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Background: Severe acute respiratory syndrome (SARS) is a newly recognized infectious disease that has recently emerged in East Asia and North America. Although the clinical features of acute infection have been well described, mildly symptomatic or asymptomatic infections have not been well characterized.Objective: To assess the spectrum of illness in health-care workers (HCWs).Methods: A prospective seroepidemiologic cohort study was conducted on 372 HCWs in a large teaching hospital in Singapore who were both exposed and not exposed to patients with SARS. Participating HCWs completed a questionnaire and provided paired serum samples, which were analyzed by 2 different laboratories blinded to clinical data, by use of an enzyme-linked immunosorbent assay based on a protocol developed by the Centers for Disease Control and Prevention and a dot-blot immunoassay, with confirmation by a viral neutralization assay.Results: A total of 21 patients with SARS were treated at our hospital. They were associated with transmission to 14 staff members, patients, and visitors in our hospital. Of the 372 HCWs participating in the present study, 8 were found to have positive antibodies to the SARS coronavirus in both samples by use of both test methods, and 6 had pneumonia and had been hospitalized for either probable or suspected SARS infection, whereas 2 had fever but did not have changes on chest radiographs. All seropositive HCWs had been exposed either directly or indirectly to patients with SARS. No asymptomatic, nonexposed staff members were found to be seropositive. There was a trend towards protection for HCWs who, while fully protected, had had contact with patients with SARS.Conclusions: Although the majority of cases of SARS are associated with pneumonia, a small number of mildly symptomatic individuals do seroconvert. HCWs who are exposed to patients with SARS can be infected with SARS, regardless of the intensity of exposure. This has implications for surveillance and infection control planning, in the event that SARS returns next winter. [ABSTRACT FROM AUTHOR]

Background: Major musculoskeletal oncology procedures often result in perioperative bleeding. This exposes patients to allogeneic red blood cell transfusion and its potential complications, thus increasing the risk of surgical wound infection and prolonged hospital stay. This study aimed to investigate the efficacy of oxidised cellulose, a topical haemostatic agent, in reducing postoperative blood loss and its subsequent risks., Methods: In this randomised controlled trial, 40 patients undergoing major musculoskeletal oncology procedures were assigned to control and intervention groups. Oxidised cellulose was inserted into the surgical wound after the resection's conclusion before the wound's closure to reduce postoperative bleeding for patients in the intervention group. Postoperative closed suction drain system (Redivac TM) volume, drop in haemoglobin level, allogeneic red blood cell transfusion rate, duration of surgery, and length of hospital stay were compared between the two groups., Results: The postoperative Redivac volume (Control: 432 MLS vs. Intervention: 431.75 MLS), drop in haemoglobin level (Control: 3.12 g/dL vs. Intervention: 3.06 g/dL), duration of surgery (Control: 134 vs. Intervention: 156 min), and allogeneic red blood cell transfusion were lower in the intervention group (Control: 204 MLS vs. Intervention: 170 MLS), but they were not statistically significant (p > 0.05) (Control: 134 vs. Intervention: 156 min). Mean hospital stay was similar in both groups (Control: 5.45 days vs. Intervention: 5.85 days)., Conclusion: Oxidised cellulose use does not significantly affect postoperative blood loss, the rate of allogeneic blood transfusion, and hospital stay. However, we believe its use contributes positively but not considerably towards lower postoperative blood loss in musculoskeletal oncology surgeries., (© 2024. The Author(s), under exclusive licence to Istituto Ortopedico Rizzoli.)

Human Enterovirus 71 (EV71) commonly causes Hand, Foot and Mouth Disease in young children, and occasional occurrences of neurological complications can be fatal. In this study, a high-throughput cell-based screening on the serine/threonine kinase siRNA library was performed to identify potential antiviral agents against EV71 replication. Among the hits, Misshapen/NIKs-related kinase (MINK) was selected for detailed analysis due to its strong inhibitory profile and novelty. In the investigation of the stage at which MINK is involved in EV71 replication, virus RNA transfection in MINK siRNA-treated cells continued to cause virus inhibition despite bypassing the normal entry pathway, suggesting its involvement at the post-entry stage. We have also shown that viral RNA and protein expression level was significantly reduced upon MINK silencing, suggesting its involvement in viral protein synthesis which feeds into viral RNA replication process. Through proteomic analysis and infection inhibition assay, we found that the activation of MINK was triggered by early replication events, instead of the binding and entry of the virus. Proteomic analysis on the activation profile of p38 Mitogen-activated Protein Kinase (MAPK) indicated that the phosphorylation of p38 MAPK was stimulated by EV71 infection upon MINK activation. Luciferase reporter assay further revealed that the translation efficiency of the EV71 internal ribosomal entry site (IRES) was reduced after blocking the MINK/p38 MAPK pathway. Further investigation on the effect of MINK silencing on heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) localisation demonstrated that cytoplasmic relocalisation of hnRNP A1 upon EV71 infection may be facilitated via the MINK/p38 MAPK pathway which then positively regulates the translation of viral RNA transcripts. These novel findings hence suggest that MINK plays a functional role in the IRES-mediated translation of EV71 viral RNA and may provide a potential target for the development of specific antiviral strategies against EV71 infection.

