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Hyperglyceridaemia-induced acute pancreatitis in pregnancy: Experience from a tertiary hospital in Singapore

Tan YH, Ong JYK, Devendra K

Med J Malaysia, 2021 07;76(4):591-593.
PMID: 34305127

Acute pancreatitis (AP) is a serious condition that can occur suddenly in pregnancy. We present a case of sudden onset of epigastric pain with severely deranged serum triglyceride levels in a 32-year-old Vietnamese primigravida with no significant past medical history in the Singapore General Hospital. The patient was managed in the intensive care unit, with plasmapheres and intravenous insulin and was eventually a healthy term foetus was delievered via ceasarian section. This case showcased multidisciplinary co operation between the obstetrics, anaesthetic, endocrinology and intensive care team and serves as a reminder to consider this rare condition for future similar presentations.
Pathogenicity and molecular analysis of an infectious bursal disease virus isolated from Malaysian village chickens

Tan DY, Hair-Bejo M, Omar AR, Aini I

Avian Dis, 2004 Apr-Jun;48(2):410-6.
PMID: 15283430

The characteristics of the pathogenic infectious bursal disease virus (IBDV) that infected avian species other than commercial chickens were largely unknown. In this study, by using in vivo and molecular methods, we had characterized an IBDV isolate (named 94268) isolated from an infectious bursal disease (IBD) outbreak in Malaysian village chickens--the adulterated descendant of the Southeast Asian jungle fowl (Gallus bankiva) that were commonly reared in the backyard. The 94268 isolate was grouped as the very virulent IBDV (vvIBDV) strain because it caused severe lesions and a high mortality rate in village chickens (>88%) and experimentally infected specific-pathogen-free chickens (>66%). In addition, it possessed all of the vvIBDV molecular markers in its VP2 gene. Phylogenetic analysis using distance, maximum parsimony, and maximum likelihood methods revealed that 94268 was monophyletic with other vvIBDV isolates and closely related to the Malaysian vvIBDV isolates. Given that the VP2 gene of 94268 isolate was almost identical and evolutionarily closely related to other field IBDV isolates that affected the commercial chickens, we therefore concluded that IBD infections had spread across the farm boundary. IBD infection in the village chicken may represent an important part of the IBD epidemiology because these birds could harbor the vvIBDV strain and should not be overlooked in the control and prevention of the disease.
Fulltext Explaining Osteomyelitis and Prosthetic Joint Infections (PJI) in terms of Biofilm - A Review

Singh S, Tan CL, Ahmad AR

Malays Orthop J, 2021 Jul;15(2):1-8.
PMID: 34429815 DOI: 10.5704/MOJ.2107.001

Osteomyelitis is a chronic infection of bones. Eradication of bone infection is usually with antibiotics and debridement, but it is slow and the infection can recur even after many years. It is now established that osteomyelitis is due to biofilm and a better understanding of the process is required. We review the development of biofilm and apply it to osteomyelitis management. The planktonic microbes' response to adverse conditions is the formation of biofilm. Bacterial infections in planktonic forms cause infections that can be controlled with antibiotics and immunisation, however the same microbe when its phenotype becomes biofilm is more resilient. The understanding of how planktonic bacteria convert to biofilm is one of the aims set out for this article.
In vitro differentiation of mesenchymal stem cells into mesangial cells when co-cultured with injured mesangial cells

Wong CY, Tan EL, Cheong SK

Cell Biol Int, 2014 Apr;38(4):497-501.
PMID: 24375917 DOI: 10.1002/cbin.10231

Mesangial cells are one of the three major cell types of the kidney glomerulus that provide physical support for the glomerular capillary lumen of the kidney. Loss of mesangial cells due to pathologic conditions, such as glomerulonephritis and diabetic nephropathy, can impair renal function. Mesenchymal stem cells (MSC) are attractive candidates for kidney repair therapy since they can enhance recovery and protect against kidney failure. MSC can differentiate into mesangial cells in vivo. We have investigated the ability of MSC to differentiate into mesangial cells in vitro; they were co-cultured with oxidant-injured mesangial cells before being analysed by flow cytometry and for contractility. MSC co-cultured with injured mesangial cells had a mesangial cell-like morphology and contracted in response to angiotensin II. They expressed CD54(-) CD62E(+) in direct contrast to the CD54(+) CD62E(-) of pure MSC. In conclusion, MSC can differentiate into mesangial cells in vitro when co-cultured with injured mesangial cells.
Fulltext Optimum DNA Extraction Methods for Edible Bird's Nest Identification Using Simple Additive Weighting Technique

