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An immunohistochemical method for the diagnosis of melioidosis

Wong KT, Vadivelu J, Puthucheary SD, Tan KL

Pathology, 1996 May;28(2):188-91.
PMID: 8743829

In order to assess the usefulness of immunohistochemistry in the diagnosis of melioidosis, an infection by Burkholderia pseudomallei, polyclonal antibodies were applied to tissues from known cases of melioidosis and to other infected tissues. Formalin-fixed, paraffin-embedded tissues were stained by a modified immunoperoxidase technique. In autopsy tissues with inflammatory lesions of melioidosis, the cytoplasm of phagocytes and intact bacilli, both intra- and extracellular, were stained very strongly positive. Relatively more focal positive staining was observed in some but not all surgical biopsies from proven cases of melioidosis. In granulomas staining was mainly found in the central necrotic areas, with little staining of peripheral phagocytes. All control materials stained negative. Immunohistochemistry appears to be a useful diagnostic tool in melioidosis.
Chemopreventive potential of Annona muricata L leaves on chemically-induced skin papillomagenesis in mice

Hamizah S, Roslida AH, Fezah O, Tan KL, Tor YS, Tan CI

Asian Pac J Cancer Prev, 2012;13(6):2533-9.
PMID: 22938417

Annona muricata L (Annonaceae), commonly known as soursop has a long, rich history in herbal medicine with a lengthy recorded indigenous use. It had also been found to be a promising new anti-tumor agent in numerous in vitro studies. The present investigation concerns chemopreventive effects in a two-stage model of skin papillomagenesis. Chemopreventive effects of an ethanolic extract of A. muricata leaves (AMLE) was evaluated in 6-7 week old ICR mice given a single topical application of 7,12-dimethylbenza(α)anthracene (DMBA 100 μg/100 μl acetone) and promotion by repeated application of croton oil (1% in acetone/ twice a week) for 10 weeks. Morphological tumor incidence, burden and volume were measured, with histological evaluation of skin tissue. Topical application of AMLE at 30, 100 and 300 mg/kg significantly reduced DMBA/croton oil induced mice skin papillomagenesis in (i) peri-initiation protocol (AMLE from 7 days prior to 7 days after DMBA), (ii) promotion protocol (AMLE 30 minutes after croton oil), or (iii) both peri-initiation and promotion protocol (AMLE 7 days prior to 7 day after DMBA and AMLE 30 minutes after croton oil throughout the experimental period), in a dose dependent manner (p<0.05) as compared to carcinogen-treated control. Furthermore, the average latent period was significantly increased in the AMLE-treated group. Interestingly, At 100 and 300 mg/ kg, AMLE completely inhibited the tumor development in all stages. Histopathological study revealed that tumor growth from the AMLE-treated groups showed only slight hyperplasia and absence of keratin pearls and rete ridges. The results, thus suggest that the A.muricata leaves extract was able to suppress tumor initiation as well as tumor promotion even at lower dosage.
Fulltext Rapid and cost-effective antenatal diagnosis of haemoglobin Bart's hydrops foetalis syndrome using a duplex-polymerase chain reaction

Wee YC, Tan KL, Tan PC, Yap SF, Tan JAMA

Med J Malaysia, 2005 Oct;60(4):447-53.
PMID: 16570706

Haemoglobin Bart's hydrops foetalis syndrome (--SEA/--SEA) is not compatible with life and contributes to a majority of the hydropic foetuses in the Malaysian Chinese alpha-thalassaemia carriers who possess the 2-alpha-gene deletion in cis (--SEA/alphaalpha). A duplex-PCR which simultaneously amplifies a normal 136 bp sequence between the psialpha-alpha2-globin genes and a 730 bp Southeast Asian deletion-specific sequence (--SEA) between the psialpha2-theta1-globin genes was established. The duplex-PCR which detects the --SEA deletion in both chromosomes serves as a rapid and cost-effective confirmatory test in the antenatal diagnosis of Haemoglobin Bart's hydrops foetalis syndrome in Malaysia. In addition, the duplex-PCR is simple to perform as both the normal and deletion-specific alpha-globin gene sequences are amplified in the same PCR reaction.
Combine-ARMS: a rapid and cost-effective protocol for molecular characterization of beta-thalassemia in Malaysia

