Background: Neuropathic symptoms and signs are common in the elderly and are often considered normal fi ndings. However, symptomatic polyneuropathy may contribute to disability and falls in the elderly. The prevalence of peripheral neuropathy in the elderly in Malaysia has not been previously reported. The objective of this pilot study is to determine the frequency of symptomatic sensory polyneuropathy in a group of elderly subjects in the community and their possible associated factors. Methods: Cross sectional survey of subjects aged 65 years and above, carried out in an urban neighbourhood in Petaling Jaya. Using a standardised questionnaire, subjects were asked about sensory neuropathic symptoms, associated medical conditions and social habits. They were examined for the ankle refl ex, vibration, joint position, and pinprick sensations. Possible symptomatic sensory polyneuropathy was defi ned as bilateral distal neuropathic symptoms, loss of pinprick sensation and proprioception sense. Results: Of the 100 subjects, 63% had neuropathic symptoms and signs and 20% had possible symptomatic sensory polyneuropathy. Subjects with polyneuropathy complained of more postural instability and giddiness and distal weakness. Diabetes mellitus was associated with the presence of neuropathic symptoms and signs but not with polyneuropathy. Age was signifi cantly associated with polyneuropathy. Conclusion: The frequency of symptomatic sensory polyneuropathy in a group of elderly subj

Translational research (TR) can be defined as research where a discovery made in the laboratory (bench) can be applied in the diagnosis, treatment or prevention of a disease. Examples of medical discoveries contributing to translational medicine (TM) include the isolation of insulin by Banting (Nobel Laureate, 1923), the discovery of penicillin by Alexander Fleming (Nobel Laureate, 1945) and recently the discovery of the role of bacterium Helicobacter pylori in the causation of gastritis and peptic ulcer by Marshall and Warren (Nobel Laureates, 2005). Clinical research (CR) would be a more appropriate term for the bulk of research work undertaken by doctors. CR embraces both clinical based and laboratory-based research. The terminology "bedside to bench" applies more to CR as opposed to "bench to bedside" in the case of TR. But regardless of who does it, as long as the discovery can be translated to the bedside and results in improvement in patient care it can be considered a contribution to TM. Our work spans a 30-year period, involving laboratory-based research, clinical trials and genomics of IgA nephritis (Nx). This is a series of work to elucidate the pathogensis and therapy of IgANx. Plasma beta-thromboglobulin (BTG) an in-vivo index of platelet aggregation and anti-thrombin III increase due to a constant thrombogenecity resulting from platelet degranulation formed the basis for anti-platelet and low-dose warfarin therapy. A study of the natural history of IgANx revealed 2 courses, a slowly progressive course with end-stage renal failure (ESRF) at 7.7 years and a more rapid course at 3.3 years. Triple therapy (cyclophosphamide, persantin and low-dose warfarin) delayed progression to ESRF by about 8 years and for some patients up to 20 years. Documentation of abnormal suppressor T cell function provided the basis for immune therapy. Four patterns of proteinuria were present in IgANx and it is the quality and not so much the quantity of proteinuria which determined the prognosis. Low molecular weight proteinuria was a bad prognostic marker. A controlled therapeutic trial using ACEI/ATRA showed that therapy decreases proteinuria, improves renal function and converts non-selective to selective proteinuria. Subsequent work confirmed that it was the ATRA, not the ACEI which contributed to improved renal function. Individual anti proteinuria response to ATRA varies depending on ACE gene polymorphism. We found that the II genotype of the ACE gene was renoprotective and patients with this genotype had significantly reduced incidence of ESRF compared to those with the DD genotype. Patients responsive to ATRA therapy can retard progression to ESRF by up to 32 years. Mild renal failure can be reversed with possible regression of glomerulosclerosis because of glomerular remodelling by ATRA.
Disease Progression ; Evidence-Based Medicine ; history ; Genetic Predisposition to Disease ; Genomics ; history ; Glomerulonephritis, IGA ; genetics ; history ; History, 20th Century ; History, 21st Century ; Humans ; Polymorphism, Genetic ; Singapore

INTRODUCTIONThe precise burden of movement disorder conditions in our movement disorders centre is unclear. This study investigated the clinical burden of the Movement Disorders Clinic (MDC) in National Neuroscience Institute (NNI) over 10 years, aiming to identify the burden and spectrum of movement disorders conditions, to facilitate future resource allocation.

MATERIALS AND METHODSWe identified all patient visits from January 2002 to December 2011 at MDC from the Movement Disorders (MD) database using a standardised data collection form.

RESULTSThere was a linear increase in the clinical burden of MDC during this period. Parkinsonism comprised 71.6% of this clinical burden of which 84.8% were Parkinson's disease (PD) patients. Dividing the incident cases of MD conditions into two 5 years' blocks, the proportion of PD cases had not changed. There was significant increase in time to diagnosis for PD, hemifacial spasm and dystonia.

