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Age, sex, haemoglobin level, and white cell count at diagnosis are important prognostic factors in children with acute lymphoblastic leukemia treated with BFM-type protocol

Ng SM, Lin HP, Ariffin WA, Zainab AK, Lam SK, Chan LL

J Trop Pediatr, 2000 Dec;46(6):338-43.
PMID: 11191144

The presenting features and treatment outcome for 575 Malaysian children (< or = 12 years of age) with newly diagnosed acute lymphoblastic leukemia (ALL), admitted to the University Hospital, Kuala Lumpur, Malaysia between 1 January 1980 and 30 May 1995 were evaluated to determine their prognostic significance. Two-year overall survival was achieved in 67 per cent of all patients and 55 per cent of patients were relapse-free at 2 years. All except 10 patients, with identified French-American-British L3 morphology were treated with the modified Berlin-Frankfurt-Munster 78 treatment protocol. Univariate analyses of failure rate conferred age, sex, white cell count and hemoglobin level as potentially significant prognostic factors. All four presenting features retained their prognostic strength in a multivariate analysis. Race, platelet count, morphological subtype, liver/spleen size, lymphadenopathy, central nervous system and mediastinal mass involvement did not show any significant effect on treatment outcome. The 2-year survival rate was significantly different with regard to age, white cell count and hemoglobin level. However, sex was not significantly related to overall survival. These prognostic factors may have implications on future stratification of risk-adjusted initial treatment in the management of childhood ALL. Our analysis of Malaysian children is similar to what could be predicted based on previous studies in other populations.
The presence of Nipah virus in respiratory secretions and urine of patients during an outbreak of Nipah virus encephalitis in Malaysia

Chua KB, Lam SK, Goh KJ, Hooi PS, Ksiazek TG, Kamarulzaman A, et al.

J Infect, 2001 Jan;42(1):40-3.
PMID: 11243752

To study the excretion of Nipah virus in the upper respiratory secretions and urine of infected patients in relation to other clinical features.
Gastro-oesophageal reflux disease in Asia

Goh KL, Chang CS, Fock KM, Ke M, Park HJ, Lam SK

J Gastroenterol Hepatol, 2000 Mar;15(3):230-8.
PMID: 10764021

Gastro-oesophageal reflux disease (GORD) occurs more frequently in Europe and North America than in Asia but its prevalence is now increasing in many Asian countries. Many reasons have been given for the lower prevalence of GORD in Asia. Low dietary fat and genetically determined factors, such as body mass index and maximal acid output, may be important. Other dietary factors appear to be less relevant. Increased intake of carbonated drinks or aggravating medicines may influence the increasing rates of GORD in some Asian countries but no strong evidence links other factors, such as the age of the population, smoking or alcohol consumption, to GORD. The management of GORD in Asia is similar to that in Europe and North America but the lower incidence of severe oesophagitis in Asia may alter the approach slightly. Also, because Asians tend to develop stomach cancer at an earlier age, endoscopy is used routinely at an earlier stage of investigation. Gastro-oesophageal reflux disease is essentially a motility disorder, so short-term management of the disease can usually be achieved using prokinetic agents (or histamine (H2)-receptor antagonists). More severe and recurrent GORD may require proton pump inhibitors (PPI) or a combination of prokinetic agents and PPI. The choice of long-term treatment may be influenced by the relative costs of prokinetic agents and PPI.
Risk factors for hemorrhage in severe dengue infections

Lum LC, Goh AY, Chan PW, El-Amin AL, Lam SK

J Pediatr, 2002 May;140(5):629-31.
PMID: 12032535

The purpose of this study was to identify the early indicators of hemorrhage in severe dengue infections in 114 patients; 24 patients had severe hemorrhage and 92 had no hemorrhage. The platelet counts were not predictive of bleeding. The duration of shock (OR, 2.11; 95% CI, 1.13 to 3.92; P =.019) and low-normal hematocrit at the time of shock (OR, 0.72; 95% CI, 0.55 to 0.95; P =.020) were risk factors of severe hemorrhage.
Complete nucleotide sequences of Nipah virus isolates from Malaysia

