Chihara Y.,University of Sydney |
Chihara Y.,Sensory Medical |
Chihara Y.,Raffles Hospital |
Wang V.,University of Sydney |
Brown D.J.,University of Sydney
Experimental Brain Research | Year: 2013
Previous studies have shown that the vestibular short-latency-evoked potential (VsEP) in response to the brief head acceleration stimulus is a compound action potential of neurons innervating the otolith organs. However, due to the lack of direct evidence, it is currently unclear whether the VsEP is primarily generated by the activity of utricular or saccular afferent neurons, or some mixture of the two. Here, we investigated the origin of the VsEP evoked by brief bone-conducted vibration pulses in guinea pigs, using selective destruction of the cochlea, semicircular canals (SCCs), saccule, or utricle, along with neural blockade with tetrodotoxin (TTX) application, and mechanical displacements of the surgically exposed utricular macula. To access each end organ, either a dorsal or a ventral surgical approach was used. TTX application abolished the VsEP, supporting the neurogenic origin of the response. Selective cochlear, SCCs, or saccular destruction had no significant effect on VsEP amplitude, whereas utricular destruction abolished the VsEP completely. Displacement of the utricular membrane changed the VsEP amplitude in a non-monotonic fashion. These results suggest that the VsEP evoked by BCV in guinea pigs represents almost entirely a utricular response. Furthermore, it suggests that displacements of the utricular macula may alter its response to bone-conduction stimuli. © Springer-Verlag Berlin Heidelberg 2013.
Kwong Y.-L.,Queen Mary Hospital |
Chan T.S.Y.,Queen Mary Hospital |
Tan D.,Raffles Hospital |
Tan D.,Singapore General Hospital |
And 10 more authors.
Blood | Year: 2017
Natural killer (NK)/T-cell lymphomas failing L-asparaginse regimens have no known salvage and are almost invariably fatal. Seven male patients with NK/T-cell lymphoma (median age, 49 years; range, 31-68 years) for whom a median of 2 (range, 1-5) regimens (including L-asparaginase regimens and allogeneic hematopoietic stem-cell transplantation [HSCT] in 2 cases) failed were treated with the anti-programmed death 1 (PD1) antibody pembrolizumab. All patients responded, according to various clinical, radiologic (positron emission tomography), morphologic, and molecular (circulating Epstein-Barr virus [EBV] DNA) criteria. Two patients achieved complete response (CR) in all parameters. Three patients achieved clinical and radiologic CRs, with two having molecular remission (undetectable EBV DNA) but minimal EBV-encoded RNA-positive cells in lesions comprising predominantly CD3+CD4+ and CD3+CD8+ T cells (which ultimately disappeared, suggesting they represented pseudoprogression) and one having detectable EBV DNA despite morphologic CR. Two patients achieved partial response (PR). After a median of 7 (range, 2-13) cycles of pembrolizumab and a follow-up of a median of 6 (range, 2-10) months, all five CR patients were still in remission. The only adverse event was grade 2 skin graft-versus-host disease in one patient with previous allogeneic HSCT. Expression of the PD1 ligand was strong in 4 patients (3 achieving CR) and weak in 1 (achieving PR). PD1 blockade with pembrolizumab was a potent strategy for NK/T-cell lymphomas failing L-asparaginase regimens. © 2017 by The American Society of Hematology.
Chen C.L.H.,National University of Singapore |
Venketasubramanian N.,Raffles Hospital |
Lee C.F.,Singapore Clinical Research Institute |
Wong K.S.L.,Chinese University of Hong Kong |
Bousser M.-G.,Lariboisiere University Hospital
Stroke | Year: 2013
BACKGROUND AND PURPOSE - Early vascular events are an important cause of morbidity and mortality in the first 3 months after a stroke. We aimed to investigate the effects of MLC601 on the occurrence of early vascular events within 3 months of stroke onset. METHODS - Post hoc analysis was performed on data from subjects included in the CHInese Medicine Neuroaid Efficacy on Stroke recovery (CHIMES) study, a randomized, placebo-controlled, double-blinded trial that compared MLC601 with placebo in 1099 subjects with ischemic stroke of intermediate severity in the preceding 72 hours. Early vascular events were defined as a composite of recurrent stroke, acute coronary syndrome, and vascular death occurring within 3 months of stroke onset. RESULTS - The frequency of early vascular events during the 3-month follow-up was significantly less in the MLC601 group than in the placebo group (16 [2.9%] versus 31 events [5.6%]; risk difference=-2.7%; 95% confidence interval, -5.1% to -0.4%; P=0.025) without an increase in nonvascular deaths. Kaplan-Meier survival analysis showed a difference in the risk of vascular outcomes between the 2 groups as early as the first month after stroke (Log-rank P=0.024; hazard ratio, 0.51; 95% confidence interval, 0.28-0.93). CONCLUSIONS - Treatment with MLC601 was associated with reduced early vascular events among subjects in the CHIMES study. The mechanisms for this effect require further study. © 2013 American Heart Association, Inc.
