely for long-term differentiate the actions of neighboring muscles and administration. to collect signals from deep muscles using the surface Faculty of Medicine 330 Dept of Orthopaedics & Traumatology 4) EMG. Recently, a number of alternative signals To use artificial neural network to predict the based on the detection of dimensional architectural joint angle and body posture using SMG as well changes of muscles or tendons during actions have as the combination of SMG and EMG; and 5) been reported. To investigate the SMG of residual muscle and In our preliminary studies, we have successfully the application of SMG for the control of demonstrated that ultrasound (signals obtained by a powered prosthesis. single transducer element or images obtained using The proposed SMG can be potentially used in various an array) can be used to obtain the continuous signal fields involving musculoskeletal monitoring and about the muscle thickness change during the control (kinetics and kinematics of normal and contraction. We defined such muscular function abnormal conditions of human movement), where related EMG or other methods are currently being used. signal obtained using sonomyography (SMG). Using ultrasound 2D as (MD06519) ultrasound imaging, we have found that the SMG signals had good linear correlation with the joint angle under Icariin, an Estrogenic Compound Purified from isotonic contraction and with the generated torque Herbal Epimedium, Developed for Prevention of under isometric contraction. The SMG signal has Steroid-Induced Osteonecrosis through a Unique been successfully obtained from the residual forearms Mechanism by Inhibiting both Intravascular of three subjects with the potential for prosthesis Thrombosis and Extravascular Lipid-deposit control. We have also found that he SMG signal was a good indicator for muscle contraction strength and QIN Ling LEUNG Kwok Sui GRIFFITH muscle fatigue. James Francis (Diagnostic Radiology & Organ The aim of this project is to systematically investigate Imaging) the behaviors of the SMG signals with respect to its (Institute of Chinese Medicine)* correlation Man Simon (Lee Hysan Clinical Research with EMG signals and other musculoskeletal parameters of forearm muscles, its 3) LEUNG Ping Chung LEE Kwong 1 January 2007 specific objectives are: 2) ZHANG Ge Laboratories) data acquisition, processing, and application. The 1) Research Grants Council (Earmarked Grants) To establish a hardware and software research platform for the development and application of Steroid-induced osteonecrosis (ON) has large impact SMG; on our orthopedic community and health-care To develop SMG sensors based on single systems since steroid is frequently indicated for transducer elements with a configuration similar treating many infectious diseases. to EMG electrode instead of using expensive 2D pathogenesis of the steroid-induced ON is known to ultrasound imaging probe; be both intravascular thrombosis-induced occlusion To systematically investigate The underlying correlations and extravascular pid-deposit-induced compression, among SMG, EMG, joint angle, muscle strength which results in an impaired structure and function of and fatigue; the intra-osseous blood supply system. The prevention strategy shall therefore specifically target on those two pathogenic pathways. Unfortunately, 331 Faculty of Medicine Dept of Orthopaedics & Traumatology up to now there are no candidates available, which Subchondral collapse induced by inadequate repair in can not only simultaneously counteract these two steroid-associated osteonecrosis (ON) has large events, but also be used safely for long-term impact on orthopaedic community and health-care administration. system as steroid is frequently indicated for treating The objective of this preclinical study is to develop a phytoestrogens agent Icariin many medical conditions. isolated by our research group from a traditionally understanding pathophysiological mechanism of the and safely used ‘Bone Strengthening’ Chinese herb inadequate repair suggested that a decrease in activity Epimedium to prevent steroid-induced ON using our of marrow stem cell pool may not provide sufficient established rabbit model. The investigators have regenerative precursor cells to meet the requirement carried out a pilot study and the preliminary findings of reparative osteogenesis. The therapeutic strategy suggested that Icariin might be capable to prevent shall therefore provide sufficient precursor cells steroid-induced ON in a dose-dependent manner via (stem cells) at early stage of steroid-associated ON to inhibiting and facilitate reparative osteogenesis. However, pioneer extravascular lipid-deposit. In order to substantiate trials using autologous marrow-mononuclear-cell our preliminary findings, the proposed study will (AMMC) implantation show less promising in systemically evaluate the effects of purified Icariin on repairing steroid-associated ON than other types of incidence and severity of the steroid-induced ON ON, which is largely attributed to decreased number using our established rabbit model through the of implanted marrow progenitors under the systemic following two specific aims: 1) to evaluate the toxicity efficacy profile in relation to Icariin dosage; and 2) to pulsed-steroid-administration. investigate the action mechanism profile in relation to hypothesis I the proposal is that a cell-based strategy Icariin dosage. The scientific findings to be by implanting autologous marrow-mononuclear-cell confirmed from our proposed study will help cryopreserved prior to pulsed-steroid-administration establish indications of Icariin for prevention of may steroid-induced ON. steroid-associated (CU06503) investigator carried out a pilot study using our both intravascular thrombosis influence facilitate Recent advance in of the previous Accordingly, reparative the osteogenesis for lesion. The osteonecrosis published steroid-associated rabbit ON model to A Novel Cell-Based Osteogenic Strategy for obtain Repairing Osteonecrosis pulsed-steroid-administration, and then the AMMC Lesion in a Rabbit Model Evaluated by an was delivered to the osteonecrotic site induced by Advanced in Vivo Micro-Computed Tomography pulsed-steroid-administration. Steroid-Associated AMMC encouraging. QIN Ling ZHANG Ge cryopreserved In order in The to prior to results are substantiate our preliminary findings, our recent in vivo MicroCT CHEUNG Wing Hoi supported by Faculty of Medicine will be employed LEUNG Kwok Sui for addressing the following two specific aims in 1 June 2007 1 volumetric density relation to time course change in ○ CUHK Research Committee Funding (Direct 2 3-D mictroarchitecture of local newly formed and ○ Grants) mineralized tissue will be evaluated in terms of the therapeutic efficacy of the hypothesized cell-based Faculty of Medicine 332 Dept of Orthopaedics & Traumatology strategy for reparative osteogenesis. Simon (Lee Hysan Clinical Research The experimental findings to be confirmed by our Laboratories) proposed study will help establish a potential novel Gustav* strategy indicated for early ON surgical treatment and Margaret ROLF WONG Christer Wan Nar subsequently for reduction of joint replacement with 2000-01 Re-defining the MRI Reference Level for poor surgical prognosis. Cerebellar Tonsil - A Study of 225 (MD06545) Adolescents - Normal vs Idiopathic Please refer to previous issues of this publication Scoliosis (MD00378) for more details of the following ongoing research CHAU Wai Wang Yiu Jack at the department: CHENG Chun GUO Xia CHAN Y. L.* Edition Title/Investigators 2000-01 The 2000-01 Low Intensity Retained Pulsed Change of of in Mineral Adolescent Idiopathic Content of Complex Tibial Fractures Patients (MD00430) (MD00354) CHAU Wai Wang CHAN Chun Wai* Sui FU Lap Kun LEE Wing 2000-01 "Subacute Synovitis of the Hip in Sze Children" 2000-01 Low Scoliosis GUO Xia CHENG Chun Yiu Jack LEUNG Kwok TSUI Hon For# Preoperative Somatosensory Evoked Potential (SSEP) Ultrasound Bone Implications Intensity Pulsed A Follow-Up Ultrasound Distinct Study Entity? of 84 Enhanced Bone Mineral Content of (MD99384) Tibial Lengthening (MD00579) CHENG Chun Yiu Jack CHAN Chun Wai* Sui CHENG Chun Yiu Jack Kin Wah Bobby Shu Hang Patrick LEUNG Kwok A Cases YUNG NG Kin Wah Bobby LAM Tsz Ping NG LEE Wing Sze - 2000-01 An HUNG Wing Yin Vivian Immunohistochemical Study on Expression of Decorin and Biglycan in Bone 2003-04 A Study of Tendon Healing in Sports Injury : The Transforming (TGF-β) Manipulation Growth on Matrix Factor Osteopenic Adolescent Idiopathic Scoliosis Girls (MD00734) of CHENG Chun Yiu Jack Beta Shengping Deposition TANG GUO Xia LEE Kwong Man, Simon* QIN Ling (CU03354) CHAN Kai Ming FU Sai Chuen 2000-01 Sternocleidomastoid Bruma (Lee Hysan Clinical Research Laboratories) of Infants LEE Kwong Man Muscular 333 Pseudotumor (SCMPOI) Torticollis and of Congenital (CMT): The Faculty of Medicine Dept of Orthopaedics & Traumatology Relation Between Pathology) Spontaneous GUO Xia* LEE Regression and Apoptosis (MD00523) Kwong Man Simon (Lee Hysan CHENG Chun Yiu Jack Clinical Research Laboratories) Shengping LIU ZQ* TANG QuanXM* 2005-06 Is There a Link between Anterior Spinal QIN JZ* ZHANG DW* Overgrowth and Functional Neurological Disturbance in Adolescent Idiopathic 2000-01 Osteopenia in Adolescent Idiopathic Scoliosis (AIS): Scoliosis? (CU05506) Preliminary CHENG Chun Yiu Jack CHU Chiu Ultrastructural Study (MD00374) CHENG Chun Yiu Jack Shengping GUO Xia Wing Winnie (Diagnostic Radiology TANG & Organ Imaging) LEE Kwong Man, Simon* QIN Ling Leung (Anatomical Pathology) 2001-02 Percutaneous Intramedullary Kirschner Wiring for Displaced CHAN Yu & Cellular QIN Ling LEE Kwong Man Simon (Lee Hysan Disphyseal Clinical Research Laboratories) Fractures in Children (MD99476) CHENG Chun Yiu Jack Shu Hang Patrick 2005-06 Cost and Clinical Effectiveness of the YUNG Hong NG Kin Wah Kong Scoliosis Screening Programme (MD05718) Bobby LAM Tsz Ping CHENG Chun Yiu Jack 2001-02 Promoting a Safer Household Kong* Environment: A Volunteer-Based Home HORIE Kaoru* XIE Fu NG Kin Wah Bobby YIP Siu Fai Paul* Visit Programme (MD01665) CHENG Chun Yiu Jack 2005-06 Distraction Osteogenesis: The Role of CIPRA Neuronal members* Innervation and Neural Peptides (MD05861) 2004-05 Effect of Low Intensity Ultrasound on RhBMP-4 Osteogensis in an CHENG Chun Yiu Jack Pulsed Induced Xia* Fusion (Lee Spinal (Collabration with Poly U) (MD02790) CHENG Chun Yiu Jack GUO LEE Kwong Man Simon Hysan Clinical Research Laboratories) YEUNG Hiu Yan GUO 2005-06 Abnormal Xia* NG Susanna* Differential Longitudinal Growth of Vertebral Column and Spinal 2004-05 Identification of Prognostic Cord in Adolescent Idiopathic Scoliosis Disease Modifier Genes in Adolescent Idiopathic (MD05899) Scoliosis - A Six-Year Longitudinal CHENG Chun Yiu Jack Follow-Up Study (CU04337) CHENG Chun Yiu Jack Leung Faculty of Medicine Sang Nelson Xia* (Lee TANG 334 GUO LEE Kwong Man Simon Hysan Laboratories) (Chemical Clinical Research CHU Chiu Wing Dept of Orthopaedics & Traumatology KUMTA Winnie (Diagnostic Radiology & Organ Imaging) Madhukar HUANG Lin (Surgery) NG Kin Wah Shekhar Bobby YEUNG Hiu Yan LEE Kwong Man Simon (Lee Hysan Clinical Research Laboratories) 2005-06 Relationship between Bone Mineral ZHENG Ming Hao* Density and Muscle Fiber Typing in Hong Kong Chinese (MD05319) CHEUNG Wing Hoi Kwok Sui QIN Ling 2000-01 Monteggia Fracture in Children - A Review of 30 Cases (MD00535) LEUNG LAM Tsz Ping MA RF* NG Kin LEE Kwong Man Simon (Lee Hysan Wah Bobby Clinical Research Laboratories) Jack CHENG Chun Yiu 2004-05 An Experimental Study on the Use of 2000-01 Anterior Spinal Fusion with Halm-Zielke Low Intensity Pulsed Ultrasound to Instrumentation System in Adolescent Optimize Patellar Tendon Donor Site Idiopathic Scoliosis (MD00788) Healing in a Rat Model (CU04338) LAM Tsz Ping HUNG Leung Kim QIN Ling Bobby CHAN Kai Ming WONG Wan Nar NG Kin Wah CHENG Chun Yiu Jack MA RF* Margaret 2000-01 Calcium Intakes in Patients with Adolescent Idiopathic Scoliosis (AIS) 2004-05 Wholesome Development for Physically Disabled Children - Therapy through (MD00838) Music and Arts (MD04417) LEE Tak Keung Warren CHEUNG HUNG Leung Kim Siu King (Surgery) LAM See Way NG Kin Wah Bobby HO Pak Cheong Sylvia LEE Ching Shun Christine* 2005-06 The Use of Antioxidants to Reduce CHAU Wai Wang CHENG Chun Yiu Jack Tendon Adhesion (MD05371) HUNG Leung Kim 崔勛* 2004-05 Establishment of Mobile Fall CHAN Kai Ming WONG Wan Nar Assessment Center (MD04727) Margaret LEUNG Kwok Sui (Lee FU Sai Chuen Bruma Hysan Clinical Research Anti-tumor Aminobisphosphonates CHAN Tan Jessica SZE Pan Ching LAM Pui Laboratories) 2005-06 Potential Risk Sze# CHEUNG Wing Hoi Effects and of 2004-05 Effect and Mechanisms of LIPUS on Prenyl Cartilage Regeneration in an Model after Transferase Inhibitors on Giant Cell Osteoarthritis Tumor of Bone (CU05508) Subchrondral Bone Drilling (MD04419) 335 Rabbit Faculty of Medicine Dept of Orthopaedics & Traumatology LEUNG Kwok Sui Pauline CHEUNG Wing Hoi 2003-04 New LUI Po Yee QIN Ling Born Formation and Cartilaginous Metaplasia Postoperative Articular Tendon Prevent Cartilage Deterioration and Improve Joint Tracking - A Partial Patellectomy Model in 2005-06 Reconstruction of Damaged Growth Plate with Bioengineered Physis Augmented Rabbits (CU03342) with Low Intensity Pulsed Ultrasound QIN Ling CHAN Kai Ming LEE Application (CU05510) Kwong Man Simon (Lee Hysan LEUNG Kwok Sui Chung (Institute Medicine) LEUNG Ping Clinical Research Laboratories) of LEUNG Kwok Sui Chinese ZHENG Yong Ping* LEE Kwong Man Simon (Lee Hysan Clinical Research 2004-05 Establishing Laboratories) CHEUNG Wing Hoi Indications for Extracorporeal Shockwave in Treatment QIN Ling of Delayed Bone-Tendon Junction Repair 2005-06 Effect of - A Preclinical Study (MD04533) High-Frequency, QIN Ling Low-Magnitude Vibration Therapy on LEUNG Kwok Sui the Healing of Femoral Fracture in Rat CHEUNG Wing Hoi LU Hong Bin Model (MD05666) LEUNG Kwok Sui GUO Xia* CHEUNG 2005-06 Electrochemical Bioactivation of Metal Wing Hoi SHI Hong Fei* Surfaces for Biomedical Applications (EE04454) 2005-06 Optimization of the Porosity of an QIN Ling LENG Yang* Injectable Hydroxyapatite and the Study of Its Effect on Bone Ingrowth with Orthopaedic Implants in Osteoporotic 2005-06 Nano-Function Bone (MD05364) Scaffolds for Tissue Engineering (EE04730) LEUNG Kwok Sui QIN Ling QIN Ling LEE Kwong Man Simon (Lee Hysan Clinical Research Laboratories) NG Stephanie* MAK F T Arthur* Robinson David G* 2005-06 Developing Novel Coating Technology CHEUNG Wing Hoi LENG Yang* for Bone-Like Mineral and Collagen Deposition into Tissue Bone in Tibial Lengthening (MD00633) Scaffolds for Bone NG Kin Wah Bobby (MD04619) 2000-01 Associated Osteoporosis of the Host Yin Vivian HUNG Wing QIN Ling CHENG Chun Yiu Jack CHIU Ziad S* Faculty of Medicine 336 Regeneration MAK F T Arthur* C.H.* Bennedsen* Engineering MORTEN NASEREDDINE, Dept of Orthopaedics & Traumatology Bone Tendon Junction Regeneration (CU05512) 2005-06 Prevention and Treatment of Steroid Induced Avascular Necrosis - WONG Wan Nar Margaret An Experimental Study (MD05629) QIN Ling GRIFFITH James QIN Ling LEE Kwong Man Simon (Lee LEUNG Kwok Sui Hysan Clinical Research Laboratories) LEUNG Kwok Sui Francis (Diagnostic Radiology & Organ Imaging) Wai Man* CHAN 2000-01 Culture of Rabbit Chondrocytes Released LEUNG Ping Chung from Rib Cage on Calcium Phosphate ZHANG Ge Ceramic (Institute of Chinese Medicine) and Collagen Sponge (MD98751) 2000-01 Treatment of "Floating Elbow" YEUNG Hiu Yan in LEE Kwong Children (MD00960) Man, Simon* CHEUNG Wing Hoi TANG Ning NG Kin Wah Bobby LAW Lai Pang (Institute of Chinese Medicine)# CHENG Chun Yiu Jack TABATA Yasuhiko* CHENG Chun Yiu Jack 2005-06 A Study on the Application of Bio-engineered Chondrocyte Pellet in 337 Faculty of Medicine Dept of Otorhinolaryngology, Head & Neck Surgery The Effectiveness of Group Intervention for RESEARCH PROJECTS Patients with Dysphonia LAW Ka Tung Thomas A Pilot Study of RetroX Digital Hearing Aid Implant for High Frequency LEE Kathy Yuet Sheung Sensorineural HO Nga Yi Fiona LUI Lai Yee WONG Hoi Wa TONG Chi Fai Michael Hearing Loss 1 May 2007 HUNG Che Wai Terry TONG Chi Fai Michael WONG Ka Cheong Terence CUHK Departmental Funding VAN Voice therapy is one of the common treatment HASSELT Charles Andrew modalities 1 September 2006 for voice disorders and there is considerable amount of literature supporting its CUHK Departmental Funding effectiveness. Generally, voice therapy is conducted RetroX (Auric GmbH, Rheine, Germany) is a new on a one-to-one basis, where patients are seen semi-implantable hearing aid proposed for high individually by speech therapist. There is very little frequency sensorineural hearing loss. Because the literature on its effectiveness when treatment is external auditory canal is not occluded, the RetroX provided in a group format. provides selective amplification of high frequency investigating the effectiveness of group intervention sounds. There are favourable results reported from for patients with dysphonia. A sample of 20 adults patients who had implantation in European centres. is invited to join a fee-paying service for voice However no reports were published regarding the assessment and intervention. Subjects are required audiological results from the Asia Pacific region. to fill in three questionnaires including demographic The purpose of our study is to document the information, subjective and objective hearing improvement of potential risk factors for voice disorders. RetroX for high frequency sensorineural hearing loss subject will also receive a comprehensive voice in Hong Kong where the sound environ of our built assessment consisting of laryngeal examination and up city and culture is unique. perceptual evaluation. Subjects will then commence The avoidance of self-perceived This study aims at voice problem and Each occlusion effect of RetroX may be a benefit for Hong a six week group voice intervention program. Kong patients when subtropical climate is a the group intervention program, an immediate precipitating factor in otitis externa and discomfort post-intervention voice questionnaire and voice for conventional hearing aid wearers. 20 suitable perceptual evaluation will be conducted to assess the candidates with high frequency sensorineural hearing intervention program’s immediate effectiveness. loss will be selected for titanium tube implantation. Subjects will also be required to attend another The procedure is undertaken in a single operation comprehensive assessment consisting of laryngeal under local anaesthesia. examination, perceptual voice evaluation as well as The RetroX hearing aid After unit will be loaded after 4 weeks. voice questionnaires at six months post treatment to (MD06513) investigate the intervention program's long term outcome. (MD06538) Faculty of Medicine 338 Dept of Otorhinolaryngology, Head & Neck Surgery Multilevel models will be used to assess the risk Voice Disorders among School Teachers in Hong factors in relation to the voice measurements. Kong: Prevalence and Risk Factors This study will be the first ever study on the prevalence of voice disorders among Hong Kong LEE Kathy Yuet Sheung Michael The identification of risk factors will provide information on specific areas that one needs WONG Ming Chung to attend to for preventing voice disorders. VAN HASSELT Charles Andrew HO Nga Yi Fiona teachers. TONG Chi Fai Furthermore, teachers identified with voice problem (School of Public Health) in the study will also receive early proper 30 June 2007 managements. CUHK Research Committee Funding (Direct (MD06377) Grants) Voice disorder is the major occupational hazard of The Prevalence of Hearing Problems, and the Use school teaching with the prevalence rate of 32% to of 57.7% as reported in the Western literature. While Against Pure-Tone Audiometry Results in Hong there is no published data on the prevalence rate of Kong Secondary School Children – A Pilot Study Self-Report Hearing Handicap Measures teachers in Hong Kong having voice disorders, our NG Hoi Yee Iris pilot study on 40 teachers showed that 55% had vocal TONG Chi Fai Michael problem presenting either with impaired voice quality VAN HASSELT Charles Andrew or vocal pathology. Yuet Sheung The present study aims at investigating 1) the LEE Kathy 26 September 2006 prevalence of voice disorders among school teachers Hear Talk Foundation in Hong Kong; and 2) the potential risk factors leading to voice disorders. This study is a pilot study to investigate the A sample of 945 teachers will be recruited by cluster prevalence of hearing loss and hearing handicap in sampling from the 18 geographic districts in Hong local secondary school- children. Hearing loss will Kong. be screened by standard Pure Tone Audiometry and Subjects will be required to fill in two questionnaires where information on their Otoacoustic Emissions Measurements in school self-perceived voice problem and potential risk environment, whereas hearing handicap will be factors will be identified. defined by responses to a self-reported screening Each subject will then receive a comprehensive voice assessment consisting questionnaire. The sensitivity and specificity of of laryngeal examination and perceptual evaluation. these tests will be compared (using pure-tone Teachers will be defined as having voice disorders if thresholds as the gold standard), and will be they 1) receive an overall severity grade of 2 or above compared to other published overseas results in a in the perceptual assessment; and/or 2) diagnosed of similar population. Correlation among hearing loss, any vocal pathology. hearing handicap and previous noise exposure The prevalence rate and its 95% confidence intervals experience will also be explored. The Institute of of teachers having voice disorders will be calculated. Human Communicative Research of The Chinese University of Hong Kong is invited by the Hear Talk 339 Faculty of Medicine Dept of Otorhinolaryngology, Head & Neck Surgery CUHK Departmental Funding Foundation to conduct the pilot study within a one-week period in a secondary school with students between age 12-18. The SNIP is well known for its high recurrence rate Previous noise exposure and malignant transformation potentials. including recreational noise exposure will be one of Radical external surgical approaches are used to be the gold the key factors to study. standard of treatment. (MD06597) resection becomes In recent years, endoscopic more and more popular. However, comparison of treatment results had been Packless Endoscopic Turbinectomy difficult due to the absence of a well recognized staging system. NG Siu Kwan LAM Chuen Kwong staging or categorization system reported in the 1 June 2007 literature. CUHK Departmental Funding a new staging system. 16 years were retrieved. All SNIP were staged with treating patients who suffer from nasal obstruction the new system according to the operative findings due to turbinates hypertrophy. However, it carries and histological reports regarding the extent of the disadvantages of more bleeding and the need of disease. very uncomfortable nasal packing post-operatively. procedure. With The recurrence rate associated with each stage of disease was reported. The authors of this study has modified this operation endsocopic The clinical notes of all the patients followed up by the investigator over the past been shown to be the most effective method of an There is no single system which is accepted worldwide. This study aims at intoruding Conventional partial/total turbinates resection has to There had been a few proposed (MD06512) good visualization and some added minor surgical steps, A Case-Control Study of the Risks Factors the turbinate resection can be achieved with minimal Associated with Sinonasal Schneiderian Papilloma bleeding and abolish the need of nasal packing. It improves patient's comfort and shorten hospital stay SHAM Cheuk Lun which is the experience of the authors. This study is LEE Lip Yen Dennis TONG Chi Fai Michael a prospective observational study to investigate the efficacy and rate of adverse effects of this modified 1 January 2007 surgical procedure. CUHK Departmental Funding (MD06686) The cause of sinonasal Schneiderian papilloma (SNSP) is unknown. Previous reported possible risk A Retrospective Review of the Treatment Results factors included age, sex, smoking, viral infection, of Sinonasal Inverted Papilloma (SNIP) Based on genital a New Staging System or determatological warts, inhalational chemical exposure, allergy, sinusitis and nasal SHAM Cheuk Lun WOO Kong Sang John polyposis. contribute to disease prevention and treatment. TONG Chi Fai Michael The aim of the present study is to evaluate the above risk 1 January 2007 Faculty of Medicine Knowing the risk factors would factors in SNSP as compared with a matched control 340 Dept of Otorhinolaryngology, Head & Neck Surgery group. Patients and controls would be interviewed and examined by investigators. SHAM Cheuk Lun A standardized KING Ann Dorothy questionnaire would be filled in and collected for (Diagnostic Radiology & Organ Imaging) statistical analysis. TONG Chi Fai Michael (MD06567) 1 January 2007 CUHK Departmental Funding The Relation of EBV, HPV, p21 and p53 Preoperative staging of disease is important for early Expression in Sinonasal Schneiderian Papilloma assessment of the severity of disease, planning of SHAM Cheuk Lun Cellular Pathology) surgical TO Ka Fai (Anatomical & approach and provide preoperative information for preoperative counseling of the patient. CHAN Kay Sheung Paul MRI scan was considered by most clinician to be (Microbiology) TONG Chi Fai Michael more accurate in this aspect because it can 1 January 2007 differentiate tumour from inflammatory diseases. CUHK Departmental Funding There had been no report on the accuracy of CT scan There had been a lot of publications on association of in preoperative staging. EBV and HPV with SNSP. study is to evaluate the staging accuracy of plain CT Most of the publications were not on Chinese subjects. highly variable. The aim of the present scan, which is the most commonly performed The results were preoperative radiological investigation. Proof of such associations would About 30 have important implications in disease prevention and plain CT scans of patient with sinonasal inverted treatment. papilloma followed up by the investigator were There had been reports on association of p21 and p53 expression with different degree of retrieved for evaluation. dysplasia and malignancy founding SNSP. Testing prior information about the clinical findings of the for p21 and p53 expression may help to screen out patients. These films were sent to the radiologist tumour with a potential for dysplasia or carcinoma. (co-investigator) would determine the extent of The aim of the present study is to evaluate the disease in the nose and each of the sinuses. prevalence of these factors in a group of SNSP seen staging system was used for staging. A preoperative in PWH over the past 16 years as compared with staging for each film was established base on the those found in two control groups. above findings. The SNSP The radiologist had no Krous’s These results were compared with would be retrieved from the paraffin blocks stored in the final staging based on intraoperative findings and the pathology department of PWH. The first control histological findings of the patients. The accuracy group would be nasal polyps from polypectomy of preoperative staging by plain CT scan was operations and the second group would be turbinates assessed. from turbinectomy operations. (MD06878) (MD06598) Self-Perceived Peoperative Staging of Papilloma (SNIP) by Sinonasal Plain Swallowing Difficulties in Nasopharyngeal Cancer Survivors: A Qualitative Inverted Study Computed Tomography. Is It Accurate? 