Chan YP, Chua KB, Koh CL, Lim ME, Lam SK

J Gen Virol, 2001 Sep;82(Pt 9):2151-5.
PMID: 11514724

We have completely sequenced the genomes of two Nipah virus (NiV) isolates, one from the throat secretion and the other from the cerebrospinal fluid (CSF) of the sole surviving encephalitic patient with positive CSF virus isolation in Malaysia. The two genomes have 18246 nucleotides each and differ by only 4 nucleotides. The NiV genome is 12 nucleotides longer than the Hendra virus (HeV) genome and both genomes have identical leader and trailer sequence lengths and hexamer-phasing positions for all their genes. Both NiV and HeV are also very closely related with respect to their genomic end sequences, gene start and stop signals, P gene-editing signals and deduced amino acid sequences of nucleocapsid protein, phosphoprotein, matrix protein, fusion protein, glycoprotein and RNA polymerase. The existing evidence demonstrates a clear need for the creation of a new genus within the subfamily Paramyxovirinae to accommodate the close similarities between NiV and HeV and their significant differences from other members of the subfamily.
Fulltext Seroprevalence of human parvovirus B19 infection in an urban population in Malaysia

Ooi SL, Hooi PS, Chua BH, Lam SK, Chua KB

Med J Malaysia, 2002 Mar;57(1):97-103.
PMID: 14569725 MyJurnal

A seroepidemiological study carried out on 800 stored serum samples collected between January 1999 to December 2000 derived from an urban population in Malaysia showed that the overall seropositive rate of human paravovirus B19 infection was 37.6%, with an overall geometric mean titre (GMT) of 18.3 IU. The seropositive rates of B19 among the male and female populations were 39.0% and 36.3% respectively. The seropositive rates among the racial groups were 37.2%, 38.2%, 38.1% and 29.4% respectively for the Malays, Chinese, Indians and other races. There was no statistical significant gender and racial differences in the B19 seropositive rates. When compared with the seroprevalence of B19 infection in other Asian countries, the seropositive rate of B19 in Malaysia was low in the younger age group and increased steadily with age. The unusual finding in this study was the presence of a high seropositive rate in those between six months to five years of age, especially in children in the one year old age group.
Fulltext Hand, foot and mouth disease: University Malaya Medical Centre experience

Hooi PS, Chua BH, Lee CSM, Lam SK, Chua KB

Med J Malaysia, 2002 Mar;57(1):88-91.
PMID: 14569723 MyJurnal

The prevalence of HFMD as well as the causative agents was unknown in peninsular Malaysia prior to May 1997. From May 1997 to June 2001, 585 patients suspected to have enterovirus infections, with 467 patients clinically diagnosed as having HFMD, were investigated in the diagnostic virology unit of the University Malaya Medical Centre. Data from this study showed that HFMD is endemic in Malaysia with the occurrence of two outbreaks during the study period. In each outbreak, a number of viruses were isolated but enterovirus 71 was the main virus isolated in both outbreaks. Echovirus 7 (Eo7) was isolated from 5 patients with HFMD in the second outbreak, a clinical entity that has not been attributed to it previously. Children aged 4 years and below, particularly those between 1 and 2 years of age, were in the main group of patients affected by the illness. HFMD by itself and without neurological involvement was relatively benign and self-limiting. There was no significant difference in the virus isolation rate with respect to gender and ethnic groups. Virus isolation was attempted in a total of 764 clinical specimens consisting of 342 stool specimens, 285 oral secretions specimens and 137 vesicular fluid specimens. Oral specimens gave the highest virus isolation rate (33.3%) followed by vesicular specimens (27.0%). Stool specimens only yielded an isolation rate of 14.0%.
Tioman virus, a novel paramyxovirus isolated from fruit bats in Malaysia

Chua KB, Wang LF, Lam SK, Crameri G, Yu M, Wise T, et al.