Tan D.,Raffles Hospital |
Tan D.,SGP General Hospital |
Chng W.J.,National University of Singapore |
Chou T.,Niigata Cancer Center Hospital |
And 6 more authors.
The Lancet Oncology | Year: 2013
Treatment of multiple myeloma has undergone substantial developments in the past 10 years. The introduction of novel drugs has changed the treatment of the disease and substantially improved survival outcomes. Clinical practice guidelines based on evidence have been developed to provide recommendations on standard treatment approaches. However, the guidelines do not take into account resource limitations encountered by developing countries. The huge disparities in economy, health-care infrastructure, and access to novel drugs in Asian countries hinder the delivery of optimum care to every patient with multiple myeloma in Asia. In this Review we outline the guidelines that correspond with different levels of health-care resources and expertise, with the aim to unify diagnostic and therapeutic guidelines and help with the design of future studies in Asia. © 2013 Elsevier Ltd.
Tan D.,Raffles Hospital |
Tan D.,Singapore General Hospital |
Tan S.Y.,Singapore General Hospital |
Tan S.Y.,National University of Singapore |
And 7 more authors.
The Lancet Oncology | Year: 2013
Treatment of B-cell non-Hodgkin lymphomas has undergone substantial developments in the past 10 years. The introduction of rituximab has greatly improved survival outcomes in patients. Clinical practice guidelines based on current evidence have been developed to provide recommendations for standard treatment approaches. However, guidelines do not take into account resource limitations in resource-poor countries. The huge disparities in economy, health-care infrastructure, and access to novel drugs between Asian countries can hinder the delivery of optimum care to patients with lymphoma in Asia. We outline guidelines appropriate to different levels of health-care resources and expertise, aiming to provide advice on diagnosis and treatment, unify interpretation of results, and allow the design of future studies in Asia. In this resource-adapted consensus, we summarise recommendations for diagnosis, staging, risk stratification, and treatment of common B-cell non-Hodgkin lymphomas in Asia. © 2013 Elsevier Ltd.
Lim K.B.,Raffles Hospital
Asian Journal of Urology | Year: 2017
Clinical benign prostatic hyperplasia (BPH) is one of the most common diseases in ageing men and the most common cause of lower urinary tract symptoms (LUTS). The prevalence of BPH increases after the age of 40 years, with a prevalence of 8%–60% at age 90 years. Some data have suggested that there is decreased risk among the Asians compared to the western white population. Genetics, diet and life style may play a role here. Recent reports suggest the strong relationship of clinical BPH with metabolic syndrome and erectile dysfunction, as well as the possible role of inflammation as a cause of the prostatic hyperplasia. Lifestyle changes including exercise and diet are important strategies in controlling this common ailment. © 2017 Editorial Office of Asian Journal of Urology
Bathla G.,University of Iowa |
Hegde A.,Raffles Hospital
Clinical Radiology | Year: 2016
Lymphoma may arise within the central nervous system (CNS), known as primary CNS lymphoma (PCNSL) or may involve the CNS secondary to systemic disease. Clinical features are non-specific. A provisional diagnosis of PCNSL can be made on imaging, potentially changing the management algorithm from neurosurgical resection to biopsy. PCNSL in immunocompetent patients generally presents late, is solid, is bright on diffusion weighted imaging and shows uniform enhancement. Contiguity with a cerebrospinal fluid (CSF) surface and perivascular enhancement are useful clues. Immunocompromised patients, on the other hand, present earlier and often have multiple, necrotic, haemorrhagic lesions with irregular or rim enhancement. Secondary CNS involvement predominantly affects the leptomeninges. This review illustrates the varied imaging features of CNS lymphoma, atypical presentations, and differential diagnoses. © 2016 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.
Macleod D.B.,Duke University |
Habib A.S.,Duke University |
Ikeda K.,Duke University |
Spyker D.A.,Alexza Pharmaceuticals Inc. |
And 3 more authors.