Tan KL, Tan JA, Wong YC, Wee YC, Thong MK, Yap SF

Genet. Test., 2001;5(1):17-22.
PMID: 11336396 DOI: 10.1089/109065701750168626

Beta-thalassemia major patients have chronic anemia and are dependent on blood transfusions to sustain life. Molecular characterization and prenatal diagnosis of beta3-thalassemia is essential in Malaysia because about 4.5% of the population are heterozygous carriers for beta-thalassemia. The high percentage of compound heterozygosity (47.62%) found in beta-thalassemia major patients in the Thalassaemia Registry, University of Malaya Medical Centre (UMMC), Malaysia, also supports a need for rapid, economical, and sensitive protocols for the detection of beta-thalassemia mutations. Molecular characterization of beta-thalassemia mutations in Malaysia is currently carried out using ARMS, which detects a single beta-thalassemia mutation per PCR reaction. We developed and evaluated Combine amplification refractory mutation system (C-ARMS) techniques for efficient molecular detection of two to three beta-thalassemia mutations in a single PCR reaction. Three C-ARMS protocols were evaluated and established for molecular characterization of common beta-thalassemia mutations in the Malay and Chinese ethnic groups in Malaysia. Two C-ARMS protocols (cd 41-42/IVSII #654 and -29/cd 71-72) detected the beta-thalassemia mutations in 74.98% of the Chinese patients studied. The CARMS for cd 41-42/IVSII #654 detected beta-thalassemia mutations in 72% of the Chinese families. C-ARMS for cd 41-42/IVSI #5/cd 17 allowed detection of beta-thalassemia mutations in 36.53% of beta-thalassemia in the Malay patients. C-ARMS for cd 41-42/IVSI #5/cd 17 detected beta-thalassemia in 45.54% of the Chinese patients. We conclude that C-ARMS with the ability to detect two to three mutations in a single reaction provides more rapid and cost-effective protocols for beta-thalassemia prenatal diagnosis and molecular analysis programs in Malaysia.
Total percutaneous endovascular aneurysm repair (pEVAR): the initial experience in Hospital Kuala Lumpur

Leong BDK, Govindarajanthran N, Hafizan TM, Tan KL, Hanif H, Zainal AA

Med J Malaysia, 2017 04;72(2):91-93.
PMID: 28473670 MyJurnal

INTRODUCTION: There has been a paradigm shift in the treatment of AAA with the advent of endovascular aneurysm repair (EVAR). Rapid progress and evolution of endovascular technology has brought forth smaller profile devices and closure devices. Total percutaneous endovascular aneurysm repair (pEVAR) involves the usage of suture-mediated closure devices (SMCDs) at vascular access sites to avoid a traditional surgical cutdown.
MATERIALS AND METHODS: We retrospectively reviewed our experience of pEVAR between April 2013 and July 2014. Primary success of the procedure was defined as closure of a common femoral artery (CFA) arteriotomy without the need for any secondary surgical or endovascular procedure within 30 days.
RESULTS: In total there were 10 pEVAR cases performed in the study period, one case in Queen Elizabeth Hospital during visiting vascular service. Patients have a mean age of 73.4 year old (66-77 year old) The mean abdominal aortic size was 7.2 cm (5.6-10.0cm). Mean femoral artery diameter was 9.0 mm on the right and 8.9 mm on the left. Mean duration of surgery was 119 minutes (98- 153 minutes). 50% of patients were discharged at post-operative day one, 30%- day two and 20%- day three. Primary success was achieved in 9 patients (90%) or in 19 CFA closures (95%). No major complication was reported.
DISCUSSION: We believe that with proper selection of patients undergoing EVAR, pEVAR offers a better option of vascular access with shorter operative time, less post- operative pain, shorter hospital stay and minimises the potential complications of a conventional femoral cutdown.
Molecular defects in the beta-globin gene identified in different ethnic groups/populations during prenatal diagnosis for beta-thalassemia: a Malaysian experience

Tan JA, George E, Tan KL, Chow T, Tan PC, Hassan J, et al.