Virology, 2001 May 10;283(2):215-29.
PMID: 11336547

A search for the natural host of Nipah virus has led to the isolation of a previously unknown member of the family Paramyxoviridae. Tioman virus (TiV) was isolated from the urine of fruit bats (Pteropus hypomelanus) found on the island of the same name off the eastern coast of peninsular Malaysia. An electron microscopic study of TiV-infected cells revealed spherical and pleomorphic-enveloped viral particles (100--500 nm in size) with a single fringe of embedded peplomers. Virus morphogenesis occurred at the plasma membrane of infected cells and morphological features of negative-stained ribonucleoprotein complexes were compatible with that of viruses in the family Paramyxoviridae. Serological studies revealed no cross-reactivity with antibodies against a number of known Paramyxoviridae members except for the newly described Menangle virus (MenV), isolated in Australia in 1997. Failure of PCR amplification using MenV-specific primers suggested that this new virus is related to but different from MenV. For molecular characterization of the virus, a cDNA subtraction strategy was employed to isolate virus-specific cDNA from virus-infected cells. Complete gene sequences for the nucleocapsid protein (N) and phosphoprotein (P/V) have been determined and recombinant N and V proteins produced in baculovirus. The recombinant N and V proteins reacted with porcine anti-MenV sera in Western blot, confirming the serological cross-reactivity observed during initial virus characterization. The lack of a C protein-coding region in the P/V gene, the creation of P mRNA by insertion of 2-G residues, and the results of phylogenetic analyses all indicated that TiV is a novel member of the genus Rubulavirus.
Fulltext Retrospective review of serologic rubella activity in University Hospital Kuala Lumpur

Chua KB, Lam SK, Hooi PS, Chua BH, Lim CT

Med J Malaysia, 2000 Sep;55(3):299-303.
PMID: 11200707

A retrospective review of rubella serological results carried out in the Virus Diagnostic Unit, University Hospital Kuala Lumpur (UHKL) from January 1993 to September 1999 showed the presence of rubella infection annually which appeared to increase periodically every two to three years. There was no statistical significant difference in the rubella positive rate between male and female population aged 14 to 48 years. Congenital rubella infections (CRI) occurred in babies delivered in UHKL yearly from 1993 to 1998 with an average incidence rate of 48 per 100,000 deliveries. Peaks of rubella cases appeared to be followed by an increase in incidence of CRI cases 6 to 9 months later. The study showed that only 50.8% clinically diagnosed rubella was confirmed by laboratory finding. This study also showed an increase of rubella activity for the months of July, August and September 1999 and this may herald an increase of CRI cases in the coming millennium.
The predictive value of uvulo-palatoglossal junctional ulcers as an early clinical sign of exanthem subitum due to human herpesvirus 6

Chua KB, Lam SK, AbuBakar S, Lim ST, Paranjothy M, Koh MT, et al.

J Clin Virol, 2000 Aug;17(2):83-90.
PMID: 10942088

BACKGROUND: The clinical sign of uvulo-palatoglossal junctional (UPJ) ulcers was first noted in 1983 in a 5.5-month-old baby with exanthem subitum (ES). An earlier prospective clinical study showed that there was a strong association of UPJ ulcers and occurrence of ES with a positive predictive value of 95.3% and negative predictive value of 100%.
OBJECTIVE: To determine the value of uvulo-palatoglossal junctional (UPJ) ulcers as an early clinical sign of exanthem subitum (ES) due to human herpesvirus 6 (HHV 6) infection.
STUDY DESIGN: A case-control study of 20 febrile children with UPJ ulcers versus 26 febrile children without UPJ ulcers. These children were followed up for any development of ES and investigated for human herpesvirus 6 (HHV 6) as the causative agents of the febrile episodes.
RESULTS: In this study, 20 out of 46 febrile children aged 3 months to 3 years with UPJ ulcers were virologically and/or serologically confirmed to be due to primary HHV 6 infection. The rest of the 26 children without ulcers did not have HHV 6 infection. Of the 20 children with UPJ ulcers, only 17 of the 19 children with adequate follow-up till subsidence of fever developed ES. None of the 26 children without UPJ ulcers developed ES.
CONCLUSION: Statistically, there was a significant association of UPJ ulcers as an early sign of ES with a positive predictive value of 89.5% and negative predictive value of 100%. This finding also suggests that the presence of UPJ ulcers is a useful pathognomic clinical sign of symptomatic primary HHV 6 infection.
Protocol for out-patient management of dengue illness in young adults