Quek MC, Chin NL, Tan SW

Foods, 2021 May 14;10(5).
PMID: 34068860 DOI: 10.3390/foods10051086

A simple additive weighting (SAW) technique was used to determine and compare the overall performance of five DNA extraction methods from conventional (SDS method) to commercial kits (Qiagen, Wizard, and NucleoSpin) for identifying origins of edible bird's nest (EBN) using end-point polymerase chain reaction (PCR). A hybrid method (SDS/Qiagen) which has been developed by combining the conventional SDS method with commercialised Qiagen was determined as the most suitable in terms of speed and cost-effectiveness. The determination of optimum extraction method was by the performances on efficiency and feasibility, extracted DNA concentration, purity, PCR amplifiability, handling time and safety of reagents used. The hybrid SDS/Qiagen method is less costly compared to the commercial kits and offered a more rapid alternative to the conventional SDS method with significant improvement in the yield, purity and PCR amplifiability. The developed hybrid SDS/Qiagen method provides a more practical alternative over the lengthy process using conventional method and expensive process using commercial kits. Using the simple additive weighting (SAW) technique and analysis, the Qiagen method is considered the most efficient and feasible method without consideration of cost as it yielded the purest extracted DNA and achieved the highest PCR amplifiability with the shortest turnaround time.
Pharmacokinetics and tissue distribution of an orally administered mucoadhesive chitosan-coated amphotericin B-Loaded nanostructured lipid carrier (NLC) in rats

Tan JSL, Roberts C, Billa N

J Biomater Sci Polym Ed, 2020 02;31(2):141-154.
PMID: 31612804 DOI: 10.1080/09205063.2019.1680926

Oral delivery of amphotericin B (AmpB) is desirable because it provides a more patient-friendly mode of administration compared to the current delivery approach akin with the marketed AmpB formulations. The goal of the study was to investigate the pharmacokinetics and tissue distribution of orally administered chitosan-coated AmpB-loaded nanostructured lipid carriers (ChiAmpB NLC) administered to Sprague Dawley rats at a dose of 15 mg/kg. Orally administered ChiAmpB NLC resulted in a two-fold increase in the area under the curve (AUC0-∞) compared to the uncoated AmpB NLC and marketed Amphotret®. This enhanced bioavailability of AmpB suggests prolonged transit and retention of ChiAmpB NLC within the small intestine through mucoadhesion and subsequent absorption by the lymphatic pathway. The results show that mean absorption and residence times (MAT & MRT) were significantly higher from ChiAmpB NLC compared to the other two formulations, attesting to the mucoadhesive effect. The ChiAmpB NLC presented a lower nephrotic accumulation with preferential deposition in liver and spleen. Thus, the limitations of current marketed IV formulations of AmpB are potentially addressed with the ChiAmpB NLC in addition to utilizing this approach for targeting internal organs in visceral leishmaniasis.
Fulltext In-vitro performance of posterior fiber reinforced composite (FRC) bridge with different framework designs

Ang Y, Tan CG, Yahaya N

Dent Mater J, 2021 May 29;40(3):584-591.
PMID: 33328396 DOI: 10.4012/dmj.2020-213

This study aimed to investigate the effect of various framework designs on the failure of posterior fiber reinforced composite (FRC) bridges and assess the post crack performances of the repaired prostheses. Thirty samples were prepared into three different groups of framework designs: cuspal support (CS), anatomic features (AF) and circular reinforcement (CR). All specimens were subjected to static loading test and acoustic emission analysis. Significant differences were found in the load and time of initial failures among the three groups (p<0.001). CS was identified as the optimum framework design. Samples with composite delamination at the pontic site were selected and repaired with a clinically simplified protocol. Significant differences were also observed between the repaired and original FRC bridges (p=0.01). The performance of these prostheses was highly dependent on the framework design and the perspective of repairing FRC bridges may warrant future investigations.
3D axial-attention for lung nodule classification

Al-Shabi M, Shak K, Tan M

Int J Comput Assist Radiol Surg, 2021 Aug;16(8):1319-1324.
PMID: 34060010 DOI: 10.1007/s11548-021-02415-z

