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Detection of false positives by incorporation of a confirmatory blocking test into a commercial enzyme-linked immunosorbent assay specific for adenovirus antigen

Kirnpal-Kaur BS, Yap KL, Tan SC

Malays J Pathol, 1997 Dec;19(2):133-6.
PMID: 10879254

A blocking test was incorporated into the commercial IDEIA Adenovirus test (DAKO Diagnostics Ltd., Cambridgeshire, UK) to detect false positive results when faecal specimens were tested for adenovirus antigen. Immune rabbit serum raised against pooled adenovirus particles from human faecal specimens, together with the pre-immune serum, was used. Assessment of positive showed that false positives were produced under two different conditions: when results were based on visual determination instead of a cut-off value determined from photometric reading, and when absorbance values were not immediately read at the end of the test. Under the optimum condition for reading and assessment of test results (immediate reading and photometric determination), 11% of 65 adenovirus-positive samples were checked by the blocking ELISA as false positives. The rest of the specimens showed blocking of positive absorbance values by 70 to 98%. ELISA was found to be more sensitive than immune electron microscopy on samples with lower antigen concentration.
Fulltext Behaviour therapy in psychiatric outpatients

Ko SM, Tan SL, Leong B

Singapore Med J, 1996 Apr;37(2):168-71.
PMID: 8942256

In a prospective study of fifty consecutive outpatients (30 men and 20 women) attending the Behaviour Therapy Clinic at a general hospital, the commonest conditions were obsessive compulsive disorders (n = 16), phobic disorders (n = 11) and generalised anxiety disorders (n = 9). Three-quarters of the referrals were from psychiatrists and family physicians. The patients received between 2 to 10 sessions of behaviour treatment; most had 4 to 6 sessions with a mean of 4.7, SD 1.82. The commonest behavioural techniques administered were exposure therapy with response prevention and relaxation therapy. Initially, treatment was therapist-aided, but subsequently self-help was encouraged with regular reviews of the patient's homework. After one month, 42 patients (84%) were assessed to have improved somewhat, with 20 (40%) showing moderate improvement. After three months, 41 (82%) continued to improve, with 33 (66%) showing moderate to great improvement. Nine patients were considered to have failed in therapy-six defaulted and three were non-responders. The reasons for defaulting treatment were unwillingness to bear with the discomfort involved in exposure therapy, lack of motivation or returning to own hometown in Malaysia. Sixteen patients (n = 32%) were treated solely with behavioural techniques while the rest had a combination of behaviour therapy and drugs, especially anxiolytics and antidepressants. However, at the end of treatment, the dosages of most medications were reduced or else discontinued completely.

Study site: Behavior therapy clinic at a general hospital
Arterial thrombosis and critical limb ischaemia in a case of nephrotic syndrome

Koh KH, Tan C, Tan S, Ngu L

Nephrology (Carlton), 2009 Sep;14(6):622.
PMID: 19712262 DOI: 10.1111/j.1440-1797.2008.01001.x
Selective extraction of salbutamol from human plasma with the use of phenylboronic acid

Koh YM, Saleh MI, Tan SC

J Chromatogr A, 2003 Feb 14;987(1-2):257-67.
PMID: 12613820

An investigation was conducted on the usage of a single-step extraction procedure involving the retention of a phenylboronate-salbutamol complex on an end-capped C18 solid-phase sorbent to determine the level of salbutamol in human plasma samples. Propranolol, a beta-blocker, was chosen as the internal standard for this assay. In this solid-phase clean-up method, 50 mM sodium carbonate buffer, pH 9.60, was used for conditioning the column as well as washing the endogenous interference. Under the optimal conditions, the recovery of salbutamol from spiked plasma samples was found to be high and reproducible with mean recoveries (n = 3) of more than 90% after elution by using 50% 1 M trifluoroacetic acid in methanol. This sample clean-up step was effectively analyzed under reversed-phase high-performance liquid chromatography with fluorimetric detection. The method was successfully applied to the routine measurement of salbutamol in human plasma from the bioequivalence study on the different administration route of salbutamol. Quantification of salbutamol was convincingly reported with the correlation of coefficient of 0.9980 for the concentration range from 0 to 1000 ng ml(-1). An adequate precision was achieved with both between- and within-day precisions of less than 10% (n = 6) for 100 and 1000 ng ml(-1) and less than 15% (n = 6) for 10 ng ml(-1).
Fulltext Recombinant proteins from new constructs of SAG1 and GRA7 sequences and their usefulness to detect acute toxoplasmosis

Kotresha D, Poonam D, Muhammad Hafiznur Y, Saadatnia G, Nurulhasanah O, Sabariah O, et al.

