2.Opposite Roles of B7.1 and CD28 Costimulatory Molecules for Protective Immunity against HSV-2 Challenge in a gD DNA Vaccine Model.
Immune Network 2005;5(2):68-77
BACKGROUND: Costimulation is a critical process in Ag-specific immune responses. Both B7.1 and CD28 molecules have been reported to stimulate T cell responses during antigen presentation. Therefore, we tested whether Ag-specific immune responses as well as protective immunity are influenced by coinjecting with B7.1 and CD28 cDNAs in a mouse HSV-2 challenge model system. METHODS: ELISA was used to detect levels of antibodies, cytokines and chemokines while thymidine incorporation assay was used to evaluate T cell proliferation levels. RESULTS: Ag-specific antibody responses were enhanced by CD28 coinjection but not by B7.1 coinjection. Furthermore, CD28 coinjection increased IgG1 production to a significant level, as compared to pgD+pcDNA3, suggesting that CD28 drives Th2 type responses. In contrast, B7.1 coinjection showed the opposite, suggesting a Th1 bias. B7.1 coinjection also enhanced Ag-specific Th cell proliferative responses as well as production of Th1 type cytokines and chemokines significantly higher than pgD+pcDNA3. However, CD28 coinjection decreased Ag-specific Th cell proliferative responses as well as production of Th1 types of cytokines and chemokine significantly lower than pgD+pcDNA3. Only MCP-1 production was enhanced by CD28. B7.1 coimmunized animals exhibited an enhanced survival rate as well as decreased herpetic lesion formation, as compared to pgD+pcDNA3. In contrast, CD28 vaccinated animals exhibited decreased survival from lethal challenge. CONCLUSION: This study shows that B7.1 enhances protective Th1 type cellular immunity against HSV-2 challenge while CD28 drives a more detrimental Th2 type immunity against HSV-2 challenge, supporting an opposite role of B7.1 and CD28 in Ag-specific immune responses to a Th1 vs Th2 type.
Animals
;
Antibodies
;
Antibody Formation
;
Antigen Presentation
;
Bias (Epidemiology)
;
Cell Proliferation
;
Chemokines
;
Cytokines
;
DNA*
;
DNA, Complementary
;
Enzyme-Linked Immunosorbent Assay
;
Herpesvirus 2, Human*
;
Immunity, Cellular
;
Immunoglobulin G
;
Mice
;
Survival Rate
;
Thymidine
3.Acute Paraplegia as a Result of Hemorrhagic Spinal Ependymoma Masked by Spinal Anesthesia: Case Report and Review of Literature.
Sang Hyo LEE ; David Jaehyun PARK ; Sin Soo JEUN
Brain Tumor Research and Treatment 2016;4(1):30-34
Ependymomas are the most common intramedullary spinal cord tumors in adults. Although a hemorrhage within spinal ependymoma on imaging studies is not uncommon, it has rarely been reported to bea cause of acute neurological deficit. In the present report, we describe a case of a 24-year-old female patient who developed acute paraplegia as a result of hemorrhagic spinal ependymoma immediately after a cesarean delivery under spinal regional anesthesia. We review the literature of hemorrhagic spinal ependymomas presenting with acute neurological deficit and discuss the most appropriate treatment for a good neurological recovery.
Adult
;
Anesthesia, Conduction
;
Anesthesia, Spinal*
;
Ependymoma*
;
Female
;
Hemorrhage
;
Humans
;
Masks*
;
Paraplegia*
;
Spinal Cord Neoplasms
;
Young Adult
4.Acute Paraplegia as a Result of Hemorrhagic Spinal Ependymoma Masked by Spinal Anesthesia: Case Report and Review of Literature.