Intravenous immunoglobulin (IVIG) is the first line treatment for Guillain-Barré syndrome and multifocal motor neuropathy, which are caused by anti-ganglioside antibody-mediated complement-dependent cytotoxicity. IVIG has many potential mechanisms of action, and sialylation of the IgG Fc portion reportedly has an anti-inflammatory effect in antibody-dependent cell-mediated cytotoxicity models. We investigated the effects of different IVIG glycoforms on the inhibition of antibody-mediated complement-dependent cytotoxicity. Deglycosylated, degalactosylated, galactosylated and sialylated IgG were prepared from IVIG following treatment with glycosidases and glycosyltransferases. Sera from patients with Guillain-Barré syndrome, Miller Fisher syndrome and multifocal motor neuropathy associated with anti-ganglioside antibodies were used. Inhibition of complement deposition subsequent to IgG or IgM autoantibody binding to ganglioside, GM1 or GQ1b was assessed on microtiter plates. Sialylated and galactosylated IVIGs more effectively inhibited C3 deposition than original IVIG or enzyme-treated IVIGs (agalactosylated and deglycosylated IVIGs). Therefore, sialylated and galactosylated IVIGs may be more effective than conventional IVIG in the treatment of complement-dependent autoimmune diseases.

Purpose: This study aimed to understand hypertensive patients' perceptions of and adherence to prescribed medication., Methods: A qualitative research study based on 23 purposely selected participants from a community health clinic in Malaysia. The participants underwent in-depth semi-structured interviews, and the data were analyzed using qualitative content analysis method., Results: The participants were presented with six types of perceptions of medication. The majority of the participants had negative perceptions of Western medicine (WM), self-adjusted their prescribed medication with complementary and alternative medicine (CAM) and concealed their self-adjusting habits from their doctors. Participants who thought positively of WM took their prescribed medication regularly. Most of the participants perceived the nature of WM as not being curative because of its side effects. Patients have the right to choose their preferred medication when they understand their illness., Conclusion: Local health care systems should provide patients with alternative health services that suit their requests., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Data on interethnic differences in the Asian stroke population are limited. We evaluated the relationships among various cardiovascular risk factors, stroke subtypes, and outcomes in a multiethnic Singaporean population comprising consecutive ischemic stroke patients presenting to our tertiary center over a 1-year period. Strokes were classified based on criteria used in the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Functional independence at hospital discharge was defined as a modified Rankin Scale (mRS) score of 0-2. The ethnic distribution of the study population (n = 481; mean age, 64.1 ± 11.9 years) was 74% Chinese, 17% Malay, and 9% Indian. The prevalence of risk factors was similar in the 3 ethnic groups except for diabetes (Chinese, 39.8%; Malay, 67.5%; Indian, 52.3%; P < .001). Hypertension and hypercholesterolemia were the most common cardiovascular risk factors. Lacunar stroke was the most frequent stroke subtype (47.9%). Large-artery atherosclerotic infarctions were more prevalent in Indians (25.0%), whereas lacunar infarctions occured more frequently in Chinese (51.8%; P < .01). No differences in in-hospital mortality and functional independence at discharge were seen among the 3 ethnic groups. Despite the differences in risk factors and in stroke subtypes classified by location or underlying etiology, short-term outcome measures were similar in the 3 different Asian ethnicities in Singapore., (Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: The rates and extent of recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (IV-tPA) remain highly variable. Hyperdense middle cerebral artery sign (HMCAS) on pretreatment unenhanced computerized tomography (CT) of the brain represents the presence of thrombus, often associated with severe neurological deficits and poor clinical outcome at 3 months. However, HMCAS is reliable only in AIS patients managed conservatively. In patients treated with systemic thrombolysis, HMCAS may disappear (representing clot dissolution) or persist (persisting clot) on the follow-up CT scan of the brain. We aimed at evaluating whether disappearance or the persistence of HMCAS on follow-up CT scan of the brain can predict the final outcome at 3 months., Methods: Data from consecutive AIS patients treated with IV-tPA, in a standardized protocol, from January 2007 to March 2010 were included in the prospective thrombolysis registry at our tertiary care center. For this evaluation, posterior circulation stroke was excluded. HMCAS was assessed on admission as well as follow-up CT by 2 independent stroke neurologists, blinded to the patient data or outcomes. Functional outcomes assessed by the modified Rankin Scale (mRS) at 3 months were dichotomized as good (mRS score 0-1) and poor (mRS score 2-6). The data were analyzed for the early predictors of poor functional outcome with SPSS version 19 for Windows., Results: Of the total of 2,238 patients admitted during the study period, 226 (11%) with anterior circulation AIS treated with intravenous thrombolysis were included. Median age of the patients was 65 years (range 19-92), 63% were males and they had a median National Institutes of Health Stroke Scale (NIHSS) score of 16 points (range 4-32). HMCAS was observed on admission CT scan in 109 (48.2%) patients and persisted on follow-up CT in 52 (47.7%) of them. Overall, 108 (47.8%) patients achieved poor functional outcome at 3 months. Admission NIHSS score (OR per 1-point increase = 1.241; 95% CI = 1.151-1.337, p < 0.0005), lesser change in NIHSS score at 24 h (OR per 1-point reduction = 0.730; 95% CI = 0.666-0.800, p < 0.0005) and persistence of HMCAS on follow-up CT scan (OR = 3.352; 95% CI = 1.991-11.333, p = 0.039) were associated with poor outcome at 3 months., Conclusion: Persistence of HMCAS on the follow-up CT scan of the brain in acute ischemic stroke patients treated with IV-tPA can be used as an early predictor of poor functional outcome., (Copyright © 2012 S. Karger AG, Basel.)

