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Fulltext A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609

Zhang R, Suwanarusk R, Malleret B, Cooke BM, Nosten F, Lau YL, et al.

J Infect Dis, 2016 Jan 1;213(1):100-4.
PMID: 26136472 DOI: 10.1093/infdis/jiv358

Recent clinical trials revealed a surprisingly rapid clearance of red blood cells (RBCs) infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite-infected RBCs exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent to the disruption of the parasite's sodium efflux pump (adenosine triphosphate 4). We also show that this peculiar drug effect is likely to cause accelerated splenic clearance of the rheologically impaired Plasmodium vivax- and Plasmodium falciparum-infected RBCs.
Factors affecting nutritional status of Malaysian primary school children

Zaini MZ, Lim CT, Low WY, Harun F

Asia Pac J Public Health, 2005;17(2):71-80.
PMID: 16425649

This paper investigates the nutritional status of a randomly selected cohort of school children and the factors affecting it. This random survey was conducted in the state of Selangor, involving 1,405 primary students (aged 9-10 years from 54 national primary schools). Physical examination was carried out on all the students. Information on the students was also obtained from the parents. Blood samples were taken by using the finger pricking technique. Body mass index (BMI) was used as a measure of physical growth. The students were mainly from urban areas (82.9%). The mean age was 9.71 years and a higher proportion was females (51%). Malays constituted 83.6%, Indians 11.6% and Chinese 4.2% of the study population. The mean weight and height were 32.30 kg and 135.18 cm respectively. The mean BMI was 17.42 kg/m2, with 1.2% of the students underweight, 76.3% normal BMI, 16.3% overweight and 6.3% were obese. Nutritional status was significantly related to blood pressure, history of breast feeding, eating fast food, taking canned/bottled drinks, income and educational level of parents. Significant differences in nutritional status between sexes and locations (rural/urban) were also found. The prevalence of overweight and obese children was of concern. There is thus an urgent need for the School Health Program to periodically monitor the school children's eating habits and physical growth. Appropriate counselling on nutritional intake and physical activities should be given not only to schoolchildren but also to their teachers and parents or caregivers.
Fulltext GIFT triplets and management problems--a case report

Wong KK, Lim CT

Med J Malaysia, 1991 Sep;46(3):294-6.
PMID: 1839929

Pregnancies conceived through assisted reproduction can present considerable management problems to the obstetric and paediatric staff. Multiple pregnancies are common. The complication of prematurity increases the morbidity and mortality rates of the neonates.
Preterm Infant Outcomes after Randomization to Initial Resuscitation with FiO2 0.21 or 1.0

Thamrin V, Saugstad OD, Tarnow-Mordi W, Wang YA, Lui K, Wright IM, et al.

J Pediatr, 2018 10;201:55-61.e1.
PMID: 30251639 DOI: 10.1016/j.jpeds.2018.05.053

OBJECTIVE: To determine rates of death or neurodevelopmental impairment (NDI) at 2 years corrected age (primary outcome) in children <32 weeks' gestation randomized to initial resuscitation with a fraction of inspired oxygen (FiO2) value of 0.21 or 1.0.
STUDY DESIGN: Blinded assessments were conducted at 2-3 years corrected age with the Bayley Scales of Infant and Toddler Development, Third Edition or the Ages and Stages Questionnaire by intention to treat.
RESULTS: Of the 290 children enrolled, 40 could not be contacted and 10 failed to attend appointments. Among the 240 children for whom outcomes at age 2 years were available, 1 child had a lethal congenital anomaly, 1 child had consent for follow-up withdrawn, and 23 children died. The primary outcome, which was available in 238 (82%) of those randomized, occurred in 47 of the 117 (40%) children assigned to initial FiO2 0.21 and in 38 of the 121 (31%) assigned to initial FiO2 1.0 (OR, 1.47; 95% CI, 0.86-2.5; P = .16). No difference in NDI was found in 215 survivors randomized to FiO2 0.21 vs 1.0 (OR, 1.26; 95% CI, 0.70-2.28; P = .11). In post hoc exploratory analyses in the whole cohort, children with a 5-minute blood oxygen saturation (SpO2) <80% were more likely to die or to have NDI (OR, 1.85; 95% CI, 1.07-3.2; P = .03).
CONCLUSIONS: Initial resuscitation of infants <32 weeks' gestation with initial FiO2 0.21 had no significant effect on death or NDI compared with initial FiO2 1.0. Further evaluation of optimum initial FiO2, including SpO2 targeting, in a large randomized controlled trial is needed.
TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Network Registry ACTRN 12610001059055 and the National Malaysian Research Registry NMRR-07-685-957.
Cross-cultural adaptation and validation of the Malay language version of the TZO-AZL Preschool Children Quality of Life questionnaire: A health-related quality of life instrument for preschool children