Sang Hyo LEE ; David Jaehyun PARK ; Sin Soo JEUN
Brain Tumor Research and Treatment 2016;4(1):30-34
Ependymomas are the most common intramedullary spinal cord tumors in adults. Although a hemorrhage within spinal ependymoma on imaging studies is not uncommon, it has rarely been reported to bea cause of acute neurological deficit. In the present report, we describe a case of a 24-year-old female patient who developed acute paraplegia as a result of hemorrhagic spinal ependymoma immediately after a cesarean delivery under spinal regional anesthesia. We review the literature of hemorrhagic spinal ependymomas presenting with acute neurological deficit and discuss the most appropriate treatment for a good neurological recovery.
Adult
;
Anesthesia, Conduction
;
Anesthesia, Spinal*
;
Ependymoma*
;
Female
;
Hemorrhage
;
Humans
;
Masks*
;
Paraplegia*
;
Spinal Cord Neoplasms
;
Young Adult
5.When less is more: can we abandon prophylactic platelet transfusion in Dengue fever?
Changa KURUKULARATNE ; Frederico DIMATATAC ; Diana Lt TEO ; David C LYE ; Yee Sin LEO
Annals of the Academy of Medicine, Singapore 2011;40(12):539-545
Dengue fever (DF) has several hematological manifestations including thrombocytopenia and increased bleeding risk. Prophylactic platelet transfusion-in the absence of major bleeding-is utilized in DF with thrombocytopenia with the intention of preventing hemorrhagic complications. However, prophylactic platelet transfusion in DF is neither standardized nor supported by clinical evidence. We conclude that risks, costs and poor resource utilization associated with prophylactic platelet transfusion in DF far outweigh any potential hematological benefit, and as such, should not constitute routine clinical practice.
Dengue
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complications
;
therapy
;
Hemorrhage
;
etiology
;
prevention & control
;
Humans
;
Platelet Transfusion
;
adverse effects
;
economics
;
Thrombocytopenia
;
etiology
;
prevention & control
6.Dengue knowledge, attitudes, and practices among primary care physicians in Singapore.
Linda K LEE ; Tun Linn THEIN ; Changa KURUKULARATNE ; Victor Ch GAN ; David C LYE ; Yee Sin LEO
Annals of the Academy of Medicine, Singapore 2011;40(12):533-538
INTRODUCTIONDengue fever remains a significant public health concern in Singapore. Appropriate, timely diagnosis and risk stratification for severe disease are crucial in the optimal management of this illness. In the outpatient setting, the primary care physician plays a key role in dengue diagnosis, management, and triage. We present a descriptive analysis of the variations in dengue knowledge, attitudes, and practices among primary care physicians (PCPs) in Singapore.
MATERIALS AND METHODSA survey of 25 multiple-choice questions was mailed to 2000 PCPs in Singapore. Responses were analysed by physician age group (21-40, 41-60, and >61) and practice setting (government subsidised polyclinic or private practice).
RESULTSOf the 3 questions assessing dengue knowledge, 89.9% chose 2 or 3 of the preferred responses. Half of the respondents utilised dengue diagnostic tests at least 50% of the time, and 75% used serology when doing so. Older respondents and those from private practices used diagnostic tests more often than their counterparts, and both groups favoured non-serology tests. About 85% of surveyed PCPs monitored confirmed or suspected cases daily, and one-third referred patients to a hospital always or often.
CONCLUSIONSWhile no major gaps in knowledge about dengue were identified in PCPs in Singapore, there were significant variations in clinical practice by physician age group and practice setting. The results of this survey provide a useful opportunity to identify strengths and areas in need of improved awareness in primary care management of dengue.
Adult ; Dengue ; Female ; Health Knowledge, Attitudes, Practice ; Humans ; Male ; Middle Aged ; Physicians, Primary Care ; Public Health ; Singapore ; Surveys and Questionnaires
7.“I'm healthy, I don't have pain”- health screening participation and its association with chronic pain in a low socioeconomic status Singaporean population.