Background and Purpose: We investigated changes in oxidative damage after ischemic stroke using multiple biomarkers., Methods: Serial blood and urine samples of ischemic stroke subjects and age-matched control subjects were assayed for F₂-isoprostanes, hydroxyeicosatetraenoic acid products, F₄-neuroprostanes, 24-hydroxycholesterol, allantoin, and urate., Results: Sixty-six stroke subjects (mean age, 65 years; median National Institutes of Health Stroke Scale 17) and 132 control subjects were recruited. A bimodal pattern of change was observed in plasma and urinary F₂-isoprostanes and plasma 24-hydroxycholesterol. The rise in plasma hydroxyeicosatetraenoic acid products, F₄-neuroprostanes, and allantoin was highest 6 to 12 hours after stroke onset, whereas plasma urate was significantly lower than controls on Days 1 to 3. After adjusting for age and baseline National Institutes of Health Stroke Scale, baseline plasma esterified hydroxyeicosatetraenoic acid products (OR, 1.01; 95% CI, 1.01 to 1.02), plasma urate (1.01; 1.00 to 1.01), and plasma free F₄-neuroprostanes (2.73; 1.76 to 3.93) were associated with 90-day good functional recovery (modified Rankin Scale ≤1)., Conclusions: Multiple markers of oxidative damage are increased immediately after stroke and remain elevated for several days. Recognition of these temporal changes may help design better antioxidant treatment trials for acute ischemic stroke.

Treatment rates with intravenously administered tissue plasminogen activator (IV-tPA) in acute ischemic stroke (IS) remain low in Asian populations. Various logistic obstacles and higher anticipated bleeding risk in Asians are major concerns. We report on the feasibility and safety of IV-tPA therapy at our tertiary care center. Consecutive acute IS patients eligible for thrombolysis were treated with low-dose (maximum 50 mg) IV-tPA between January 2000 and September 2006 and with standard-dose (maximum 90 mg) IV-tPA between October 2006 and May 2008. The efficacy of IV-tPA was assessed by the modified Rankin Scale (mRS) score at 3 months and by absolute changes in the National Institute of Health Stroke Scale (NIHSS) score at hospital discharge and 3 months. The safety of IV-tPA was assessed by the rate of symptomatic intracranial hemorrhage (SICH). A total of 130 patients were included (mean age, 60±13 years; 60% males; median NIHSS score, 14). A total of 48 patients received low-dose IV-tPA, and 82 patients received standard-dose IV-tPA. The median onset to treatment time was 160 minutes. Some 59% of the patients achieved functional independence (mRS score 0-1) at 3 months with standard-dose tPA, compared with 35% in the low-dose group (P=.011). SICH occurred more frequently with the low dose (14.5%) than with the standard dose (1.2%; P=.004). In a multivariate logistic regression model, lower admission NIHSS score (odds ratio [OR]=0.78 per 1-point increase; 95% confidence interval [CI]=0.70-0.88), lower pretreatment blood glucose level (OR=0.76 per 1 mmol/L increase; 95% CI=0.60-0.95), shorter time from symptom onset to IV-tPA bolus (OR=0.97 per 1-minute increase; 95% CI=0.94-1.0), and standard-dose IV-tPA (OR=12.49; 95% CI=2.9-53.89) were associated with a higher likelihood for functional independence at 3 months. Our data indicate that standard-dose IV-tPA (0.9 mg/kg) was feasible and safe for treating acute IS in our multiethnic Asian population in Singapore., (Copyright © 2010 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

The primary aim of thrombolysis in acute ischemic stroke is recanalization of an occluded intracranial artery. Recanalization is an important predictor of stroke outcome as timely restoration of regional cerebral perfusion helps salvage threatened ischemic tissue. At present, intravenously administered tissue plasminogen activator (IV-TPA) remains the only FDA-approved therapeutic agent for the treatment of ischemic stroke within 3 hours of symptom onset. Recent studies have demonstrated safety as well as efficacy of IV-TPA even in an extended therapeutic window. However, the short therapeutic window, low rates of recanalization, and only modest benefits with IV-TPA have prompted a quest for alternative approaches to restore blood flow in an occluded artery in acute ischemic stroke. Although intra-arterial delivery of the thrombolytic agent seems effective, various logistic constraints limit its routine use and as yet no lytic agent have not received full regulatory approval for intra-arterial therapy. Mechanical devices and approaches can achieve higher rates of recanalization but their safety and efficacy still need to be established in larger clinical trials. The field of acute revascularization is rapidly evolving, and various combinations of pharmacologic agents, mechanical devices, and novel microbubble/ultrasound technologies are being tested in multiple clinical trials.

Acute vertebrobasilar ischemia is a potentially sinister pathology with high mortality and poor functional outcome in survivors. We report the findings of multi-modal assessment (MRI and cerebrovascular ultrasonography) of cerebral hemodynamics in a patient who suffered from acute brainstem infarction with National Institute of Health Stroke Scale (NIHSS) score of 16 points. Our patient demonstrated reversal of blood flow in the basilar artery on the second day of his stroke and this was associated with significant and rapid clinical recovery over the following 2 days (NIHSS score dropped to 4 points). He had recovered completely when seen in the outpatient clinic 3 months later.