341 Faculty of Medicine Dept of Otorhinolaryngology, Head & Neck Surgery TONG Chi Fai Michael LO Suk Yee Phoebe supportive 1 September 2006 recommendations for future research scopes. a the patients and making Clinical Trial of HiRes® 120 and Auria+TM Sound standard modality for primary treatment of nasopharyngeal carcinoma (NPC). to (MD06614) CUHK Departmental Funding Background: Radiation therapy is care Processor Chronic dysphagia is a common sequela of the therapy. Previous studies of TONG Chi Fai Michael dysphagia in NPC patients are limited to the LUK Pui Ki, Betty* WONG Ka Cheong Terence investigation of prevalence rates, clinical assessment methods and quality of life. 1 February 2007 Little attention has CUHK Departmental Funding been paid to patient behaviour or support needs. The purpose of this study is to explore patient This study is to evaluate the benefit of a new speech concerns, psycho-social processing strategy offered by one of the cochlear consequences and coping mechanism in relation to implant system (Advance Bionics). Subjects will be the swallowing difficulties. required to use a research speech processor Methods: This study uses qualitative in-depth programmed with the new strategy for 3 months. interviews with phenomenological approach to Their ability of tone perception and speech explore patients’ views on the swallowing problems. perception will then be evaluated. An estimation of 50 subjects for the in-depth be compared with the results obtained when the interviews will be selected from a consecutive sample subjects use their own speech processor. The new of patients (estimated n=120) who attend the NPC speech processing strategy is designed to provide follow-up clinic in the ENT Outpatient Department greater number of channels. With increased number of the Prince of Wales Hospital. After the of channels, it was hypothesized that more spectral completion of written consent, the consecutive information would be available and would enhance sampling patients will respond to a series of survey speech perception. questions, and a quick appearance will then be (MD06404) lifestyle impact, Results will then conducted with them to identify their eligibility to participate in the following in-depth appearance. Perceptual Channels Using Current Steering in The in-depth interview lasting for about 30 minutes Cochlear Implant will be audio-taped and transcribed verbatim onto a personal computer to form a textual database for TONG Chi Fai Michael analysis. Data will be analyzed concurrently with data collection following LUK Pui Ki, Betty* WONG Ka Cheong Terence Colaizzi’s 1 February 2007 phenomenological methodology. CUHK Departmental Funding Implications: The collected data will provide healthcare professionals with the information how This clinical study is being conducted to determine patients view the swallowing problems. Findings the number of perceptual channels (or different are expected to be useful for identify areas to give pitches) that can be resolved by postlingually Faculty of Medicine 342 Dept of Otorhinolaryngology, Head & Neck Surgery deafened adults who use the cochlear implant. VAN HASSELT Charles Andrew The number of perceptual channels will be compared to Chung Kwong (Surgery) speech perception ability and program parameters (1) (Institute of Chinese Medicine) to determine how perceptual channels contribute to Chi Man (Surgery) implant benefit; and (2) to provide information for YEUNG SREEDHAR Biji AU YEUNG 15 March 2007 enhancing sound processing. The long-term goal is CUHK Research Committee Funding (Direct to develop improved sound-processing systems for Grants) patients with cochlear implant. (MD06486) Conventional filling cystometry (CFC) has ever been considered as the Gold Standard investigation of detrusor function. However, it is performed using International Robotic Surgery Symposium temporary catheters with a relatively short duration VAN HASSELT Charles Andrew and artificial bladder filling. The behavior of the 20 January 2007 bladder is interpreted from data in such studies obtained Chindex Hong Kong Ltd General Support nonphysiological and stressful conditions. Program, Innovation & Technology Commission under Natural filling cystometry (NFC) has been widely Income from the Project used in urology. This technique is performed using Minimally Invasive Surgery (MIS) has proven patient bladder filling with urine at natural rats. Clinical benefits of near scar-less surgery, faster recovery and less studies have shown interesting differences in the pain. With the innovation of robotic surgical system in results obtained between the techniques. the last couples of years, MIS technique and its post generally acknowledged that NFC technique is operative patient care is moving towards a new ear. performed under physiological condition and the Robotic assisted surgery enhances the dexterity in MIS quality of such measurement is superior. However, which enable surgeons to carry out sophisticated and this technique has not well been characterized in difficult MIS operations. Hong Kong is one of a few small experimental animals. areas in the Asian Pacific region mastering the robotic cystometric studies used in rats to date are, in surgical skill. The proposed conference, which is the principles, essentially similar to those of conventional second of its kind in the world and first in Asia, is human studies, therefore, are non-physiological. envisaged to be an ideal platform for the exchange of Recently, radiotelemetry technology for monitoring experience and novel idea in this new surgical technology, small experimental animals has been commercial and to consolidate Hong Kong’s status as the leading available, reliable, and affordable. medical centre in the region. physiological (MD06370) technique is superior. measurements It is The techniques of The quality of using telemetry Therefore, the aim of this study is to characterize the natural filling cystometry Radiotelemetered Cystometry in Rats: Validation by using rediotelemetery in rats. and Comparison of Natural Filling Versus Twenty rats of both sexes will be used in this study. Conventional Cystometry The rat bladder will be implanted a radiotelemetered transmitter (TL11M2-C50-PXT, DSI, USA). After 343 Faculty of Medicine Dept of Otorhinolaryngology, Head & Neck Surgery 7 days of recovery, a radiotelemetered cystometry therefore appear that the activity of NF-kB is related using natural filling will be performed in conscious to the activity of ERK. Based on these data, we and freely moving rats using the DSI telemetry hypothesize that estrogen stimulates the proliferation system of and then both radiotelemetered and thyroid cancer cells conventional cystometries using artificial filling nongenomic pathway. under conscious and Urethane-sedated conditions this hypothesis. will be performed subsequently for the comparison. (MD06514) via an ERK-related This proposal aims to test The data will be compared statistically. (MD06726) The Relative Sensitivities and Specificities of EBV IgA VCA and EA Serology and Plasma Cell-Free Estrogen Stimulates the Proliferation of Thyroid EBV DNA for the Detection of Nasopharyngeal Cancer Carcinoma Cells in an Extracellular-Regulated Kinase-Related Nongenomic Pathway VLANTIS Alexander Chris VAN HASSELT Charles Andrew CHEN Gong Dennis (Chemical Pathology) George (Surgery) VLANTIS Alexander Chris LO Yuk Ming TSANG King Yin Raymond WOO Kong Sang John TONG Chi Fai Michael CHAN Kwan Chee (Chemical 1 May 2007 Pathology) VAN HASSELT Charles Andrew CUHK Research Committee Funding (Direct 8 January 2007 Grants) CUHK Departmental Funding Epidemiological data strongly indicate a relationship between thyroid cancer and female hormones. Nasopharyngeal carcinoma (NPC) is the commonest Recently we have shown that estrogen significantly head and neck cancer and the 6th commonest cancer promotes the proliferation of thyroid carcinoma cells. in men in Hong Kong. In the 20-44 year old age We have recently shown that exposure to estrogen group, NPC is the commonest cancer in men and the increases the levels of extracellular signal-regulated 4th commonest cancer in women. kinase (ERK) in thyroid carcinoma cells and that the is not straight forward and requires experience and levels rise as early as 15 minutes after treatment with suitable equipment. estrogen. needed as symptoms of NPC, especially in the early It is not possible for a genomic Diagnosing NPC A high index of suspicion is mechanism to be responsible for such an early rise in stages, are vague. levels. ERK is one of the major mitogen-activated has become part of the diagnostic work-up in most protein kinases (MAPKs) which couples cell surface centres. The objective of serology is to predict or receptor signals to transcription factors. exclude a diagnosis of NPC. One The result is that EBV serology Plasma EBV transcription factor known to be regulated by ERK is IgA-VCA is sensitive but not very specific, while nuclear factor-kappa beta (NF-kB). We have shown EBV IgA-EA is specific but not very sensitive. As that the activity of NF-kB is increased in thyroid no single test can reliably predict and exclude NPC, carcinoma cells and that the increased activity of the two tests are used in combination to improve their NF-kB contributes to the resistance of thyroid overall accuracy, with VCA having a high negative carcinoma cells to cell death stimulation. predictive value and EA a high positive predictive Faculty of Medicine It would 344 Dept of Otorhinolaryngology, Head & Neck Surgery value. If both tests are positive, the patient should has shown that there is a potential interaction be worked up for NPC, and if both are negative, the between E7 and p65, a subunit of nuclear factor patient most likely does not have NPC. kappa beta (NF-kB), in laryngeal cancer cells. The Our sensitivity of cell-free EBV DNA has been reported laboratory has also shown that the activity of NF-kB to be higher than that of IgA-EA, and so the use of is constitutively active in laryngeal cancer cells cell-free EBV DNA to eliminate false-positive transfected with E7. NF-kB is generally believed to IgA-VCA results may offer an improvement in the function as a cell survival factor. detection of NPC. activation of NF-kB is presumed to play a role in the However, the concentrations of Therefore the EBV DNA and IgA VCA titres vary according to growth of laryngeal cancer cells. cancer stage or tumour load. explore the pathway by which E7 leads to an increase This study will This study aims to compare the relative sensitivities and specificities of in NF-kB activity in laryngeal cancer cells. EBV IgA VCA and EA and plasma cell-free EBV (MD06610) DNA to the stage of newly diagnosed NPC to determine their accuracy and hence determine their Please refer to previous issues of this publication role ins screening patients in the general community for more details of the following ongoing research for NPC. at the department: (MD06418) Edition Title/Investigators The Induction of Nuclear Factor KappaB (NF-κB) by Human Papillomavirus-16 Oncoprotein E7 in 2005-06 Speech Discrimination in Quiet and Laryngeal Cancer Cells Noise in Chronic Suppurative Otitis Media VLANTIS Alexander Chris George (Surgery) CHEN Gong (CSOM) Undergoing Tympanoplasty (MD04787) VAN HASSELT Charles CHAN Hing Sang Andrew TONG Chi Fai Michael LEUNG Kwok Shun 18 April 2007 2005-06 A CUHK Research Committee Funding (Direct Randomized Comparing Grants) Controlled Bipolar Diathermy Trial and Chemical Cautery for the Treatment of The portion of a population chronically infected with Recurrent Epistaxis (MD04325) human papillomavirus-16 (HPV-16) has an increased CHAN Yap Joseph SOO Gordon risk of developing cancer. E6 and E7 are the main Ming Soon LEE Lip Yen Dennis viral oncoproteins of HPV-16 that lead to the HO Yee Man uncontrolled growth of infected cells. E6 and E7 ABDULLAH Victor VAN HASSELT Charles Andrew alter a variety of cell proliferation and growth molecules, and it may be these alterations that lead to tumor development. 2005-06 Long-Term Outcome of the Hong Kong In addition to inhibiting tumor Vascularised Temporalis Flap for suppressor proteins p53 and pRb, E6 and E7 also affect a number of other molecules. Our laboratory 345 Faculty of Medicine Dept of Otorhinolaryngology, Head & Neck Surgery Mastoid Cavity (CLNTN) - An Outcome Measurement Reconstruction Instrument for Children with Hearing (MD04837) HUNG Che Wai Terry Chung TONG Chi Fai Michael Impairment (MD04359) LIU Kwok TONG Chi Fai Michael VAN HASSELT Charles Andrew (Electronic Engineering) Chi Pun 2005-06 Patient Satisfaction after Closed LEE Tan YUEN VAN HASSELT Charles Andrew Reduction of Nasal Fractures (MD04907) HUNG Che Wai Terry Fai Michael 2005-06 Assessing Quality of Life in Patients with TONG Chi Nasopharyngeal VAN HASSELT Newly Charles Andrew Developed Instrument: Throat Surgery: Case-Presentations Final Multicenter Year Yee Phoebe CAO Junpeng* Network (MD04913) Ming* ZHANG Ting* Alexander Chris Michael CHENG Wai 2005-06 A Study on Dysphagia in Patients with TONG Chi Fai Nasopharyngeal VAN HASSELT Charles Carcinoma Post-Radiotherapy: The Diagnosis, Use of Impairment Screening Investigations TONG Chi Fai Michael Elderly Chinese Population (MD04803) Ming Peter LEE Ting Hon Sheung TONG Chi Fai YUEN Chi Pun Shu On Peter and Surgical Intervention (MD05479) and Depression/Depressive Symptoms in an Michael LO Suk VLANTIS Andrew 2005-06 Hearing Study CHEN Chuqun* Medical Students Using an Audiovisual HUNG Che Wai Terry a Disease-Specific TONG Chi Fai Michael Real-Time for A Using (MD04457) 2005-06 Student Telecast Teaching in Ear, Nose and Carcinoma KU Ka LEE Kathy Yuet AHUJA Anil Tejbhan (Diagnostic Radiology & Organ TANG Imaging) VAN HASSELT Charles Andrew CHAN Anthony Tak Cheung (Clinical Oncology) VAN HASSELT Charles Andrew 2005-06 The Development of Word Lists for Cantonese Speech Audiometry 2005-06 Childhool Dysphonia among School (MD04750) LEUNG Kwok Shun Aged in Hong Kong (MD05428) YUEN Chi TONG Chi Fai Michael Pun WONG Ka Cheong Terence LI Shu Ying* Yi Fiona 2004-05 The Development of the Cantonese Lexical Neighborhood Tests in Noise Faculty of Medicine Children HO Nga LEE Kathy Yuet Sheung VAN HASSELT Charles Andrew WONG Ming Chung (School of Public Health) 346 Dept of Otorhinolaryngology, Head & Neck Surgery TONG Chi Fai Michael 2003-04 Estradiol Inhibits Promoting the Apoptosis by Expression of YUEN Chi Pun Metallothionein II and NF-kappaB in 2004-05 The Functional Inhibition of NF KappaB Human Thyroid Cancer Cells (CU03387) in Squamous Epithelial Cells Infected VAN HASSELT Charles Andrew with HPV 16 Promotes Apoptosis VLANTIS Alexander Chris CHEN (MD04925) Gong George (Surgery) CHERIAN VLANTIS Alexander Chris CHEN M. George* Gong George (Surgery) LEUNG Chi Hang Bertrand (Surgery) HASSELT CHAN 2004-05 Molecular Regulation of Bak by Charles Kay VAN Andrew Sheung Paul (Microbiology) HPV16E6 and E7 in Laryngeal Cancer (MD04481) 2005-06 The Significance of Bak Expression in VAN HASSELT Charles Andrew Laryngeal Cancer Cells Infected with CHEN Gong George (Surgery) HPV-16 (CU05557) VLANTIS VLANTIS Alexander Chris CHEN Alexander Chris TSANG King Yin Raymond Gong George (Surgery) VAN HASSELT Charles Andrew 2005-06 The Role of ZBP-89 in Chemotherapy of Hepatocellular Carcinoma (CU05556) VAN HASSELT Charles Andrew CHEN Gong George (Surgery) 2005-06 Complementary DNA Microarray Analysis to Establish Tumour-Specific Genetic Expression Profiles in Laryngeal Cancer (MD05672) VLANTIS Alexander Chris VLANTIS Alexander Chris TONG 2005-06 The Critical Elements for Speech Chi Fai Michael CHEN Gong Recognition in Cantonese - Implications George (Surgery) VAN HASSELT for the Design of Digital Hearing Aid Charles Andrew Amplification Algorithms for Chinese Tonal Languages (MD05366) VAN HASSELT Charles Andrew LEE Tan (Electronic Engineering) 347 Faculty of Medicine Dept of Paediatrics settings, as well as for treatment of other neural RESEARCH PROJECTS degenerative conditions. (CU06505) Thrombopoietin Protects Against Hypoxia-Ischemia Encephalopathy in Murine Long Term Neurocognitive Effects in Children Models, and Signals Proliferation, Anti-Apoptosis Exposed to Low Dose Prenatal Methylmercury and Pro-Survival in Neural Progenitor Cells Exposure FOK Tai Fai NG Pak Cheung YEW Tai Wai FOK Tai Fai LAM Hugh Simon Hung San* David (Anatomy) LI Kwai Har Karen 1 June 2007 ANTONIO Gregory (Diagnostic Radiology & CUHK Research Committee Funding (Direct Organ Imaging) YANG Mo# Grants) 1 September 2006 Large-scale Research Grants Council (Earmarked Grants) epidemiological studies have demonstrated long-term adverse health effects of Perinatal hypoxia-ischemia encephalopathy (HIE) is a low-dose fetal methylmercury exposure. We have a major cause of acute mortality and chronic neurologic large, morbidity. The overall predicted risk of death was documented fetal methylmercury exposure and a rich reported to be over 12%, and a significant number of data set documenting characteristics that may survivors suffered from neuropsychological handicaps, influence health outcomes such as parental smoking, including mental retardation, cerebral palsy, epilepsy parental alcohol intake, environmental factors, and and learning disability. demographic characteristics. Our hypothesis is that well-defined cohort of subjects with We have previously thrombopoietin (TPO) might be an effective agent for demonstrated that in our locality fetal methylmercury the treatment of HIE and the mechanism could be exposure is significantly associated with maternal mediated by anti-apoptotic and pro-survival signals. fish consumption. We plan to recruit 100 subjects Our objectives are to establish an optimized protocol from using TPO for treatment of brain damage induced by neurocognitive testing to study the associations HI in neonatal rats. The 7-day and 14-day postnatal between rats will be used as our models because their brain methylmercury histology bears similarity to those of preterm neurocognitive development of these children. An (32-34-week human accurate assessment of the adverse neurocognitive newborns, respectively. For in vitro analysis of the effects of low-dose fetal methylmercury exposure in mechanism of neuroprotection, the C17.2 neonatal our region will allow us to make evidence progenitor cell line and primary neurospheres in recommendations for maternal fish consumption and culture, upon hypoxia and withdrawal of nutrient, target mercury exposure levels. will be treated with TPO. (MD06400) gestation) and full-term If proven efficacious, TPO could be developed for reducing mortality and chronic sequelae of perinatal asphyxia in clinical Faculty of Medicine 348 this cohort these and subject perform characteristics, exposure and extensive prenatal long-term Dept of Paediatrics CUHK Research Committee Funding (Direct A Pilot Study to Investigate the Response of Grants) IMD-0354 Ointment in Patients with Atopic Dermatitis Childhood atopic dermatitis (AD) is a distressing HON Kam Lun disease associated with pruritus and sleep disturbance. LUK Nai Ming Tommy The pathophysiology of pruritus is complex. Studies (Medicine & Therapeutics) have 11 September 2006 neuroimmune mediators and Substance P (SP) have a role in AD and are possibly involved in the pathogenesis of itch. BDNF The purpose of this pilot study is to evaluate the is a growth factor initially found in nervous system. effectiveness and safety of an investigational product, Increased IMD-0354 in patients with atopic dermatitis. disease severity. Molecular Design, Inc. (IMMD), Japan, for the treatment of atopic dermatitis. blood levels of BDNF has been documented in AD patients and correlated with IMD-0354 is developed by Institute of Medicinal SP is another neuropeptide probably involved in the pathogenesis of AD via the The safety of neuroimmunocutaneous system, and significantly IMD-0354 has been tested in a phase 1 clinical study correlated with disease activity. Our study aims to IMD-0354 has been evaluate how closely BDNF and SP are associated shown to be safe and well tolerated in that study. with disease severity, quality of life and nocturnal A total of 20 patients with atopic dermatitis aged scratching in AD. AD patients ≤18 years will be (12-64 yrs) both males/females will be recruited. They will be asked to apply the study ointment (0.3%) recruited. Disease severity will be assessed with the SCORing Atopic Dermatitis (SCORAD) index, and on the affected areas twice daily at an interval of 12 hours for 3 weeks. that including Brain-derived neurotrophic factor (BDNF) Institute of Medicinal Molecular Design Inc. conducted in Hong Kong. suggested quality of life with the Children’s Dermatology Life The effectiveness of IMD-0354 Quality Index (CDLQI). Concentrations of plasma ointment will be evaluated by assessing the change in BDNF, SP, AD-associated chemokines (cutaneous T the SCORAD scoring and the Physician’s Global cell attracting cytokine, CTACK; thymus and Assessment scores by that of the baseline scores, activation regulated chemokine, TARC), serum total while the safety of the IMD-0354 ointment will be IgE, and eosinophil counts will be measured in these learned by routine clinical examination, laboratory patients. tests as well as the patient’s reporting of abnormal All children are instructed to wear the DigiTrac monitor on their dominant wrist before symptoms. sleeping. (MD06496) The monitor is programmed to record limb motion between 10 pm and 8am the following morning. In preliminary study, we find serum levels of BDNF Pathophysiology of Nocturnal Scratching in and SP strongly correlate with nocturnal wrist Childhood Atopic Dermatitis: The Role of BDNF movements and suggest that they are the pathogenic and Substance P factors of the annoying symptoms of scratching. If confirmed, further trials in leukotriene B4 receptor HON Kam Lun LEUNG Ting Fan antagonist and 5-lipoxygenase inhibitor as novel 29 June 2007 349 Faculty of Medicine Dept of Paediatrics anti-pruritic drugs in place of antihistamines will be antibiotics in childhood asthma management in Hong advocated. Kong. (MD06499) (MD06870) Are Respiratory Viruses and Atypical Bacteria Clinical Triggers of Severe Asthma Exacerbation in Hong β2-Adrenergic Kong Children? Asthmatic Patients LEUNG Ting Fan and Functional Receptor LEUNG Ting Fan CHAN Kay Sheung Paul Correlates Gene in of Chinse KO Wai San Fanny (Microbiology) WONG Wing Kin Gary FOK (Medicine & Therapeutics) TANG Leung Sang Tai Fai NG Pak Cheung Nelson (Chemical Pathology) WONG Wing Kin Gary HUI Shu Cheong David (Medicine & 1 November 2006 Therapeutics) Research Fund for the Control of Infectious 1 May 2007 Diseases CUHK Research Committee Funding (Direct Asthma is a chronic inflammatory disease of the airways. Grants) Respiratory infections are a common trigger of asthma exacerbation in these patients. Asthma is a major healthcare burden worldwide, and Epidemiologic studies showed that up to 80% of is characterized by repeated and reversible airflow childhood asthma attacks are associated with viral limitation, β-agonist is the first-line rescue therapy upper respiratory infections in the Caucasian for bronchospasm in these patients. However, the population. However, the spectrum of respiratory clinical response to p-agonist treatment is variable. infections that leads to asthma exacerbation in Hong Several in vitro and clinical studies suggested this Kong children is unclear. In this study, we aim to finding to be related to functional polymorphisms in define whether respiratory infections trigger severe the gene encoding β2-adrenergic receptor (ADRB2). asthma attacks in local children and to delineate the Over the past few years, many studies reported that epidemiology of viruses and atypical bacteria causing ADRB2 SNPs were associated with severe or infections in these patients. nocturnal asthma, lung function and bronchodilator Asthmatic children aged 3 years and above who are hospitalised for responsiveness in the Caucasian population. asthma exacerbation are eligible. recent meta-analyses also confirmed some of these Nasopharyngeal Two aspirate sample will be collected for the molecular associations. detection of a panel of respiratory viruses and not detect such association, we found significant atypical bacteria. These subjects will also undergo inter-ethnic difference in allele frequencies of two clinical and lung function assessments to define their ADRB2 SNPs between Chinese and Caucasians. asthma severity. The primary outcome in this study Despite these findings, several studies reported is the association between asthma exacerbation and increased the occurrence of infection (or co-infection) by homozygous asthmatics respiratory pathogens. The results will better define β-agonists. The present study will determine the benefits for respiratory virus vaccines and genotypes and haplotypes of ADRB2 in Chinese Faculty of Medicine 350 Although our published study could adverse outcomes treated among Argl6 with regular Dept of Paediatrics population. This study will also ascertain any will be investigated. (B) The expression profiles of pharmacogenetic association between ADRB2 and adhesion bronchodilator responsiveness in our subjects. chemokines/receptors/extracellular The molecules/ matrix in the results generated from this study will add invaluable migrated CD34+ cells will be determined. data to asthma pharmacogenetics in Chinese, which ultimate homing activities of these cells will be facilitates future research to delineate the optimal analysed by the short- and long-term