Trop Biomed, 2012 Mar;29(1):129-37.
PMID: 22543613 MyJurnal

In this study we have cloned unreported gene fragments of Toxoplasma gondii GRA7 and SAG1 and expressed the corresponding recombinant proteins, followed by evaluation of their usefulness for the serological diagnosis of toxoplasmosis. Both recombinant proteins were expressed efficiently in insoluble form, purified by single step Ni-NTA affinity chromatography and their antigenicity to detect toxoplasma specific IgG antibodies were determined by immunoblotting. A total of 60 serum samples from three groups of individuals based on their anti-toxoplasma antibody profiles were tested, namely (I) IgM+, IgG+ (n=20), (II) IgM-, IgG+ (n=20) and (III) IgM-, IgG- (n=20). Both recombinant proteins exhibited high sensitivity (100%) with sera from Group I. rGRA7 and rSAG1 reacted 40% and 80% respectively with Group II sera. The specificity of the recombinant proteins based on reactivities with Group III sera were 100% and 80% with rGRA7 and rSAG1 respectively. Thus rGRA7 was found to be better at discriminating probable acute from chronic phases of toxoplasmosis, and it also showed higher specificity.
Human leukocyte antigen (HLA) class II association in chronic hepatitis B patients with hepatocellular carcinoma in a Malay population: A pilot study

Krishnan PB, Abdullah M, Hudu SA, Sekawi Z, Tan SS, Amin-Nordin S

Trop Biomed, 2019 Sep 01;36(3):703-708.
PMID: 33597492

Asian countries account for almost three quarter of hepatocellular carcinoma (HCC) reported globally and chronic hepatitis B infection is one of the main contributors. Clinical observations show that Malay patients with chronic hepatitis B and HCC tend to have a worse outcome, when compared to other two major races in Malaysia. The objectives of this study was to determine the frequency of human leukocyte antigen (HLA) class II alleles in chronic hepatitis B patients with HCC among Malays compared to the general population to identify potential associations of HLA alleles with this disease. HLA class II typing was performed in chronic hepatitis B patients with hepatocellular carcinoma (n=12) by -polymerase chain reaction, sequence specific primer (PCR-SSP) method. There were higher allelic frequencies of certain HLA-DQB1 and HLA-DRB1 alleles; HLA-DQB1*03 (07) (41.7%), and HLA-DRB1*12 (41.7% vs 28.6%) and compared to controls (41.7% vs 29.7%). However, there was no significant statistical correlation found when compared with the normal healthy general population. This study provides an insight into the HLA Class II association with chronic hepatitis B and hepatocellular carcinoma in Malays. However, findings from this study should be validated with a larger number of samples using a high resolution HLA typing.
Fulltext The effects of different velogenic NDV infections on the chicken bursa of Fabricius

Kristeen-Teo YW, Yeap SK, Tan SW, Omar AR, Ideris A, Tan SG, et al.

BMC Vet Res, 2017 May 31;13(1):151.
PMID: 28569155 DOI: 10.1186/s12917-017-1071-y