PURPOSE: In recent years, Non-Local-based methods have been successfully applied to lung nodule classification. However, these methods offer 2D attention or limited 3D attention to low-resolution feature maps. Moreover, they still depend on a convenient local filter such as convolution as full 3D attention is expensive to compute and requires a big dataset, which might not be available.
METHODS: We propose to use 3D Axial-Attention, which requires a fraction of the computing power of a regular Non-Local network (i.e., self-attention). Unlike a regular Non-Local network, the 3D Axial-Attention network applies the attention operation to each axis separately. Additionally, we solve the invariant position problem of the Non-Local network by proposing to add 3D positional encoding to shared embeddings.
RESULTS: We validated the proposed method on 442 benign nodules and 406 malignant nodules, extracted from the public LIDC-IDRI dataset by following a rigorous experimental setup using only nodules annotated by at least three radiologists. Our results show that the 3D Axial-Attention model achieves state-of-the-art performance on all evaluation metrics, including AUC and Accuracy.
CONCLUSIONS: The proposed model provides full 3D attention, whereby every element (i.e., pixel) in the 3D volume space attends to every other element in the nodule effectively. Thus, the 3D Axial-Attention network can be used in all layers without the need for local filters. The experimental results show the importance of full 3D attention for classifying lung nodules.
Interdisciplinary differences in patient safety culture within a teaching hospital in Southeast Asia

Krishnasamy K, Tan MP, Zakaria MI

Int J Clin Pract, 2021 Aug;75(8):e14333.
PMID: 33969596 DOI: 10.1111/ijcp.14333

BACKGROUND: Patient safety represents a global issue which leads to potentially avoidable morbidity and mortality. The healthcare providers perception and their role are utmost important in delivering quality care and patient safety. This study aimed to determine the interdisciplinary differences in patient safety culture in a tertiary university hospital.
METHOD: A cross-sectional study using the Safety Attitude Questionnaire (SAQ) self-administered electronically in the English and Malay languages to evaluate safety culture domains. A positive percentage agreement scores of 60% was considered satisfactory. Comparisons were made between doctors, nurses, allied health professionals, nursing assistants and support staff.
RESULTS: Of 6562 respondents, 5724 (80.4%) completed the questionnaire; 3930 (74.5%) women, 2263 (42.9%) nurses, and 1812 (34.2%) had 6-10 years of working experience. The mean overall positive percentage agreement scores were 66.2 (range = 31.1 to 84.7%), with job satisfaction (72.3% ± 21.9%) and stress recognition (58.3 ± 25.6%) representing the highest and lowest mean domain scores, respectively. Differences were observed between all five job categories. Linear regression analyses revealed that the other four job categories scored lower in teamwork, safety climate, job satisfaction and working conditions compared to nurses.
CONCLUSIONS: The overall mean SAQ score was above the satisfactory level, with unsatisfactory percentage agreement scores in the stress recognition domain. Interventions to improve patient safety culture should be developed, focusing on stress management.
Laparoscopic splenic artery ligation in a patient with immune thrombocytopenia with intracranial haemorrhage (two clips that stopped a timebomb)

Chan YQ, Lee ZM, Tan SL

Med J Malaysia, 2020 07;75(4):433-435.
PMID: 32724010

Intracranial haemorrhage (ICH) in a patient with relapse of idiopathic thrombocytopaenic purpura (ITP) can be lethal. The site of haemorrhage, compounded by low platelets in this disease, makes its management extremely challenging, especially when a neurosurgical procedure is warranted. We report a case report of an unconventional way of increasing platelet counts in ITP rapidly in an emergency setting.
Effects of IL-6, IL-10 and TGF-β on the expression of survivin and apoptosis in nasopharyngeal carcinoma TW01 cells

Poh YW, Gan SY, Tan EL

Exp Oncol, 2012 Jul;34(2):85-9.
PMID: 23013758

The aim of this study is to investigate whether IL-6, IL-10 and TGF-β are able to confer resistance to apoptosis in nasopharyngeal carcinoma cells by upregulating the expression of survivin.
Fulltext Editorial: Research Model Innovations in Advancing Neonatal Care

Cheah FC, Tan GC, Shi Y

Front Pediatr, 2021;9:711409.
PMID: 34222156 DOI: 10.3389/fped.2021.711409
Preparation of antibodies to king cobra (Ophiophagus hannah) venom hemorrhagin and investigation of their cross-reactivity