presence of strategies to treat our asthmatic patients. human hematopoietic CD45+ cells and subsets in the (MD06719) bone marrow, spleen and peripheral blood of NOD/SCID mice. (C) The Findings of this study will Ex vivo Expansion and Homing of Cord Blood contribute to better facilitating the technology of ex Hematopoietic Stem/Progenitor Cells by the vivo expansion, utilization of cord blood stem cells Stromal Cell-Derived Factor-1 (SDF-1) /CXCR4 for adult transplantation and application of various Axis and Signals stem cells for regenerative medicine. (CU06509) LI Kwai Har Karen LAU Tze Kin (Obstetrics & Gynaecology) Regulation of Makorin-2 Gene Expression in Normal and Malignant Hematopoiesis 1 January 2007 Research Grants Council (Earmarked Grants) LI Kwai Har Karen CHEN Yangchao (Medicine & Therapeutics) A major limitation on using umbilical cord blood for transplantation, especially for adult patients, is the 1 March 2007 insufficient quantity of hematopoietic stem and CUHK Research Committee Funding (Direct progenitor cells in a collection. To address this issue, Grants) the ex vivo expansion of cord blood stem cells, in the presence of early-promoting cytokines, has been Makorin-2 is a RING zine finger gene recently proposed and investigated. However, there has been identified evidence showing that this procedure might lead to stem/progenitor cells. It shares a sequence of 105bp compromise in the 3’ untranslated region with the proto-oncogene of the self-renewal and properties of hematopoietic stem cells. homing The in human CD34+ hematopoietic Raf-1 in a reversed transcription orientation. Our objectives of this study are (1) to provide a protocol pilot study on Xenopus (X) animal cap explants for the optimal utilization of SDF-1 for the expansion showed that Xmakorin-2 regulated hematopoiesis and of cord blood stem and progenitor cells with high α-globin efficiency of homing; and (2) to investigate the BMP-4/GATA-1/GATA-2 pathways. Our hypothesis homing mechanism of these expanded cells by their is that makorin-2 has significant functions in normal differential expression profile in the presence of and malignant hematopoiesis in human. SDF-1. To achieve our objectives, (A) the in vitro objectives are to apply clinically relevant models of migration and attachment properties of cord blood hematopoiesis, representing different windows of CD34+ cells, before and after ex vivo expansion, to development to investigate (1) effects of makorin-2 stromal cell microenvironments (transwell system) expression on ex vivo expansion of human cord blood 351 expression mediated by the Our Faculty of Medicine Dept of Paediatrics CD34+ cells by lentiviral-transduced over-expressing endothelial function and OSAS were carried out in and siRNA inhibition; and (2) expression of children. makorin-2 function is increasingly being used as a useful means in malignant hematopoiesis. Our Physiological testing of endothelial read-out system includes multilineage differentiation of to and intervention. Using this type of testing in childhood megakaryocyte cells, and mechanism on BMP-4 OSAS may allow early identification of individuals signals. who are at high risk for cardiovascular events but are the myeloid, erythroid, lymphoid Our findings would contribute to the assessing vascular risk and response to understanding of makorin-2 gene functions and yet to manifest clinical features. clinical applications of these cell systems. that childhood OSAS also leads to endothelial (MD06399) dysfunction reflected by reduced FMD, as assessed by Endothelial Function in Children high-resolution We hypothesize ultrasonography and this endothelial dysfunction is reversible with treatment with Obstructive Sleep Apnoea Syndrome (OSAS): a for OSAS. In this study, we will evaluate Case-Control Study endothelium-dependent FMD in the brachial artery in children with OSAS compared with matched controls, and assess its response following treatment for LI Man Chim Albert Martin WING Yun Kwok (Psychiatry) SUNG Yn Tz Rita Ming (Chemical Pathology) OSAS. CHAN Ho (CU06508) ABDULLAH Victor (Otorhinolaryngology, Head and Neck S) Use of Leukotriene Receptor Antagonist in the 1 October 2006 Treatment of Allergic Rhinitis Research Grants Council (Earmarked Grants) LI Man Chim Albert Martin Obstructive sleep apnoea syndrome (OSAS) has been CHAN Ho Ming closely linked with hypertension and cardiovascular (Chemical Pathology) disease (Otorhinolaryngology, Head and Neck S) LAM including atherosclerosis cross-sectional and prospective studies. in both ABDULLAH Victor Wai Kei Christopher (Chemical Pathology) Increased sympathetic activity and hypoxia associated with 1 October 2006 apnoeic episodes in patients with OSAS are CUHK Departmental Funding suggested mechanisms, likely through the induction of systemic inflammation endothelium-dependent (FMD). and flow-mediated impaired Allergic rhinitis is a complex inflammatory disease dilation of the upper airway characterized by sneezing, nasal The latter is recognized as a preclinical pruritus, rhinorrhoea and nasal obstruction. It is a vascular disease and it precedes the development of common condition, and its prevalence has been atherosclerotic lesions. A wealth of evidence from shown to be increasing. both experimental and clinical studies has confirmed prevalence of school-aged children with allergic that the link between inflammation, endothelial rhinitis is between 35 to 44%. If the condition is left dysfunction and structural arterial disease emerges untreated or symptoms are only partially taken care remarkably early during childhood. However, none of, significant morbidity can result. of the studies that examined the interaction between Faculty of Medicine 352 In Hong Kong, the Dept of Paediatrics Cysteinyl leukotrienes are inflammatory mediators Neck S) Bu Wei* CHAN Che Ting* KAM common to both the upper and lower airways, which Kai Man* LI Chi Kong has prompted therapeutic investigators potential to in evaluate allergic their 1 October 2006 rhinitis. CUHK Departmental Funding Leukotriene receptor antagonists (LTRAs) offer the exciting possibility of once-daily oral therapy with Sleep is defined as a reversible behavioural state of few adverse effects, and also avoiding the discomfort decreased responsiveness and interaction with the of nasal sprays. In vitro studies, montelukast and environment. Studies suggest that sleep is important pranlukast reduced levels of nasal pro-inflammatory in maintaining optimal health. mediators studies in adult humans and animals have focused on and inhibited antigen-induced Sleep deprivation microvascular leakage. physiologic and immunologic consequences of sleep Using subjective symptom score as the main output loss and suggest that sleep is involved in maintenance measure, montelukast as monotherapy is effective in of normal bodily functions and optimal immune the treatment of allergic rhinitis. However, data performance. Specifically, sleep is believed to play relating to the combined effects of LTRAs and a role in the growth and healing of body tissues, histamine H1 -receptor antagonists on nasal symptoms learning and processing of memory, and central in allergic rhinitis offer conflicting results. In nervous system repair. Inadequate sleep quality or majority of these previous studies, the outcome quantity can have a negative impact on the ability to measures involved symptom score and subjective pay assessment of efficacy. behavioral, and emotional functioning. Nevertheless, studies attention and concentrate cognitive, regarding the efficacy of montelukast in addition to Beta-thalassaemia is current antihistamine therapy in local Chinese has not characterized chronic been documented. resulting from mutations that affect haemoglobin In this randomized controlled experience trial, we synthesis. hypothesize that LTRA would provide additional osteoporosis and expansion of marrow space in the symptom relief and anti-inflammatory effects in local skull and facial bones thus predisposing this group of asthmatic children with allergic rhinitis already taking patients to upper airway obstruction especially during regular anti-histamine. We will study nasal cytokine sleep. A study on patients with thalassaemia found levels as a more objective outcome measure to significantly more arousals and periodic limb evaluate the efficacy of LTRA. movements in patients compared to normal controls. (MD06358) This study however, consisted of only 10 patients of by a and Ineffective hereditary haemolytic erythropoiesis condition anaemia causes whom six were of the thalassaemia major type. The Daytime Sleepiness and Obstructive Sleep Apnoea true prevalence of OSA among patients with in thalassaemia is thus still unknown. It is nowadays Children and Adolescents with rare for thalassaemia major patients to have Beta-Thalassaemia Intermediate-A Pilot Study significant facial skeletal deformity as early diagnosis LI Man Chim Albert Martin and regular blood transfusion would have kept CHU Chiu Wing Winnie (Diagnostic Radiology & Organ Imaging) extra-medullary erythropoiesis at a minimum. This NG Siu Kwan (Otorhinolaryngology, Head and may not hold true for those with thalassaemia 353 Faculty of Medicine Dept of Paediatrics intermediate as chronic anaemia would still provide a straightforward stimulus for bone marrow expansion and hence a risk curative and usually well tolerated. Nevertheless, for airway obstruction. significant risks and problems are associated with There is accumulating adenotonsillectomy such dysfunction and cardiovascular diseases especially complications may include adverse anaesthetic hypertension. events, infection and haemorrhage. is therefore of paramount operative procedure. being evidence to suggest OSA leads to endothelial It an with General Children with importance to identify OSA in thalassaemic patients OSAS are at risk for postoperative respiratory especially those with thalassaemia intermediate who compromise caused by upper airway oedema, are already at risk of suffering from myocardial strain increased as a result of chronic anaemia so that further insult to associated with analgesics and anaesthetic agents and myocardial function is minimized. post-operative pulmonary oedema. Objectives of postoperative respiratory complications in OSAS (1) To investigate for the presence and severity of has been reported to be 16% to 27%. In addition, daytime sleepiness and obstructive sleep apnoea adenotonsillectomy can result in some degree of pain in and family stress. children and adolescents with beta-thalassaemia intermediate; (2) To assess correlation secretions, respiratory depression The incidence Thus many would advocate alternative treatment for those paediatric cases with between degree of mild disease. objective sleepiness with haemoglobin and Nasal corticosteroids have recently been examined ferritin levels; and as an alternative to adenotonsillectomy in the (3) To delineate anatomical levels of obstruction in thalassaemic patients confirmed to have OSA. (MD06479) otherwise healthy child with OSAS. In a prospective, study, randomised, double-blinded children with mild to moderate OSAS were given 6-week course of either nasal corticosteroids or Nasal Corticosteroids as Treatment for Childhood placebo. The authors were able to demonstrate Obstructive Sleep Apnoea only a modest improvement in treated cases. The group was unable to show significant changes in LI Man Chim Albert Martin adenoidal size assessed by lateral neck radiograph, ABDULLAH, possibly related to their inhomogenous sample Victor J.* WING Yun Kwok (Psychiatry) population and short treatment duration. 10 June 2007 For paediatric patients with OSAS too mild to justify CUHK Research Committee Funding (Direct surgery, nasal corticosteroids, if proven to be Grants) effective may be the alternative treatment of choice. Obstructive sleep apnoea syndrome (OSAS) in We aim to carry out an exploratory randomized, children is increasingly being recognised and reports double-blinded, placebo-controlled trial to test the suggested that if the condition is left untreated, a hypothesis that topical nasal corticosteroids given for variety of complications including failure to thrive a period of 4 months would decrease the severity of and neurocognitive dysfunction may result. mild childhood OSAS. The treatment for the majority of children with interest is the change from baseline the apnoea uncomplicated moderate to severe OSAS is relatively Faculty of Medicine 354 The primary endpoint of Dept of Paediatrics hypopnoea index (AHI) as documented by overnight Thus, a reliable set infection markers are required to polysomnography after treatment. promptly and accurately identify the infected cases (MD06904) so that treatment can be started without delay. Equally difficult is the exclusion of infection in A Quantitative Evaluation of Soluble Triggering infants with suspected sepsis, as continuation of Receptor Expressed on Myeloid Cells-1 (sTERM-1) broad-spectrum antibiotics for presumptive bacterial for infection frequently leads to unnecessary treatment Diagnosis of Late-Onset (Nosocomial) and emergence of resistant organism. Bacterial and Fungal Infection in Preterm Infants Hence, this study attempts to define the optimal cutoff value for NG Pak Cheung Yuen Yee LI Kwai Har Karen plasmatic sTREM-1 in detecting genuine bacterial CHAN and fungal infection in preterm, VLBW infants. WONG Pui On Raymond (Lee (MD06887) Hysan Clinical Research Laboratories) 1 June 2007 Mechanism of Thrombopoietin in the Protection CUHK Research Committee Funding (Direct of Cardiomyopathy Induced by Doxorubicin: Grants) Endothelial Progenitor Cell Mobilization and The Neonatal Team at the Prince of Wales Hospital Angiogenesis is one of the world leading teams for research in SUNG Yn Tz Rita PONG Nga Hin Henry LI diagnostic markers of infection for newborn infants. Kwai Har Karen Recent key publications in this field are listed in the reference section of the proposal (References 2-4, 8-9, 30 June 2007 47-48). CUHK Research Committee Funding (Direct This study aims to evaluate the usefulness of a novel Grants) marker sTREM-1 for early diagnosis of late-onset (>72 hours of age) neonatal infection in preterm, Thrombopoietin (TPO) has been shown to have very low birth weight infants. protective effects against doxorubicin (DOX) induced Late-onset nosocomial bacterial infection is an myocardial injury in our previous study. However, important cause of morbidity and mortality in infants the mechanisms of the protective effects remain requiring intensive care. unclear. Preterm, very low birth Recent studies indicated that hematopoietic weight (VLBW) infants are particularly vulnerable growth factors, such as erythropoietin, were capable because of immune immaturity, severe underlying to mobilize endothelial progenitor cells (EPCs) from conditions, and frequent requirement of invasive bone marrow (BM). procedures such as umbilical and indwelling long cells have been reported to possess TPO receptor lines. new indicating that TPO may play a role in angiogenesis broad-spectrum antibiotics and advanced life support for tissue regeneration. We hypothesize that TPO treatment, a significant proportion of infected infants protects still follows a rapid downhill course leading to through mobilization of EPCs from bone marrow to septicaemic the injured heart tissue and enhances angiogenesis and Despite shock, the development disseminated of intravascular coagulation, and death within hours of deterioration. against Moreover, vascular endothelial DOX-induced cardiomyopathy neovascularization in damaged myocardium. 355 Our Faculty of Medicine Dept of Paediatrics objectives are (1) to investigate the effect of TPO on manifestations of atopy and asthma in Chinese mobilizing EPCs, characterized by co-expression of children. stem and endothelial cell markers, using multicolor (CU06512) flow cytometry, in bone marrow and peripheral blood in vivo; (2) to assess the proangeogenic effect of TPO EuroPrevall – The Prevalence, Cost and Basis of in myocardium by immunohistochemistry staining of Food Allergy vascular endothelium with anti-CD31 antibody; and (3) to investigate the correlation of gene expressions WONG Wing Kin Gary LEUNG Ting Fan of cardiomyocyte, apoptotic and signaling pathways LAM Wai Kei Christopher (Chemical Pathology) using gene array analysis and real time PCR confirmation, to the histopathologic and WONG Chun Kwok (Chemical Pathology) 1 March 2007 electronmicroscopic changes. The cardiac functions European Union will be assessed by Doppler echocardiography. The protective mechanism of TPO against DOX-induced Food allergy is an emerging global problem. cardiomyopathy, have However, there is currently little information on food significant clinical implications such as incorporating allergies regarding prevalence or patterns of allergies TPO with other protective reagents through different across Asia. mechanisms to achieve a synergistic effect against prevalence and pattern of food allergies in Hong doxorubicin-induced cardiac dysfunction in the Kong and Beijing using the EUROPREVALL DOX-treated cancer patients. protect. (MD06472) (MD06455) Relationship of Microbial Exposure and Asthma Please refer to previous issues of this publication in Chinese Children for more details of the following ongoing research if established, could This study proposes to study the at the department: WONG Wing Kin Gary CHEN Yu Zhi* LEUNG Ting Fan LAM Wai Kei Christopher (Chemical Pathology) Edition Title/Investigators WONG Chun Kwok (Chemical Pathology) 2005-06 The Role of G-Protein Receptors and Its 1 January 2007 Ligand Melatonin on Thrombopoiesis Research Grants Council (Earmarked Grants) (MD05411) CHIK Ki Wai YANG Mo# Asthma is one of the most common chronic disorders in childhood. There is marked variation of the 2005-06 Development of a Novel Mouse Model of prevalence of asthma in Chinese children from Severe different regions of China. Dehydrogenase (G6PD)-Deficiency for There is also evidence of lower prevalence in rural areas. This study In Vivo Assessment of Haemolytic proposes to investigate the life style factors, and the relationships between Faculty of Medicine microbial exposure Glucose-6-Phosphate Toxicity to Red Blood Cells (MD05525) and 356 Dept of Paediatrics FOK Tai Fai LI Kwai Har Karen JAMES Anthony 2002-03 The Role and Mechanism of Stem Cells in Regenerative Medicine (MD02328) Edward LI Kwai Har Karen NG Ho Keung (Laboratory Animal Services Centre) (Anatomical & Cellular Pathology) 2004-05 A Randomized, Double-Blind, Placebo-Controlled Study Chung Ngor Juliana the (Medicine & Therapeutics) CHAN Therapeutic Effect and Safety of a Hsiao Chang (Physiology) SUNG Traditional Chinese Medicine (TCM) for Yn Tz Rita FOK Tai Fai LEUNG Atopic Po Sing (Physiology) Dermatitis of CHAN in Children (MD04981) HON Kam Lun LEUNG Ting Fan 2005-06 In Vitro Induction of Human Embryonic LEUNG Ping Chung (Institute of Stem Cells into Functional, Multi-Potent Hematopoietic Stem Cells Using a Novel, Chinese Medicine)* Chronological Genetic Coronavirus Diversity NL63 of (CU05518) Human in Mimicking Normal Embryonic Microenvironments 2005-06 The Epidemiology, Disease Spectrum and Approach LI Kwai Har Karen Children (MD05544) TSANG Kam Sze Kent (Anatomical & Cellular LEUNG Ting Fan Sheung Paul Pathology) CHAN Kay (Microbiology) WONG Wing Kin Gary Margaret (Microbiology) LAU Tze Kin (Obstetrics & Gynaecology) IP 2005-06 Stem Cells and Tissue Regeneration CHENG (MD05424) Wai Tsoi Frankie NG Pak Cheung LI Kwai Har Karen NG Ho Keung 2005-06 Identification of Molecular Biomarkers (Anatomical & Cellular Pathology) for Tobacco Smoke-Associated Lung POON Wai Sang (Surgery) Diseases in Exhaled Breath (MD05944) Tai Fai LEUNG Ting Fan Ming (Epithelial Fanny* David Therapeutics) Yiu HUI Shu (Medicine SUNG Yn Tz Rita Research Centre) TO Ka Fai (Anatomical & Cellular Pathology) Cheong KO Wai San & WONG Wing Kin Gary Jack Cell FOK LI Biology CHENG Chun (Orthopaedics & Traumatology) (Physiology) CHAN Chung Ngor LEUNG Po Sing Juliana (Medicine & Therapeutics) WANG Chi Chiu (Obstetrics & 2005-06 Genetic Modulation of HbF in Gynaecology) Beta-Thalassemia (MD05760) LI Chi Kong CHIK Ki Wai 2002-03 An Epidemiological Study of Obstructive Sleep Apnoea Syndrome in Hong Kong Chinese Children (CU02161) 357 Faculty of Medicine Dept of Paediatrics LI Man Chim Albert Martin Tai Fai NELSON Edmund Anthony Severn FOK LAM Chuen Kwong (Otorhinolaryngology, Neck S) (Centre for Head TAM and Siu Lun John (Microbiology)# LAU Tak Fai Joseph Biostatistics) and 2005-06 Obstructive Sleep Apnoea and Insulin WING Yun Kwok Resistance in Obese Chinese Children Epidemiology (MD05454) (Psychiatry) NELSON Edmund Anthony Severn 2004-05 Cardiovascular Complication in Children with Obstructive Sleep Apnoea LI Man Chim Albert Martin CHAN Syndrome - A Case Control Study Ho Ming (Chemical Pathology) (MD04990) LI Man Chim Albert Martin 2004-05 A Quantitative Evaluation of a Leukocyte WING Yun Kwok (Psychiatry) Marker CD64 and Human Inflammatory ABDULLAH Cytokines for Diagnosis of Early-Onset Victor (Otorhinolaryngology, Head (<72 Hours of Life) Neonatal Infection and Neck S) (MD04463) SUNG Yn Tz Rita NG Siu Kwan (Otorhinolaryngology, Neck S) Head NG Pak Cheung and Karen FOK Tai Fai CHAN Ho Ming Michael (Chemical Pathology)* LAU Tak 2005-06 A Fai Joseph (Centre for Epidemiology LAM Wai Kei Quantitative Evaluation Preterm Infants (CU05520) NG Pak Cheung Complications the Diagnosis of Necrotising Enterocolitis in Christopher (Chemical Pathology) FOK Tai Fai 2005-06 Neurocognitive of Neutrophil Marker – CD64 for Early and Biostatistics) CHAN Dorothy* LI Kwai Har in LI Kwai Har Karen Children with Obstructive Sleep Apnoea - A Case-Control Study (MD05446) LI Man Chim Albert Martin 2005-06 Neuroprotection by the Stem Cell/Homing Signal of Stromal-Derived Factor-1 WING Yun Kwok (Psychiatry) (SDF-1)/CXCR4 Neonatal Rat Hypoxia-Ischemia 2003-04 A Phase III, Double-Blind, Randomized, Axis Models in of Encephalopathy Placebo-Controlled, Multi-Country and (MD05613) Multi-Center NG Pak Cheung FOK Tai Fai LI Study to Assess the Efficacy and Safety of Two Doses of Kwai Har Karen GSK Biologicals' Oral Live Attenuated Human Rotavirus (HRV) Vaccine in 2005-06 Effect Healthy Infants (MD03539) Faculty of Medicine and Mechanism of Thrombopoietin on the Protection against 358 Dept of Paediatrics Doxorubicin-induced Man Cardiotoxicity SUNG Yn Tz Rita Elsby Martin SANDERSON (Medicine 2005-06 Correlation & YANG Mo# (Anatomy) between Airway Inflammatory Measures and Obstructive Therapeutics)# LI Kwai Har Karen Albert NELSON Edmund Anthony Severn (CU05521) John Chim Sleep Apnoea Severity in Children CHAN Wood Yee (MD05620) LI Ming (Epithelial SUNG Yn Tz Rita Cell Biology Research Centre) LI Man Chim Albert Martin 2005-06 A Comparative Study of Nasopharyngeal Aspirate and Nasal Swab Specimens for 2005-06 Exhaled Nitric Oxide in the Diagnosis of Causative Agent in Children (MD05340) Acute WONG Wing Kin Gary Viral Respiratory Infection (MD05850) SUNG Yn Tz Rita Chinese LEUNG Ting Fan CHAN Kay Sheung Paul (Microbiology) LI 359 Faculty of Medicine Dept of Pharmacology HP infection in the stomachs of rats. RESEARCH PROJECTS With this animal model, we shall examine the role of cathelicidin in ulcer healing, especially its action on Cathelicidin : A Potential Peptide for Gastric cell proliferation and angiogenesis, the two major Ulcer Healing processes in ulcer healing. The signal transduction pathway through which these biological processes are CHO Chi Hin Xia Hua* activated will be studied with regard to its respective CHEUNG S.M. receptor activation and stimulation of epidermal Stephen* growth factor/MAPK/ERK kinase in isolated gastric 1 September 2006 epithelial cells and endothelial cells. Research Grants Council (Earmarked Grants) This signal pathway has been implicated in the actions of Cathelicidine is evolutionary conserved antimicrobial cathelicidin peptide vascularization. On completion of this project we present in mammals. It provides on cutaneous wound broad-spectrum defence against infection by acting as expect to achieve the following goals: natural antibiotics. 