The demographic and laboratory predictors of long-stay patients with ischemic stroke were sought in this retrospective hospital-based study. In the univariate and multivariate analysis, advanced age, male gender, leukocytosis, elevated creatinine, low-serum albumin, elevated alkaline transaminases, and lactate dehydrogenase were identified as independent predictors of "long" stayers. At an optimal probability cut-offs, the receiver operating curve incorporating these variables was 0.70, sensitivity 68%, specificity 80%, positive-predictive value 39% and negative-predictive value 95%. Application of this information may assist physicians to triage patients at risk of severe stroke for early therapy and care.

Introduction: Venous thromboembolism (VTE), including its most serious clinical subtype, pulmonary embolism (PE), is a potentially preventable disease. While current assessment tools do not include ethnicity as a risk factor, studies suggest that Asians have lower risk of VTE compared to Caucasians. This study aims to describe 2006 in-hospital and projected population based incidence rates of VTE and PE in Singapore., Materials and Methods: Data on 2006 admissions at 3 major NHG hospitals, cases of VTE and their demographics were obtained from the ODS, a large administrative database of the National Healthcare Group (NHG). Demographic characteristics of the 2006 Singapore resident population were obtained from the 2006 Singapore Statistics website., Results: In 2006, there were 860 cases of VTE out of 98,121 admissions in these 3 hospitals. Overall and secondary VTE age adjusted in-hospital burden was 73 and 54 per 10,000 patients, respectively. Caucasians and Eurasians had VTE rates in excess of 100 per 10,000 while Chinese, Malays and Indians each had rates below 100 per 10,000. Assuming that 42.5% of the 2006 Singapore population was served by NHG, the estimated population-based incidence of VTE and PE is 57 and 15 per 100,000, respectively., Conclusions: As patterns across ethnic groups point to lower VTE rates among Asians compared to Caucasians and Eurasians, analytic studies should be considered to test this hypothesis. There may be a need to develop locally applicable risk assessment tools which can be used to support local guidelines for VTE prophylaxis, thus leading to more acceptable and cost-effective care.

Aim: To examine the readiness of our hospital for the potential pandemic threat of avian influenza, we developed and implemented simulation case scenarios in our hospital., Methods: Two volunteers, who assumed the identity of 'actual' patients, were trained to simulate acute respiratory symptoms following a visit to an avian influenza-affected area, and their identities and locations were kept confidential prior to the readiness exercise. A team of auditors was stationed at high-risk areas to assess adherence to the use of personal protective equipment (PPE) and infection control procedures., Results: A total of 324 healthcare workers and 84 administrators participated in this hospital-wide exercise. Following disclosure of their symptoms, the 'patients' were masked and isolated in negative-pressure rooms. A quarantine order was enforced on 38 inpatients and 45 healthcare workers who were present in the affected wards at the time of the exercise, which mandated the use of PPE. Although all affected healthcare workers were competent in the use of PPE, we observed breaches in PPE and isolation procedures in eight medical and nursing students, and 10 healthcare attendants. The exercise concluded after H5N1 tests returned negative., Conclusion: We recommend the use of case simulation as an effective means of assessing potential breaches in infection control procedures.

Background: The circle of Willis provides collateral pathways to perfuse the affected vascular territories in patients with severe stenoocclusive disease of major arteries. The collateral perfusion may become insufficient in certain physiological circumstances due to failed vasodilatory reserve and intracranial steal phenomenon, so-called 'Reversed-Robinhood syndrome'. We evaluated cerebral hemodynamics and vasodilatory reserve in patients with symptomatic distal internal carotid (ICA) or middle cerebral artery (MCA) severe steno-occlusive disease., Methods: Diagnostic transcranial Doppler (TCD) and TCD-monitoring with voluntary breath-holding according to a standard scanning protocol were performed in patients with severe ICA or MCA steno-occlusive disease. The steal phenomenon was detected as transient, spontaneous, or vasodilatory stimuli-induced velocity reductions in affected arteries at the time of velocity increase in normal vessels. Patients with exhausted vasomotor reactivity and intracranial steal phenomenon during breath-holding were further evaluated by (99)technetium(m)-hexamethyl propylene amine oxime single photon emission computed tomography (HMPAO-SPECT) with acetazolamide challenge., Results: Sixteen patients (age 27-74 years, 11 men) fulfilled our TCD criteria for exhausted vasomotor reactivity and intracranial steal phenomenon during the standard vasomotor testing by breath holding. Acetazolamide-challenged HMPAO-SPECT demonstrated significant hypoperfusion in 12 patients in affected arterial territories, suggestive of failed vasodilatory reserve. A breath-holding index of ≤0.3 on TCD was associated with an abnormal HMPAO-SPECT with acetazolamide challenge. TCD findings of a breath holding index of ≤0.3 and intracranial steal during the procedure were determinants of a significant abnormality on HMPAO-SPECT with acetazolamide challenge., Conclusion: Multimodal evaluation of cerebral hemodynamics in symptomatic patients with severe steno-occlusive disease of the ICA or MCA is helpful in the identification and quantification of failed vasodilatory reserve. This approach may be useful in selecting patients for possible revascularization procedures.