Clin Exp Med, 2004 Dec;4(3):142-7.
PMID: 15599663 DOI: 10.1007/s10238-004-0048-x

Beta-thalassemia is the most-common genetic disorder of hemoglobin synthesis in Malaysia, and about 4.5% of the population are heterozygous carriers of the disorder. Prenatal diagnosis was performed for 96 couples using the Amplification Refractory Mutation System and Gap-Polymerase Chain Reaction. We identified 17 beta-globin defects-initiation codon for translation (T-G), -29 (A-G), -28 (A-G), CAP +1 (A-C), CD 8/9 (+G), CD 15 (G-A), CD 17 (A-T), CD 19 (A-G), Hb E (G-A), IVS1-1 (G-T), IVS1-5 (G-C), CD 41/42 (-CTTT), CD 71-72 (+A), IVS2-654 (CT), poly A(A-G), 100-kb Ggamma(Agammadeltabeta) degrees and 45-kb Filipino deletions. The 192 beta-alleles studied comprised Chinese (151 patients), Malay (21), Orang Asli from East Malaysia (15), Filipino (1), Indian (1), Indonesian Chinese (2), and Thai (1). In the Chinese, 2 beta-globin defects at CD 41/42 and IVS2-654 were responsible for 74% of beta-thalassemia. beta-mutations at CD 19, IVS1-1 (G-T), IVS1-5, poly A, and hemoglobin E caused 76% of the hemoglobin disorders in the Malays. The Filipino 45-kb deletion caused 73.3% of bthalassemia in the Orang Asli. Using genomic sequencing, the rare Chinese beta-mutation at CD 43 (G-T) was confirmed in 2 Chinese, and the Mediterranean mutation IVS1-1 (G-A) was observed in a Malay beta-thalassemia carrier. The beta-globin mutations confirmed in this prenatal diagnosis study were heterogenous and 65 (68%) couples showed a different globin defect from each other. The use of specific molecular protocols has allowed rapid and successful prenatal diagnosis of beta-thalassemia in Malaysia.
Alpha-thalassaemia in association with beta-thalassaemia patients in Malaysia: a study on the co-inheritance of both disorders

Wee YC, Tan KL, Kuldip K, Tai KS, George E, Tan PC, et al.

Community Genet, 2008;11(3):129-34.
PMID: 18376108 DOI: 10.1159/000113874

BACKGROUND/AIMS: Individuals with double heterozygosity for alpha- and beta-thalassaemia and heterozygous beta-thalassaemia show a similar haematological picture. Co-inheritance of alpha- and beta-thalassaemia in both partners may result in pregnancies with either Hb Bart's hydrops foetalis or beta-thalassaemia major, or pregnancies with both disorders.
METHODS: The co-inheritance of alpha-thalassaemia in 322 beta-thalassaemia carriers in Malaysia was studied.
RESULTS: The frequency of alpha-thalassaemia in the beta-thalassaemia carriers was 12.7% (41/322), with a carrier frequency of 7.8% for the SEA deletion, 3.7% for the -alpha(3.7) deletion, 0.9% for Hb Constant Spring and 0.3% for the -alpha(4.2) deletion.
CONCLUSION: Double heterozygosity for alpha- and beta-thalassaemia was confirmed in 5 out of the 41 couples and the risk of the fatal condition Hb Bart's hydrops foetalis was confirmed in two of these couples. Detection of the Southeast Asian (SEA) deletion in the Malaysian Malays in this study confirms that Hb Bart's hydrops foetalis can occur in this ethnic group. Results of this study have provided new information on the frequency and different types of alpha-thalassaemia (--(SEA), -alpha(3.7) and -alpha(4.2) deletions, Hb Constant Spring) in Malaysian beta-thalassaemia carriers.
Combined team management of diabetes mellitus in pregnancy

Ng CS, Lim LS, Chng KP, Lim P, Cheah JS, Yeo PP, et al.

Ann Acad Med Singap, 1985 Apr;14(2):297-302.
PMID: 4037689

225 women with diabetes in pregnancy were managed by a team of obstetricians, physicians (endocrinologists) and paediatricians from the National University of Singapore. A protocol of management was formulated and followed. The incidence of 1.1% or 1 in 90 pregnancies was found, with significantly higher incidence in Indians and lower in Malays. There were 37 established diabetics and 188 diagnosed during pregnancy. Of these (188), 74 were gestational diabetics. All the women were treated with Insulin and Diet or Diet alone. 177 (79%) were treated with Insulin and Diet. Blood sugar profiles were done for monitoring diabetic control. 72.8% of the women were between para 0 and 1 and 85.2% between the ages of 20 and 34. 72.5% of the women delivered at 38 weeks gestation or later. 48.9% went into spontaneous labour, 32.4% were induced and 18.7% had elective caesarean section. 62.2% of the women had labour of less than 12 hours. The overall caesarean section rate was 41.7%. There were 3 stillbirths and 2 neonatal deaths. The perinatal mortality rate was 2.2%. Thirteen babies had congenital malformations (5.8%). 77.8% of the babies had Apgar score of 7 or more at 5 minutes after delivery. 79.1% of the babies weighed between 2.5 kgm and 3.9 kgm. Pre-eclamptic toxaemia was the commonest complication in pregnancy followed by Urinary Tract Infection and Polyhydramnios. Postpartum complications in the mother were confined to 14 women (6.2%), and wound infection or breakdown was the commonest cause.
Extremes of foetal birthweight for gestation in infants of diabetic mothers

Kek LP, Ng CS, Chng KP, Ratnam SS, Cheah JS, Yeo PB, et al.