1. Cathelicidin has been detected repair and Establish a new role for cathelicidin in gastric on mucosal surfaces, such as skin, respiratory and ulcer, especially that associated with HP gastrointestinal (GI) epithelia. Early studies on skin infection; 2. indicate that in addition to antimicrobial action Define the complete signal transduction pathway cathelicidin is involved in re-epthelialization of for a new action of cathelicidin on epithelial and wounds suggesting that it plays a part in epithelial endothelial cell proliferation; and 3. cell proliferation and wound closure. Our study also Provide a new type of therapeutic agent that shows that it stimulates proliferation of isolated rat combines antibacterial and ulcer healing actions gastric epithelial cells. for future implementation in the treatment of that regulation of Recent studies demonstrate the gene expression gastric ulcer. of (MD06656) antimicrobial peptides is closely associated with gastric infection such as that by Helicobacter pylori (HP) and they may play an antibacterial role in Psychological Stress and Cigarette Smoking on HP-induced gastritis. All these findings suggest that Colon Cancer cathelicidin may have dual actions in the ulcerated stomach. On the one hand it provides antibacterial CHO Chi Hin action against HP infection, and on the other hand it 30 June 2007 may promote mucosal repair at the ulcer site. CUHK Research Committee Funding (Direct This unique and naturally produced protein that combines Grants) antibacterial with possible ulcer healing actions may provide a most effective therapeutic approach in the Epidemiological and experimental animal studies treatment of infectious ulcer diseases of the GI tract. showed that psychological stress increases the Our study aims to consolidate this hypothesis by incidence and promotes the development of cancers. using an animal model with chronic ulcer disease and It modulates the growth of tumors via neuroendocrine regulation. Faculty of Medicine 360 Also, cigarette smoking is associated Dept of Pharmacology with colonic adenoma formation. People often cholesterol-independent (pleiotropic) effects after a Therefore, long-term treatment. The existence of this enzyme studying the interaction between stress and smoking in the cardiovascular tissues and the ion channel on in modulation of the vascular tissues by statins are Our unknown. However, it is important to demonstrate previous studies showed that adrenaline (a stress the extra-hepatic existence of this enzyme in order to hormone) and nicotine (an active component of establish the pleiotropic effects of statins observed cigarette smoke) stimulate colon cancer growth clinically in the cardiovascular systems. through β-adrenoceptors. In addition, nicotine can hypotheses that HMG CoA reductase exists in human increase adrenaline synthesizing enzymes and release cardiovascular tissues, and an alteration of HMG CoA adrenaline from colon cancer cells. It is likely that reductase activities has pronounced effects on ion adrenaline may directly modulate colon cancer channels opening of blood vessels. Hence, in this development. Furthermore, studying the interaction study, we will employ molecular biology techniques between stress and cigarette smoking on cancer and patch-clamp electrophysiology to evaluate the growth will give us insights about the pathogenic existence of HMG CoA reductase in different mechanisms of colon cancer. With this study, we cardiovascular tissues and the effect of simvastatin could develop an effective therapeutic intervention, on the K+ channels gatings change of coronary artery in particular using the β-adrenoceptor blockers in smooth muscle cells. treating and preventing colon cancer. (MD06678) smoke under stressful conditions. colon cancer is an important issue understanding the pathogenesis of the disease. We (MD06438) Identification An Investigation of the Existence and the Role of Extra-hepatic HMG CoA Reductase of Cardiovascular Active Ingredients in Danshen in LAM Fu Yuen Cardiovascular Systems YEUNG Hok Keung John KWAN Yiu Wa KWAN Yiu Wa WAN Song (Surgery) 1 June 2007 CHIM Siu Chung Stephen (Obstetrics & CUHK Research Committee Funding (Direct Gynaecology) Grants) 1 June 2007 Danshen is the dried root of Salvia miltiorrhiza. It CUHK Research Committee Funding (Direct is a traditional Chinese medicine commonly used in Grants) Chinese communities throughout the world including 3-Hydroxy-3-methyl-glutaryl coenzyme A (HMG Hong Kong, mainland China, and the United States CoA) reductase is the rate-limiting enzyme that is for the treatment of diseases of the heart and blood involved in the endogenous cholesterol synthesis. vessels. However, the scientific basis for its clinical Statin e.g. use is not well established, and which of the simvastatin) have been shown to decrease mortality substances contained in Danshen are important for its from cardiovascular diseases of patients that are therapeutic actions are still uncertain. (HMG CoA reductase inhibitor It is also mainly related to the cholesterol-lowering and 361 Faculty of Medicine Dept of Pharmacology unclear how well Danshen and its ingredients can be also limited the numbers of studies reported so far. absorbed into the blood stream. In the current study, large numbers of homogenous This study will identify and quantify the major human mast cells will be cultured from fresh buffy cardiovascular active ingredients in Danshen. Their coat CD34+ progenitor cells to overcome these oral bioavailability, potencies, and mechanisms of problems. actions in affecting vascular tone will be examined in pharmacological tools are now available to better rats. These studies will reveal the important define the roles of adenosine in human mast cells. constituents in Danshen and give support for their Results obtained will be useful to the future design of uses in treatments of cardiovascular diseases. anti-asthmatic therapies targeted at the adenosine The In addition, a more extensive range of findings could also serve as a platform for receptors on mast cells. developing novel drug therapies from the active (CU06515) ingredients identified. (MD06776) Interaction between Mast Cells and PAR-2 Receptor in Knee Joint Inflammation Characterisation of Adenosine Receptors on LAU Hang Yung Alaster LAM Fu Yuen Human Mast Cells 25 June 2007 LAU Hang Yung Alaster WISE Helen CUHK Research Committee Funding (Direct 1 October 2006 Grants) Research Grants Council (Earmarked Grants) Protease activated receptors (PARs) are G protein Adenosine is an endogenous nucleoside whose level coupled receptors which activation is uniquely is increased in asthmatic patients and contributes initiated by the proteolytic cleavage of their towards the pathophysiology of inflammatory airway N-terminal domain and the subsequent interaction of diseases. Adenosine is believed to induce its airway the exposed “tethered ligand” with another region of action through activation of cell surface receptors on the receptor. PAR2 is the subtype that is activated mast cells. only by trypsin and related serine proteases. There are four subtypes of adenosine Recent receptors, namely A1, A2A, A2B and A3, and studies have provided strong evidence supporting an potentiation of mediator release from mast cells has essential role of PAR2 receptor activation in joint been attributed to the A3 receptor in rodent mast cells inflammation. but the A2B receptors in the human mast cell line serve both as a source of endogenous PAR2 agonists HMC-1. The effects of adenosine on human lung and an important inflammatory effector cell is die mast cells however have not been clearly defined. mast cell. Conflicting observations ranging from inhibitory to endogenous PAR2 agonists, mast cell tryptase is a enhancing effects on human lung mast cells have well recognized activator of PAR2 and increase in been reported. mast cell numbers is a clinical feature of rheumatoid Such discrepancy may have been A potential candidate which can With respect to being a source of caused by differences in the purity of mast cell arthritis and osteoarthritis. preparations used. The difficulties in obtaining inflammatory effector cell, the mast cell is pivotal in large number of homogenous human mast cells have the pathogenesis of allergic and inflammatory Faculty of Medicine 362 As for being an Dept of Pharmacology reactions through the synthesis and release of a wide The proposed study aims to investigate the potential spectrum of chemical mediators and cytokines. The use of a Chinese medicinal herb Danggui with hypothesis that endogenous PAR2 agonists may affect anticancer drugs to improve the clinical outcomes. mast cell function is supported by observations that Danggui (roots of Angelica sinensis) contains high PAR2 agonists are capable of inducing mast cell contents of polysaccharides and phthalide derivatives. activation and the identification of PAR2 expression The crude Danggui polysaccharide extract has been in both human and rat mast cells. Interaction demonstrated to have protective effects against between mast cells and PAR2 hence appears to be an anticancer therapy-associated adverse effects/toxicity. important feature in joint inflammation and it is the While, some of the naturally occurring phthalides aim of the current proposal to investigate directly have been reported to be anti-proliferative, possibly such interaction in an in vivo rat model of joint leading to beneficial anticancer activity. inflammation and in isolated rat mast cells. previous studies only investigated the crude herbal (MD06762) extracts, the detailed chemical base and mechanism of However, such beneficial effects of Danggui remains unknown. Investigation into the Effect of A New Calcium Therefore, the present study will emphasize on 1) Formulation on Osteoporosis purified phthalides to investigate their antitumor effects by using human colon adenocarcinoma cell LIN Ge QIN Ling (Orthopaedics line (HT-29) model; 2) the fractionated Danggui & polysaccharides to determine their preventive action Traumatology) against cisplatin-induced bone marrow suppression 1 May 2007 and nephrotoxicity in mice; and 3) the fractionated Life Angel Limited Danggui polysaccharides to assess their anti-emetic This research project investigates a new calcium effects in the Sunucs murinus cisplatin-induced formulation. The results obtained from the studies emesis model. will reveal the oral absorption and bioavailability of from about three studies will be compared with those calcium of the new formulation calcium, and the obtained from the corresponding Danggui extracts effects of the new formulation on osteoporosis. conducted in parallel. (MD06306) provide significant scientific information on the Furthermore, the effects obtained The obtained results will potential and rational use of Danggui and other Study of the Modulating Role of Danggui in the phthalides and polysaccharides-containing Chinese Cytotoxic and Systemic Adverse Effects of medicinal herbs in conjunction with conventional Anticancer Drugs anticancer drugs for the better treatment of cancer. (MD06748) LIN Ge CHO Chi Hin RUDD John Anthony Evaluation of Anti-Emetic Activity of a Novel 30 June 2007 Compound CUHK Research Committee Funding (Direct Grants) RUDD John Anthony SANGER Gareth J* 363 Faculty of Medicine Dept of Pharmacology 1 August 2006 Interstitial Cells of Cajal Networking in the GlaxoSmithKline Research & Development Senescence-Accelerated Mouse Limited Nausea and vomiting can be serious side effects caused by several life saving drug therapies. RUDD John Anthony YEUNG Chi Kong The YEW Tai Wai David (Anatomy) ROWLANDS present project will evaluate the anti-emetic potential Dewi Kenneth (Laboratory Animal Services of a novel compound supplied by GlaxoSmithKline. Centre) P.L.R. Andrews* (MD06526) 30 June 2007 CUHK Research Committee Funding (Direct Profiling of Emetic Potential of Novel Compounds Grants) RUDD John Anthony CHENG Jun* Motor disorders of the gastrointestinal tract are very 1 October 2006 common Organon Laboratories Ltd pathophysiology. and have a poorly understood Interstitial cells of Cajal have recently been identified as pacemaker cells for Current drug therapies to treat disorders of the central contractile activity of the gastrointestinal tract. nervous system may be associated with nausea and These cells generate the electrical ‘slow-wave’ emesis. The project aims to profile novel drugs to activity that determines the characteristic frequency identify characteristics predicting side effects prior to of phasic contractions of the stomach, small intestine, clinical testing. and colon. (MD06997) and velocity of propagation of peristaltic activity, and Slow waves also determine the direction they are in concert with the enteric nervous system. Evaluation of the Potential of a Novel Compound In the proposed studies, we will investigate the to Inhibit Cisplatin-Induced Acute and Delayed functional networking of interstitial cells of Cajal Emesis cells in age matched senescence-accelerated (SAMP8) and control mice (SAMPR1) using a microelectrode RUDD John Anthony David Manning* array recording system in an attempt to understand 1 February 2007 potential differences that may occur during ageing Albany Molecular Research Inc. with particular reference to the serotonergic and cholinergic system. Complimentary studies will The treatment of cancer using chemotherapeutic also involve an assessment of gastric myoelectric drugs such as cisplatin is associated with severe activity (EGG) and peristaltic sensitivity. It is nausea and vomiting that may discourage patients hoped new from life saving therapy. The project will information necessary for understanding drug action investigate the anti-emetic potential of novel on the gastrointestinal tract and would aid in securing compounds supplied by Albany Molecular Research funding for future studies. Inc. (MD06462) (MD06307) Faculty of Medicine 364 that the studies would provide Dept of Pharmacology A Study of Gi/o Proteins as Neuroprotective cardiovascular system as a vasodilator and as an Agents inhibitor of cytokine production during sepsis, acting via the ghrelin receptor (GRLN-R). We have shown WISE Helen WONG Yung-hou* that the truncated GRLN-R polypeptide (GHS-R1b) 1 September 2006 acts as a dominant-negative mutant and decreases the cell Research Grants Council (Earmarked Grants) surface expression of GRLN-R when co-transfected into human embryonic kidney 293 The neuronal cells of the dorsal root ganglia (DRG) cells. are an extremely useful model system to study the HEK 293 cells with GRLN-R and prostanoid factors which control the growth and regeneration of receptors can also decrease cell surface expression of neurites. Nerve growth factor (NGF) is one such GRLN-R, possibly by the formation of heterodimers. neurotrophic factor which appears to use components We propose to determine the physiological relevance of G protein-coupled receptor signalling pathways to of these interactions by studying the expression of promote neuronal cell survival. GRLN-R, GHS-Rlb and three prostanoid receptors in We have recently We have also shown that co-transfection of identified a unique Gi/o-dependent mechanism in primary cultures DRG neurones which prevents retraction of neurites endothelial and smooth muscle cells. In addition, in response to stress, and in this project, we propose since inflammation can increase GRLN-R expression to examine the relationship between NGF and Gi/o in rat vascular smooth muscle, and since GRLN-R proteins in regulating this neuroprotective response. expression is increased in coronary artery disease, we By better understanding the endogenous mechanisms also in DRG cells which enable them to survive under lipopolysaccharide on the relative expression of these stressful conditions, we should become closer to proteins. producing better therapeutic agents for the treatment (MD06331) propose of to human investigate coronary the artery effect of of spinal cord injuries and neurodegenerative disorders. Modulation of CYP Enzymes Activities and Drug (CU06516) Transporters by Isolated Components of Salvia Miltiorrhiza : A Screening Protocol for Herb-CYP Interaction Potential Regulation of Receptor Expression in Human Endothelial Cells and Vascular Smooth Muscle YEUNG Hok Keung John Cells in Response to LPS Challenge 1 October 2006 WISE Helen CHENG Cho Chak (Biochemistry Research Grants Council (Earmarked Grants) (Science))# This study will investigate the effects of Danshen 1 May 2007 (Salvia miltiorrhiza), a commonly used herb listed in CUHK Research Committee Funding (Direct the Grants) Chinese Pharmacopoeia for treatment of cardiovascular diseases, on the activities of CYP The hunger hormone ghrelin has recently been isoforms (1A2, 1B1, 2C9, 2D6, 2E1 and 3A) and proposed to have an additional role in the drug transporters such as P-glycoprotein (Pgp) and 365 Faculty of Medicine Dept of Pharmacology 2005-06 Biological Characterization of a Herbal multi-drug resistance-associated protein 2 (Mrp2). The crude extract of Danshen, the water-soluble and Hair Tonic (MD05337) lipid-soluble fractions, and individual, chemically KWAN Yiu Wa defined active components are studied for their 2005-06 Mechanisms herb-drug interaction potentials in in vitro systems Responsible for the including sub-cellular fractions, cDNA expressed Enhanced specific CYP enzymes and isolated rat and human Lipolysis of Omental Adipocytes of hepatocytes. Obese Chinese Subjects (MD05656) The combined in vitro and in vivo KWAN Yiu Wa protocols developed in this study will be a useful screening tool for studying other β3-Adrenoceptor-Mediated NGAI Sai Ming (Biology) YU Almon* herb-CYP interactions and contribute to the advancement of 2005-06 Pre-Clinical Evaluation of Combination research, development and safe use of Traditional Chinese Medicine. Therapy for the Treatment of Arthritis (CU06517) (MD05651) LAM Fu Yuen Please refer to previous issues of this publication 2003-04 Interaction between Nitric Oxide and for more details of the following ongoing research Human Mast Cells (CU03337) at the department: LAU Hang Yung Alaster Edition Yu (Physiology) Title/Investigators HUANG WONG Chun Kwok (Chemical Pathology) 2005-06 Cyclooxygenase-2 and its upstream 2005-06 Characterization of Mast Cells from signal transduction mediators in the promotion of gastric cancer development Suncus Murinus: A Preliminary by cigarette smoke (MD05855) Investigation into the Roles of Mast Cells CHO Chi Hin Chu Kent Man* in Emesis (MD05922) LAU Hang Yung Alaster 2002-03 The Role of Nitric Oxide RUDD John Anthony and Mitogen-Activated Protein Kinase in Mediating Inhibition by b3-Adrenoceptor Activation of Voltage-Dependent L-type Channels the of 2002-03 Investigation Materials LIN Ge Single Ken (Anatomy) GAP Standard LI Songlin# CHUNG LIU Wing Keung 2005-06 Investigation TSUI Kwok Wing of the Pyrrolizidine (Biochemistry (Medicine)) Chinese Faculty of Medicine with Herbal Hoi Sing# Ventricular myocytes (CU02166) KWAN Yiu Wa Chuanxiong (MD02951) Calcium Guinea-pig of 366 Medicinal Toxicities of Alkaloid-containing Herbs and the Dept of Pharmacology RUDD John Anthony HO WM* Alternative Plant Sources for These Herbs (CU05526) LIN Ge Peter P. FU* 2002-03 Growth ZHAO Hormone Secretagogue Receptors: Cell Signalling and Receptor Zhongzhen* Oligomerization (CU02267) WISE Helen 2004-05 Defining the Pathways Involved in Acute and Delayed Chemotherapy-Induced Christopher Emesis and the Roles of Tachykinins and (Medicine)) CHENG Hon Ki (Biochemistry Glucocorticoids (MD04967) RUDD John Anthony 2004-05 Mapping Signal Transduction Networks By a Genomic Approach (BL03768) WISE Helen IP Y Nancy* TSIM 2005-06 Broad Spectrum Anti-Emetic Potential of Olvanil in the Ferret (CU05527) RUDD John Anthony Karl W K* P.L.R. 2005-06 The Andrews* Interaction between Growth Hormone Secretagogue Receptors in the 2005-06 Potential Involvement Glucagon-Like of Peptide-1 Control of Cell Survival and Cell Death the (MD05719) (GLP-1) WISE Helen System in Emesis Control (MD05448) RUDD John Anthony LIN Ge Christopher CHENG Hon Ki (Biochemistry (Medicine)) LUI Grace* KUNG Kenny* 2005-06 Anti-Emetic Investigation of Compound A in High Dose and Low Dose Cisplatin Models of Emesis in the Ferret (MD05720) 367 Faculty of Medicine School of Pharmacy Method: Rat Experiment (randomized controlled RESEARCH PROJECTS design) will be carried out. Antiviral and pharmacokinetics of the active metabolite following oseltamivir with and without CM formulae will be Quality Assurance Test on Drug Tablets determined. (MD06300) CHOW Hee Lum Albert LAM Siu Ling 27 December 2006 Emerging Opportunities in Hong Kong Hospital Hong Kong Baptist University System Quality assurance test on drug tablets (Gliclazide, Metformin, Paracetamol and Ranitidine) according to LEE Wing Yan Vivian the British Phannacopeia 2005 Protocol. 1 May 2007 (MD06735) Pfizer (US) Co., Ltd Interaction of Oseltamivir and Chinese Medicine In Formulae commissioned the School of Public Health of the late 1997, the Hong Kong government Harvard University to study Hong Kong’s healthcare CHOW Sing Sum Moses Paul (Microbiology) system and to propose alternative options to improve CHAN Kay Sheung ZUO Zhong its financing and delivery of healthcare. Three major CHAN areas Yan Keung Thomas (Medicine & Therapeutics) of weakness were identified: 1) CHE Chun Tao (School of Chinese Medicine) compartmentalization in the delivery of services; 2) JAMES Anthony Edward (Laboratory Animal variable quality of care particularly in the private sector; Services Centre) and 3) questionable financial and organizational sustainability. The report proposed 15 January 2007 alternative options to improve the financing and Hong Kong Hospital Authority delivery of healthcare. As a result, the healthcare for financing system will be modified and changed in the prevention and treatment of avian influence by the next decade. These modifications will definitely have Hospital Authority (HA). In addition, HA’s Expert an impact not only on the healthcare sector but also Panel on Chinese medicine has recommended 4 on the business sectors, such as, pharmaceutical and specific Chinese medicine (CM) formulae for the insurance industries. prevention and treatment of avian influenza in The objective of this project is to conduct an conjunction with western medicine (WM). In view information synthesis of the available data sources of lack of information on such combination, the for health services research purposes in Hong Kong. present proposal aims to determine the potential Identification of such data sources should encompass, interaction of oseltamivir in combination with 2 but not be restricted to, local language publications, specific Chinese medicine (CM) formulae in animals. abstract and peer-reviewed articles, internet searches, Objective: Oseltamivir is recommended as well as data held by or available through interviews with Key Opinion Leaders in Health Faculty of Medicine 368 School of Pharmacy Services Research / Outcomes Research / Health warfarin doses and the doses calculated by the economics / Pharmaco-Economics area. algorithm in another cohort of 50 patients stable on (MD06517) warfarin therapy recruited in the anticoagulation clinic. Is Clinical Translation of Pharmacogenetics Significance: Based upon the effect size of the Possible in Anticoagulation Therapy? genetic variants (in addition to the clinical and demographic information), more accurate dosing YOU Hoi Sze Joyce ZUO Zhong Gregory (Medicine & Therapeutics) CHENG algorithm can be developed for computerized dosing WAYE programs for initiation of warfarin therapy and dosage adjustment during therapy, and potentially Mary Miu Yee (Biochemistry (Medicine)) lead to reduction in long-term cost and improvement 1 January 2007 in anticoagulation control of warfarin therapy. Research Grants Council (Earmarked Grants) (CU06519) Background: Chinese patients require almost a 50% lower maintenance dose of warfarin and are more High-Throughput vulnerable to bleeding complications than Caucasian Transporters Involved in the Disposition of patients. Flavonoid Baicalein using Transfected Cell Line Polymorphisms of genes relating to pharmacokinetics and pharmacodynamics of Identification of Efflux Membrane Vesicles Systems warfarin both contribute to the variation in warfarin dosing and sensitivity. ZUO Zhong LIN Ge (Pharmacology) Objectives: To evaluate the effect size of genetic 1 June 2007 variants of VKORCI, Factors II & VII, GGC, and CUHK Research Committee Funding (Direct CYP2C9 on warfarin dosing requirement in Hong Grants) Kong Chinese patients and to develop and validate a warfarin dosing algorithm based on genetic, clinical Flavonoids are polyphenolic phytochemicals present and demographic information. extensively in our daily diet, medicinal plants and Methods: In this 24-month cohort study, genotyping herbal remedies. of the target genes will be conducted in 200 patients extensive on stable maintenance dose of warfarin, recruited glucuronidation, methylation and sulfation) followed from the anticoagulation clinic of the Prince of Wales by active efflux in the small intestine is involved in Hospital. Clinical and demographic data will also the poor absorption of flavonoids. be collected. Multiple linear regression model extensive research has been conducted for the including genetic, clinical and demographic factors metabolic mechanism of flavonoids, the efflux will be constructed for normalized maintenance dose transporters of the formed glucuronides and sulfates to determine the effect size of each factor. Factors are barely studied mainly due to the lack of fast that are significantly associated with warfarin dose screening approach for the enrolled transporters. will be considered in a stepwise regression model to With the recently developed high through put compute the stable warfarin dose. The dosing screening approach using in vitro transfected cell line algorithm will be validated by comparing the current membrane vesicles systems, its application on the 369 Phase It has been suggested that the II metabolism (mainly Even though Faculty of Medicine School of Pharmacy glucuronides and sulfates of flavonoids and other 2005-06 Preliminary Feasibility Testing of the related naturally occurring components become Rapid Mucosal Delivery of Meloxicam feasible. and Meclizine (MD05892) and Based on our extensive biopharmaceutic pharmacokinetic research experience CHOW Sing Sum Moses on ZUO Zhong WANG Yanfeng flavonoids, baicalein was selected as the model compound. We aim to 1) prepare the glucuronides and sulfates of baicalein using in vitro enzymatic 2005-06 Development of an In-Vitro Method for incubation system; and 2) investigate the specific Achieving Rapid Sublingual Delivery - transporters (including MRPl, MRP2, MRP3, MXR Application and MDR1) involved in the efflux of these (MD05529) glucuronides and sulfates using the in vitro high CHOW Sing Sum Moses to Analgesic Agents ZUO through put approach by transfected cell line Zhong membrane vesicles. The proposed study will set as a (Anaesthesia & Intensive Care) pilot study for the in vitro high throughput screening TOMLINSON Brian (Medicine & for the transporters involved in the disposition of Therapeutics) JOYNT Gavin Matthew flavonooids in vivo so as to use flavonoid-containing 2004-05 Synergistic TCM products more efficiently and also predict Interaction between potential transporter-based herb-drug interactions. Platinum-Based Antitumor Agents and (MD06854) Demethylcantharidin, a Modified Traditional Chinese Medicine (CU04357) HO Yee Ping Please refer to previous issues of this publication AU-YEUNG Chik Fun Steve (Chemistry) for more details of the following ongoing research at the department: 2005-06 The Edition Anti-Leukemia Immunomodulatory Title/Investigators Agaricus 2004-05 Aqueous-Aqueous Emulsion LEUNG ZUO FUNG Kwok K N (Biochemistry 2005-06 Cost-Effectiveness of Pneumococcal (Science)) 2005-06 Extended Service of Stability Study (2 Vaccination for Infants with the 7-Valent year) (MD05383) Pneumococcal Conjugate Vaccine In LAM Siu Hong Kong: Analysis with the Markov Ling Process (MD05386) Faculty of Medicine of Extracts Pui (Biochemistry (Medicine)) Zhong CHOW Hee Lum Albert Murill LAU Bik San Clara for Sustained Release (MD04857) Activities (CU05531) for Microencapsulation of Delicate Proteins CHOW Hee Lum Albert Blazei and 370 School of Pharmacy LEE Kwing Chin Kenneth Kam Lun (Paediatrics) HON (Biochemistry CHENG LEE Wing Gregory (Medicine & Therapeutics) Yan Vivian 2005-06 Economic (Medicine)) Impact of 2005-06 Isoflavone Therapy for Patient with Substituting Lamivudine with Entecavir in Chronic Watchful Hepatitis B Patients in the Public Health Hyperlasia - A Cost-Utility Analysis Care Sector of Hong Kong (MD05886) (MD05680) LEE Kwing Chin Kenneth YOU Hoi Sze Joyce LEE Waiting Benign Prostate Wing Yan Vivian 2005-06 Role of Interplay between UGT Isozymes and MRP Transporters in the Oral 2004-05 The Role of 5' - Flanking Region Polymorphisms of CYP2C9 on Warfarin Absorption of Baicalein (MD05602) Metabolism in Chinese Patients - Is it the ZUO Missing Link? (MD04361) Zhong LIN Ge (Pharmacology) YOU Hoi Sze Joyce ZUO Zhong WAYE Mary Miu Yee 371 Faculty of Medicine Dept of Physiology 未知功能的新基因和蛋白研究 RESEARCH PROJECTS 在前項 973 項目“生殖健康基础研究”初期中,本課 題組分離鑒定了 128 條與睪丸發育/精子發生/精子 成熟/精子功能相關的基因,在對其中部分基因的 Epithelial Cell Biology Research Center 功能進行研究的過程中,建主了一系列研究精子功 CHAN Hsiao Chang 能的技術平台。