Tan NH, Saifuddin MN, Jaafar MI

Toxicon, 1990;28(11):1355-9.
PMID: 2128424

Hannahtoxin, the major hemorrhagin purified from king cobra (Ophiophagus hannah) venom, elicits hemorrhages in rabbits but not in mice. Two antisera against hannahtoxin were prepared: one raised against purified hannahtoxin, while the other was raised against glutaraldehyde cross-linked and detoxified hannahtoxin. The antisera were refined by pepsin digestion and ammonium sulfate precipitation. They are of approximately equal potency in their ability to neutralize the hemorrhagic activity of king cobra venom in rabbits. The antisera did not form a precipitin line with venom of snakes of the Viperidae family nor neutralize hemorrhages elicited in mice by any of these venoms. However, when the hemorrhagic activity was assayed in rabbits, both antisera were able to abolish the hemorrhages elicited by all of the venoms tested. These results suggest that hannahtoxin displays few epitopes in common with hemorrhagins of viperid venoms, except those involved in the neutralization of hemorrhagic activity in rabbits. The epitopes of viperid venom hemorrhagins involved in the neutralization reaction in rabbits are different from those in mice.
Molecular mechanism of cell death induced by king cobra (Ophiophagus hannah) venom l-amino acid oxidase

Fung SY, Lee ML, Tan NH

Toxicon, 2015 Mar;96:38-45.
PMID: 25615711 DOI: 10.1016/j.toxicon.2015.01.012

Snake venom LAAOs have been reported to exhibit a wide range of pharmacological activities, including cytotoxic, edema-inducing, platelet aggregation-inducing/platelet aggregation-inhibiting, bactericidal and antiviral activities. A heat-stable form of l-amino acid oxidase isolated from king cobra (Ophiophagus hannah) venom (OH-LAAO) has been shown to exhibit very potent cytotoxicity against human tumorigenic cells but not in their non-tumorigenic counterparts, and the cytotoxicity was due to the apoptosis-inducing effect of the enzyme. In this work, the molecular mechanism of cell death induced by OH-LAAO was investigated. The enzyme exerts its apoptosis-inducing effect presumably via both intrinsic and extrinsic pathways as suggested by the increase in caspase-8 and -9 activities. Oligonucleotide microarray analysis showed that the expression of a total of 178 genes was significantly altered as a result of oxidative stress induced by the hydrogen peroxide generated by the enzyme. Of the 178 genes, at least 27 genes are involved in apoptosis and cell death. These alterations of gene expression was presumably caused by the direct cytotoxic effect of H2O2 generated during the enzymatic reaction, as well as the non-specific oxidative modifications of signaling molecules that eventually lead to apoptosis and cell death. The very substantial up-regulation of cytochrome P450 genes may also contribute to the potent cytotoxic action of OH-LAAO by producing excessive reactive oxygen species (ROS). In conclusion, the potent apoptosis inducing activity of OH-LAAO was likely due to the direct cytotoxic effect of H2O2 generated during the enzymatic reaction, as well as the non-specific oxidation of signalling molecules.
The use of enzyme-linked immunosorbent assay for the quantitation of Calloselasma rhodostoma (Malayan pit viper) venom and venom antibodies

Tan NH, Yeo KH, Jaafar MI

Toxicon, 1992 Dec;30(12):1609-20.
PMID: 1488770

The specificity and sensitivity of an indirect and two (an 'ordinary' and a 'rapid') double sandwich enzyme-linked immunosorbent assay (ELISA) procedures for the quantitation of Calloselasma rhodostoma (Malayan pit viper) venom were examined. The three assays were equally sensitive and the accuracy of the assays was not substantially affected by individual variation in the venom composition. The specificity of the assays was examined against 26 venoms from snakes of the families Viperidae and Elapidae. While the double sandwich ELISA procedures were sufficiently specific to be used in the clinical immunodiagnosis of C. rhodostoma bite in Malaysia, the indirect ELISA procedure exhibited extensive cross-reactivity with other Malaysian pit viper venoms. Attempts were made to improve the specificity of the indirect ELISA procedure for the quantitation of C. rhodostoma venom. A 'low ELISA cross-reactivity' venom fraction (termed VF52) was isolated from C. rhodostoma venom by repeated Sephadex G-100 gel filtration chromatography. The indirect ELISA procedure using antibodies to VF52 as immunoreagent showed an improvement in specificity. The use of the indirect ELISA procedure for the detection of C. rhodostoma antibodies was also examined and the results show that the assay was sufficiently specific to be used for retrospective diagnosis of C. rhodostoma bite in Malaysia, in particular when VF52 was used as the coating antigen.
Snake bite in Kelantanese children: a five year experience