Background and Aim: Intravenously-administered tissue plasminogen activator (IV-TPA) induces thrombolysis and remains the only FDA-approved therapy for acute ischaemic stroke. IV-TPA thrombolysis has been approved recently in Singapore for acute stroke. Continuous exposure of clot to 2-MHz pulsed-wave transcranial Doppler (TCD) ultrasound during IV-TPA infusion is known to augment thrombolysis. We aimed to determine the feasibility, safety and efficacy of ultrasound-assisted thrombolysis in acute ischaemic stroke in Singapore., Subjects and Methods: Consecutive patients with acute ischaemic stroke due to intracranial arterial-occlusions were treated with standard IV-tPA and continuously monitored with 2-MHz TCD according to the CLOTBUST-trial protocol. Arterial recanalisation was determined with Thrombolysis in Brain Ischemia (TIBI) flow-grading system. Safety and efficacy of ultrasoundassisted thrombolysis were assessed by rates of symptomatic intracranial haemorrhage (sICH) and functional recovery at 1 month, respectively., Results: Five consecutive patients (mean age 58 years, 3 men and 3 of Chinese ethnicity) were included. Mean time elapsed between symptom onset and presentation to emergency room was 98 minutes (range, 50 to 135 minutes) while the mean time interval between symptom onset to IV-TPA bolus was 144 minutes (range, 125 to 180 minutes). Partial or complete recanalisation with reduction in the stroke severity was noted in 4 out of the 5 patients during IV-TPA infusion (mean change in NIHSS = 4 points; range 2 to 8 points). None of our patients developed sICH while 4 patients demonstrated good functional outcome at 1 month., Conclusions: Our preliminary study demonstrates the feasibility, safety and efficacy of ultrasound-assisted thrombolysis in acute ischaemic stroke in Singapore. Continuous TCD-monitoring during IV-TPA infusion provides real-time information, enhances thrombolysis and improves functional outcomes in acute ischaemic stroke.

The S218L CACNA1A mutation has been previously described in two families with familial hemiplegic migraine. We present three siblings with the mutation with the novel association of childhood seizures, and highlight the dynamic changes seen on electroencephalography during hemiplegic migraine attacks. Depressed activity contralateral to the hemiparesis was seen on electroencephalography during acute hemiplegic migraine attacks, which may be due to changes to calcium channels caused by the S218L mutation. Both parents were asymptomatic and did not carry the S218L mutation in their blood. This suggests the presence of mosaicism in the transmitting parent.

We describe two Chinese families with a mild form of the myotonia congenita due to novel chloride channel (ClCN1) mutations. In one case, heterozygous I553F and H555N mutations were found. The patient shared the I553F mutation with his healthy father, and his mother had a history of mild myotonia when she was younger. In another family, autosomal dominant myotonia congenita was due to a L844F change. The physiological effects of the mutations were examined by using the two-electrode voltage-clamp technique after expression of the channels in Xenopus oocytes. All mutations drastically shifted the voltage required for half-maximal activation, more under conditions mimicking the homozygous situation, than under conditions mimicking the heterozygous situation. The larger effect was seen in the compound heterozygous situation combining the I553F and the H555N mutations. Our data suggest that myotonia congenita caused by CLCN1 mutations in Chinese have similar variable features to those found in the West.

Introduction: Transcranial Doppler (TCD) is an established tool for the non-invasive assessment of cerebral blood flow. Since TCD results vary with the skills and experience of the sonographer, it requires validation against contrast angiography. We evaluated the diagnostic accuracy of TCD against computed tomography angiography (CTA) and the feasibility of the latter as an additional screening tool in our acute ischaemic stroke patients., Materials and Methods: Our stroke unit manages about 700 patients annually. Acute stroke patients undergo TCD for vascular assessment of major arteries of the circle of Willis. Randomly selected acute stroke patients with significant stenosis on TCD underwent high-resolution cranial CTA with multidetector helical scanner. CTA was performed within 24 hours of TCD and images were interpreted by a neuroradiologist blinded to TCD findings. An independent neurosonologist reevaluated TCD if CTA findings were contradictory. Additional information by either modality was also noted., Results: Fifteen patients (12 men, mean age 61 +/- 15years) with cerebral ischaemia and moderate (>50%) stenosis in > or =1 large intracranial arterial segment on routine TCD were evaluated by CTA. Compared with 21 segments of significant stenosis on CTA, TCD showed 16 true-positive, 3 false-positive and 5 false-negative results (sensitivity: 76.2%, positive predictive value: 84.2%). In 3 cases, TCD showed findings complementary to CTA (real-time embolisation, collateral flow patterns, evidence of distal M2 branch occlusion)., Conclusion: TCD in our neurovascular laboratory shows a satisfactory agreement with cranial CTA in evaluating patients with cerebral ischaemia. TCD can provide additional real-time dynamic findings complementary to information provided by CTA.

Reversible posterior leucoencephalopathy syndrome (RPLS) has been increasingly recognized and reported in the literature. While the condition has been well described in patients with acute hypertension, pre-eclampsia, eclampsia, post-transplantation and chemotherapy, RPLS has been increasingly identified in patients with autoimmune diseases such as systemic lupus erythematosus (SLE). Though experience in the diagnosis and management of RPLS in patients with SLE is likely accumulating, few have systematically worked out the strategy to distinguish RPLS from neuropsychiatric SLE (NPSLE) and lupus-related complications of the central nervous system (CNS). Prompt recognition of, and differentiation between, these conditions is essential since their clinical presentations substantially overlap and yet their management strategy and subsequent outcomes can be entirely different. Indeed, inappropriate treatment such as augmentation of immunosuppression may be detrimental to patients with RPLS. A high index of suspicion of RPLS, prompt magnetic resonance imaging of the brain, including diffusion imaging, exclusion of CNS infection and metabolic derangement, a comprehensive medication review accompanied by timely and aggressive control of blood pressure and seizure are keys to successful management of RPLS. Such treatment strategy ensures a very high chance of total neurological recovery in lupus patients with RPLS.