本課題將在此基础上,繼續對上述 LI Ming (Epithelial Cell 克隆的新基因進行其功能研究。此外,在前項 973 Biology Research Centre) ZHOU Zhen 項目研究後期,本課題組已運用蛋白質組學技術分 1 August 2006 析了人睪丸組織和小鼠睪丸組織的蛋白質表達,並 Focused Investments Scheme - Major Area of 構建了人睪丸 1415 個蛋白的譜系,分離鑒定到了 Biomedical Sciences 一批與精子功能相關的蛋白,其中還包括正常睪丸 The Epithelial Cell Biology Research Centre 與生精紊亂睪丸及热作用睪丸差異表達蛋白。根據 (ECBRC), the first of its kind promoted and 其表達特點和功能研究情況,這些蛋白可以分為以 supported Science 下四類﹕已知的精子功能蛋白;己知在體細胞中功 Foundation of China (NSFC), was established in 能,但在子精子中未知功能的蛋白;GenBank 中已 1999 institutions 克隆但没有相關能研究的蛋白質,主要包括以 throughout China. With substantial support from the KIAA 命各的假想蛋白;不同修飾的同一種蛋白。 University, ECBRC will further develop its existing 以上述未知功能的蛋白和已克隆的新基因同時作 strengths, infrastructure and research capabilities to 為研究的起點﹕深入探討其在精子運動。精子獲。 establish a word class multidisciplinary center for 頂體反應能、精卵識別和精卵融合等一系列事件的 epithelial cell biology research. 作用,肧時開展精子功能相關蛋白表達障礙與生殖 (MD06743) 疾病的研究,闡明其在精子功能障礙中的分子機 with by the over National 20 Natural collaborating 理。 精子功能相關蛋白質與疾病 已知體細胞功能而未知精子功能的基因和蛋白研 Sperm Function Related Protein and Diseases 究在精子功能蛋白中,有一類蛋白同時也在體細胞 中表達,而且,其中部分蛋白已知其在體胞中的功 許陳小章 CHAN Hsiao Chang 能,我們能够根據這些功能信息應用於精子功能的 DUAN En 研究中。以 CFTR 為例,本課題組長期以來玫力於 Kui* SHA Jia Hao* ZHANG Yong Lian* 研究 CFTR 在生殖系統中的作用,証實了 CFTR 在 1 September 2006 女性生殖道的表達並在子宮內膜中直接參與了 National Basic Research Program of China - 973 HCO3 的轉運。此外,CFTR 介導的女性生殖道上 本課題以已建立的功能基因組研究技術、蛋白質組 皮 HCO3 分泌受損可導致精子獲能以及受精能力 學研究技術、精子功能研究技術和上皮細胞研究技 的低下,提示該現象能是女性不育的一個重要病 術,深入研究精子功能相關基因和蛋白 (包括未知 因。CFTR 直接參與了子宮內膜 HCO3 的轉運,那 功能的基因和蛋白和已知體細胞中功能而未知精 麼它有没有可能也參與介導精子獲能所需要的 子功能的基因和蛋白) 在精子運動、精子獲能、頂 HCO3 轉運呢?進一步研究我們發現 CFTR 在人和 體反應、精卵識別和精卵融合等一系列事件中的作 小鼠精子有表達。因此我們提出以下假設﹕精子膜 用。 上 CFTR 介導精子獲能所需的 HCO3 轉運,而 CFTR Faculty of Medicine 372 Dept of Physiology 基因缺陷會影響精子受精能力的獲得,並引起不 and paracrine proteins with important roles in 育。為了驗証這一假說,我們將分別以離體和在體 metabolism 的水平,對 CFTR 在正常生育男子和各種病因引起 Dysfunction of protein secretion by adipose tissue 的男性不育症精子細胞的表達及其對精子膜上 has been reported in obesity-related diseases, such as CFTR 參與介導 HCO3 轉運的可能性及具體機制進 diabetes mellitus, hypertension, atherosclerosis and 行深入研究。 coronary artery disease. Thus, adipocytes seem to 除此之外,在前期研究所建立的精子功能相關蛋白 play crucial roles in the development of metabolic 表達譜系中,我們還發現一類特殊的蛋白,它們不 syndrome and vascular disease. 僅在譜系中特異高表達,也有文獻表明在一些腫瘤 between obesity, insulin resistance and hypertension 組織中高表達,而在其他正常組織没有表達,這類 is 蛋稱為 CT(Cancer/Testis) 抗原。其實腫瘤發生和 mechanisms involved remain relatively unclear. 配子發育,尤其是精子發生/精子功能之間存在很 Circulating 大的相似性,比如血管形成。廣泛低甲基化以及 identified CT 抗原的表達等。目前已有 47 個 CT 抗原,其中 predominantly from the fat cells are reduced in 部分部抗原已被証實與腫瘤發生發展和精子發生 obesity and type 2 diabetes. 及其功能的發揮密切相關。而如何解釋腫瘤發生和 demonstrate several biological actions of adiponectin 配子發育之間的相似性則要依賴於對兩者基因和 against the development of inflammation, diabetes, 蛋白調節水平的具體研究,因此對 CT 抗原的功能 and 研究有助於了解兩者的共性。本課題組擬運用精子 adiponectin 功能研究平台,開展這部分蛋白與精子功能及生殖 cardiovascular 疾病相關的研究,不僅可以拓展補充 CT 抗原數據 understanding of adiponectin signaling network 庫,有助於闡述腫瘤發生以配子發育之間的共性, among adipocytes, insulin sensitive tissue and 同時也能更深入闡明精子功能。 vascular function should lead to novel strategies for (MD06646) the early intervention and treatment of obesity, well and cardiovascular recognized, levels of however atherosclerosis. may Thus, serve risk The relationship the adiponectin, insulin-sensitizing as function. molecular a recently hormone secreted Recent studies adipocyte-derived another biomarker. diabetes and related vascular complications. useful Better This Adiponectin and Periadventitial Regulation of project is directed at understanding the role of Arterial Tone abdominal fat in the development of chronic vascular disease and will lead to the development of the novel HUANG Yu WONG Jack* concept that periadventitial adipocytes play a role in LEUNG Fung vascular dysfunction. Ping WONG Christine* LAU Chi Wai Along with changes in endothelial function, this may be responsible for the 29 June 2007 increased cardiovascular risk in obesity, diabetes, and CUHK Research Committee Funding (Direct hypertension. Grants) This proposed study will primarily focus on the role of adipocyte-derived adiponectin as Obesity, especially central obesity, is the most an important paracrine regulator of vascular tone. common nutritional disorder in industrial countries The results will offer unique insights into the and it is associated with increased cardiovascular mechanisms by which abdominal obesity is one of morbidity and mortality mainly through insulin the leading risk factors for chronic vascular disease resistance. Adipose tissue secretes many endocrine and hypertension. 373 Abnormalities in the responses Faculty of Medicine Dept of Physiology of both conduit and resistance vessels to adiponectin treatment and might also lead to novel therapeutic in obesity and diabetes will be investigated by approaches to improve the clinic treatment of PD studying the regulation of vascular reactivity using patients. well-established mouse models of obesity and (MD06770) diabetes. (MD06483) Investigation of Cell-Specific Functions of the Clear Cells in the Epididymis in Relation to Acid Effects of L-DOPA on DMT1-Mediated Iron Secretion Uptake by Neurons WONG Patrick Yee Ding KE Ya 1 August 2006 30 June 2007 Research Grants Council (Earmarked Grants) CUHK Research Committee Funding (Direct It has been known for a long time that the fluid inside Grants) the epididymis of many species including man has a The mechanisms of the neurotoxicity caused by very different composition compared to blood plasma. L-DOPA treatment of Parkinson’s disease (PD) are The Na+ concentration decreases but that of K+ unknown although L-DOPA is still the most effective increases as the fluid flows through the epididymal treatment for PD currently. Recently, we found that tubule. At the same time, the H+ ion concentration treatment of C6 cells with L-DOPA induced a rises (pH decreases). An acid environment inside the significant increase in DMTl(-IRE) expression and epididymis is thought to prevent premature activation ferrous uptake. Based on this finding and other of the biochemical events that lead to fertilization and available data, we therefore hypothesized that is therefore crucial in maintaining spermatozoa in a changes in brain iron metabolism induced by viable state during storage. Understanding the L-DOPA might be partly associated with the mechanisms secretion L-DOPA induced-neurotoxicity. epididymis has far-reaching implications for human To confirm this hypothesis, a detailed analysis on the reproduction. To date, our knowledge of the causes relationship between L-DOPA and iron transport in of male infertility is scanty. neurons in vitro and in vivo is necessary. abnormal pH of the epididymal fluid caused by As the underlying the the It is possible that genetic to determine whether L-DOPA can significantly environmental factors may have a role to play in some increase in the expression of DMT1(-IRE) and forms of unexplained infertility. DMTl-mediated iron uptake in neuronal cells in vitro. processes by which acid is secreted into the lumen of To my knowledge, the proposed study is the first the epididymis could help devise ways to treat investigation on the relationship of L-DOPA with infertility caused by abnormal acid-base transport in the DMT1 expression and iron transport in neurons. epididymis. The other side of the coin is that it may The study will provide a key insight into prove possible to interfere with acid secretion as a understanding the pathophysiological relevance of novel way to interfere with fertility. In this project, iron metabolism for toxicity during L-DOPA we propose to take a novel approach by isolating clear 374 of by first step, experiments in this project will be designed Faculty of Medicine mutations acid requisite genes or Unraveling the Dept of Physiology cells (cells responsible for acid secretion) from the rat CNGA2 in the endothelium-dependent vascular epididymis and applying electrophysiology and dilation in response to cAMP-elevating agents. This cellular physiology techniques on them with a view to proposal aims at clarifying the functional role of understand and CNGA2 channels in endothelial cell Ca2+ influx as the well as endothelium-dependent vascular dilatation in the physiological underlying control of mechanisms acidification of epididymal fluid. response to cAMP-elevating agonists. The results (CU06525) from this study should provide novel information of how CNGA2 and its related signal cascade contribute Functional Role of Cyclic to the control of endothelium-dependent vascular Nucleotide-Gated CNGA2 Channels in cAMP-Regulated Ca2+ function. Influx in Endothelial Cells (CU06526) YAO Xiaoqiang Possible Role of Polycystin 1 and Polycystin 2 in KUNG Hsiang Fu (Stanley Ho CEID) Flow-Induced Vascular Dilation 1 January 2007 YAO Xiaoqiang Research Grants Council (Earmarked Grants) 1 March 2007 cAMP-elevating agonists have diverse effect on CUHK Research Committee Funding (Direct endothelium-dependent vascular functions such as Grants) vascular tone control, vascular wall remodeling, vascular cell proliferation and vascular permeability The regulation. At least in some cases, the effect of these endothelial cells to release nitric oxide (NO), 2+ hemodynamic force stimulates vascular agonists depends on Ca influx into endothelial cells. endothelium-derived hyperpolarization factor (EDHF) We have previously found the expression of a cyclic and prostacyclin (PGI2). These factors then act on nucleotide-gated channel CNGA2 in human vascular the endothelial cells in situ and in mouse heart microvessel vasodilatation and thus lowering blood pressure. Up endothelial H5V cells in culture. Functional studies to the present, however, the mechanism of how flow indicate that CNGA2 mediates endothelial cell Ca2+ leads to the vasodilatation is still unsettled. influx in response to 8-BrcAMP, adenosine and Interestingly, Recent studies from the principal adrenaline. These results suggest a general role of investigator’s lab strongly suggest that flow may CNGA2 functions induce dilatation in a Ca2+-dependent manner. In this These results provide a new mechanistic clue as to proposal, we plan to dissect the signal transduction how flow could lead to vascular dilatation, because a pathway of how adenosine and β-adrenergic agonists rise in endothelial cytosolic Ca2+ is expected to lead to the activation of CNGA2 channels. We will stimulate the activity of endothelial nitric oxide also determine whether CNGA2 may contribute to synthase (eNOS) and phospholipase A2 (PLA2), two in endothelium-dependent associated with cAMP-elevating agents. 2+ endothelial Ca influx in response to two other underlying key enzymes smooth muscle cells, causing that control the production of cAMP-elevating agents CGRP and adrenomedullin. endothelium-derived vasodilatory agents including Furthermore, we will explore the possible role of NO, PGI2 and EDHF (Busse et al. 2003). In this 375 Faculty of Medicine Dept of Physiology proposal, we will explore whether polycystin Please refer to previous issues of this publication 2+ l-polycystin2 complex mediate flow-induced Ca for more details of the following ongoing research influx at the department: and subsequent vascular dilation. Identification of the molecules responsible for flow-induced Ca2+ influx should provide biochemists Edition Title/Investigators and pharmacologists with a real molecule to target against hypertensive diseases 2003-04 Investigation of the Role of a Novel (MD06941) Epididymis-Specific Gene, Bin-1b, in Sperm Maturation (CU03365) Mechanisms Underlying Late-phase Long-Term the Regulation Potentiation of CHAN Hsiao Chang by ZHANG Yong Lian* Brian-Derived Neurotrophic Factor 2005-06 Effects of an Epididymis-Specific YUNG Wing Ho PANG Petti* Defensin, Bin1b, on Sperm Fertilizing 1 October 2006 Capacity in vitro and in vivo (CU05534) Research Grants Council (Earmarked Grants) CHAN Hsiao Chang The ability to memorize is arguably one of the most important functions of the brain. 2004-05 Effects of Selective Estrogen Receptor Long-term Modulators on Coronary Artery memory is believed to be mediated by the protein Reactivity synthesis-dependent cellular phenomenon known as Ovariectomized Rabbits (CU04362) late-phase long-term potentiation (L-LTP). HUANG Yu Our in Cholesterol-Fed, VANHOUTTE Paul recent studies provided evidence that brain-derived Michel Georges* neurotropic factor (BDNF) is a key or the only protein synthesis product required for L-LTP (Science)) YAO Xiaoqiang CHEN Zhenyu (Biochemistry expression. Paralleling the reports that there are two temporally distinct stages in the 2005-06 Cardiovascular Research Programme hippocampus-dependent long-term memory, here we (Basic Division) (MD05313) hypothesize that L-LTP can be divided into two HUANG Yu YAO Xiaoqiang stages: an induction stage and a maintenance stage. CHEN Zhenyu Both stages require BDNF, but are mediated by (Science)) different BDNF signaling downstream pathways. (Anatomy) Results of the present study will unveil the molecular (Stanley Ho CEID) basis of two temporally distinct stages in L-LTP, Hung which is critical in understanding the mechanism of (Pharmacology) LAM Fu Yuen different stages in long-term memory formation. (Pharmacology) HE Guo Wei (CU06527) (Surgery) WAN Song (Surgery) Faculty of Medicine 376 (Biochemistry CHAN Leung Franky KUNG Hsiang Fu KWAN KO Wing Yiu Wa Dept of Physiology 2005-06 Raloxifene Modulation of Myogenic 2005-06 The Pancreatic Islet Renin-angiotensin Tone and Flow-dependent Vasodilatation System and Beta Cell Dysfunction in Rat Resistance Vessels (MD05825) (CU05537) HUANG Yu HENRION Daniel* LEUNG Po Sing KWOK Ming Yao* Hugh MONTGOMERY* 2005-06 Role of Adipose-Derived Vasoactive Products in Vascular Dysfunction 2005-06 Involvement of the local (MD05842) Renin-angiotensin System in control of HUANG Yu GOLLASCH Maik* enterocyte fluid and glucose uptake (MD05331) LEUNG Po Sing ES Debnam* 2004-05 Protective Role of Blockade of the Renin-Angiotensin System with Losartan on Pancreatic b-cell Function and Repair 2005-06 Microenvironment Approach to and its Relationships with Oxidative Enhancing Stress in Impaired Glucose Tolerance and Maturation of Pancreatic Stem Cells into Type 2 Diabetes (MD04976) Insulin-Producing Beta Cells (MD05860) LEUNG Po Sing LEUNG Po Sing Ngor CHAN Chung Juliana (Medicine 2004-05 Regulation Channels of the Renin-Angiotensin of TRPC3 by Protein and TRPC6 Kinase G Phosphorylation (CU04366) Pancreatic System: and & Therapeutics) 2004-05 Inhibition Differentiation YAO Xiaoqiang Its Regulatory Mechanism for Pancreatic CHAN Tak Wah Dominic (Chemistry) Microcirculation, Oxidative Stress and Cytokine-Mediated Inflammatory 2005-06 Flow-Induced Endothelial Production of Response in Pancreatitis (CU04364) H2O2 and Its Relationship with Ca2+ LEUNG Po Sing IP Siu Po (School Influx in Endothelial Cells (MD05415) YAO Xiaoqiang of Chinese Medicine) 2004-05 Evaluation of Potential 2003-04 The Neurotrophic Action of Secretin in Synergistic Effects of Valsartan Combined with the Developing Cerebellum (MD03619) GLP-1 or LAF237 on Pancreatic Islet YUNG Wing Ho Function, Endothelial Function and Shing* Glucose Tolerance in Type-2 Diabetes CHAN Ying CHOW K C Billy* WANG Jian Jun* Mellitus (MD04711) LEUNG Po Sing 2005-06 Mechanisms Underlying the Regulation CARLSSON of Late-Phase Long-Term Potentiation by Per-Ola* Brain-Derived Neurotrophic Factor (MD05834) 377 Faculty of Medicine Dept of Physiology YUNG Wing Ho Faculty of Medicine 378 Dept of Psychiatry Is the Hippocampal Volume an Independent RESEARCH PROJECTS Predictor of Delayed Dementia Following an Ischemic Mood and Somatic Conditions: A Prospective Magnetic Resonance Imaging Study Psychometric Analysis of Neurasthenia and Its Related Stroke? A TANG Wai Kwong Comparative Study on Chinese in Different LAM Chiu Wa WONG Ka Sing Lawrence (Medicine & Therapeutics) Cultural Settings LAM Wai Man Wynnie (Diagnostic Radiology CHIU Fung Kum Helen & Organ Imaging) WONG Kit Ching (Psychology) YIP Siu Fai Paul* 1 January 2007 1 July 2006 Research Grants Council (Earmarked Grants) The Second Xiangya Hospital of Central South Dementia affects 7% of the general population older University than 65 (Lobo et al. 2000). Vascular dementia The present study aims to investigate the construct of (VAD) is the second largest cause of dementia neurasthenia, a clinical syndrome of mental fatigue worldwide and may be the commonest cause of and exhaustion, in different cultural settings, by way dementia of psychometric and clinical approach. It seeks to Poststroke dementia (PSD) is one example of VAD, identify the distinctive characteristics of neurasthenia, which occurs in up to a third of stroke survivors as well as its relationship with other related mood and (O'Brien et al. 2003). somatic conditions. Medial temporal lobe consists of parahippocampal A battery of self-report in Asian populations (Chen 2004). measures and a newly developed Neurasthenia Scale gyrus and hippocampus. will be used for comparison between Chinese and atrophy (MTLA) is strongly associated with VAD. Western adults in three different cultural settings, The aim of our study is to evaluate if hippocampal namely Hong Kong SAR, Mainland China and volume (HC) predict the development of dPSD in Australia. Participants will be adults who are living 700 local Chinese patients with first or recurrent in the community, parents of Chinese school students, stroke who receive treatment in the Acute Stroke Unit or participants of public lectures. of the Prince of Wales Hospital over 24 months. They will be Medical temporal lobe A asked to complete a set of questionnaires with a total magnetic Resonance Imaging (MRI) examination of 7 scales and a cover sheet on personal information. will be performed within the first 7 days admission. Descriptive and inferential statistics will be applied A radiologist, who is blind to the psychiatric for diagnosis, will measure the HC. examining the sample characteristics comparison of group differences. and assistant Factor analyses will administer detailed A research cognitive for ascertaining the validity and reliability for applied examination and a psychiatrist will diagnose PSD scales and measures will also be conducted. three months after the index stroke, then annually. (MD06893) The HC will be compared between patients with and without dPSD. In addition, other putative risk factors for dPSD will be examined. (CU06529) 379 Faculty of Medicine Dept of Psychiatry Please refer to previous issues of this publication A Pilot Study on the 5-Hydroxytryptamine 1A for more details of the following ongoing research Receptor Gene Polymorphism in Post-Stroke at the department: Fatigue Edition TANG Wai Kwong TANG Leung Sang Nelson (Chemical Pathology) WONG Ka Sing Lawrence (Medicine & Therapeutics) 2005-06 Cerebrovascular LAM Risk Factors and Late-Life Suicide (MD05630) Wai Man Wynnie (Diagnostic Radiology & Organ Imaging) Title/Investigators CHAN Sau Man Sandra MOK Chung Tong Vincent Fung Kum Helen (Medicine & Therapeutics) CHIU LEE Wai Chi Edwin* 30 June 2007 2004-05 To Establish a Functional Enhancement CUHK Research Committee Funding (Direct Program Grants) for the Improvement of Emotional and Functional Well Beings of Poststroke fatigue (PSF) is a common distressing Demented Elders (MD04494) condition among stroke survivors and it adversely LAM Chiu Wa affects their quality of life. Serotonin dysfunction is Victor* found KO Flora* in patients with chronic fatigue. 5-Hydroxytryptamine 1A receptor plays an important LUI Wing Cheong CHAN Sau Man Sandra LEUNG Pui Yiu Vivian* role in the regulation of serotonin activity in the brain. Hence the 5HT1A gene may be influential in PSF. 2004-05 Diffusion Weighted Magnetic Resonance The effect of this gene on the risk of developing PSF is Imaging Correlates of Depression after unknown. Acute The objective of this study is to examine the role of the Population (CU04369) 5HT1A TANG Wai Kwong gene variants (polymorphisms) the Ischemic Stroke in Chinese WONG Ka development of PSF in a group of stroke survivors. Sing Three hundred Chinese patients with stroke will be Therapeutics) evaluated. Three months after their index stroke, a Wynnie (Diagnostic Radiology & psychiatrist will assess PSF. Blood samples will be Organ Imaging) collected and different variants of 5HT1A gene will Sandor Lawrence (Medicine & LAM Wai Man UNGVARI Gabor be analysed. In addition, a host of demographic, clinical and brain imaging characteristics will be 2004-05 Emotional Incontinence in Stroke: collected. The distribution of the variants of genes in Testing the Prefrontal Cortex Hypothesis patients with and without PSF will be compared, after (MD04988) controlling the possible confounding variables. TANG Wai Kwong (MD06316) CHAN Sui Yin Agnes (Psychology) WONG Ka Sing Lawrence (Medicine & Faculty of Medicine 380 Dept of Psychiatry Therapeutics) 2005-06 Mental Health Impact of SARS to LAM Wai Man Wynnie (Diagnostic Radiology & Patients: Organ Imaging) (MD05335) UNGVARI Gabor A Prospective WING Yun Kwok Sandor Study LEUNG Chi Ming 2005-06 The "Hidden Client" - Carers of Patients with Pneumoconiosis: Psychiatric 2005-06 A 3-Month Epidemiological Study to Morbidity, Quality of Life, Burden of Establish Care and Service Needs (MD05947) Patients with Acute Major Depressive TANG Wai Kwong Disorder (MD05503) UNGVARI Characteristics WING Yun Kwok Gabor Sandor of Asian KWONG Wai Man* FONG Yat Yuk Samson 381 Faculty of Medicine School of Public Health round postal Delphi survey amongst Chinese and RESEARCH PROJECTS western healthcare professionals will be conducted to achieve a consensus based policy framework for Self Management and the Role of Pharmacists in self-management. Developing an Effective Primary Care System : Outcome: Developing a Consensus Based Policy Framework 1. Updated, sequential analysis of self management and medication prevalence amongst Hong Kong YEOH Eng Kiong (Community and Family Medicine) Chi Ho* Cindy* population; GRIFFITHS Sian Meryl (School of Pharmacy) 2. CHUNG Attitudes of primary care doctors and pharmacists LAM Lo Kuen in both Chinese and western medical professions YOU Hoi Sze Joyce towards effective patient self management and LAU Chun Hong LI Donald* development of the role of pharmacists; MERCER Stewart 3. Attitudes of the public towards self management LAM Tai Pong* CHAN Wan Kin (Community and the proposal of the roles of pharmacists in and Family Medicine) primary care; and William (Community and Family Medicine) 4. 1 June 2007 framework for developing self management in Food and Health Bureau - Studies in Health primary care, for chronic non communicable Services diseases. Objective: To develop a consensus based policy framework A consensus based, locally relevant policy for self-management of (MD06405) chronic non-communicable diseases in primary care. Please refer to previous issues of this publication Design: The study will include both quantitative and for more details of the following ongoing research qualitative elements. Firstly, the current practice of at the department: self-medication amongst Hong Kong population will be described by analyzing data from Thematic Edition Title/Investigators Household Surveys (THS), which are census scale datasets including self medication pattern and other 2003-04 Promotion of Evidence Based Nursing factors like health status and pattern of health service Practice (MD03828) utilization. THOMPSON The analysis will be used as the basis of Chun Robert focus group discussion amongst Chinese and western CHAU medicine profession. Nethersole School of Nursing) Findings from the focus groups Pak David Janita (The as well as those from the THS will guide questionnaire construction of a population based telephone survey, 2003-04 A Longitudinal Cohort Study of Burnout which will be utilized to explore the acceptability and and attitude towards pharmacist led self-management using (MD03934) western and Chinese medicines among Hong Kong THOMPSON population. From the inputs of these studies, a two Faculty of Medicine 382 Attrition in Nursing David Students Robert WATSON Roger* DEARY Ian* Centre for Epidemiology & Biostatistics LAU Tak Fai Joseph CHAN Shuk Yee* CUI RESEARCH PROJECTS Tong Kui* MAK Wing Sze Winnie (Psychology) TSUI Hi Yi The Follow-Up Related Study of HIV Infected 1 August 2006 Cases in Shenzhen City in Mainland China National Research Institute for Family Planning LAU Tak Fai Joseph SU Xiaoyou GU Jing A significant number of HIV infections in China are TSUI Hi Yi attributed to commercial plasma donation in Henan, a 6 July 2006 province in central China, ranks second in the total number of reported HIV cases. Shenzhen Centre for Disease Control and It is known that people living with HIV/AIDS Prevention (PLWHA) are more stressed, have more mental HIV infected people go through a series of episode health problems and low quality of life than healthy after people. It is necessary to provide timely assessment being informed about HIV serostatus. According to the previous studies, factors related to and psychological support services to them. dropout during follow up for medical counselling Based on empirical evidence of the study on PLWHA among include who were infected by injecting dug or sexual support, transmission, we assume that mental health of HIV infected stigma/discrimination, lack people of social intravenous drug use etc. PLWHA who were former plasma donors (FPD) is The present study aims to identify factors related to important, alongside with medical treatment and whether returning for CD4 test among the HIV newly behavioral intervention. The study subjects of our confirmed people. study are FPDs and their family members in Henan The study will be conducted from July 2006 to December 2007 in Shenzhen in province. collaboration with the Shenzhen CDC. The objectives of our study include: The study population comprises newly confirmed 1. To investigate the mental health status (e.g. HIV cases who are, for the first time, obtaining the quality of life, depression, post-traumatic growth, confirmative result of their HTV status from etc.); 2. Guangzhou CDC (or district CDC) and Shenzhen To investigate factors that are associated with CDC (or district CDC). The questionnaire will be mental health status (attribution of causes of anonymous. diseases, Specially trained health care workers will seek discrimination, treatment); 3. informed consent from the respondents, administer household structure, perceived To explore the resilience of PLWHA and their the questionnaires and engage in the follow up work. family, as well as to identify vulnerable people (SS06668) with low level of resilience; 4. To investigate relationships between mental A Study on Mental Health and Care in AIDS health and resilience in these PLWHA and their Families in Shanghai, Henan, China family members; 5. To assess the needs for psychological support services of PLWHA; and 383 Faculty of Medicine Centre for Epidemiology & Biostatistics 6. To conduct a randomized control study to A Study of HIV-Related Prevention and Control evaluate the effectiveness of an intervention for in Hengyang, China promoting resilience and mental health. (SS06392) LAU Tak Fai Joseph SU Xiaoyou 30 September 2006 Review on Students’ Progress after Completing the Three-Year Understanding Intensive Adolescent Program Project of Hunan Centre for Disease Control and the Prevention (Primary) Hengyang has the highest HIV prevalence among all (2004/05 to 2006/07) cities in Hunan province, China, and since year 2005 LAU Tak Fai Joseph LAU Man Chun Mason HIV-related interventions launched in Hengyang. 