Liang En WEE ; David SIN ; Wen Qi CHER ; Zong Chen LI ; Tammy TSANG ; Sabina SHIBLI ; Gerald KOH
The Korean Journal of Pain 2017;30(1):34-43
BACKGROUND: We sought to determine the association between chronic pain and participating in routine health screening in a low socioeconomic-status (SES) rental-flat community in Singapore. In Singapore, ≥ 85% own homes; public rental flats are reserved for those with low-income. METHODS: Chronic pain was defined as pain ≥ 3 months. From 2009−2014, residents aged 40−60 years in five public rental-flat enclaves were surveyed for chronic pain; participation in health screening was also measured. We compared them to residents staying in adjacent owner-occupied public housing. We also conducted a qualitative study to better understand the relationship between chronic pain and health screening participation amongst residents in these low-SES enclaves. RESULTS: In the rental-flat population, chronic pain was associated with higher participation in screening for diabetes (aOR = 2.11, CI = 1.36−3.27, P < 0.001), dyslipidemia (aOR = 2.06, CI = 1.25−3.39, P = 0.005), colorectal cancer (aOR = 2.28, CI = 1.18−4.40, P = 0.014), cervical cancer (aOR = 2.65, CI = 1.34−5.23, P = 0.005) and breast cancer (aOR = 3.52, CI = 1.94−6.41, P < 0.001); this association was not present in the owner-occupied population. Three main themes emerged from our qualitative analysis of the link between chronic pain and screening participation: pain as an association of “major illness”; screening as a search for answers to pain; and labelling pain as an end in itself. CONCLUSIONS: Chronic pain was associated with higher cardiovascular and cancer screening participation in the low-SES population. In low-SES populations with limited access to pain management services, chronic pain issues may surface during routine health screening.
Asian Continental Ancestry Group
;
Breast Neoplasms
;
Chronic Pain*
;
Colorectal Neoplasms
;
Dyslipidemias
;
Early Detection of Cancer
;
Humans
;
Mass Screening*
;
Pain Management
;
Public Housing
;
Singapore
;
Social Class*
;
Uterine Cervical Neoplasms
8.Ertapenem for treatment of extended-spectrum beta-lactamase-producing and multidrug-resistant gram-negative bacteraemia.
David Chien LYE ; Limin WIJAYA ; Joey CHAN ; Chew Ping TENG ; Yee Sin LEO
Annals of the Academy of Medicine, Singapore 2008;37(10):831-834
INTRODUCTIONImipenem and meropenem are treatment of choice for extended-spectrum betalactamase (ESBL)-positive gram-negative bacteraemia. They may select for carbapenemresistant Acinetobacter baumannii and Pseudomonas aeruginosa; ertapenem may not do so as it is inactive against these bacteria. Clinical efficacy of ertapenem in ESBL-producing gramnegative bacteraemia is limited.
MATERIALS AND METHODSRetrospective study of patients with ESBL-positive gram-negative bacteraemia treated with ertapenem was undertaken.
RESULTSForty-seven patients with multidrug-resistant gram-negative bacteraemia (79% produced ESBL) were treated with ertapenem for a median duration of 11 days. The median age was 70 years. Septic shock occurred in 19% and mechanical ventilation was needed in 17%. Klebsiella pneumoniae comprised 53% and Escherichia coli 26%. Urinary infection accounted for 61% and hepatobiliary 15%. Favourable clinical response occurred in 96%. Attributable mortality was 4%.
CONCLUSIONErtapenem is promising in culture-guided step-down therapy of ESBL-positive gram-negative bacteraemia.
Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents ; pharmacology ; therapeutic use ; Bacteremia ; drug therapy ; etiology ; Drug Resistance, Multiple, Bacterial ; Escherichia coli ; drug effects ; enzymology ; Escherichia coli Infections ; drug therapy ; microbiology ; Female ; Gram-Negative Bacteria ; drug effects ; enzymology ; Gram-Negative Bacterial Infections ; drug therapy ; microbiology ; Humans ; Klebsiella Infections ; drug therapy ; microbiology ; Klebsiella pneumoniae ; drug effects ; enzymology ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Retrospective Studies ; Urinary Tract Infections ; complications ; drug therapy ; beta-Lactamases ; biosynthesis ; beta-Lactams ; pharmacology ; therapeutic use
9.Review of human infections with avian influenza H5N1 and proposed local clinical management guideline.