BACKGROUND: Virulent Newcastle disease virus (NDV) was reported to cause rapid depletion of chicken bursa of Fabricius. Severe pathological condition of the organ is commonly associated with high levels of virus replication, intense inflammatory response and also the degree of apoptosis. In this study, the responses of chicken bursa of Fabricius infected with two different strains of velogenic NDV, namely AF2240 and IBS002, were investigated by observing cell population changes, oxidative stress, viral replication and cytokine expression in the organ. Subsequently, apoptosis of enriched bursal IgM+ cells was determined to help us elucidate possible host pathogen relationships between the chicken bursa of Fabricius and NDV infection.
RESULTS: The depletion of IgM+ cells and infiltration of macrophages were observed to be higher in bursa infected with AF2240 as compared to IBS002. In line with the increment of the macrophage population, higher nitric oxide (NO) and malondialdehyde (MDA) contents which indicated higher oxidative stress were also detected in bursa infected with NDV AF2240. In addition, higher pro-inflammatory cytokines and chemokine gene expression such as chicken CXCLi2, IL-18 and IFN-γ were observed in AF2240 infected bursa. Depletion of IgM+ cells was further confirmed with increased cell death and apoptosis of the cells in AF2240 infected bursa as compared to IBS002. However, it was found that the viral load for NDV strain IBS002 was comparatively higher than AF2240 although the magnitude of the pro- inflammatory cytokines expression and cell apoptosis was lower than AF2240.
CONCLUSION: The results of our study demonstrated that infection of NDV strains AF2240 and IBS002 caused apoptosis in bursa IgM+ cells and its severity was associated with increased expression of pro-inflammatory cytokines/chemokine, macrophage infiltration and oxidative stress as the infection duration was prolonged. However, of the two viruses, we observed that NDV AF2240 induced a greater magnitude of apoptosis in chicken bursa IgM+ cells in comparison to IBS002. This might be due to the high level of oxidative stress and inflammatory cytokines/chemokine as well as lower IL10 expression which subsequently led to a high rate of apoptosis in the chicken bursa of Fabricius although the detected viral load of AF2240 was lower than IBS002.
Comparison of oxidative damage in Malaysian end-stage renal disease patients with or without non-insulin-dependent diabetes mellitus

Kuppusamy UR, Indran M, Ahmad T, Wong SW, Tan SY, Mahmood AA

Clin Chim Acta, 2005 Jan;351(1-2):197-201.
PMID: 15563890 DOI: 10.1016/j.cccn.2004.09.014

BACKGROUND: Comparisons of oxidative indices and total antioxidant status between end-stage renal disease (ESRD) patients with or without diabetes is scant, especially in the Asian population.
METHOD: The assays were carried out according to known established protocols.
RESULT: The present study showed that ESRD patients with or without non-insulin-dependent diabetes mellitus (NIDDM) did not have any significant differences in antioxidant enzyme activities, advanced glycated end products (AGE), advanced oxidized protein products (AOPP) and ferric reducing ability of plasma (FRAP), indicating that hyperglycemia does not exacerbate oxidative damage in ESRD. The regulation of catalase and glutathione peroxidase is also altered in ESRD. Elevated FRAP was observed in both ESRD groups (with and without NIDDM). The dialysis process did not alter the antioxidant enzyme activities but decreased AGEs and FRAP and increased AOPP levels.
CONCLUSION: Oxidative stress is present in ESRD but this is not significantly exacerbated by hyperglycemia. The contribution of components in the pathology of renal failure towards oxidative stress exceeds that of hyperglycemia.
Fulltext Genetic dissection of sympatric populations of brown planthopper, Nilaparvata lugens (Stål), using DALP-PCR molecular markers

Latif MA, Rafii MY, Mazid MS, Ali ME, Ahmed F, Omar MY, et al.

ScientificWorldJournal, 2012;2012:586831.
PMID: 22593700 DOI: 10.1100/2012/586831