1 September 2006 This study aims to deeply understand HIV-related high risk behaviors and psychological status among Education and Manpower Bureau, HKSAR HIV-related high risk populations and people living Government with HIV and AIDS (PLWHA), to prevent HIV The main purpose of this exercise is to review the transmission from the source population into the progress on the students who joined the three-year general population, and to evaluate the effectiveness Intensive Program of the Understanding Adolescent of MMT and NEP services in HIV prevention. Project (Primary) in around 134 UAP schools for the The study consists of four different parts: study of 2004/05 - Primary 4 students cohort. The baseline HIV-related high risk behaviors among male and measurement was collected when the screening female process conducted from September to December evaluating methadone maintenance treatment (MMT) 2004. They were randomly assigned into 5 clusters services, evaluation of the effectiveness of Needle (Family Anger Exchange Program (NEP), and stress, coping and Management, Goal setting & problem solving and psychosocial problems among PLWHA in Hengyang. Self-esteem & behavioral indicators). The total study will be conducted from Sept. 2006 to expressiveness, Optimism, Questions injecting drug users, monitoring and related to the specify aim of each cluster were asked. May 2009 in collaboration with Hunan CDC. To review the students' progress, a follow-up data The study populations will include male and female collection will be conducted for this cohort when injecting drug users who also have risky sexual these students are in primary 6 in 2006/07 school behaviors, MMT users, NEP users, and PLWHA. year. All target populations will be reached by help of The changes of individual students could be traced to see whether improvements have been made peers and CDC heath workers. after the Intensive Program. A statistical report on interviews will be used to collect data and all the program effectiveness results in all participated questionnaires are anonymous. Special training will schools joining this exercise will be submitted to help investigators to understand the purpose, EMB in October 2007. background and data collection procedures of the (ED06704) study. The participation in the study is completely voluntary. (SS06635) Faculty of Medicine 384 Face to face Centre for Epidemiology & Biostatistics LAU Tak Fai Joseph TSUI Hi Yi LAU Man Chun Mason Research on Evaluation of the Smoking (Public Health) (Amendment) Bill 2005 1 February 2007 Department of Health, Hong Kong SAR LAU Tak Fai Joseph LAU Man Chun Mason The present study aims to obtain surveillance data on CHAN Mei Wah (School of Public Health) sexually transmitted diseases (STD) from the private 1 October 2006 sectors. Tobacco Control Office, Department of Health Currently, these data are- very limited. The study includes 3 strata of doctors in the private To evaluate the acceptability and effectiveness of the sectors in Hong Kong. These include dermatologists, new indoor anti-smoking law which became effectine special doctors in obstetrics and gynaecology (O&G), from January 1st 2007, the Tabacco Control Office, and general practitioners (GP). Department of Health commissioned the Centre for doctors are invited to join the study. With informed Epidemiology and Biostatistics, School of Public consent, they provide information on the distributions Health, Faculty of Medicine, The Chinese University of STD/reproductive tract infections (RTI) or of Hong Kong to conduct a series of evulation surveys suspected STD/RTI cases that they are taking care of before and after the enactment of the law. during the same 14-day study period. A total of 4 cross-sectional anonymous random sample sizes for these 3 strata respectively are all telephone surveys will be conducted. These include: registered dermatologists, 100 O&G doctors, and 300 (1) Stage I (Pre-study) - a baseline evaluation survey GP in Hong Kong. before the enactment of the Amendment Bill; (2) (MD06564) These private The target Stage II (Post-study 3) - the first evaluation survey at 3 months after the extension of statutory no smoking The areas; (3) Stage III (Post-study 9) - the second Cognitive-Behavioral evaluation survey at 9 months after the extension of HIV Intervention Prevention Trials for At-risk statutory no smoking areas; and (4) Stage IV Monogamous Chinese Women Attending Public (Post-study 12) - the third evaluation survey at 12 STD Clinics in Hong Kong Implementation and Evaluation Randomized of a Controlled months after the extension of statutory no smoking areas. The study population comprises LAU Tak Fai Joseph all TSUI Hi Yi YIP Ying Chi (Paediatrics) Cantonese-speaking Hong Kong males and females aged between 15 and 69 residing in Hong Kong. A 1 March 2007 random sample of about 1,000 respondents will be Council for the AIDS Trust Fund recruited for each of the 4 telephone interviews. (MD06831) The present study aims to develop and evaluate a cognitive-behavioral based HIV/STD intervention Provision of Research on the Pattern of Sexually program targeting women (with a single sex Transmitted Diseases in People Seeking Care in partner only) attending public STD clinics in Hong the Private Sectors for Social Hygiene Service Kong for medical consultation. 385 This is a Faculty of Medicine Centre for Epidemiology & Biostatistics randomized controlled trial study. improve the mental health status of people living with It will be commenced in March 2007. HIV/AIDS. The target sample size is around 250 women This study will be conducted in Shenzhen city seeking medical care for STD from the public STD collaborating with Shenzhen CDC in mainland China. clinics. With informed consent, they will be The study includes 3 parts: The first part is to develop randomized into 2 groups: the Intervention group and validate a HIV/AIDS stressor scale specific for (receiving both the intervention program and Chinese standard-of-care) and the Control group (receiving HIV/AIDS infected subjects will be interviewed and the standard-of-care only). complete a questionnaire under the administration of The primary outcome of the study is condom use Health care workers. with the single sex partner. Secondary outcomes -sectional study involved 200 people to study the include and stress, coping and psychosocial problems among this be population. The third part is to conduct a follow up administered at baseline and at the end of the study among the previous approved project on newly intervention program. confirmed HIV/AIDS people and implement a small HIV/STD-related perceptions, etc. knowledge Measurements will people living with HIV/AIDS, 180 The second part is a cross scale intervention on 20 subjects. (MD06739) (SS06543) Psychosocial Problems and Intervention Study Among People Living with HIV/AIDs in Mainland Provision of Influenza Vaccination Coverage and China Self-reported Reasons for not Receiving Influenza Vaccination among Different Groups of Hong LAU Tak Fai Joseph MAK Wing Sze Winnie Kong Community (Psychology) SU Xiaoyou 1 March 2007 LAU Tak Fai Joseph TSUI Hi Yi Shenzhen Centre for Disease Control and 6 March 2007 Centre for Health Protection, Department of Prevention Health, HKSAR Government People living with HIV/AIDS face numerous stressor during their daily life after they know their The study aims to obtain data on the coverage of HIV/AIDS infection, including concerns about influenza vaccination and relevant information from physical health, stigma, employment, sexual life etc. selected populations of the Hong Kong community, These stressors may play a very important role during who have been recommended by the Scientific the course of adaptational adjustment. If the Committee on Vaccine Preventable Diseases, Centre subjects can cope the situation appropriately, he/she for Health Protection to receive influenza vaccination. can have a better mental health. Therefore, to These include: a) community-dwelling elderly aged understand stressors HIV/AIDS infected people 65 or above; b) the general population aged 2 to 64; c) confronted is the utmost important thing for the persons with chronic diseases; d) pregnant women in health care workers to provide further intervention to their 2nd or 3rd trimester; and e) children aged 6 to 23 months. A total of 5 survey studies were conducted Faculty of Medicine 386 Centre for Epidemiology & Biostatistics to achieve these purposes. 1 April 2007 Telephone interviews were conducted for the first 3 populations, and the Health Care & Promotion Fund target sample sizes respectively for these 3 surveys were 1,000, 1,000, and 700. Face-to-face interviews Although physical activity is recommended for were conducted for the other 2 populations, and the management of diabetes, 60 percent of the diabetes respective target sample sizes were both 400 and 400. patients were found to not performing adequately, Anonymous structured questionnaire will be used to thus not receiving the benefits from physical activity, collect data. These 5 surveys were conducted from which includes better glycaemic control, decrease April through June 2006. insulin resistance, weight loss, visceral body fat (MD06558) reduction, etc. Currently, the advices that are given out to the diabetics are very general without attending Accessing MSM through Social Network – the to individual patient’s needs. Moreover, the nursing Application of Respondent – Driven Sampling staffs might not be trained in proper motivational Method to Compare Characteristics and Service skills, which make individual advice ineffective. Needs of MSM Who are and are not Venue-Based Counselling by trained health educator over a telephone was found to be effective in facilitating increase of physical activity in a variety of LAU Tak Fai Joseph TSUI Hi Yi populations in oversea studies. However, the health 1 April 2007 educators need to be monitored by senior staff to Council for the AIDS Trust Fund ensure consistency and quality. Moreover, the The present study uses the Respondent-Driven service cannot be easily expanded to accommodate Sampling method to recruit men who have sex with increase demand for the service since that involves men (MSM) respondents. It aims to examine considerable costs to hire and train more staffs. HIV-related behaviors and service needs of MSM Therefore, a more cost-effective way to deliver recruited from this sampling method and to compare quality behavioural modification to patients is needed. these characteristics with those of the MSM recruited TLC-PA from venues. fully-computerized, telephone counselling system to (MD06318) deliver individualized advice to increase physical is a cost-effective, automated, activity to the WHO-recommended level (three or Application of a Cost-Effective, Computer-Based, more days per week of moderate-intensity physical Telephone-Counselling activity for at least 30 minutes per day). System to Increase The program is based on established psychological Physical Activity in Diabetes in Hong Kong theories to achieve behavioural change. This project FRIEDMAN Robert H.* aims to adopt, adapt, and deploy the TLC-PA system CHAN Chung Ngor Juliana (Medicine & in Hong Kong for the diabetics at the Diabetes and LAU Tak Fai Joseph Therapeutics) Endocrine Centre at the Prince of Wales Hospital. CHOW Chun Chung Francis (Medicine & Therapeutics) Winnie (Psychology) (MD06334) MAK Wing Sze MUI, LANCELOT WAI HO (School of Public Health) 387 Faculty of Medicine Centre for Epidemiology & Biostatistics Evaluation of the “Do it Safely” MSM HIV Cross-border HIV risk behaviors among Hong Kong Prevention Campaign men who have sex with men (MSM) has been of increasing concern. The present study aims to LAU Tak Fai Joseph TSUI Hi Yi investigate the pattern of sexual activities and 1 April 2007 HIV-related behaviors/attitudes of Hong Kong MSM in Shenzhen. Relevant data on HIV-related behaviors Department of Health, Hong Kong SAR and attitudes will also be collected from MSM in During August 2006 through April 2007, the Special Shenzhen who reported to have served Hong Kong Preventive Programme of the Department of Health MSM. Anonymous structured questionnaires will be has launched a “Do it Safely” MSM HIV Prevention designed to collect data. Campaign with a series of HIV-related prevention (MD06975) activities targeting local MSM (men who have sex with men). The present study aims to investigate Training and Technical Support of the Hong the prevalence of MSM respondents being exposed to Kong Student Information Form under the these prevention activities in the Campaign, assess Understanding their perceived acceptance and effectiveness of these 2007/08 Adolescent Project (Primary) activities and solicit their views on HIV-related risk communications. LAU Tak Fai Joseph LAU Man Chun Mason The study population includes Hong Kong Chinese males who self-reported having 1 May 2007 had sex with another man. Survey respondents will Education and Manpower Bureau, HKSAR be recruited via outreach services in local gay Government establishments (e.g., bars, saunas) and via internet as well. The target sample size would be around 300 The main purposes of this exercise are to report the from venues and 150 from the internet. An screening results in the UAP schools for the 2007/08 anonymous structured questionnaire is used to collect - Primary 4 students cohort under the Understanding data. The study will be conducted from around Adolescent Project (primary) (UAP), to conduct one April to October 2007. The study is commissioned 2-hour training session for school personnel on the by the Special Preventive Programme, Department of operation of the CD-ROM of HKSIF in May 2007. Health. The training sessions will include demonstration, (MD06547) practical exercises and question & answer period to strengthen the users’ understanding on the operation Cross-border HIV Related Behaviors Among of the CD-ROM of HKSIF and to provide telephone MSM from Hong Kong and the Male Sex Workers help desk service or on-site technical support if Serving Hong Kong MSM Clients necessary to all UAP schools from 1 June 2007 to 30 June 2007 and from 1 September 2007 to 31 LAU Tak Fai Joseph TSUI Hi Yi December 2007. 1 April 2007 (MD06894) Council for the AIDS Trust Fund Faculty of Medicine 388 Centre for Epidemiology & Biostatistics LAU Tak Fai Joseph Behavioural Surveillance Surveys of the Male Clients of Female Sex Workers (FSW) Population Hee (Community in Hong Kong Medicine) KIM Jean and Family 2003-04 Clinical Data Management and Medical LAU Tak Fai Joseph TSUI Hi Yi Statistics Functions for CK Life Sciences 1 August 2007 Development Inc. (MD03532) Council for the AIDS Trust Fund LAU Tak Fai Joseph The present 3-year study is a continuation of a series of HIV behavioral surveillance surveys among the 2005-06 Sexual Dysfunction and Sterility Among male clients of female sex workers population in Married Couples Living in Shenzhen Hong Kong since year 1998. It aims to keep track (SS05673) of changes, if any, in HIV-related behaviors and LAU Tak Fai Joseph TSUI Hi Yi SU Xiaoyou attitudes among the studied population and to examine factors associated with such behaviors. Anonymous telephone interview, using a structured 2005-06 Program Enhancement of CD-ROM and questionnaire, will be conducted to collect data. A the Screening Exercise of the HKSIF total of 3 surveys will be carried out annually from 2006/07 Understanding the Adolescent 2007 to2010. In each round of the 3 surveys, about Project (Primary) (ED05848) 2,000 Hong Kong Chinese male adults aged 18-60 LAU Tak Fai Joseph LAU Man Chun Mason will be randomly sampled from the male general population and be interviewed by a specially designed 2005-06 Epidemiology interactive computerized data collection method. of Influenza/Influenza-Like Illness (ILI) in (MD06353) Hong Kong Community (06/07) Please refer to previous issues of this publication (SS05616) for more details of the following ongoing research LAU Tak Fai Joseph TSUI Hi Yi CHAN Mei Wah (School of Public at the department: Health) Edition Title/Investigators 2002-03 Surveillance and Intervention Research for Different Communities in Hong Kong (MD02369) 389 Faculty of Medicine Dept of Surgery 1-day screening period, up to 2 weeks of receiving RESEARCH PROJECTS the study medication, and a final visit with the study doctor 10-28 days after their last dose of the study Open-label medication. Comparison of the Safety and Efficacy of (MD06869) A Multicenter, Randomized, Tigecycline with that of Ampicillin-Sulbactam or Amoxicillin-Clavulanate to Treat Complicated Targeting Apoptosis: A Study of Laser Induction Skin and Skin Structure and Hyaluronan Modulation in Keloid Derived Cells BURD David Andrew Ross IP Margaret BURD David Andrew Ross (Microbiology) WONG Shiu Yuen HUANG Lin CHEN Gong George 1 September 2006 1 January 2007 Wyeth Pharmaceuticals, Inc. Research Grants Council (Earmarked Grants) The purpose of this study is to compare the safety and effectiveness (how well it works) of Tygacil Apoptosis is a genetically regulated process whereby (Tigecycline) the with another antibiotic cells quietly involute and die in a amoxicillin-clavulanate) characteristically controlled manner which does not when given to hospitalised subjects for complicated induce an inflammatory response. In the course of skin infections. Another antibiotic (vancomycin or our laser studies where we have been looking at teicoplanin) cellular (ampicillin-sulbactam or may be added to the response to specific wavelengths of ampicillin-sulbactam or amoxicillin-clavulanate if electromagnetic radiation we have observed that we certain bacteria are present in the skin infection site. can induce a wave of cell death propagated by Approximately 500 subjects will take part in this non-irradiated cells. study at centers worldwide. The test article subjects these cells are dying through apoptotic mechanisms. receive will be decided by chance. A further observation is that we can modulate this Subjects will by altering Preliminary studies indicate have an equal chance of receiving one of the process the extracellular matrix following test articles: specifically by adding hyaluronan (HA) of varying • Treatment A Tygacil. molecular weights. This model of apoptosis opens • Treatment or up the possibility of promoting targeted cellular amoxicillin-clavulanate. Another antibioticmay events that lead to specific cell to cell signaling be added within the first 72 hours of enrollment if which can induce apoptosis. the study doctor thinks or knows that a certain strategy would have far reaching implications in bacteria developing B: called ampicillin-sulbactam methicillin. Resistant novel Such a therapeutic treatments based on Staphlococcus aureus (MRSA) is in the skin electromagnetic energy as compared to chemical infection site. (pharmacological induced) energy. A major clinical Subjects participation in this study will last for interest is wound healing and scarring. approximately 3 to 6 weeks. This period includes a scarring is a pathological form of extreme scarring that is prevalent in all racial groups. Faculty of Medicine 390 Keloid The incidence Dept of Surgery increases with increasing racially defined would have wide reaching implications for all pigmentation and it is a major problem in our surgical disciplines. Chinese population. (MD06850) Published studies of keloid cellular behaviour suggested that, inhibition, of apoptosis of fibroblasts is a major factor in the Treatment of Hepatocellular Carcinoma with development of keloid scar. Combination In this project we propose to explore in vitro a potential in vivo of Adenoviral Bid and Chemotherapeutic Agents therapeutic strategy whereby apoptosis will be induced in keloid cells by laser irradiation and CHEN Gong George LAI Bo San Paul modulated by HA. 28 December 2006 (CU06460) Research Grants Council (Earmarked Grants) An Investigation of the Potential Therapeutic Hepatocellular carcinoma (HCC) affects millions of Application of Human Umbilical Cord Lining individuals worldwide, particularly in Southeast Asia Epithelium for the Reconstruction of the Skin and including Buccal Mucosal Epithelial Defects treatments have been tried, HCC remains one of the Hong Kong. Although multiple most difficult tumors to treat when the tumor is BURD David Andrew Ross HUANG Lin advanced and unresectable. 1 June 2007 novel therapy, our studies have shown that the expression CUHK Research Committee Funding (Direct of In order to develop a pro-apoptotic protein Bid is significantly decreased in liver tumor tissues than Grants) non-tumor liver tissues from HCC patients and that Human umbilical cord represents an ethically decreased expression of Bid is related to the x protein acceptable, free and constant source of epithelial stem of hepatitis B virus, which is positive in about 90% cells. of HCC patients in Hong Kong. The potential clinical application of tissue or These results cells derived from human umbilical cord for suggest that a deficiency in the expression of Bid epithelial reconstitution is completely unexplored. may contribute to the development of HCC and that The hypothesis which we seek to explore in the the enforced expression of Bid may be useful in the present study is that human umbilical cord lining treatment of HCC. epithelium will differentiate and organize into a recombinant adenoviral AFPtBid, which contains structure appropriate for the recipient site. That is to tBid gene driven by an alpha-fetoprotein (AFP) say that when intact explants or cell cultures derived promoter from human umbilical cord lining are transplanted AFP-producing HCC cells. into specific post-natal epithelial environments (e.g. overexpression of tBid significantly and specifically skin or buccal mucosa), the epithelium and/or cells induced apoptosis in AFP-producing HCC cells will selectively differentiate to provide reconstitution either in vitro cell culture or in vivo HCC cells of recipient site specific epithelium. This pilot implanted in the frank region of nude mice. We study focuses on two specific epithelial constructs but have also observed that the combination of tBid and in Recently we have constructed a order to specifically target We found that chemotherapy (doxorubicin or 5-fluorouracil) can 391 Faculty of Medicine Dept of Surgery greatly enhance HCC cell death in the cell culture adenocarcinoma cells, nasopharyngeal carcinoma system. cells, ovarian cancer cells, promyelocytic leukemia The proposed study will continue our research in this direction. We will test the cells, and thyroid cancer cells. To our knowledge, adenoviral AFPtBid in an orthotopic xenograft tumor similar study has not been reported by other groups. model of HCC. The new tumor model is different Our experiment has also revealed that the inhibition of from the tumor inoculated in the frank region of mice, tumor cells by 5F is via a mitochondrial-mediated as the tumor formed by the former is located in the apoptotic mechanism involving an increase in p38 liver whereas by the latter is under the frank skin. MARK and a decrease in NF-kappa B. Therefore, the model will resemble naturally comparing the effect of 5F with a well known occurring HCC and the result obtained using this anticancer new model will be more reliable and convincing. undergoing clinical evaluation as an antitumor drug in On the other hand, though we have previously tested the United State and Japan, we show that 5F is able to the combination of tBid and chemotherapy against induce apoptosis of cancer cells in a similar manner to HCC in vitro culture system, the in vivo test has not UCN01. yet performed. Therefore, we wish to test this novel anticancer agent as potent as the patented UCN0l. combination treatment in this new orthotopic The proposed study is to further test 5F in vivo in two xenograft tumor model of HCC. It is believed that established animal tumor models of lung and liver. the proposed study may lay a new platform for future (MD06862) drug, UCN0l which is By currently Therefore, 5F can be considered to be a clinical trials. (CU06534) Levels of Endogenous Peroxisome Proliferators-Activated Receptor-Gamma Ligands Ent-11 α-hydroxy-15-oxo-kaur-16-en-19-oic-acid in Lung Cancer (5F), a Potential Anticancer Drug from Chinese CHEN Gong George WU Tangchun* Herb 31 March 2007 CHEN Gong George LIANG Nianci* CUHK Research Committee Funding (Direct 1 March 2007 Grants) GDMC Development Center for Medical and Lung cancer is the most prevalent malignancy in Pharmaceutical Science Guangdong Yihe Hong Kong. Pharmaceutical Co Ltd ITF - Guangdong-Hong Conventional chemotherapy and radiotherapy are still of limited effectiveness. The Kong Technology Cooperation Funding Scheme peroxisome proliferator-activated receptor-gamma (Platform Research Scheme) (PPAR-γ) is a member of the nuclear hormone Our previous studies have demonstrated that receptor superfamily of ligand-activated Ent-1lα-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F), a transcription factors and a crucial regulator of compound isolated from the Chinese herbal medicine cellular differentiation. plant Pteris semipinnata L, can significantly kill a and antiproliferative effects of PPAR-γ suggest that variety of tumor cells in vitro including colon cancer PPAR-γ might be useful as an effective anticancer cells, gastric cells, liver adenocarcinoma cells, lung agent. In humans, PPAR-γ is expressed in multiple Faculty of Medicine 392 Differentiation-inducing Dept of Surgery tissues, including adipose tissue, the breast, colon, with formation of contractile myofibroblast cells in lung, ovary, and placenta. the wound. Several ligands for PPAR-γ have been described, including the synthetic Sonic hedgehog (Shh) is a gene expressed in the skin thiazolidinedione (TZD) class of insulin-sensitizing stem agents, such as troglitazone (TGZ), and the natural epithelial-mesenchymal interaction. prostaglandin 15-deoxy-12,14-prostaglandin cells and plays an important role in Shh signaling J2 has been shown to expand the hair follicle epithelial acid stem/progenitor cell population. We have recently (12S-HETE) and 15-hydroxy-eicosatetraenoic acid demonstrated that Shh also inhibits smooth muscle (15S-HETE). cell differentiation. Laboratory studies suggest that (PGJ2), 12-hydroxy-eicosatetraenoic The result from my group has indicated that human lung cancer tissues and cell Shh may be involved in wound healing. lines have abundant PPARγ but the incidence of We proposed to apply topical Shh gene DNA on full apoptosis remains very low, suggesting that there thickness skin wounds. may be a defect in the activation of PPARγ Our promotes re-epithelialization via its action on the further stem/progenitor cells; and ii) reduces wound experiments found that by We will assess if it: i) 15-hydroxy-eicosatetraenoic acid (15S-HETE) was contracture inhibiting myofibroblast significantly decreased in the serum of patients with differentiation. The Shh gene therapy is applicable lung cancer. Therefore, it is assumed that a defect to wounds from bums, trauma and chronic ulcers, in endogenous PPAR-γ ligands may contribute to the accelerating the wound healing and minimizing the growth of lung cancer. The proposed study is to scarring. investigate the level of endogenous PPAR-γ ligands costs. in the circulatory system and human lung tissues. (MD06565) It will also greatly reduce the medical (MD06721) Use of Self-Expandable-Metallic-Stent (SEMS) for Shh Gene Therapy to Accelerate Wound Healing the Relief of Dysphagia in Patients with Advanced Esophageal Cancer CHENG Wei 30 June 2007 CHIU Wai Yan Philip NG Enders Kwok-wai CUHK Research Committee Funding (Direct 1 January 2007 S.K. Yee Medical Foundation Grants) Failure of wound healing is a challenging clinical a. Ways in which the project is of direct benefit to the problem. poor and sick: Each year, on a global base, 20 million people sustain major burns and 1 million of them Cancer of the esophagus is the seventh leading cause require hospitalization. Despite skin grafts, many of of cancer death in Hong Kong. the large wounds fail to heal. The failure of wound however, carry a grave prognosis with a 5 year healing is characterized by lack of re-epithelialization survival less than 20%. The disease usually occurs (skin growth) and excessive wound contraction. at the age of 70-80, affecting mainly the lower social While stem cells in hair follicles contribute to class. It is related to smoking habit and nutritional re-epithelialization, wound contracture is associated deficiency. 