CONCLUSIONThere was nearly 4-fold increase in the burden of movement disorders conditions in our tertiary condition within a decade. However, we did not find increasing proportion of PD cases which would be in line with an ageing population. This could be due to the fact that we are still in the early stages of an ageing population and we postulate that this proportion will go up in the future. The increased time to diagnosis may indicate increasing waiting time to see a movement disorders specialist and that current outreach effort to promote awareness may not be reaching its target audience. The upward trend of clinical burden indicates a need for increased resource allocation to cope with demand for movement disorders services.

Aged ; Cost of Illness ; Female ; Humans ; Male ; Middle Aged ; Movement Disorders ; epidemiology ; Retrospective Studies ; Tertiary Care Centers ; Time Factors

UNLABELLEDThe aim of this paper was to study the efficacy, side effects and complications of radiofrequency (RF) ablation of primary and metastatic liver malignancies.

MATERIALS AND METHODSWe retrospectively reviewed 57 patients (39 men, 18 women; mean age, 63 years; age range, 44 to 83 years) who underwent RF ablation for liver malignancies from January 2002 to December 2004. A total of 87 tumours were ablated - 71 (81.6%) hepatocellular carcinomas and 16 (18.4%) metastases (from primaries in the colon, stomach and pancreas). RF ablation was performed either percutaneously (n = 71) under conscious sedation or intraoperatively (n = 16) under general anaesthesia. Follow-up ranged from 1 month to 41 months (mean, 15.2) and included computed tomography (CT) 1 day, 1 month and 3 months after ablation, and half-yearly thereafter. Patients were observed for local tumour progression and for the emergence of new tumours.

RESULTSFour patients with a total of 5 tumours were lost to follow-up. Of the remaining 82 tumours treated, complete ablation was attained in 66 tumours after a single procedure, giving a primary effectiveness rate of 80.5%. Seven (8.5%) required 2 procedures to achieve complete ablation, giving a secondary effectiveness rate of 89% after 2 ablations. One tumour (1.2%) required 3 procedures to achieve complete ablation. One tumour required 4 procedures to date, with the latest follow-up CT still demonstrating incomplete ablation. Two tumours (2.4%) had an initial RF ablation and subsequent transarterial chemoembolisation (TACE). One tumour had an initial RF ablation followed by 32Phosphorus-biosilicon (BrachySil) injection, the latter as part of a Phase IIA trial. One tumour required 2 RF ablations and a subsequent TACE. Lastly, 3 tumours received initial RF ablation but subsequent local tumour progression was not treated as the patients were deemed unfit for repeat ablation. No procedure-related deaths or major complications were encountered. Minor complications were reported in 2 patients (3.8%) - subcapsular haematoma and thermal injury to the adjacent gastric antrum, both not necessitating surgical intervention.

CONCLUSIONSRF ablation is an effective, safe and relatively simple procedure for the treatment of unresectable liver malignancies.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Hepatocellular ; mortality ; secondary ; surgery ; therapy ; Catheter Ablation ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Female ; Hospitals, General ; Humans ; Liver Neoplasms ; mortality ; secondary ; surgery ; therapy ; Male ; Middle Aged ; Retreatment ; Retrospective Studies ; Singapore ; Surgery, Computer-Assisted

INTRODUCTIONThe purpose of the present study was to evaluate the validity of the EQ-5D in patients with Parkinson's disease (PD) in Singapore.

MATERIALS AND METHODSIn a cross-sectional survey, patients with PD completed English or Chinese version of the EQ-5D, the 8-item Parkinson's disease questionnaire (PDQ-8), and questions assessing socio-demographic and health characteristics. Clinical data were retrieved from patients' medical records. The validity of the EQ-5D was assessed by testing a-priori hypotheses relating the EQ-5D to the PDQ-8 and clinical data.

RESULTSTwo hundred and eight PD patients (English speaking: 135) participated in the study. Spearman correlation coefficients between the EQ-5D and PDQ-8 ranged from 0.25 to 0.75 for English-speaking patients and from 0.16 to 0.67 for Chinese-speaking patients. By and large, the EQ-5D scores were weakly or moderately correlated with Hoehn and Yahr stage (correlation coefficients: 0.05 to 0.43), Schwab and England Activities of Daily Living score (correlation coefficients: 0.10 to 0.60), and duration of PD (correlation coefficients: 0.16 to 0.43). The EQ-5D index scores for patients with dyskinesia or "wearing off" periods were significantly lower than those without these problems. The EQ-5D Visual Analog Scale (EQ-VAS) scores also differed for English-speaking patients with deferring dyskinesia, "wearing off" periods, or health transition status; however, such differences were not observed in patients who completed the survey in Chinese.

CONCLUSIONSThe EQ-5D questionnaire appears valid for measuring quality of life in patients with PD in Singapore. However, the validity of EQ-VAS in Chinese-speaking patients with PD should be further assessed.

Aged ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease ; physiopathology ; Quality of Life ; Singapore ; Surveys and Questionnaires ; standards

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Background: and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. Methods: This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). Results: Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. Conclusions In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin ( 1) and variecolactone ( 2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues ( 5- 7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.