Ann Acad Med Singap, 1985 Apr;14(2):303-6.
PMID: 4037690

100 patients were registered at the Diabetic Clinic in 1981, where they were managed by a team of physician, obstetrician and paediatrician, based on a preset protocol. Only 92 patients were eventually analysed. The study showed a 1.3% incidence of pregnancies complicated by diabetes mellitus. The mean birthweights of infants of both gestational and established diabetics were heavier than that of the general population by race and gestation. 25% of the 92 infants of diabetic mothers have birthweight exceeding the 90th centile of population. Further division of the 92 patients into the "true gestational" diabetics, as shown by an oral glucose tolerance test performed 6 weeks post-natally, also showed a 25% incidence of macrosomia. Late antenatal booking, delayed detection of abnormal glucose tolerance and treatment attributed to the high incidence of macrosomia. Only one infant had birthweight below the tenth centile. There were no perinatal mortality in the 92 patients studied. Macrosomia is a common complication in infants of diabetic mothers despite a physician-obstetrician joint-care system. Also, the risk of having macrosomia amongst gestational diabetics is high.
Smart Home-based IoT for Real-time and Secure Remote Health Monitoring of Triage and Priority System using Body Sensors: Multi-driven Systematic Review

Talal M, Zaidan AA, Zaidan BB, Albahri AS, Alamoodi AH, Albahri OS, et al.

J Med Syst, 2019 Jan 15;43(3):42.
PMID: 30648217 DOI: 10.1007/s10916-019-1158-z

The Internet of Things (IoT) has been identified in various applications across different domains, such as in the healthcare sector. IoT has also been recognised for its revolution in reshaping modern healthcare with aspiring wide range prospects, including economical, technological and social. This study aims to establish IoT-based smart home security solutions for real-time health monitoring technologies in telemedicine architecture. A multilayer taxonomy is driven and conducted in this study. In the first layer, a comprehensive analysis on telemedicine, which focuses on the client and server sides, shows that other studies associated with IoT-based smart home applications have several limitations that remain unaddressed. Particularly, remote patient monitoring in healthcare applications presents various facilities and benefits by adopting IoT-based smart home technologies without compromising the security requirements and potentially large number of risks. An extensive search is conducted to identify articles that handle these issues, related applications are comprehensively reviewed and a coherent taxonomy for these articles is established. A total number of (n = 3064) are gathered between 2007 and 2017 for most reliable databases, such as ScienceDirect, Web of Science and Institute of Electrical and Electronic Engineer Xplore databases. Then, the articles based on IoT studies that are associated with telemedicine applications are filtered. Nine articles are selected and classified into two categories. The first category, which accounts for 22.22% (n = 2/9), includes surveys on telemedicine articles and their applications. The second category, which accounts for 77.78% (n = 7/9), includes articles on the client and server sides of telemedicine architecture. The collected studies reveal the essential requirement in constructing another taxonomy layer and review IoT-based smart home security studies. Therefore, IoT-based smart home security features are introduced and analysed in the second layer. The security of smart home design based on IoT applications is an aspect that represents a crucial matter for general occupants of smart homes, in which studies are required to provide a better solution with patient security, privacy protection and security of users' entities from being stolen or compromised. Innovative technologies have dispersed limitations related to this matter. The existing gaps and trends in this area should be investigated to provide valuable visions for technical environments and researchers. Thus, 67 articles are obtained in the second layer of our taxonomy and are classified into six categories. In the first category, 25.37% (n = 17/67) of the articles focus on architecture design. In the second category, 17.91% (n = 12/67) includes security analysis articles that investigate the research status in the security area of IoT-based smart home applications. In the third category, 10.44% (n = 7/67) includes articles about security schemes. In the fourth category, 17.91% (n = 12/67) comprises security examination. In the fifth category, 13.43% (n = 9/67) analyses security protocols. In the final category, 14.92% (n = 10/67) analyses the security framework. Then, the identified basic characteristics of this emerging field are presented and provided in the following aspects. Open challenges experienced on the development of IoT-based smart home security are addressed to be adopted fully in telemedicine applications. Then, the requirements are provided to increase researcher's interest in this study area. On this basis, a number of recommendations for different parties are described to provide insights on the next steps that should be considered to enhance the security of smart homes based on IoT. A map matching for both taxonomies is developed in this study to determine the novel risks and benefits of IoT-based smart home security for real-time remote health monitoring within client and server sides in telemedicine applications.
Echocardiographic and electrocardiographic presentations of patients with endomyocardial biopsy-proven cardiac amyloidosis