Anesthesia and Analgesia | Year: 2012
BACKGROUND: Rapid delivery of potent opioid to the systemic circulation is an important feature for the effective treatment of acute and acute-on-chronic breakthrough pain. The delivery of different opioids by the pulmonary route has been inconsistent, usually resulting in low bioavailability of the drug. Staccato® Fentanyl for Inhalation is a handheld inhaler producing a single metered dose of aerosolized fentanyl during a single inspiration. The aerosol is of high purity (≥98%) at a particle size (1 to 3.5 microns) shown to be best for pulmonary absorption.METHODS: We conducted the study in healthy volunteers in 2 stages. In the crossover stage, 10 subjects received IV fentanyl 25 μg and inhaled fentanyl 25 μg on separate occasions. The dose escalation stage was a multidose, randomized, double-blind, placebo-controlled, single-period dose escalation study of inhaled fentanyl (50 to 300 μg). Serial blood sampling was performed over an 8-hour period after drug administration to determine the pharmacokinetic profile, and serial pupillometry was performed as a measure of pharmacodynamic effect.RESULTS: In the crossover stage the pharmacokinetic profiles of the inhaled and IV fentanyl showed similar peak arterial concentrations and areas under the curve. The time to maximum concentration was slightly shorter for the inhaled than IV fentanyl, 20.5 and 31.5 seconds, respectively. In the dose escalation stage the administration of repeated doses resulted in predictable, dose-dependent serum concentrations.CONCLUSIONS: This study has demonstrated that the pharmacokinetic profile of single doses of inhaled fentanyl is comparable to IV administration. Copyright © 2012 International Anesthesia Research Society.
Anil G.,Singapore General Hospital |
Anil G.,Changi General Hospital |
Tay K.-H.,Singapore General Hospital |
Howe T.-C.,Raffles Hospital |
Tan B.-S.,Singapore General Hospital
CardioVascular and Interventional Radiology | Year: 2011
This study reviews our experience with dynamic computed tomographic angiography (CTA) as an imaging modality in the evaluation of popliteal artery entrapment syndrome (PAES). Eight patients with surgically proven PAES were included in this study. Dynamic CTA studies performed with the feet in neutral and plantar flexed positions were reviewed for the detailed anatomy of the region and to define the location and extent of the stenosis, occlusions and collateral circulation. These findings were compared with intraoperative observations. CTA provided adequate angiographic and anatomic information required to arrive at the diagnosis and make a surgical decision. Thirteen limbs were affected in eight patients. There was popliteal artery occlusion in four limbs, stenosis at rest that was accentuated on stress imaging in two limbs, and patent popliteal artery with marked stenosis on stress imaging in seven limbs. Long-segment stenosis was seen in functional entrapment compared to short-segment stenosis in anatomic PAES. Anteroposterior compression of the popliteal artery in anatomic PAES unlike the side-to-side compression in functional PAES was a unique observation in this study. The CTA and surgical characterisation and classification of PAES matched in all the patients, except for misinterpretation of compressing fibrous bands as accessory slips of muscles in three limbs. In conclusion, dynamic CTA is a robust diagnostic tool that provides clinically relevant information and serves as a rapidly performed and easily available "one-stop-shop" imaging modality in the management of PAES. © 2010 Springer Science+Business Media, LLC.
Zhang J.,Zhengzhou University |
Ho K.-Y.,Raffles Hospital |
Wang Y.,Zhengzhou University
British Journal of Anaesthesia | Year: 2011
Multimodal treatment of postoperative pain using adjuncts such as gabapentin is becoming more common. Pregabalin has anti-hyperalgesic properties similar to gabapentin. In this systematic review, we evaluated randomized, controlled trials (RCTs) for the analgesic efficacy and opioid-sparing effect of pregabalin in acute postoperative pain. A systematic search of Medline (1966-2010), the Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar was performed. We identified 11 valid RCTs that used pregabalin for acute postoperative pain. Postoperative pain intensity was not reduced by pregabalin. Cumulative opioid consumption at 24 h was significantly decreased with pregabalin. At pregabalin doses of ≥300 mg, there was a reduction of 8.8 mg [weighted mean difference (WMD)]. At pregabalin doses <300 mg, cumulative opioid consumption was even lower (WMD, -13.4 mg). Pregabalin reduced opioid-related adverse effects such as vomiting [risk ratio (RR) 0.73; 95% confidence interval (CI) 0.56-0.95]. However, the risk of visual disturbance was greater (RR 3.29; 95% CI 1.95-5.57). Perioperative pregabalin administration reduced opioid consumption and opioid-related adverse effects after surgery. © The Author . Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.