Tay CG, Jalaludin MY, Low WY, Lim CT

J Child Health Care, 2015 Jun;19(2):167-81.
PMID: 24154842 DOI: 10.1177/1367493513503583

The aim of this study is to evaluate the psychometric properties of the translated Malay language version of TZO-AZL Preschool Children Quality of Life (TAPQOL) questionnaire in preschool children. Preterm children and term children aged between two and five years were enrolled into the study. The Malay language version of TAPQOL and a set of questions regarding the child's health status were answered by the caregivers. The internal consistency, Spearman's correlation coefficients and principal component analysis (PCA) with Varimax rotation and Mann-Whitney U test for group comparison were employed to evaluate the psychometric properties of this instrument. A total of 258 children (120 preterm children and 138 term children) were recruited to this study with a response rate of 94%. All (sub)domains except one had Cronbach's α coefficients of more than .7. The Spearman's correlation coefficients between 12 subdomains were generally low. PCA supported the structural unidimensionality of the items in the instrument. Preterm children had lower quality of life scores than that of term children. Malay version of TAPQOL has multidimensional construct. It is a reliable and valid instrument for preschool children, with almost similar psychometric properties to the original version.
Fulltext Partially Reversible Acute Renal Cortical Necrosis Secondary to Hyperhomocysteinemia - A Case Report and Literature Review

Tan W, Abd Ghani F, Seong Lim CT

Indian J Nephrol, 2019 8 20;29(4):288-290.
PMID: 31423065 DOI: 10.4103/ijn.IJN_153_18

Acute renal cortical necrosis (ACN) is a potentially fatal renal condition. Our objective is to report a case of ACN in a young man who had developed premature atherosclerotic vascular disease and required intermittent hemodialysis support. His renal biopsy showed diffuse cortical necrosis. Subsequently, 2 weeks after the renal insult, he developed a cardioembolic stroke and was anticoagulated with low-molecular-weight heparin. Thrombophilia screen revealed elevated serum homocystein and he was treated with folate supplement and vitamin B12 injection. With these treatments, he had partial renal recovery and became dialysis independent. In conclusion, this is a rare case of ACN, which may have occurred as a complication of hyperhomocysteinemia.
Prenatal diagnosis of an extensive haemangioma of the fetal leg: a case report

Raman S, Ramanujam T, Lim CT

J Obstet Gynaecol Res, 1996 Aug;22(4):375-8.
PMID: 8870422

Extensive haemangioma with platelet consumption (Kasabach-Merritt syndrome) is rare. The lesion is usually a single cutaneous cavernous haemangioma similar to that found in our patient. Multiple superficial strawberry naevi were also seen all over the rest of the body. This condition was diagnosed antenatally in this patient with the use of colour Doppler. There is one recent report where the thrombocytopaenia was diagnosed by cordocentesis. Unfortunately the baby developed heart failure with intractable coagulopathy and died 2 days later.
Prenatal diagnosis of a posterior fossa cyst

Raman S, Rachagan SP, Lim CT

J Clin Ultrasound, 1991 Sep;19(7):434-7.
PMID: 1658071
Fulltext Methicillin resistant Staphylococcus aureus--first case of bacteremia in the University Hospital, Kuala Lumpur

Puthucheary SD, Lim CT, Parasakthi N, Tan A, Lam KL

Singapore Med J, 1987 Oct;28(5):456-8.
PMID: 3433116
Fulltext Targeted Oxygen in the Resuscitation of Preterm Infants, a Randomized Clinical Trial

Oei JL, Saugstad OD, Lui K, Wright IM, Smyth JP, Craven P, et al.