393 Most patients, Faculty of Medicine Dept of Surgery Knowing that the sole function of the esophagus is to investigate the coronary and pulmonary arteries transmit food from oral cavity to the stomach, it is preserved in currently used preservation solutions and understandable that patients with esophageal cancer to test the hypothesis that the contractility and have a poor quality of living as they are not able to endothelial function of the coronary or pulmonary eat. In patients with metastatic or locally advanced artery decreased by prolonged hypoxia-reoxygenation esophageal cancer, surgical excision is impossible. and that the protective effect of the current heart or The primary goal of therapy then is to allow the lung preservation solutions is limited. patient to eat again. Self expandable metallic stent knowledge derived from this proposed project, the (SEMS) is an effective way of palliating dysphagia in effect of clinically used heart and lung preservation patients with esophageal cancer. solutions on the vascular endothelial function under The SEMS is currently a patient purchase item in the conditions similar to the clinical setting is defined and Hospital Authority. This project aims to financially better understood. This will provide knowledge for assist those poor and sick patients with terminal the development of new generation heart and lung esophageal cancer so that they can regain swallowing preservation solutions. despite the incurable nature of the disease. gained from the proposed project will have important b. Aims: significance in further improvement of transplantation To deliver a service on endoscopic stenting for surgery. palliation of dysphagia in patients with cancer of the (MD06673) With the Therefore, the knowledge esophagus. (MD06980) An Investigation of the Plasticity of Human Umbilical Cord Blood-Derived Stem Cells in Coronary and Pulmonary Vascular Function after Hypothermic Preservation with Tissue-engineering of Skin Organ HUANG Lin Preservation Solutions BURD David Andrew Ross LI Kwai Har Karen (Paediatrics) HE Guo Wei YANG Qin 1 June 2007 1 June 2007 CUHK Research Committee Funding (Direct CUHK Research Committee Funding (Direct Grants) Grants) This proposal seeks to explore the plasticity of human Normal coronary function plays a key role in organ umbilical cord blood (UCB)-derived stem cells in the perfusion. tissue engineering of skin. In heart or lung transplantation, the We propose to use a donor heart or lung is inevitably subjected to 3-dimensional acellular dermal matrix and populate it ischemia-reperfusion (I-R). The clinical strategy to with UCB stem cells. protect the organ is to preserve the organ in explored including primary modulation of UCB stem preservation solutions under hypothermia (4°C). cell differentiation by epidermal differentiation There is evidence that the preservation so far is factors imperfect. Early or late complications may occur due incorporating them into the dermal matrix as well as to the preservation method. priming the matrix with epidermal keratinocytes Faculty of Medicine We propose to 394 and/or Several strategies will be keratinocyte co-cultures before Dept of Surgery before incorporating the UCB stem cells. Since PCa cells by miRNA microarray to identify the human umbilical cord blood is a free human resource differentially expressed miRNAs related to which is readily available, potentially safe and treatments; 2) employ real-time stem loop PCR assay ethically acceptable, the demonstration of their to verify the treatment induced changes of miRNAs potential utility for skin reconstruction would have expression in the cells; and 3) determine the estrogen overwhelming benefits to the survival and outcome receptors (ERs) dependency of this hormonal of burns patients worldwide. regulation by siRNA approach. (MD06476) this proposal could provide insight in regulation of The outcomes of miRNA expression in cancer cells and further Genome-Wide Identification Antiestrogen-Regulated of Estrogen-and enhance our understanding of ERs in prostate cancer. in (MD06430) miRNAs Prostate Cancer Cells Molecular Changes in Central Neural Pathways NG Chi Fai LAU Kin Mang (Anatomical & Cellular Pathology) CHAN Shu Yin Eddie Induced by Bladder Disorder NG Yuen Keng YEUNG Chung Kwong HO Shuk Mei* 1 April 2007 1 April 2007 CUHK Research Committee Funding (Direct CUHK Research Committee Funding (Direct Grants) Grants) Prostate cancer (PCa) is the 4th common male cancer Enuresis or bedwetting, is a common clinical in Hong Kong. problem in children and adolescents in Hong Kong. observed in A rapid increasing incidence is the last two decades. It is It has been showed that enuretic children are more well-established that estrogens play important roles in difficult to be awoken. carcinogenesis that demonstrated of PCa. estrogen We and/or previously antiestrogens severe fragmentation enuretic and Recently we have shown children reduced have functional sleep bladder significantly inhibited prostate cancer cell growth via capacity. Furthermore, our studies suggest that the estrogen bladder disorder is the underlying cause for the sleep receptor-beta dependent mechanism. Recent emerging evidences point towards the problem in enuretic children. importance of microRNA (miRNA) deregulations as indicates that voiding is preceded by arousal from critical events driving cancer development. In sleep in human infants. The arousal from sleep by silico-analysis of bladder distension is mediated by the locus coeruleus indicates the presence Clinical evidence estrogen-responsive elements (EREs) in one third of noradrenergic pathways in the brainstem. miRNA putative promoters, suggesting the estrogenic addition, the corticotrophin releasing factor (CRF) and antiestrogenic regulations in miRNA expression. neural pathway is important for the modulation of the In this proposal, we will explore this novel regulatory locus coeruleus neurons. mechanism for miRNA expression in PCa cells. We unknown how bladder disorder affects the central will 1) comprehensively study the miRNA expression neural pathways, resulting in the altered sleep pattern profiles of estrogen/antiestrogen treated and untreated of enuretic patients. In this study, we will use adult 395 In At present, it is still Faculty of Medicine Dept of Surgery male Wistar rats with reduced bladder capacity as a daily for 10 consecutive days. bladder disorder model. observation period for each patient will be three We will investigate the molecular changes in the central neural pathways months. after the bladder reduction with (1) protein (MD06744) The clinical expression measurement by quantitative RT-PCR; and (2) proteomics hypothalamus. in the brainstem and Surgical Audit Programme The findings of this study will provide (i) new evidence to support the discovery of UNDERWOOD Malcolm John WAN Song a novel functional interaction between the CNS and 1 February 2007 bladder; (ii) insights on the visceral modulation of the Contribution from Applicant New Method CNS; and (iii) new molecular targets for further College Ltd Professional Services studies on the neurobiological interactions between Development Assistance Scheme, Commerce, sleep regulation and bladder disorder. Industry and Technology Bureau, HKSAR Govt (MD06940) Sorin Group Asia Pte Ltd A Randomized, Double-Blind, Placebo-Controlled Clinical Audit (data collection and analysis of clinical Clinical Trial to Evaluate the Safety and Efficacy outcome) within surgical specialties as part of of Cerebrolysin in Patients with Acute Ischemic ‘Quality Assurance’ programmes is well established Stroke Internationally. The ability to do this provides clinicians not only with the possibility of maintaining POON Wai Sang WONG Kwok Chu KWOK and improving the outcome for patients, but also Siu Man Sharman* WONG Chi Keung* allowing personal and Departmental development following data comparison with Internationally 1 September 2006 accepted standards. In Hong Kong, the practice of EBEWE Pharma (Asia) Ltd surgical audits is still in its infancy. Surgical audits The objective of the study is to assess the clinical carried out are usually one-off, labour intensive efficacy and safety of a 10-day course of therapy with processes. This is in contrast with the international daily standard of audit, which should be continual and intravenous administration of 30ml Cerebrolysin based on a comparison with placebo. cyclical It will be carried out as a prospective, randomized, performance and ongoing improvement. double-blind, placebo-controlled, parallel group, project is designed to implement a computerized data multicentre study. Enrolment is expected to last for collection process within the Department of Surgery, 12 months. The target population would be adult which has inherent ability to consolidate individual patients acute patient data into the relevant database specialties and hemispheric infarcts within 12 hours after the onset also provide simple and complex outcome analysis of symptoms. for patient sub-groups. with a clinical diagnosis of Group 1 will be given 30ml (MD06979) Cerebrolysin IV and l00mg acetylsalicyclic acid PO. Group 2 will be given normal saline IV and 100mg acetylsalicyclic acid. Study drug will be given once Faculty of Medicine leading 396 to continued validation of This Dept of Surgery The Effect of “Hot Shot” Blood Cardioplegia on help devise better strategies to improve myocardial Clinical Outcome, Myocardial Metabolism and protection during valve surgery. Reperfusion (EE06373) Injury in Patients Undergoing First-time Elective Heart-Valve Surgery Gene Therapy for the Prevention of Vein Graft UNDERWOOD Malcolm John WAN Song Failure: Pre-clinical Evaluation SUILEMANN Nilesh* WAN Song 30 June 2007 YIM Ping Chuen Anthony ARIFI Ahmed A* BAKER Andrew H* CUHK Research Committee Funding (Direct 1 October 2006 Grants) Research Grants Council (Earmarked Grants) Hyperkalaemic cardioplegic solutions remain the most commonly used technique for protecting the Saphenous vein bypass grafts are the most widely heart against ischaemia during open-heart surgery. used conduits for surgical revascularization in both The principle is that high potassium arrests the heart ischemic heart disease and peripheral vascular and therefore reduces energy demands and help disease. preserving energy substrates during ischaemia. remains the mainstay of treatment for patients with Techniques of myocardial protection have largely severe been developed for hearts with coronary disease yet particularly in those with diabetes and impaired are routinely applied to all hearts irrespective of their cardiac function. However, the long-term success pathology. of CABG is significantly limited by late vein graft Hearts of patients with valve disease Coronary artery bypass grafting (CABG) multi-vessel coronary artery disease, have different metabolic demands and undergo failure. different remodelling compared to coronary disease accelerated atherosclerosis in venous bypass grafts is and a major clinical burden, resulting in high occlusion therefore are likely to have different susceptibility to ischaemia and reperfusion. Cold In particular, neointima formation and rates that are not responsive to pharmacological cardioplegic solutions (blood or crystalloid) are therapies. widely used however, Our prior work has established the validity of myocardial protection remains suboptimal and is intraoperative gene therapy as a strategy to modify associated injury. early bypass graft remodeling by prevention of vein Reperfusion with warm cardioplegia (hot shot) is graft neointima formation. We have evaluated first known to improve protection and reduce injury generation adenoviral-mediated overexpression of a during coronary artery surgery. The objective of candidate therapeutic gene p53 using an in vivo pig this proposal is to compare cold blood versus cold vein graft model. We now propose to further extend blood followed by warm blood cardioplegia “hot this study by assessing the longer-term (i.e., 3 months) shot” during mitral valve surgery. To achieve these efficacy objectives, we shall follow a comprehensive metalloproteinases -3 (TIMP-3) gene therapies in the approach pig model using GLP grade virus stocks in a during valve with of significant monitoring surgery; myocardial clinical myocardial injury and metabolism. outcome, It is expected of side-by-side that this work will provide important information to p53 and comparison tissue of inhibitor clinically of useful transgenes. 397 Faculty of Medicine Dept of Surgery We envisage that these pre-clinical experiments to H-R or hyperkalemia. Further, an IKca activator 1 could lead directly to translation to human clinical -EBIO that has been demonstrated in our preliminary trials. studies to recover the IKca-related hyperpolarization (CU06542) and relaxation, will be used to examine whether this kind of pharmacological tool may restore the Alteration of Potassium Channels in Coronary H-R-related alteration of IKca on molecular level. Circulation due to Hypoxia and Hyperkalemia This project will provide knowledge for the and Pharmacological Prevention development of new methods to reduce the H-R injury to the heart due to ischemic heart disease or YANG Qin HE Guo Wei open heart surgery and therefore has clinical YAO Xiaoqiang significance. (Physiology) (MD06408) 30 June 2007 CUHK Research Committee Funding (Direct Please refer to previous issues of this publication Grants) for more details of the following ongoing research Coronary dysfunction is one of the major causes for at the department: reduced coronary flow and related morbidity and mortality. In ischemic (coronary) heart disease and Edition Title/Investigators open heart surgery, the heart is subjected to hypoxia-reoxygenation (H-R). Coronary function is 2003-04 The Design and Development of a Novel related to a variety of potassium channels that may Bio-Interactive Electro-Chemical Wound involve Dressing both endothelium-dependent -independent mechanisms. and In the smooth muscle Incorporating the Physical Vapour Deposition of Nanoscale Silver cell (SMC), BKca is related to endothelium-dependent Ions (MD03739) and -independent relaxation; in endothelial cells, IKca BURD David Andrew Ross is related to the endothelium-dependent, non-nitric Margaret (Microbiology) oxide non-prostacyclin (NNONPG) pathway. Wai To protect the heart, hyperkalemic solutions are used in Kei Christopher IP LAM (Chemical Pathology) POON Kwok Man# open heart surgery but those hyperkalemic solutions have been demonstrated to reduce the 2005-06 The Technological Upgrading and NNONPG-mediated hyperpolarization and relaxation Clinical Validation of a Prototypical Near in the coronary circulation. This study is designed Infrared Spectrophotometer (MD05461) to clarify the role of the two pathophysiological BURD David Andrew Ross LIN factors (H-R and hyperkalemia) on BKca in the SMC Chinlon (Information Engineering)# and IKca in the endothelial cell. Electrophysiological method (patch-clamp) will be used to measure the Engineering) current change of BKca and molecular methods will (Electronic Engineering) be used to determine the possible alteration of the Lin mRNA or protein related to endothelial IKca, subjected Faculty of Medicine 398 CHEN Lian Kuan (Information LUO Yuhui HUANG Dept of Surgery CHENG Wei YEUNG Chung Kwong 2005-06 A Study of Paracrine Modulation of Cutaneous Pigmentation Using Pulsed, 2005-06 DNA Hypermethylation in Squamous Frequency Doubled Nd: YAG 532nm Cell Carcinoma of Esophagus - A Laser Irradiation (MD05715) BURD David Andrew Ross Correlation Study with Clinical Outcome after HUANG Lin Definitive Chemo-Radiotherapy (MD05730) CHIU Wai Yan Philip 2003-04 4-(methylnitrosamino)-1-(3-pyridyl Kwok-wai )-1-butanone (NNK), a Tobacco-Specific Carcinogen, Regulates NG Enders LEUNG Wai Keung (Medicine & Therapeutics) Apoptotic Molecules via a Nuclear Factor Kappa 2001-02 The Interaction between Endothelium B-Dependent Pathway (CU03390) and Smooth Muscle/Cardiac Myocytes CHEN Gong George During Heart Surgery and Clinical Chuen Anthony Tony YIM Ping Significance (MD01127) MOK Shu Kam (Clinical Oncology) HE Guo Wei WARNER Timothy D.* 2003-04 Function of Potassium Channels in the Coronary / Pulmonary Arteries during 2004-05 Expression of Estrogen Receptors and the Peroxisome Heart / Lung Surgery (CU03383) Proliferators-Activated HE Guo Wei Receptor Gamma in Thyroid Cancer (MD04322) CHEN (Physiology) Gong HASSELT George Charles Andrew and 2004-05 Effect of Hypoxia-Reoxygenation and VLANTIS Alexander Preconditioning on the Release of Nitric (Otorhinolaryngology, Neck S) YAO Xiaoqiang (Physiology) VAN HUANG Yu Head Chris (Otorhinolaryngology, Head Oxide and Neck S) Hyperpolarizing TSE Man Kit Gary and Coronary (Anatomical & Cellular Pathology) Endothelium-Derived Factor from Endothelium during the Heart Surgery (MD04318) HE Guo Wei 2005-06 Influence of Hepatitis B Virus X on Oxidant Stress in Hepatocellular 2005-06 Experimental Carcinoma (MD05519) CHEN Gong George Studies of Pulmonary Vessels in COPD (Chronic Obstructive LAI Bo San Pulmonary Paul Disease) Patients with Relevance to New Therapeutic Strategies (MD05307) 2005-06 Role of Bmp4 in Bladder Smooth Muscle Differentiation (MD05429) 399 Faculty of Medicine Dept of Surgery HE Guo Wei Anthony YANG LAI Bo San Paul YIM Ping Chuen Qin CHEN Gong George CHAN Yung Wai# SHIGEMURA Norihisa# 2004-05 Prospective Randomised Study of 2005-06 Towards Regeneration: The Role of Endovenous Radiofrequency Obliteration Hyaluronan-stem Cell Complexes in (Closure Procedure) Versus Ligation and Modulating Stripping in the Treatment of Varicose Epithelial-Mesenchymal Interactions (CU05550) HUANG Lin Veins BURD Andrew Ross Madhukar (Orthopaedics Traumatology) Michael a Hong Kong Chinese Population (MD04317) David LAU Yun Wong James KUMTA Shekhar in HO Sin & Yee Stella (Diagnostic Radiology & M Organ Imaging) LEUNG Yee Fong YANG* (Diagnostic Radiology & Organ Imaging) 1997-98 Prospective Study on the Relationship of Central Venous Pressure and Blood Loss During Hepatectomy (MD96217) LAI Bo San Paul Joseph Use of Non-Contrast Helical Computerized Tomogram in Predicting Treatment Outcome of Upper Ureteric CHUI Po Tong Stone by Extracorporeal Shock Wave LAU Wan Yee Lithotripsy Using the Sonolith 4000+ of Lithotriptor (MD04438) (Anaesthesia & Intensive Care) LEOW Chon Kar 2005-06 The (Faculty Medicine NG Chi Fai (Planning Office)) WONG Ka Tak Jeffrey (Diagnostic Radiology & 2005-06 The Role of ZBP-89 in Chemotherapy of Organ Imaging) CHENG Chi Wai Hepatocellular Carcinoma (CU05551) LAI Bo San Paul 2005-06 Evaluation of Zoledronic Acid to Prevent CHEN Gong Bone Loss in Men Receiving Androgen George Deprivation Therapy for Prostate Cancer (MD04377) 2005-06 A Multicenter, Open-Label, Randomized NG Chi Fai CHENG Chi Wai Comparative Study of Tigecycline vs Ceftriaxone Sodium plus Metronidazole for the Treatment Subjects with of Hospitalized 2005-06 The Effect of Vardenafil on Blood Complicated Pressure in Patients with Erectile Intra-Abdominal Infection (MD05650) Dysfunction who Received Concomitant LAI Bo San Paul Doxazosin GITS for the Treatment of Benign Prostatic Hyperlasia (MD05362) NG Chi Fai CHENG Chi Wai 2005-06 The Suppressive Effects of Octreotide on Human Hepatocellular Carcinoma Cells (MD05549) Faculty of Medicine 400 Dept of Surgery BACTISEAL 2003-04 Surveillance of Bleeding Peptic Ulcers Using Wireless Capsule External Drainage (EVD) System (MD05599) Endoscopy POON Wai Sang (CU03382) NG Enders Kwok-wai Leung Francis Therapeutics) WONG Kwok Chu IP Margaret (Microbiology) CHAN Ka (Medicine Ventricular & 2005-06 Decompressive SUNG Joseph Jao Yiu (Medicine & Therapeutics) Craniectomy for Uncontrollable Elevation of Intracranial Pressure: WONG Kin Hung Simon How Does It Work? (MD05865) POON Wai Sang 2005-06 Prevention of Transcoelomic Spread of Stomach Cancer through the CHAN Matthew Tak Vai (Anaesthesia & Intensive Anti-Angiogenic Pathway of COX-2 Care) Specific Inhibitors: from Bench Top to Wai Bedside (MD05634) Radiology & Organ Imaging) NG Enders Kwok-wai Wai Keung POON Wai Sang (Anatomical Function: SHI Head Injury (CU03386) Shuen (Diagnostic An Animal Study (MD05584) 2003-04 A CT Decision-Making Tool for Mild Wynnie LAM 2005-06 Effects of Reduced Bladder Capacity on Brain Pathology) Man & Therapeutics) Leung WONG Kwok Chu WONG Wai Sun Vincent* LEUNG (Medicine Yimin CHAN Yu Kwong & (Physiology) Cellular Kenneth LEUNG Clarence Hin YEUNG Chung CHAN Hsiao Chang ROWLANDS Dewi (Laboratory Animal Services Centre) CAMERON Peter Alistair (Accident and Emergency Medicine Academic Unit)# 2005-06 A YU Ly Mee Prospective, Randomized, Ashley (Centre for Clin. Trials & Double-Blind, Epidemiological Research)# Assessing the Safety and Efficacy of ZHU Multicenter Trial Intravenous Administration Bay 12-8039 Xian Lun Cannon (Moxifloxacin) 400mg Every 24 H 2005-06 A Multi-Centre Clinical Study in Spinal Compared to Intravenous Ceftriaxone 2 g Cord Injury Patients in Mainland China Every 24 H and Metronidazole 500mg and Hong Kong (MD05418) Every 12 H for the Treatment of Patients POON Wai Sang with SUN Tin Fung Complicated Infections (MD05965) David SIU Wing Tai 2005-06 Establishment Intra-Abdominal of Baseline and (Microbiology) Comparative Infection Rates for Codman 401 LAI Wai Man CHEUNG Ka Yin NG Enders Kwok-wai Faculty of Medicine Dept of Surgery Hypoxia-Reoxygenation 2005-06 Evaluation of Sustained Efficacy of Venous Bypass Graft Gene Therapy Surgery (MD05622) (MD05940) YANG Qin WAN Song 2004-05 Efficacy of Conventional Acupuncture Therapy Registry Cardiac YIM Ping Chuen Anthony CHEN Ge* 2005-06 A in for Versus Acupuncture-Point Comparing Overnight Transcutaneous Catheter-Related Infection Rates among Electrical Various Shunt Systems in the Treatment (ACU-TENS) Therapy for Children with of Hydrocephalus (MD05750) Severe Primary Nocturnal Enuresis: A WONG Kwok Chu Clinical POON Wai Nerve and Stimulation Neurophysiological Comparative Study (MD04900) Sang SUN Tin Fung David YEUNG Chung Kwong 2005-06 Clinical Study on Cognitive Impairment after Aneurysmal LEUNG Ping Chung (Institute of Chinese Subarachnoid Medicine) CHAN Yu Leung Hemorrhage (SCISH) (MD05527) (Anatomical & Cellular Pathology) WONG Kwok Chu PHILIP David* Sang POON Wai ZHU Xian Lun Cannon MOK Chung Tong (Medicine & Therapeutics) 2005-06 Augmented Reality System for Image Vincent Sui Yin Agnes (Psychology) Guided CHAN Minimally Invasive Surgery (MD05508) FAN YEUNG Chung Kwong Shu Ping Dorothy (Ophthalmology and Visual Sciences) Luc* HENG SOLER Pheng Ann (Computer Science and Engineering) + 2005-06 Effect of K and Mg 2+ on Endothelial Nitric Oxide Release: Interaction with Faculty of Medicine 402 Accident and Emergency Medicine Academic Unit Participants: 783 subjects having sustained isolated RESEARCH PROJECTS soft tissue limb injury without significant fracture presenting to the ED of Prince of Wales Hospital Cost-Effectiveness Analysis of Oral Paracetamol Main outcome measures: Pain relief profiles of and Ibuprofen for Treating Pain after Soft Tissue paracetamol, ibuprofen and the combination of both; Limb adverse effect profiles of paracetamol, ibuprofen and Injuries: Double-Blind, Randomized, the combination of both; overall cost effectiveness of Controlled Trial paracetamol, ibuprofen and the combination of both from the perspective of the healthcare provider GRAHAM C A MAN Shin Yan WOO Wing (MD06760) Keung RAINER Timothy Hudson 1 June 2007 Development Hong Kong College of Emergency Medicine Matrix Marker in Acute Stroke Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen GRAHAM C A are commonly used oral analgesics in emergency Pathology) departments (ED) not only