Roslan A, Kamsani SH, Nay TW, Tan KL, Hakim N, Tan AM, et al.

Med J Malaysia, 2018 12;73(6):388-392.
PMID: 30647209

OBJECTIVE: Cardiac amyloidosis is under diagnosed and its prevalence is unknown. This is a retrospective, nonrandomised, single centre study of patients with endomyocardial biopsy-proven cardiac amyloidosis focusing on their echocardiographic and electrocardiogram (ECG) presentations. This is the first case series in Malaysia on this subject.
METHODS: We identified all of our endomyocardial biopsyproven cardiac amyloidosis patients from January 2010 to January 2018 and reviewed their medical records. All patients echocardiographic and ECG findings reviewed and analysed comparing to basic mean population value.
RESULTS: In total there are 13 biopsy-proven cardiac amyloidosis patients. All of the biopsies shows light chain (AL) amyloid. Majority of the patients (8, 61.5%) is male, and most of our patients (8, 61.5%) is Chinese. All seven patients on whom we performed deformation imaging have apical sparing pattern on longitudinal strain echocardiogram. Mean ejection fraction is 49.3%, (SD=7.9). All patients have concentric left ventricular hypertrophy and right ventricular hypertrophy. Diastolic dysfunction was present in all of our patients with nine out of 13 patients (69.2%) having restrictive filling patterns (E/A ≥2.0 E/e' ≥15). On electrocardiogram, 12 (92%) patients have prolonged PR interval (median 200ms, IQR 76.50ms) and 9 (69.2%) patients have pseudoinfarct pattern.
CONCLUSION: Echocardiography plays an important role in diagnosing cardiac amyloidosis. The findings of concentric left ventricular hypertrophy with preserved ejection fraction without increased in loading condition should alert the clinician towards its possibility. This is further supported by right ventricular hypertrophy and particularly longitudinal strain imaging showing apical sparing pattern.
Diastolic dysfunction grading, echocardiographic and electrocardiogram findings in 50 patients with apical hypertrophic cardiomyopathy

Aslannif R, Suraya K, Koh HB, Tey YS, Tan KL, Tham CH, et al.

Med J Malaysia, 2019 12;74(6):521-526.
PMID: 31929479

INTRODUCTION: Apical Hypertrophic Cardiomyopathy (Apical HCM) is an uncommon variant of hypertrophic cardiomyopathy, but it is relatively more common in Asian countries. This is a retrospective, non-randomised, single centre study of patients with Apical HCM focusing on their diastolic dysfunction grading, echocardiographic parameters and electrocardiograms (ECG).
METHODS: All Apical HCM patients coming for clinic visits at the Institut Jantung Negara from September 2017 to September 2018 were included. We assessed their echocardiography images, grade their diastolic function and reviewed their ECG on presentation.
RESULTS: Fifty patient were included, 82% (n=41) were males and 18% (n=9) females. The diastolic function grading of 37 (74%) patients were able to be determined using the updated 2016 American Society of Echocardiography (ASE) diastolic guidelines. Fifty percent (n=25) had the typical ace-ofspades shape left ventricle (LV) appearance in diastole and 12% (n=6) had apical pouch. All patients had T inversion in the anterior leads of their ECG, and only 52% (n=26) fulfilled the ECG left ventricular hypertrophy (LVH) criteria. Majority of our patients presented with symptoms of chest pain (52%, n=26) and dyspnoea (42%, n=21).
CONCLUSION: The updated 2016 ASE guideline makes it easier to evaluate LV diastolic function in most patients with Apical HCM. It also helps in elucidating the aetiology of dyspnoea, based on left atrial pressure. Clinicians should have a high index of suspicion for Apical HCM when faced with deep T inversion on ECG, in addition to a thick LV apex with an aceof- spades appearance during diastole.

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