David C B LYE ; Brenda S P ANG ; Yee-Sin LEO
Annals of the Academy of Medicine, Singapore 2007;36(4):285-292
INTRODUCTIONThe current avian and human H5N1 influenza epidemic has been in resurgence since 2004. We decided to evaluate published evidence in relation to epidemiology, clinical features and course, laboratory diagnosis, treatment and outcome of human H5N1 influenza, and develop institutional clinical management guidelines.
METHODSA search of PubMed was conducted for all English language articles with search terms "avian", "influenza" and "H5N1". The bibliography of articles was searched for other references of interest.
RESULTSPublished case series from Hong Kong in 1997, and Thailand and Vietnam since 2004 have indicated a rapidly progressive primary viral pneumonia resulting in acute respiratory distress syndrome. The majority of human H5N1 infections can be linked to poultry exposure. Hitherto there has been no evidence of efficient human-to-human transmission. Case fatality rates have varied from 71% in Thailand to 100% in Cambodia. Oseltamivir appears to be the only potentially effective antiviral therapy. H5N1 isolates in Vietnam have become resistant to oseltamivir, resulting in persistent viral replication and death. There is as yet no effective human H5N1 vaccine.
CONCLUSIONSNational and international preparedness plans are well advised. Clinical trials to evaluate higher dose oseltamivir therapy and immunomodulatory treatment are urgently needed.
Animals ; Birds ; Disease Outbreaks ; prevention & control ; Global Health ; Health Planning ; Humans ; Influenza A Virus, H5N1 Subtype ; Influenza Vaccines ; Influenza in Birds ; epidemiology ; prevention & control ; virology ; Influenza, Human ; epidemiology ; prevention & control ; virology ; Practice Guidelines as Topic
10.Load response of the natural tooth and dental implant: A comparative biomechanics study
Dale ROBINSON ; Luis AGUILAR ; Andrea GATTI ; Jaafar ABDUO ; Peter Vee Sin LEE ; David ACKLAND
The Journal of Advanced Prosthodontics 2019;11(3):169-178
PURPOSE: While dental implants have displayed high success rates, poor mechanical fixation is a common complication, and their biomechanical response to occlusal loading remains poorly understood. This study aimed to develop and validate a computational model of a natural first premolar and a dental implant with matching crown morphology, and quantify their mechanical response to loading at the occlusal surface. MATERIALS AND METHODS: A finite-element model of the stomatognathic system comprising the mandible, first premolar and periodontal ligament (PDL) was developed based on a natural human tooth, and a model of a dental implant of identical occlusal geometry was also created. Occlusal loading was simulated using point forces applied at seven landmarks on each crown. Model predictions were validated using strain gauge measurements acquired during loading of matched physical models of the tooth and implant assemblies. RESULTS: For the natural tooth, the maximum vonMises stress (6.4 MPa) and maximal principal strains at the mandible (1.8 mε, −1.7 mε) were lower than those observed at the prosthetic tooth (12.5 MPa, 3.2 mε, and −4.4 mε, respectively). As occlusal load was applied more bucally relative to the tooth central axis, stress and strain magnitudes increased. CONCLUSION: Occlusal loading of the natural tooth results in lower stress-strain magnitudes in the underlying alveolar bone than those associated with a dental implant of matched occlusal anatomy. The PDL may function to mitigate axial and bending stress intensities resulting from off-centered occlusal loads. The findings may be useful in dental implant design, restoration material selection, and surgical planning.
Bicuspid
;
Crowns
;
Dental Implants
;
Dental Occlusion
;
Finite Element Analysis
;
Humans
;
Mandible
;
Periodontal Ligament
;
Stomatognathic System
;
Tooth