in Hong Kong but Timothy Hudson throughout the world. Metalloproteinase-9 mRNA as an Early Diagnostic and Prognostic Research Fund Background: of There are no large-scale CHAN Wing Yan (Chemical LAM Yuk Lan RAINER 30 June 2007 (n>100), prospective, randomised studies comparing CUHK Research Committee Funding (Direct paracetamol with ibuprofen in the management of Grants) acute soft tissue injury. As paracetamol is cheaper than most NSAIDs, may be as effective in the Cerebrovascular diseases, including stroke, are one management of acute pain and possibly with fewer of the leading causes of death worldwide and also a adverse effects, a large-scale, randomised, controlled major cause of disability. trial is needed to answer questions of relative mortality analgesic efficacy, safety and cost-effectiveness. maintained for at least another 20 years. Previous comparative studies on NSAIDS have been Although neuroimaging methods enable detection done in this unit and have suggested equivalence and localization of stroke and acute brain damage, between two NSAIDs and paracetamol, but numbers frequent and repeated measurement is not practical. were small and drug doses were modest. There is growing evidence that the dysregulation of Objective: To compare the efficacy, safety and cost various proteins and RNA in injured brain tissues between oral ibuprofen and paracetamol in pain may be of pathological relevance. control for acute soft tissue injuries in an ED setting MMP9 is a zinc-dependent protease which is Design: randomised involved in the degradation of basal lamina and controlled trial with three arms: oral paracetamol extracellular matrix, leading to the disruption of the with blood brain barrier. Prospective, placebo; oral double-blind, ibuprofen with placebo; suggest that Projections of global this position will be Both protein and RNA levels of MMP9 were found to be elevated in brain tissues paracetamol and ibuprofen in combination and 403 correlated to stroke severity. Recent Faculty of Medicine Accident and Emergency Medicine Academic Unit microarray studies demonstrated that MMP9 is one On one hand, healthcare workers try to control costs of the highly expressed genes in leukocytes after by reducing unnecessary hospital admissions whilst stroke and traumatic brain injury. Our preliminary on the other hand, they have to safeguard patients study showed an elevation of MMP9 mRNA in who are seriously affected by admitting them for blood cells of stroke patients. inpatient care. In Hong Kong, the issue has been Therefore, the present study aims to investigate further complicated after the SARS outbreak and a whether MMP9 mRNA detected in blood cells is a clinical decision rule was felt to be a possible pathologically relevant marker for stroke and its solution for the problem. potential clinical applications. With the use of real We aim to develop a new predictive rule by time quantitative RT-PCR technique, we will study performing a prospective observational study that the profile of MMP9 RNA in the circulation and could reliably classify CAP patients into different evaluate its value in diagnosis, risk-stratification and risk groups and guide clinical management decisions. prognosis of patients with stroke. The cohort will be used for new rule derivation and determine whether it may We will also be a potential validation. Prognostic factors for CAP patients will discriminator of ischaemic and haemohagic stroke, be identified for new rule construction in the and its value as a predictor of morbidity and derivation cohort and the new rule will subsequently mortality, and its temporal relationships be validated in the validation cohort. (MD06531) (MD06759) Decision Rule for Pneumonia in Hong Kong A Multi-Center, Randomized, Double-Blind, Parallel Group, Placebo Controlled Trial to MAN Shin Yan GRAHAM C A RAINER Evaluate the Efficacy and Safety of Activated Timothy Hudson Recombinant Factor VII (rFVIIa/NovoSeven/NiaStase) in Severely Injured 1 May 2007 Trauma Patients with Bleeding Refractory to Hong Kong College of Emergency Medicine Standard Treatment Research Fund RAINER Timothy Hudson Community acquired pneumonia (CAP) has a wide GRAHAM C A CHEUNG Nai Kwong range of clinical presentations and its severity varies CHENG Chi Hung from a mild illness to a rapidly fatal disease. There YEUNG Hiu Hung is no consensus among clinicians with respect to (Anaesthesia & Intensive Care) deciding the location (inpatient or outpatient) of care (Anaesthesia & Intensive Care) for CAP patients despite the development of clinical guidelines by different international societies. HO Ming Hei Anthony LI Tze Yan 1 October 2006 None Novo Nordisk Hong Kong Ltd of these rules are primarily designed for use in ED, and coupled with the stressful and busy nature of ED, A multi-center, randomized, double-blind, parallel most group, placebo-controlled trial will be conducted to emergency physicians have had prior experience of difficulties in deciding the location of evaluate care for CAP patients shortly after the consultation. (NovoSeven®/NiaStase®) in patients with blunt Faculty of Medicine 404 the efficacy and safety of rFVIIa Accident and Emergency Medicine Academic Unit and/or penetrating trauma injuries. Patients meeting YIM Wai Ting entry criteria will be randomized and receive study RAINER Timothy Hudson drug (NovoSeven®/NiaStase® or placebo) as an GRAHAM C A adjunct to standard treatment. Therapeutics) Patients eligible for randomization must have Lung* TING Soo Moi* received a minimum of 4 units and a maximum of 8 units of red blood cells (RBC). WOO Jean (Medicine & WONG Tai Wai LAU Fei 1 June 2007 Patients with Food and Health Bureau - Studies in Health confirmed clinical indicators for active hemorrhage Services refractory to standard treatment will be randomized to one of two treatment groups: Background: Elder emergency department (ED) 1. Three single doses of rFVIIa (200 mcg/kg + 100 patients (>65 years) are at increased risk for mcg/kg + 100 mcg/kg); and acute hospital admission and return ED visits, 2. Three single doses of placebo (volumes when compared with younger patients. The administered identical to active treatment). Identification of Seniors at Risk (ISAR) tool is Randomized patients will receive the first dose of a validated screening tool specifically for study drug (NovoSeven®/NiaStase® or placebo) high-risk elderly in the ED. administered intravenously as a slow-bolus injection, stratifies elderly patients at risk for adverse no earlier than upon the completion of the 4th unit of health RBC and no later than by the completion of the 8th unit admission and functional decline). of RBC. A second dose will be administered one scores ≥2 predict adverse health outcomes hour after the initial dose, and a third dose will be within 6 months of index ED visits. Patients administered three hours after the initial dose. Safety screening ISAR positive had lower rates of and efficacy endpoints will be evaluated at different functional decline when ED-based nursing time points from Randomization through Day 30. assessment and community-based intervention Serious Adverse Events (SAEs), mortality, and patient were performed. status will be followed through Day 90. Objectives: Specific procedures including physical examination, 1. Derive a Hong Kong version of ISAR; measurement 2. Validate this new tool (‘HK-ISAR’) in the local of vital signs, and laboratory assessments will be conducted at defined intervals outcomes (death, It detects and long-term care ISAR population; throughout the trial. The outcomes are transfusion 3. requirements, organ function, adverse events and Compare it to original ISAR using ROC analysis; and mortality. 4. (MD06543) Using the validated ISAR/HK-ISAR tool, identify high-risk elderly and study effects of structured ED intervention on hospitalisation and institutionalisation within six months. Emergency Department Intervention for High Risk Elders in Hong Kong: Validation of an Design: Identification Randomized Study 1: Prospective derivation and validation cohort Controlled Trial to Reduce Hospitalization and study in EDs of three local hospitals (Aims 1, 2 and Institutionalization 3). Strategy and 405 Faculty of Medicine Accident and Emergency Medicine Academic Unit Study 2: Prospective multi-centre randomized GRAHAM C A RAINER Timothy controlled trial of ISAR positive elderly ED patients Hudson (Aim 4). Participants: Pathology) Study 1: Elderly patients presenting to the ED in (Chemical Pathology) CHIK Ki Wai (Paediatrics) LO Yuk Ming Dennis (Chemical CHAN Wing Yan stable clinical condition. Study 2: Elderly patients ready to be discharged from 2003-04 Investigation into Circulating Nucleic the ED. Acids in Patients with Stroke (CU03402) Primary outcome measure: RAINER Timothy Hudson Any one of the following: Wai Long-term care admission (>3 months in Radiology & Organ Imaging) nursing home); Yuk Acute hospital admission within 6 months of ED Pathology) attendance; and Constantine (Diagnostic Radiology High ED utilization (>3 visits following index & Organ Imaging)# attendance) during 6 months after index ED Sing visit. Therapeutics) Man Wynnie LAM Ming (Diagnostic Dennis LO (Chemical METREWELI Lawrence WONG Ka (Medicine & (MD06736) 2005-06 Investigation of the Value of Early Please refer to previous issues of this publication Clinical Features and for more details of the following ongoing research Electrocardiographic at the department: Cardiospecific Protein Tests and Novel Changes, Rapid Circulating Nucleic Acids in the Early Edition Diagnosis of Acute Coronary Syndrome Title/Investigators in 2004-05 Cost-Effectiveness Analysis of the Emergency (MD05441) Oral RAINER Paracetamol and Ibuprofen for Treating Timothy Pain after Soft Tissue Limb Injuries: Renneberg, Double-Blind, Randomized, Controlled SANDERSON Trial (MD04974) (Medicine GRAHAM C A MAN Shin Yan WOO Wing Keung RAINER 2005-06 A Single Nucleotide Polymorphism (SNP) Based Method to Investigate the Origin Circulating Brain-Derived RNA (MD05367) Faculty of Medicine 406 Hudson Reinhard* & GRAHAM C A Timothy Hudson JACOBS Philip* of Department John Elsby Therapeutics)# Clinical Immunology Unit known to influence the functions of Bcl-2 proteins RESEARCH PROJECTS will also be investigated. Understanding of the range and mechanism of this powerful anti-apoptotic protein will provide a new therapeutic means to In Vivo Anti-Apoptotic Activity of BRE diseases involving dysfunctional apoptosis, which CHUI Yiu Loon include neurodegeneration and cancer, just to name a 1 March 2007 few. (MD06330) CUHK Research Committee Funding (Direct Grants) Please refer to previous issues of this publication BRE is a novel death receptor-associated intracellular for more details of the following ongoing research protein shown to have anti-apoptotic activity in cell at the department: lines. Ectopic expression of the protein can lead to Edition attenuated cellular apoptotic response to TNF-α, anti-Fas agonist antibody, and a variety Title/Investigators of Stable transfection of a 2004-05 BRE - Investigation of Its Roles in Death mouse Lewis lung carcinoma clone, D122, with Receptor Signaling, Human Cancers and human BRE could enhance its growth as tumor in Its Primary Function (MD04756) mice. CHUI Yiu Loon stress-related stimuli. The site of anti-apoptotic action of BRE has been narrowed down to the events proximal to 2005-06 Expression Regulation Study of BRE mitochondrial permeabilization. Recently, we have generated a liver-specific transgenic human BRE (MD05422) mouse strain, which showed significantly less liver CHUI Yiu Loon damage in response to injection of anti-Fas agonist antibody, compared with the 2005-06 Expression, Purification and Supply of non-transgenic littermates, thus demonstrating for the first time in Influenza vivo anti-apoptotic activity of BRE. Glycoproteins (BL05575) Here, it is H5N1 Haemagglutinin LIM Pak Leong LEUNG Tze Ming proposed to extend the in vivo work using the transgenic mice to other death receptor-dependent 2005-06 Help Determine Telomerase Gene and and -independent apoptotic stimuli, such as TNF-α, and tunicamycin, respectively. Protein Expression in Fish (Medaka) The aim is to establish the in vivo anti-apoptotic range of BRE. It Tissue (BL05524) is also proposed to investigate the mechanism of the LIM Pak Leong AU Doris W T* anti-apoptotic activity by analyzing the protein LEUNG Tze Ming expression levels and activation status of the Hung TAM Chi Hang Frankie MA Chun pro-survival and pro-apoptotic Bcl-2 family proteins, which are the key mitochondria-proximal events. players in the MAPK pathways 407 Faculty of Medicine Clinical Immunology Unit 2005-06 Induction of Suicide in Autoantibody-Producing Cells In Vitro and In Vivo (MD05451) LIM Pak Leong LEUNG Tze Ming WONG Chun Kwok (Chemical Pathology) Faculty of Medicine 408 Epithelial Cell Biology Research Centre LI Ming RESEARCH PROJECTS SANDERSON John Elsby (Medicine & Therapeutics)# LEE Ka Ho Kenneth (Anatomy) Please refer to previous issues of this publication 2003-04 Salvage for more details of the following ongoing research of Ischemic/Infarcted Myocardium by Dagencao Induced Rapid at the department: Angiogenesis and Myogenesis and Its Edition Development (MD03801) Title/Investigators LI Ming SANDERSON John Elsby (Medicine & Therapeutics)# 2001-02 Salvage of Infarcted Myocardium by an Extract of Dagencao with Dual Effects on YU Angiogenesis and Cardiomyogenesis and Therapeutics) LEE Ka Ho Kenneth Investigation of Molecular (Anatomy) Mechanism Involved Dagencao Edmund* Induced the in Angiogenesis Man (Medicine CHEUNG N & M & 2005-06 Characterization and Cloning of the Cardiomyogenesis (MD01972) LI Ming Cheuk Novel Mitogen(s) that Induces Cardiac SANDERSON John Elsby (Medicine & Therapeutics)# Myocyte Dividing (MD05776) LEE Ka Ho Kenneth (Anatomy) LI Ming TSUI Kwok Wing LEUNG Ping Chung (Institute of (Biochemistry (Medicine)) Chinese Medicine) CHENG Lei (Physiology) 2003-04 Purification and Cloning of the Novel Muscle Healing Protein(s) that Enhances Muscle Repair and Regeneration (CU03450) 409 Faculty of Medicine Epithelial Cell Biology Research Centre CHENG YAM FK Frances RESEARCH PROJECTS Albert (Community and LEE Family Medicine) Please refer to previous issues of this publication 2004-05 Colourful for more details of the following ongoing research and Vegetables at the department: Bright Project - Fruits Creating and a Supportive Eating Environment for New Edition Generation (MD04397) Title/Investigators HO Man LEE Albert (Community and Family Medicine) 2005-06 Study on Investigating the Health Status Mei Wan of Office Workers and the Workplace Safety and Health Performance in Hong Kong (MD05803) Faculty of Medicine 410 KEUNG Stanley Ho Centre for Emerging Infectious Diseases HE Mingliang RESEARCH PROJECTS SUNG Joseph Jao Yiu (Medicine & Therapeutics) CHAN Lik Yuen Henry (Medicine & Therapeutics) Improvement on Whole Genome Amplification of 1 January 2007 Hepatitis B Virus Sequence Research Grants Council (Earmarked Grants) DING Chunming Chronic HBV infection is a major risk factor for the CHAN Lik Yuen Henry (Medicine & Therapeutics) development of hepatocellular carcinoma (HCC); SUNG Joseph Jao however, the pathogenesis of HBV-induced HCC is Yiu (Medicine & Therapeutics) poorly understood. Our clinical studies have shown 30 June 2007 that some subgenotypes/hot spot mutations are CUHK Research Committee Funding (Direct associated with increased risk for HCC. Grants) In this study, we extend our clinical observation to It is estimated that 400 million people world-wide are virological and biological studies. suffering from chronic hepatitis B virus (HBV) determine if HBV strains isolated from old infection. [1] Hong Kong is endemic for HBV asymptomatic HBV carriers or young HCC patients infection, with a hepatitis B surface antigen (HBsAg) display any characteristic changes in terms of carrier rate of about 10%. [2] HBV infection is a replication risk factor for cirrhosis and hepatocellular carcinoma signaling in the host cells. We will also create point (HCC). HBV develops mutations at a relatively high mutants on reference strains in accordance with hot rate in the genome. Such mutations may affect spots mutations observed in our clinical studies, and replication capacity, drug resistance, or change test for virological and/or biological changes that immune response. Thus, it is essential to carry out could be associated with HCC development. sequence analysis of the HBV genome. HBV whole addition, we will also investigate whether new genome amplification is an essential step in cloning mutations causing amino acid residues substitutions the HBV genome from clinical samples for functional in X gene lead to altered functions. analysis such as drug resistance tests and replication from this study would enhance our knowledge of efficiency assays. In this proposal, we aim to HBV biology, and may provide molecular markers in improve the sensitivity and fidelity of the existing predicting the disease process, prognosis as well as method for HBV whole genome amplification. supporting better management of HBV patients. (MD06494) (CU06428) Functional Characterization Subgenotypes/Mutations of Novel Associated capacities, promoter We will activities, and In The results HBV Polymorphisms of GRP78 Gene and Their with Association with Chronic HBV Infection and HBV-Associated Liver Cancer Increased Risk for Hepatocellular Carcinoma (HCC) HE Mingliang KUNG Hsiang Fu CHAN Lik Yuen Henry (Medicine & Therapeutics) 411 Faculty of Medicine Stanley Ho Centre for Emerging Infectious Diseases TANG Leung Sang Nelson (Chemical KUNG Hsiang Fu Pathology) LIN Marie MC* HE Mingliang SUNG Joseph Jao Yiu (Medicine & 30 June 2007 Therapeutics) CUHK Research Committee Funding (Direct CHAN Kay Sheung Paul (Microbiology) Grants) 1 February 2007 Common diseases are the consequence of Research Fund for the Control of Infectious complicated interactions between environmental Diseases factors and alleles of many genes. HBV-associated diseases (hepatitis, cirrhosis and hepatocellular We undertake to evaluate the potency of 23 different carcinoma is one of the major threatening for public isoforms of Type I IFNs in inhibiting avian H5N1 health leading to over one million deaths worldwide influenza A virus replication and/or infection. annually. particular, we would identify and characterize the However, the molecular mechanisms and In genetic factors are not fully understood. most potent isoform(s) as compared to that of Stress is involved in multiple steps of many diseases. IFN-α2A. Specifically, we aim at (1) To determine GRP78, a member of HSP70 family, is elevated in the efficacy of these 23 different isoforms of IFNs on HBV-associated HCC specimen. Our proteomics money kidney Vero, FRhk-4 and primary alveolar studies was obviously epithelial cells using anti-viral assay; (2) To further upregulated by induction of HBV reproduction in characterize the effects of the most potent isoforms of HepAD38 cells, suggesting GRP78 be a key gene IFNs on viral replication before and after avian H5N1 response to HBV infection and disease progression. infection using quantitative RT-PCR and plaque Here we plan to investigate the single nucleotide assay; (3) To determine the effect of the most potent polymorphisms (SNPs) of GRP78 gene and their IFN isoform on the global gene expression profile associations with HBV-associated diseases. We using the cDNA microarray technology; and (4) To will collect over 200 blood samples for each group, elucidate the anti-H5N1 mechanism and its respective including health Chinese, hepatitis, and HCC patients. downstream effectors targeted by the most potent Genomic DNA will be isolated for exploring SNPs IFN isoform in H5N1-infected cells using proteomics by PCR based DNA sequencing and/or allelic and bioinformatic technologies. discriminative real time PCR. (MD06439) revealed that GRP78 The associations among individual SNPs and disease will be discovered by statistic assays. The output of this The Assessment of Recently Acquired HIV study would not only reveal the relationship between Infection in Men Having Sex with Men (MSM) in GRP78 and HBV associated diseases, but possibly Hong Kong identity a new target for anti-HBV associated liver diseases as well. LEE Shui Shan TAM Ka Po HO Irene* (MD06727) 1 September 2006 Centre for Health Protection, Department of Super Interferons for the Treatment of Bird Flu Health, HKSAR Government (Avian H5N1 Influenza A) Faculty of Medicine 412 Stanley Ho Centre for Emerging Infectious Diseases Over the years, HTV situation in Hong Kong has HIV-infected patients who are failing their current been described as one of a low level epidemic in ART regimen and have limited or no therapeutic accordance with UNAIDS/WHO definition. The options. MK-0518 is an HIV integrase inhibitor in main route of transmission is sexual contact. phase III clinical development. To date there are no Infection as a result of needle-sharing in injection approved drugs that target the integration stage of the drug users has so far been uncommon. There were HIV-1 lifecycle. Data from ongoing studies suggest however recent reports of an increasing number of that MK-0518 is generally safe and well tolerated and men having sex with men (MSM) diagnosed with has the promise to be a clinically effective therapeutic HIV, alongside a higher prevalence in the very option for chronic HIV infection in highly treatment community. experienced patients. Due to its novel mechanism In response to the changing pattern of HIV of action, potent efficacy and tolerability, patients epidemiology, the current study aims to assess the with advanced HIV and limited therapeutic options risk of HTV spread among MSM in HK. The may benefit from early access to the drug. However, research comprises a qualitative study involving the it is important to carefully assess the risks versus interview of MSM, care providers and people in the potential benefits of using a drug before its safety community. profile has been completely characterized in clinical This would be followed by a self-administered questionnaire survey administered on HIV infected MSM. to be trials The results (MD06428) would be integrated with that of other epidemiology study, leading to an assessment report on the current Characterisation of Sexual Networks of MSM pattern, and the potential risk of future spread in the Preceding HIV Infection coming years. (MD06777) LEE Shui Shan TAM Ka Po 1 June 2007 Early Access of MK-0518 in Combination with an Council for the AIDS Trust Fund Optimized Background Antiretroviral Therapy (OBT) in Highly Treatment Experienced HIV-1 The aim of the study is to determine the HIV Infected Patients with Limited to No Treatment transmission potential in men having sex with men Options (MSM) in Hong Kong, with the objectives of (a) describing the social network configuration of MSM LEE Shui Shan WU Che Yuen Justin (Medicine & Therapeutics) prior to infection and (b) developing a framework for LEE Lai Shun Nelson (Medicine & Therapeutics) supporting case investigation. CHOI Kin A questionnaire is constructed through an adaptation of the UNAIDS Wing* questionnaire for tracing sexual networks. About 100 newly diagnosed HIV positive MSM would be 7 May 2007 recruited from an HIV service of the Department of Merck Sharp & Dohme (Asia) Ltd Health to join the study. The main themes of the There is an acute medical need for novel and potent study antiretroviral therapy (ART) for ART experienced relationship attributes, behavioural repertoire, and the 413 are: demographics, partners' attributes, Faculty of Medicine Stanley Ho Centre for Emerging Infectious Diseases types of establishments frequented by the subjects. 2004-05 Development of Interfering RNA Agents Participants are asked to self-complete one part of the to Inhibit SARS Associated Coronavirus study and join an in -depth interview. Infection and Replication (BL04674) Analysis HE Mingliang would be made on the network structures, behaviours and the risk of HIV dissemination, and the correlation of partnership attributes to behavioural risks. 2005-06 Development of Infectious HBV Rat Ethical approval would be obtained from the Ethics Model via AAV-Vector Mediated Gene Committee of Chinese University of Hong Kong, and Delivery (MD05419) the Department of Health. HE Mingliang (MD06659) 2005-06 Establishment of HIV-1 Assay Replication Please refer to previous issues of this publication Capacity for Enhancing for more details of the following ongoing research Management of AIDS Patients in Hong at the department: Kong (MD06450) HE Mingliang KUNG Hsiang Fu Edition LEE Shui Shan HUANG Yu* Title/Investigators 2004-05 Molecular 2005-06 Characteristics of Circulating Cell-Free Basis for the Telomere DNA in the Plasma (MD05439) Dysfunction and Anti-Tumor Activities DING Chunming LO Yuk Ming of a C-terminal Polypeptide of Human Pathology) Telomerase Dennis (Chemical Reverse Transcriptase LEUNG Tse Ngong (Obstetrics & (hTERTC27) (MD03854) Gynaecology) KUNG Hsiang Fu LAU Tze Kin LAM Lo Kuen Cindy* OHAYON Roger* (Obstetrics & Gynaecology) Functional 2004-05 Functional Characterization of Makorin-2 Regulation of TBX3 in Retina Formation and Its Interacting Proteins in Xenopus (BS03524) Embryonic Development (BL03394) HE Mingliang KUNG Hsiang Fu KUNG Hsiang Fu 2004-05 Transcriptional and King* 2004-05 The Mechanisms of a HE Mingliang TSUI Kwai OHAYON Roger* Novel HCC-associated Oncongene (HCAO) in Hepatocellular 2004-05 The Proteomics of the Brains of Human Carcinogenesis (BL04361) and Primate in Development (MD04603) HE Mingliang KUNG Hsiang Fu KUNG Hsiang Fu YEW Tai Wai David (Anatomy) FAWCELL JW* Faculty of Medicine 414 Stanley Ho Centre for Emerging Infectious Diseases 2004-05 Characterizing the Role of 2005-06 Novel Anti-HIV Drug: A Cyclosporine PI3K Signaling Cascade in Xenopus Neural Anolog (MD06833) Induction (BL04767) KUNG Hsiang Fu HE Mingliang KUNG Hsiang Fu LEE Shui Shan 2004-05 Research and Development of a New 2005-06 Molecular Epidemiology of HIV in TCM-Based Antidepressant (MD04822) Injection Drug Users (MD05708) KUNG LEE Shui Shan Hsiang Fu KONG Lingdong# LU Xiaobo TSUI Kwok Wing (Biochemistry (Medicine)) CHAN Kay Sheung Paul (Microbiology) 2005-06 Research into Integrative Medical Sciences (MD05627) KUNG Hsiang Fu Chang (Physiology) CHAN Hsiao POON Chuen Wai (Medicine & Therapeutics) 415 Faculty of Medicine The following symbols are used throughout the Research Projects section: " Investigator(s) Commencement Date Source(s) of Fund * Name of external researcher # Name of staff who has left the University as of 1 September 2007
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