Chin CK, Kang BH, Liew BK, Cheah PC, Nair R, Lam SK

J Trop Med Hyg, 1993 Aug;96(4):259-63.
PMID: 8345549

A prospective study on the practicality of an out-patient management protocol for dengue infection in adults was carried out during a 2-month period. Doctors were requested to follow the protocol and assessment was done on the patients' outcome, the admission rate, and the compliance to the protocol by doctors and patients. One hundred and sixty-two patients (mean age 27.3 years) were clinically diagnosed to have dengue illness. Among them, 82.7% had dengue fever (DF); 13.0% had dengue haemorrhagic fever (DHF) and 4.3% had dengue shock syndrome (DSS). Dengue aetiology was confirmed in 69.4% of the DF group and 85.7% of the DHF and DSS groups. There were no deaths among the 162 patients. The admission rate was 43.8%. A high compliance rate of 86.4% by the doctors and a low patient default rate of 16.4% showed that the protocol was practical.
Neurogenic pulmonary oedema and enterovirus 71 encephalomyelitis

Lum LC, Wong KT, Lam SK, Chua KB, Goh AY

Lancet, 1998 Oct 24;352(9137):1391.
PMID: 9802304
Vertical transmission of dengue

Chye JK, Lim CT, Ng KB, Lim JM, George R, Lam SK

Clin Infect Dis, 1997 Dec;25(6):1374-7.
PMID: 9431381

Dengue, an important mosquito-borne flavivirus infection, is endemic in Southeast Asia. We describe two mothers who had acute dengue 4 and 8 days before the births of their infants. One mother had worsening of her proteinuric pregnancy-induced hypertension, liver dysfunction, and coagulopathy and required multiple transfusions of whole blood, platelets, and fresh frozen plasma. Her male infant was ill at birth, developed respiratory distress and a large uncontrollable left intracerebral hemorrhage, and died of multiorgan failure on day 6 of life. Dengue virus type 2 was isolated from the infant's blood, and IgM antibody specific to dengue virus was detected in the mother's blood. The second mother had a milder clinical course; she gave birth to a female infant who was thrombocytopenic at birth and had an uneventful hospitalization. Dengue virus type 2 was recovered from the mother's blood, and IgM antibody specific to dengue virus was detected in the infant's blood. This report highlights not only the apparently rare occurrence of vertical transmission of dengue virus in humans but also the potential risk of death for infected neonates.
Prevention of duodenal ulcer relapse with omeprazole 20 mg daily: a randomized double-blind, placebo-controlled study

Goh KL, Boonyapisit S, Lai KH, Chang R, Kang JY, Lam SK

J Gastroenterol Hepatol, 1995 1 1;10(1):92-7.
PMID: 7620115

We report the first double-blind, placebo-controlled study that assesses the efficacy and safety of omeprazole 20 mg daily in the maintenance treatment of duodenal ulcer. For the healing phase, 128 patients with endoscopically proven active duodenal ulcer and a history of three or more relapses during the 2 years prior to the study were treated until healing with omeprazole 40 mg daily for 2 and up to 8 weeks. One hundred and twenty-three patients whose ulcers were healed were randomized to receive omeprazole 20 mg daily (n = 60) or placebo (n = 63) for 12 months as maintenance treatment. Patients were interviewed at 3, 6, 9 and 12 months, and endoscopy was performed at 3, 6 and 12 months and whenever symptoms recurred. The healing rates of the 124 patients completing the healing phase were 84, 98 and 100% at 2, 4 and 8 weeks, respectively. During the maintenance phase, eight and four patients discontinued treatment from the omeprazole and placebo groups, respectively. The proportion of patients in remission in the omeprazole group and placebo group after 12 months were 94 and 9% respectively (life table estimates, P < 0.0001). No significant clinical or laboratory changes were observed in patients on therapy with omeprazole. Patients with a history of frequent relapses thus continued to have a very high relapse rate without prophylactic treatment. Omeprazole 20 mg daily was effective and safe in maintaining such patients in remission.
Preventive transfusion in Dengue shock syndrome-is it necessary?