Background: The modified essay question (MEQ), featuring an evolving case scenario, tests a candidate's problem-solving and reasoning ability, rather than mere factual recall. Although it is traditionally conducted as a pen-and-paper examination, our university has run the MEQ using computer-based testing (CBT) since 2003., Aims: We describe our experience with running the MEQ examination using the IVLE, or integrated virtual learning environment (https://ivle.nus.edu.sg), provide a blueprint for universities intending to conduct computer-based testing of the MEQ, and detail how our MEQ examination has evolved since its inception., Methods: An MEQ committee, comprising specialists in key disciplines from the departments of Medicine and Paediatrics, was formed. We utilized the IVLE, developed for our university in 1998, as the online platform on which we ran the MEQ. We calculated the number of man-hours (academic and support staff) required to run the MEQ examination, using either a computer-based or pen-and-paper format., Results: With the support of our university's information technology (IT) specialists, we have successfully run the MEQ examination online, twice a year, since 2003. Initially, we conducted the examination with short-answer questions only, but have since expanded the MEQ examination to include multiple-choice and extended matching questions. A total of 1268 man-hours was spent in preparing for, and running, the MEQ examination using CBT, compared to 236.5 man-hours to run it using a pen-and-paper format. Despite being more labour-intensive, our students and staff prefer CBT to the pen-and-paper format., Conclusions: The MEQ can be conducted using a computer-based testing scenario, which offers several advantages over a pen-and-paper format. We hope to increase the number of questions and incorporate audio and video files, featuring clinical vignettes, to the MEQ examination in the near future.

Seven Malaysian medicinal plants were screened for their antiplasmodial activities in vitro. These plants were selected based on their traditional claims for treatment or to relieve fever. The plant extracts were obtained from Forest Research Institute Malaysia (FRIM). The antiplasmodial activities were carried out using the pLDH assay to Plasmodium falciparum D10 strain (sensitive strain) while the cytotoxic activities were carried out towards Madin- Darby bovine kidney (MDBK) cells using MTT assay. The concentration of extracts used for both screening assays were from the highest concentration 64 microg/ml, two fold dilution to the lowest concentration 0.03 microg/ml. Goniothalamus macrophyllus (stem extract) showed more than 60% growth inhibition while Goniothalamus scortechinii root and stem extract showed a 90% and more than 80% growth inhibition at the last concentration tested, 0.03 microg/ml. The G. scortechini (leaves extract) showed an IC50 (50% growth inhibition) at 8.53 microg/ml, Ardisia crispa (leaves extract) demonstrated an IC50 at 5.90 +/- 0.14 microg/ml while Croton argyratus (leaves extract) showed a percentage inhibition of more than 60% at the tested concentration. Blumea balsamifera root and stem showed an IC50 at 26.25 +/- 2.47 microg/ml and 7.75 +/- 0.35 microg/ ml respectively. Agathis borneensis (leaves extract) demonstrated a 50% growth inhibition at 11.00 +/- 1.41 microg/ml. The study gives preliminary scientific evidence of these plant extracts in line with their traditional claims.

Introduction: Patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal or M-protein and skin changes) syndrome exhibit a wide range of clinical manifestations and are often seen by a variety of specialists prior to diagnosis., Clinical Picture: We describe a case of POEMS syndrome that first presented with significant neuropathy but progressed to develop further manifestations of the condition, including marked gastrointestinal symptoms., Treatment: The patient was commenced on localised radiotherapy and chemotherapy in addition to immunomodulatory therapy for the neuropathy., Conclusion: We highlight several learning points that may benefit physicians from varied specialties. This case is also unique for its marked gastrointestinal manifestation. To our knowledge, this is the second reported case in the literature with this feature.

Introduction: The management of psychogenic movement disorders is fraught with difficulties. Empathy and a non-judgmental manner are essential in dealing with patients, and a neurobiological explanation of the symptoms may help to foster trust, acceptance, understanding and recovery., Clinical Picture: We report a 17-year-old Chinese girl with psychogenic blepharospasm. Her parents refused psychotherapy and pharmacotherapy., Treatment and Outcome: Placebo therapy (with parental consent) was prescribed with favourable results., Conclusion: We examine the ethical considerations for and against placebo therapy, and explore the role of placebo therapy in the management of psychogenic movement disorders.

Background: Computer-based testing (CBT) has become increasingly popular as a testing modality in under- and postgraduate medical education. Since 2004, our medical school has utilised CBT to conduct 2 papers for the third- and final-year assessments - Paper 3, with 30 multiple choice questions featuring clinical vignettes, and the modified essay question (MEQ) paper., Aims: To obtain feedback from final-year students on their preferred mode of testing for Paper 3 and MEQ components of the Medicine track examination, and the reasons underlying their preferences., Methods: An online survey was carried out on 213 final-year undergraduates, in which they were asked to provide feedback on Paper 3 and MEQ papers. Students were asked if they thought that the CBT format was preferable to the pen-and-paper (PNP) format for Paper 3 and the MEQ, and why., Results: One hundred and fourteen out of 213 (53.5%) students completed the online survey. For Paper 3, 91 (79.8%) felt that CBT was preferable to PNP, 11 (9.6%) preferred the PNP format and 12 (10.5%) were unsure. For the MEQ, 62 (54.4%) preferred CBT over PNP, 30 (26.3%) preferred the PNP format and 22 (19.3%) were unsure. Reasons given to explain preference for CBT over PNP for Paper 3 included independence from seating position, better image quality (as images were shown on personal computer screens instead of projected onto a common screen) and the fact that CBT allowed them to proceed at their own pace. For the MEQ, better image quality, neater answer scripts and better indication of answer length in CBT format were cited as reasons for their preference., Conclusions: Our survey indicated that whereas the majority of students preferred CBT over PNP for Paper 3, a smaller margin had the same preference for the MEQ.