Direct amplified length polymorphism (DALP) combines the advantages of a high-resolution fingerprint method and also characterizing the genetic polymorphisms. This molecular method was also found to be useful in brown planthopper, Nilaparvata lugens species complex for the analysis of genetic polymorphisms. A total of 11 populations of Nilaparvata spp. were collected from 6 locations from Malaysia. Two sympatric populations of brown planthopper, N. lugens, one from rice and the other from a weed grass (Leersia hexandra), were collected from each of five locations. N. bakeri was used as an out group. Three oligonucleotide primer pairs, DALP231/DALPR'5, DALP234/DALPR'5, and DALP235/DALPR'5 were applied in this study. The unweighted pair group method with arithmetic mean (UPGMA) dendrogram based on genetic distances for the 11 populations of Nilaparvata spp. revealed that populations belonging to the same species and the same host type clustered together irrespective of their geographical localities of capture. The populations of N. lugens formed into two distinct clusters, one was insects with high esterase activities usually captured from rice and the other was with low esterase activities usually captured from L. hexandra. N. bakeri, an out group, was the most isolated group. Analyses of principal components, molecular variance, and robustness also supported greatly to the findings of cluster analysis.
Fulltext Food assimilated by two sympatric populations of the brown planthopper Nilaparvata lugens (Delphacidae) feeding on different host plants contaminates insect DNA detected by RAPD-PCR analysis

Latif MA, Omar MY, Tan SG, Siraj SS, Ali ME, Rafii MY

Genet. Mol. Res., 2012;11(1):30-41.
PMID: 22290463 DOI: 10.4238/2012.January.9.4

Contamination of insect DNA for RAPD-PCR analysis can be a problem because many primers are non-specific and DNA from parasites or gut contents may be simultaneously extracted along with that of the insect. We measured the quantity of food ingested and assimilated by two sympatric populations of brown planthopper (BPH), Nilaparvata lugens, one from rice and the other from Leersia hexandra (Poaceae), a wetland forage grass, and we also investigated whether host plant DNA contaminates that of herbivore insects in extractions of whole insects. Ingestion and assimilation of food were reduced significantly when individuals derived from one host plant were caged on the other species. The bands, OPA3 (1.25), OPD3 (1.10), OPD3 (0.80), OPD3 (0.60), pUC/M13F (0.35), pUC/M13F (0.20), BOXAIR (0.50), peh#3 (0.50), and peh#3 (0.17) were found in both rice-infesting populations of brown planthopper and its host plant (rice). Similarly, the bands, OPA4 (1.00), OPB10 (0.70), OPD3 (0.90), OPD3 (0.80), OPD3 (0.60), pUC/ M13F (0.35), pUC/M13F (0.20), and BOXAIR (0.50) were found in both Leersia-infesting populations of brown planthopper and the host plant. So, it is clear that the DNA bands amplified in the host plants were also found in the extracts from the insects feeding on them.
PCR cycle sequencing protocol for population mitochondrial cytochrome b analysis

Lau CH, Yusoff K, Tan SG, Yamada Y

Biotechniques, 1995 Feb;18(2):262-6.
PMID: 7727128

Laboratories intending to adopt cycle sequencing of PCR products in their routine analysis often face a confusing range of methods and kits. Through the study of mitochondrial cytochrome b, we have shown that clean and highly reproducible sequences could be obtained by using a combination of existing simple and economical methods in the preparation of DNA templates, PCR, purification of PCR products and sequencing. Our protocol is useful in itself or as a standard in typing other PCR-amplified DNA at the population level.
Genetic diversity of Asian water buffalo (Bubalus bubalis): mitochondrial DNA D-loop and cytochrome b sequence variation

Lau CH, Drinkwater RD, Yusoff K, Tan SG, Hetzel DJ, Barker JS

Anim. Genet., 1998 Aug;29(4):253-64.
PMID: 9745663

Swamp and river buffalo mitochondrial DNA (mtDNA) was sequenced for 303 bp of the cytochrome b gene for 54 animals from 14 populations, and for 158 bp of the D-loop region for 80 animals from 11 populations. Only one cytochrome b haplotype was found in river buffalo. Of the four haplotypes identified in swamp buffalo, one found in all populations is apparently ancestral both to the other swamp haplotypes and to the river haplotype. The phylogenetic relationships among the 33 D-loop haplotypes, with a cluster of 11 found in swamp buffalo only, also support the evolution of domesticated swamp and river buffalo from an ancestral swamp-like animal, most likely represented today by the wild Asian buffalo (Bubalus arnee). The time of divergence of the swamp and river types, estimated from the D-loop data, is 28,000 to 87,000 years ago. We hypothesise that the species originated in mainland south-east Asia, and that it spread north to China and west to the Indian subcontinent, where the rive type evolved and was domesticated. Following domestication in China, the domesticated swamp buffalo spread through two separate routes, through Taiwan and the Philippines to the eastern islands of Borneo and Sulawesi, and south through mainland south-east Asia and then to the western islands of Indonesia.
Fulltext Computed tomographic findings of cerebral fat embolism following multiple bone fractures