Lum LC, Abdel-Latif Mel-A, Goh AY, Chan PW, Lam SK

J Pediatr, 2003 Nov;143(5):682-4.
PMID: 14615749

We compared 53 patients with Dengue shock syndrome (DSS) who received preventive transfusions with 53 who did not. Significant differences in the development of pulmonary edema and length of hospitalization (P
Identification of enterovirus 71 isolates from an outbreak of hand, foot and mouth disease (HFMD) with fatal cases of encephalomyelitis in Malaysia

AbuBakar S, Chee HY, Al-Kobaisi MF, Xiaoshan J, Chua KB, Lam SK

Virus Res, 1999 May;61(1):1-9.
PMID: 10426204

Thirteen enterovirus 71 (EV71) isolates were obtained from both fatal and non-fatal infections of patients seen in Peninsula Malaysia and in Sarawak during an outbreak of hand, foot and mouth disease (HFMD) in Malaysia in 1997, with incidences of fatal brainstem encephalomyelitis. The isolates were identified using immunofluorescence staining, neutralization assays, and partial sequencing of the 5' untranslated regions (UTR). Assessment of the potential genetic relationships of the isolates using the partial 5'UTR sequences suggested clustering of the isolates into at least two main clusters. Isolates from Peninsula Malaysia were found in both clusters whereas Sarawak-derived isolates clustered only in cluster II. Isolates derived from fatal infections, however, occurred in both clusters and no distinctive nucleotide sequences could be attributed to the fatal isolates. Examination of the nucleotide sequences revealed at least 13 nucleotide positions in all the isolates which differ completely from the previously reported EV71 5'UTR sequences. In addition, at least 11 nucleotide position differences within the 5'UTR were noted which differentiated cluster I from cluster II. Predicted secondary RNA structures drawn using the nucleotide sequences also suggested differences between isolates from the two clusters. These findings suggest the presence of at least two potentially virulent EV71 co-circulating in Malaysia during the 1997 HFMD outbreak.
Fulltext Selection of suitable endogenous reference genes for qPCR in kidney and hypothalamus of rats under testosterone influence

Gholami K, Loh SY, Salleh N, Lam SK, Hoe SZ

PLoS One, 2017;12(6):e0176368.
PMID: 28591185 DOI: 10.1371/journal.pone.0176368

Real-time quantitative PCR (qPCR) is the most reliable and accurate technique for analyses of gene expression. Endogenous reference genes are being used to normalize qPCR data even though their expression may vary under different conditions and in different tissues. Nonetheless, verification of expression of reference genes in selected studied tissue is essential in order to accurately assess the level of expression of target genes of interest. Therefore, in this study, we attempted to examine six commonly used reference genes in order to identify the gene being expressed most constantly under the influence of testosterone in the kidneys and hypothalamus. The reference genes include glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin beta (ACTB), beta-2 microglobulin (B2m), hypoxanthine phosphoribosyltransferase 1 (HPRT), peptidylprolylisomerase A (Ppia) and hydroxymethylbilane synthase (Hmbs). The cycle threshold (Ct) value for each gene was determined and data obtained were analyzed using the software programs NormFinder, geNorm, BestKeeper, and rank aggregation. Results showed that Hmbs and Ppia genes were the most stably expressed in the hypothalamus. Meanwhile, in kidneys, Hmbs and GAPDH appeared to be the most constant genes. In conclusion, variations in expression levels of reference genes occur in kidneys and hypothalamus under similar conditions; thus, it is important to verify reference gene levels in these tissues prior to commencing any studies.
Validation of the Iranian/Persian Version of the Perceived Therapeutic Efficacy Scale for Type 2 Diabetes

Azami G, Lam SK, Shariff-Ghazali S, Said SM, Aazami S, Mozafari M, et al.