Various movement disorders are known manifestations of nonketotic hyperglycemia (NKH). Hyperglycemic tremors are rare, with only two cases resembling flapping tremors reported in literature. We present a unique case of reversible hyperglycemic Holmes' tremor associated with NKH and postulate the underlying pathophysiology of this condition., (Copyright (c) 2005 Movement Disorder Society.)

Background: During the 2003 severe acute respiratory distress syndrome epidemic, healthcare workers mandatorily wore the protective N95 face-mask., Methods: We administered a survey to healthcare workers to determine risk factors associated with development of headaches (frequency, headache subtypes and duration of face-mask wear) and the impact of headaches (sick days, headache frequency and use of abortive/preventive headache medications)., Results: In the survey, 212 (47 male, 165 female) healthcare workers of mean age 31 years (range, 21-58) participated. Of the 79 (37.3%) respondents who reported face-mask-associated headaches, 26 (32.9%) reported headache frequency exceeding six times per month. Six (7.6%) had taken sick leave from March 2003 to June 2004 (mean 2 days; range 1-4 days) and 47 (59.5%) required use of abortive analgesics because of headache. Four (2.1%) took preventive medications for headaches during this period. Multivariate logistic regression showed that pre-existing headaches [P = 0.041, OR = 1.97 (95% CI 1.03-3.77)] and continuous use of the N95 face-mask exceeding 4 h [P = 0.053, OR = 1.85 (95% CI 0.99-3.43)] were associated with development of headaches., Conclusions: Healthcare providers may develop headaches following the use of the N95 face-mask. Shorter duration of face-mask wear may reduce the frequency and severity of these headaches.

We describe cervical dystonia occurring in a 31-year-old, previously well, primigravid, primiparous Chinese woman at 4 weeks' amenorrhea, which was ameliorated with low-dose clonazepam and disappeared completely by the end of the second trimester without recurring despite her being tapered off benzodiazepine therapy. Investigations were unremarkable for structural and biochemical causes of dystonia. Chorea, paraballismus, and restless legs syndrome are known to occur during pregnancy, attributable to high estrogen levels. Dystonia, on the other hand, has not been described to occur de novo in pregnancy. This association should be considered in women of reproductive age who present with cervical dystonia., (Copyright (c) 2005 Movement Disorder Society.)

Botulinum toxin (BTX) is an important therapeutic tool in the treatment of overactive skeletal and smooth muscles, as well as hypersecretory and painful disorders. Despite advances in our understanding of how BTX works, much remains to be elucidated, such as how BTX ameliorates pain, how it produces weakness remote from the site of injection and the fate of the heavy and light chain components of the BTX molecule following endocytosis into the presynaptic membrane. BTX, conjugated to radionuclides, allows investigators to track the molecule both in vitro and in vivo. However, altering the BTX molecule may cause structural changes or pharmacokinetic and pharmacodynamic alterations, and disrupt its normal action. We propose instead to bind the biomarkers (appropriate dyes, radionuclides or MRI contrast agents) to monoclonal antibodies directed against either heavy or light chain components of BTX, thus allowing administration of native (i.e. unaltered) BTX.

Palmar, plantar and axillary hyperhidrosis, though benign, may be burdensome and occupationally restrictive, even hazardous. Treatment modalities range from topical antiperspirants, iontophoresis, systemic medications such as anticholinergics and benzodiazepines and injections of botulinum toxin, to thoracic sympathectomy. Intradermal injections of botulinum toxin (BTX), though effective, are painful especially when multiple injections are required. Iontophoretic administration of BTX has been described, the BTX entering the eccrine sweat glands via the sweat pores and through the sweat ducts. We postulate that BTX can be administered topically, either unassisted or assisted by application of an electrical gradient, low-frequency ultrasound or excipients such as dimethylsulfoxide. We examine the rationale and feasibility for such a treatment modality and route of administration.

Two components are essential for the development of an attack of bronchial asthma: inflammation and bronchoconstriction, the latter being mediated by smooth muscle contraction. Despite the efficacy of chronic therapy, many asthmatics relapse. Measures to inhibit contraction of the airway smooth muscle, such as vagotomy and thermoablation, may decrease the bronchoconstrictor component of the asthma attack and help to decrease morbidity and mortality from the disease. Botulinum toxin acts to weaken skeletal and smooth muscle by preventing the docking of the acetylcholine vesicle on the inner surface of the presynaptic membrane, thus causing chemical denervation and paresis of skeletal or smooth muscle. We explore the possibility that administration of botulinum toxin may achieve the same effect in bronchial asthma and examine the evidence to support this hypothesis.