Law HL, Wong SL, Tan S

Singapore Med J, 2013 Feb;54(2):e28-30.
PMID: 23462838

Fat embolism to the lungs and brain is an uncommon complication following fractures. Few reports with descriptions of computed tomographic (CT) findings of emboli to the brain or cerebral fat embolism are available. We report a case of cerebral fat embolism following multiple skeletal fractures and present its CT findings here.
Fulltext Wernicke's Encephalopathy in a Patient with Nasopharyngeal Carcinoma: Magnetic Resonance Imaging Findings

Law HL, Tan S, Sedi R

Malays J Med Sci, 2011 Jul;18(3):71-4.
PMID: 22135604

We report a case of Wernicke's encephalopathy in a patient with nasopharyngeal carcinoma with a 3-month history of poor oral intake related to nausea and vomiting due to chemotherapy. The patient later developed deep coma while receiving in-patient therapy. Magnetic resonance imaging of the brain revealed typical findings of Wernicke's encephalopathy. The patient was treated with thiamine injections, which resulted in subsequent partial recovery of neurological function. This paper stresses the importance of magnetic resonance imaging for prompt diagnosis of Wernicke's encephalopathy.
Pharmacokinetics of propofol infusion in Asian patients undergoing coronary artery bypass grafting

Lee HS, Khoo YM, Chua BC, Ng AS, Tan SS, Chew SL

Ther Drug Monit, 1995 Aug;17(4):336-41.
PMID: 7482686

The pharmacokinetics of propofol was studied in 11 Asian patients with fentanyl-isoflurane anaesthesia during cardiopulmonary bypass (CPB) and undergoing elective coronary artery bypass grafting (CABG). Instead of the usual increments of morphine and a benzodiazepine, propofol (4 mg/kg/h) was initiated at the start of CPB and ceased at CPB separation. Whole blood propofol concentrations were determined during and postinfusion using high-performance liquid chromatography with fluorescence detection. Data from four patients seemed to fit a two-compartment model, whereas those from seven patients were significantly (F test, p < 0.05) better fitted to a three-compartment model. The pharmacokinetic parameters were as follows: The mean (SD) of the initial distribution phase t1/2 pi, intermediate distribution phase t1/2 alpha, and elimination phase t1/2 beta were 2.22 (1.04) min, 42.9 (16.4) min, and 370 (138) min, respectively. The mean clearance of 1.31 (0.50) L/min was lower than those reported from other studies, whereas the mean blood concentration of 2.2 (1.0) mg/L at the 1-h infusion period was higher. The mean calculated apparent Css was 3.9 (1.5) mg/L. The low clearance is likely to be due to hemodynamic changes during CPB and CABG, thereby affecting drug distribution and blood flow to the liver.
Clinical characteristic and management of haemophilia patients in Malaysia: A single centre experience

Lee KT, Tan SK, Goh AS

Med J Malaysia, 2024 Mar;79(2):170-175.
PMID: 38553922

INTRODUCTION: Haemophilia is one of the commonest inherited bleeding disorders which may lead to long term disabilities if not treated properly. Our aim of study is to understand the clinical characteristic, treatment and complications of adult haemophilia patients in our centre.
MATERIALS AND METHODS: A retrospective cross-sectional review of all adult haemophilia A (HA) or haemophilia B (HB) patients who received treatment in Hospital Pulau Pinang from January 2021 to December 2022 was conducted. Data was retrieved from patients' medical records.
RESULTS: A total of 75 haemophilia patients (64 HA and 11 HB) were included in this study with median age of 37 years (range 19 70). 42 of them had severe haemophilia (50% of HA, 91% of HB). All HB and 93.8% of severe HA patients were on prophylaxis. Six severe and one mild HA patients developed inhibitor with four of them currently on non-factor prophylaxis. 24 patients (32%) had prior hepatitis C infection and all of them have been successfully treated. The mean annual bleeding rate for severe haemophilia patients were 1.77 (SD ±3.6). Target joints were observed in 9.3% of patients with ankle joint (71.4%) being the most affected joint. More than one quarter (26.7%) of our patients have comorbidities with majority of them having hypertension (17/20), followed by diabetes mellitus (5/20) and ischemic heart disease (5/20).
CONCLUSION: Our study showed that a significant number of adult patients with haemophilia have comorbidities. Apart from optimising factor replacement therapy, future planning should include improvement in screening, risk modification and prevention of cardiovascular disease.
A retrospective study on breast cancer presentation, risk factors, and protective factors in patients with a positive family history of breast cancer