Pediatrics, 2017 01;139(1).
PMID: 28034908 DOI: 10.1542/peds.2016-1452

BACKGROUND AND OBJECTIVES: Lower concentrations of oxygen (O2) (≤30%) are recommended for preterm resuscitation to avoid oxidative injury and cerebral ischemia. Effects on long-term outcomes are uncertain. We aimed to determine the effects of using room air (RA) or 100% O2 on the combined risk of death and disability at 2 years in infants <32 weeks' gestation.
METHODS: A randomized, unmasked study designed to determine major disability and death at 2 years in infants <32 weeks' gestation after delivery room resuscitation was initiated with either RA or 100% O2 and which were adjusted to target pulse oximetry of 65% to 95% at 5 minutes and 85% to 95% until NICU admission.
RESULTS: Of 6291 eligible patients, 292 were recruited and 287 (mean gestation: 28.9 weeks) were included in the analysis (RA: n = 144; 100% O2: n = 143). Recruitment ceased in June 2014, per the recommendations of the Data and Safety Monitoring Committee owing to loss of equipoise for the use of 100% O2. In non-prespecified analyses, infants <28 weeks who received RA resuscitation had higher hospital mortality (RA: 10 of 46 [22%]; than those given 100% O2: 3 of 54 [6%]; risk ratio: 3.9 [95% confidence interval: 1.1-13.4]; P = .01). Respiratory failure was the most common cause of death (n = 13).
CONCLUSIONS: Using RA to initiate resuscitation was associated with an increased risk of death in infants <28 weeks' gestation. This study was not a prespecified analysis, and it was underpowered to address this post hoc hypothesis reliably. Additional data are needed.
Speech stimuli and nasalance scores for the assessment of resonance in in Mandarin speaking Malaysian children

Mohd Ibrahim H, Lim HW, Ahmad Rusli Y, Lim CT

Clin Linguist Phon, 2020 06 02;34(6):554-565.
PMID: 31537131 DOI: 10.1080/02699206.2019.1668480

This study was designed to develop language-specific stimuli for the assessment of resonance and to obtain nasalance scores using the newly developed speech stimuli in Mandarin. Gender and age influences on nasalance scores for each of the stimulus were also examined. Participants recruited were typically developing Mandarin-speaking ethnic Chinese children aged 6;00-7;11 growing up in Malaysia. Perceptual ratings of nasality were made based on the GOS.SP.ASS.'98 (revised) for children while nasalance scores were recorded for each stimulus using the Nasometer II (Model 6400). Fifty Mandarin-speaking children (24 males and 26 females) were recruited. None of the participants were perceived with abnormal nasality on the three stimuli. The mean nasalance scores for the Mandarin stimuli were 16.08% (SD = 2.57, 95% CI = 15.35-16.81) for the Oral passage, 25.20% (SD = 3.63, 95% CI = 24.17-26.23) for the Oral-Nasal passage and 55.44% (SD = 4.17, 95% CI = 54.25-56.63) for the Nasal passage. No significant age- and gender-related differences were observed for all the three stimuli. This is the first set of Mandarin stimuli and nasalance norms for Mandarin-speaking children in Malaysia. The influence of phonetic content on nasalance is supported. Findings call for language-specific normative nasalance data and careful selection of stimuli for the assessment of resonance.
Fulltext Population pharmacokinetics of vancomycin in premature Malaysian neonates: identification of predictors for dosing determination

Lo YL, van Hasselt JG, Heng SC, Lim CT, Lee TC, Charles BG

Antimicrob Agents Chemother, 2010 Jun;54(6):2626-32.
PMID: 20385872 DOI: 10.1128/AAC.01370-09