Arch Iran Med, 2018 08 01;21(8):356-361.
PMID: 30113857

BACKGROUND: The theory if self-efficacy is the central concept of social cognitive theory with emphasis on the constructs of efficacy expectation, outcome expectation. Efficacy expectation is defined as the person's confidence to carry out a specific behavior. Outcome expectation is beliefs that carrying out a specific behavior will lead to a specific outcome. While the benefit of measuring outcome expectations has been established, there has been no large scale within the Iranian context. The purpose of this study is to examine the reliability-validity of the Persian version of the Perceived Therapeutic Efficacy Scale (PTES).
METHODS: This study was conducted among 160 patients with type 2 diabetes mellitus (T2DM) using a self-administered instrument measuring outcome expectation. We used a methodological study design to assess the validity and reliability of the translated Persian version of the instrument.
RESULTS: The findings of the present study support the uni-dimensionality of the Persian version of the instrument. The 10 items of the scale account for 73.54% of the total variance and the un-rotated factor loadings ranged from 0.66 to 0.93. Moreover, this study offers support for convergent validity and internal consistency of the scale.
CONCLUSION: Our study demonstrated good convergent validity, factor structure and internal consistency in a sample of 160 Iranian adults with T2DM. Therefore, the Persian version of the scale is a valid and reliable instrument and can be used in research and clinical settings.
Depression among older adults in Malaysian daycare centres

Leong OS, Ghazali S, Hussin EOD, Lam SK, Japar S, Geok SK, et al.

Br J Community Nurs, 2020 Feb 02;25(2):84-90.
PMID: 32040358 DOI: 10.12968/bjcn.2020.25.2.84

With the older population increasing worldwide, depressive disorder in this cohort is a serious public health problem that contributes to increased healthcare costs and mortality. This study aimed to determine the prevalence of depression among older adults in Malaysia who attended a daycare centre and to identify the relationship between depression and demographic factors. A cross-sectional study was conducted with 159 older adults recruited following screening for mental capacity. The Malay Geriatric Depression Scale questionnaire was distributed among the participants to obtain descriptive data on the symptoms of depression. Some 59.1% of the participants experienced depression. The most common factors associated with depression were being divorced, low education levels and low income. The findings indicate the need to revise and re-evaluate the activities and programmes in daycare centres for older adults in order to objectively cater to their physical and emotional needs.
Fulltext Effects of stress associated with academic examination on the kynurenine pathway profile in healthy students

Myint K, Jacobs K, Myint AM, Lam SK, Henden L, Hoe SZ, et al.

PLoS One, 2021;16(6):e0252668.
PMID: 34081742 DOI: 10.1371/journal.pone.0252668

The effects of stress on the neuroendocrine, central nervous and immune systems are extremely complex. The kynurenine pathway (KP) of the tryptophan metabolism is recognised as a cross-link between the neuroendocrine- and immune systems. However, the effects of acute stress from everyday life on KP activation have not yet been studied. This study aims to investigate changes in the levels of the KP neuroactive metabolites and cytokines in response to stress triggered by academic examinations. Ninety-two healthy first year medical students benevolently participated in the study. Parameters were measured pre- examination, which is considered to be a high-stress period, and post-examination, as a low-stress period. Stress induced by academic examinations significantly increases the perceived stress scores (p<0.001), serum cortisol levels (p<0.001) and brain-derived neurotrophic factor (BDNF) levels (p<0.01). It decreased IL-10 levels (p<0.05) but had no effect on IL-6 and TNF-alpha levels. Only the KP neuroactive metabolite, 3-hydroxykynurenine (3-HK) significantly increased (p<0.01) in the post-examination period. In addition, the stress scores positively correlated with the levels of cortisol (r2 = 0.297, p<0.01) at post examination. Acute stress triggered by academic examinations increases cortisol and BDNF production and suppresses the anti-inflammatory cytokine, IL-10, but did not increase significantly the levels of other pro-inflammatory cytokines, tryptophan, kynurenine and downstream KP metabolites. The concomitant increased levels of BDNF under the duress of acute examination stress appear to limit the levels pro-inflammatory markers, which may attenuate the action of cortisol and the neuroinflammatory branch of the KP.

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