Liaw YY, Loong FS, Tan S, On SY, Khaw E, Chiew Y, et al.

Breast J, 2020 Mar;26(3):469-473.
PMID: 31486157 DOI: 10.1111/tbj.13520

Women with a positive family history of breast cancer are greatly predisposed to breast cancer development. From January 2007 to December 2016, 1101 patients with a histologically confirmed breast cancer were divided into two groups: patients with and without a positive family history of breast cancer. Variables including age at presentation, ethnicity, tumor size, age at menarche, age at menopause, oral contraceptive pill (OCP) use, hormone replacement therapy (HRT), alcohol intake, smoking, body mass index (BMI), diabetes mellitus, parity, and breastfeeding were recorded. One hundred and fifty-nine out of 1101 (14.4%) of the patients had a family history of breast cancer. There was no significant difference in the incidence of breast cancer among Malays, Chinese, and Indians. Both patient groups presented at a mean age of about 60 years (+FH 60; -FH 61.2 P-value = .218). Significantly higher prevalence of history of benign breast disease (11.3%, P .018), nulliparity (13.2%, P .014), tumor size at presentation of more than 5 cm (47.3%, P 0.001), and bilateral site presentation (3.1%, P 0.029) were noted among respondents with a positive family history of breast cancer compared to those with a negative family history of breast cancer. The odds of having a tumor size larger than 5cm at presentation were almost two times higher in patients with a positive family history as compared to those without a family history (adjusted OR = 1.786, 95% CI 1.211-2.484) (P-value .003). Women in Malaysia, despite having a positive family history of breast cancer, still present late at a mean age of 60 with a large tumor size of more than 5 cm, reflecting a lack of awareness. Breastfeeding does not protect women with a family history from developing breast cancer.
The role of wrist anthropometric measurement in idiopathic carpal tunnel syndrome

Lim PG, Tan S, Ahmad TS

J Hand Surg Eur Vol, 2008 Oct;33(5):645-7.
PMID: 18662961 DOI: 10.1177/1753193408093326

Anthropometric wrist measurement ratios were examined for an association with idiopathic carpal tunnel syndrome (CTS). Wrist measurements were recorded in 67 patients with CTS and in a matched control group of 67 healthy volunteers. The Wrist Ratio (WR) (wrist anterior to posterior dimension/wrist medial-lateral dimension) and the Wrist Palm Ratio (wrist anterior to posterior dimension/palm length) were calculated for each case. We found that a WR of > or =0.70 and a Wrist Palm Ratio of >0.342 were significantly associated with idiopathic CTS.
Fulltext The occurence of point mutations in the dihydrofolate reductase-thymidylate synthase (DHFR) gene in Thai isolates of Plasmodium falciparum

Lim PK, Looareesuwan S, Chindanond D, Saleh AM, Tan SK

Southeast Asian J. Trop. Med. Public Health, 1998 Sep;29(3):525-8.
PMID: 10437950
Fulltext The occurrence of dihydrofolate reductase (DHFR) point mutation (SER-108-->ASN-108) in Malaysian isolates of Plasmodium falciparum

Lim PK, Tan SK, Khoo AS, Noor Rain A, Nagappan S, Mak JW

Southeast Asian J. Trop. Med. Public Health, 1998 Mar;29(1):27-30.
PMID: 9740263

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