Spastic toe clawing describes extension at the metatarsophalangeal joints of the feet, flexion at the proximal interphalangeal joints and flexion at the distal interphalangeal joints that results from upper motor neuron lesions, such as stroke, intracranial hemorrhage, cervical myelopathy and brain tumors. Even though toe clawing is often asymptomatic, it can be painful. Previous studies have described the efficacy of injections of botulinum toxin type-A (BTX-A) to the long flexors of the toes, but this is often unsatisfactory as high dosages (up to 175 units) have been required, and patients often report significant residual toe clawing. We performed an open label, prospective study to assess the efficacy of BTX-A injections, targeting the long and short flexors of the toes, performed with electrical (motor point) stimulation under electromyographic guidance. Outcome measures, which included timed walking over 20m, objective assessment of toe clawing (modified Ashworth scale and a visual analog scale rating) and patient assessment of functional disability, were assessed before injections and at six-weeks' follow-up. Seven patients (five male and two female) of mean age 51 (range 38-70) were recruited. Four had spasticity from underlying intracranial hemorrhage, the remaining three from cerebral infarct, astrocytoma and post-traumatic cervical myelopathy. The total dose of BTX-A injected for toe clawing ranged from 40 to 90 units. Improvements were observed in all outcome measures except timed walking. Injecting BTX-A to the long and short flexors of the toes, with electrical stimulation under electromyographic guidance, is well tolerated and efficacious in the treatment of toe clawing from spasticity, allowing for lower dosages to be used.

Introduction: The basal ganglia-thalamocortical motor circuits are postulated to play a key role in the aetiopathogenesis of stuttering. The main dysfunction is thought to be an impairment in the ability of the basal ganglia to produce timing cues for the initiation of the next motor segment of speech, explaining the association of acquired and re-emergent stuttering with diseases such as dystonia and Parkinson's disease., Clinical Picture: We describe a 61-year-old man presenting with re-emergent stuttering and mild hypomimia, only to develop unilateral rest tremors, hypo- and bradykinesia, rigidity and gait difficulties one year later., Treatment and Outcome: His parkinsonism responded well to treatment with bromocriptine, but he continued to stutter., Discussion: This case illustrates the association between acquired or re-emergent stuttering and basal ganglia disorders, and highlights the need to assess such patients for an underlying aetiology.

Intractable epilepsy is commonly believed to be the main cause of uncontrolled seizures and hospitalization in epileptic patients. We study frequency and types of potential provocative factors in epileptic patients admitted with seizures, and suggest methods to decrease seizure occurrence and hospitalization. Over 6 months we prospectively studied all epileptic patients hospitalized for seizures. A structured interview and laboratory investigations were used to determine type and number of potential seizure precipitants. Precipitants thought to be avoidable through actions taken by the patient or physicians were termed potentially preventable provocative factors (PPPF). Patients' awareness and knowledge of seizure precipitants were also assessed. Three quarters of all seizures leading to admission were associated with PPPF, the commonest being non-compliance (71%), sub-therapeutic doses of antiepileptic drugs (26%) and sleep deprivation (9%). Only one patient had intractable epilepsy. Patients' knowledge of seizure precipitants was poor. The majority of hospital admissions for seizures in epileptic patients are associated with potentially preventable causes amenable to education programmes. Patient education involving epilepsy nurse educators may play an important role in decreasing seizure occurrence and possibly unnecessary hospital admissions.

Introduction: To characterise a homogeneous group of patients with new-onset refractory status epilepticus (NORSE syndrome)., Materials and Methods: This is a descriptive, semiprospective review of all cases of NORSE syndrome seen between 2000 and 2004 at a tertiary care public hospital in Singapore. A review of the literature was performed to identify possible additional similar cases for comparison., Results: Seven patients with NORSE syndrome were identified. Characterising features were female gender, young age, previous good health, cerebrospinal fluid pleocytosis (in 4), antecedent febrile illness (in 5), extraordinarily prolonged status epilepticus (average 32 days), failure of extensive investigations to reveal an underlying cause, catastrophic outcome as well as temporal lobe and leptomeningeal abnormality on brain magnetic resonance imaging. A review of the literature identified 12 similar patients, comprising both adults and children., Conclusions: Based on our patients and those described in the literature, we characterise the NORSE syndrome. Increased recognition of this clinical entity is needed to help delineate the underlying aetiology of this unique severe illness.

The Medical School was founded in 1905 in response to the need to train doctors for Singapore. In 2005, this School, now the Faculty of Medicine in the National University of Singapore, will celebrate her 100th year. This brief review attempts to chronicle the way in which the medical course has been designed over the years to address the principal aims of undergraduate medical education. From the inception of the Straits and Federated Malay States Government Medical School to the present, strong clinically based teaching was the key element, although there was some distinction between the foundational preclinical years and the clinical phases of training. Initially, this was necessitated by the fact that students were too poorly equipped in the sciences to have a more integrated curriculum. Over time, the structure of the course, learning objectives and teaching pedagogy and techniques became better developed. Of late, many of these elements have been revised and better articulated by the Faculty following a review. The method, frequency and emphasis of student evaluations have also changed as medical knowledge grows and the population becomes developed, with attendant disease pattern changes. The clinical relevance of the course and the need to train competent doctors remain the main mission of the Faculty of Medicine even in this age of molecular medicine and a technology-enhanced practice setting. Competency alone is, however, incomplete without good role models in the art of the practice of medicine. It is heartening to note that medical ethics and communications skills continue to be emphasised in the modern curriculum.