Tan KK, Choo KE, Ariffin WA

Toxicon, 1990;28(2):225-30.
PMID: 2339437

The records associated with 83 children from 16 months to 12 years of age who were admitted with snake bite to Kota Bharu General Hospital and University Hospital, Universiti Sains Malaysia over a 5 year period were reviewed. Elapid bites were more common than viper bites while sea-snake bites were not recorded. Symptoms were relatively mild, the common clinical features being pain and local swelling. Antivenom therapy was required in 11 children. Only three of the 11 children developed minor adverse reactions to antivenom. Four of the 83 required ventilatory support for respiratory failure and two children died.
Isolation and characterization of a hemorrhagin from the venom of Calloselasma rhodostoma (Malayan pit viper)

Ponnudurai G, Chung MC, Tan NH

Toxicon, 1993 Aug;31(8):997-1005.
PMID: 8212052

The major hemorrhagin (termed rhodostoxin) of the venom of Calloselasma rhodostoma (Malayan pit viper) was purified to electrophoretic homogeneity by Sephadex G-200 gel filtration followed by high performance ion exchange chromatography. The purified hemorrhagin also yielded a single peak in reversed-phase HPLC. It had an isoelectric point of 5.3 and a mol. wt of 34,000. Rhodostoxin exhibited potent proteolytic, hemorrhagic and edema-inducing activities but was not lethal to mice at a dose of 6 microgram/g (i.v.). Treatment of rhodostoxin with EDTA eliminated both the proteolytic and hemorrhagic activities completely. The N-terminal sequence of rhodostoxin was determined to be NHEIKRHVDIVVVXDSRFCTK.
An investigation into the antigenic cross-reactivity of Ophiophagus hannah (king cobra) venom neurotoxin, phospholipase A2, hemorrhagin and L-amino acid oxidase using enzyme-linked immunosorbent assay

Tan NH, Lim KK, Jaafar MI

Toxicon, 1993 Jul;31(7):865-72.
PMID: 8212031

The antigenic cross-reactivity of four Ophiophagus hannah (king cobra) venom components, the neurotoxin (OH-NTX), phospholipase A2 (OH-PLA2), hemorrhagin (OH-HMG) and L-amino acid oxidase (OH-LAAO) were examined by indirect and double sandwich ELISAs. The indirect ELISAs for OH-NTX, OH-PLA2 and OH-HMG were very specific when assayed against the various heterologous snake venoms and O. hannah venom components, at 25 ng/ml antigen level. At higher antigen concentrations (100-400 ng/ml), there were moderate to strong indirect ELISA cross-reactions between anti-O. hannah neurotoxin and venoms from various species of cobra as well as two short neurotoxins. However, anti-O. hannah hemorrhagin did not cross-react with any of the venoms tested, even at these high antigen concentrations, indicating that O. hannah hemorrhagin is antigenically very different from other venom hemorrhagins. Examination of the indirect ELISA cross-reactions between anti-O. hannah PLA2 and several elapid PLA2 enzymes suggests that the elapid PLA2 antigenic class has more than two subgroups. The antibodies to O. hannah L-amino acid oxidase, however, yielded indirect ELISA cross-reactions with many venoms as well as with OH-NTX, OH-PLA2 and OH-HMG, indicating that OH-LAAO shares common epitopes even with unrelated proteins. The double sandwich ELISAs for the four anti-O. hannah venom components, on the other hand, generally exhibited a higher degree of selectivity than the indirect ELISA procedure.
A comparative study of the biological properties of venoms from juvenile and adult inland taipan (Oxyuranus microlepidotus) snake venoms

Tan NH, Ponnudurai G, Mirtschin PJ

Toxicon, 1993 Mar;31(3):363-7.
PMID: 8470140

The biological properties of adult and juvenile inland taipan (Oxyuranus microlepidotus) snake venoms were examined. The enzymatic activities, intravenous median lethal dose and procoagulant activity of the juvenile venom samples were not significantly different from those of the adult venom samples. Also, the juvenile and adult venoms exhibited similar electrophoretic patterns, indicating that they possessed similar protein composition.
Proteolytic specificity of rhodostoxin, the major hemorrhagin of Calloselasma rhodostoma (Malayan pit viper) venom

Tan NH, Ponnudurai G, Chung MC

Toxicon, 1997 Jun;35(6):979-84.
PMID: 9241791

The proteolytic specificity of rhodostoxin, the major hemorrhagin from Calloselasma rhodostoma (Malayan pit viper) venom was investigated using oxidized B-chain of bovine insulin as substrate. Six peptide bonds were cleaved: Ser9-Hist10, His10-Leu11, Ala14-Leu15, Tyr16-Leu17, Gly20-Glu21 and Phe24-Phe25. Deglycosylated rhodostoxin, however, cleaved primarily at Arg22-Gly23.

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