The present study determined the pharmacokinetic profile of vancomycin in premature Malaysian infants. A one-compartment infusion model with first-order elimination was fitted to serum vancomycin concentration data (n = 835 points) obtained retrospectively from the drug monitoring records of 116 premature newborn infants. Vancomycin concentrations were estimated by a fluorescence polarization immunoassay. Population and individual estimates of clearance and distribution volume and the factors which affected the variability observed for the values of these parameters were obtained using a population pharmacokinetic modeling approach. The predictive performance of the population model was evaluated by visual inspections of diagnostic plots and nonparametric bootstrapping with replacement. Dosing guidelines targeting a value of > or =400 for the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC(24)/MIC ratio) were explored using Monte Carlo simulation. Body size (weight), postmenstrual age, and small-for-gestational-age status are important factors explaining the between-subject variability of vancomycin pharmacokinetic parameter values for premature neonates. The typical population parameter estimates of clearance and distribution volume for a 1-kg premature appropriate-for-gestational-age neonate with a postmenstrual age of 30 weeks were 0.0426 liters/h and 0.523 liters, respectively. There was a 20% reduction in clearance for small-for-gestational-age infants compared to the level for the appropriate-for-gestational-age control. Dosage regimens based on a priori target response values were formulated. In conclusion, the pharmacokinetic parameter values for vancomycin in premature Malaysian neonates were estimated. Improved dosage regimens based on a priori target response values were formulated by incorporating body size, postmenstrual age, and small-for-gestational-age status, using Monte Carlo simulations with the model-estimated pharmacokinetic parameter values.
Quality of life in dialysis: A Malaysian perspective

Liu WJ, Musa R, Chew TF, Lim CT, Morad Z, Bujang A

Hemodial Int, 2014 Apr;18(2):495-506.
PMID: 26820998 DOI: 10.1111/hdi.12108

There is a growing interest to use quality of life as one of the dialysis outcome measurement. Based on the Malaysian National Renal Registry data on 15 participating sites, 1569 adult subjects who were alive at December 31, 2012, aged 18 years old and above were screened. Demographic and medical data of 1332 eligible subjects were collected during the administration of the short form of World Health Organization Quality of Life questionnaire (WHOQOL-BREF) in Malay, English, and Chinese language, respectively. The primary objective is to evaluate the quality of life among dialysis patients using WHOQOL-BREF. The secondary objective is to examine significant factors that affect quality of life score. Mean (SD) transformed quality of life scores were 56.2 (15.8), 59.8 (16.8), 58.2 (18.5), 59.5 (14.6), 61.0 (18.5) for (1) physical, (2) psychological, (3) social relations, (4) environment domains, and (5) combined overall quality of life and general health, respectively. Peritoneal dialysis group scored significantly higher than hemodialysis group in the mean combined overall quality of life and general health score (63.0 vs. 60.0, P
Fulltext The effectiveness of surfactant replacement therapy for preterm infants with respiratory distress syndrome

Lim WL, Lim CT, Chye JK

Med J Malaysia, 1998 Dec;53(4):376-84.
PMID: 10971981

Thirty preterm infants weighing > or = 800 g with clinical and radiological evidence of respiratory distress syndrome (RDS) requiring mechanical ventilation with FiO2 of > or = 40% were given modified bovine surfactant (Survanta). They were compared with equal number of historical controls. Infants who received surfactant showed prompt and highly significant improvement in FiO2, mean airway pressure, arterial/alveolar oxygen tension ratio and ventilatory index. There was significant improvement in mortality rate (10% vs 33%; p = 0.03). Among the survivors, surfactant-treated infants required shorter duration of continuous positive airway pressure (CPAP) (3.4 vs 9.6 days; p = 0.04). For survivors with birthweight of > 1000 g, surfactant-treated infants required shorter duration of ventilatory support (intermittent positive pressure ventilation + CPAP) (7.5 vs 18.9 days, p = 0.02). Overall, surfactant-treated infants achieved full enteral feeds sooner (15.7 days vs 24.6 days; p = 0.03) and required shorter duration of total parenteral nutrition (13.9 days vs 25.6 days; p = 0.02). We concluded that surfactant replacement therapy was effective in the treatment of preterm infants with RDS.
Fulltext The significance of tubular and glomerular proteinuria in critically ill patients with severe acute kidney injury

Lim CT, Tan HK, Lau YK

Pak J Med Sci, 2014 Nov-Dec;30(6):1186-90.
PMID: 25674105 DOI: 10.12669/pjms.306.5684

Critically ill patients with acute kidney injury (AKI) frequently need acute renal replacement therapy (aRRT). We evaluated an inexpensive, rapid quantitative and qualitative analysis of proteinuria on the course of AKI patients requiring aRRT in intensive care.
Fulltext Risk profiles of referred chronic kidney disease patients in a tertiary nephrology centre

Lim CT, R R, A S MZ

Pak J Med Sci, 2016 Mar-Apr;32(1):27-30.
PMID: 27022339 DOI: 10.12669/pjms.321.8214

OBJECTIVES: The aims of this study were to determine the seroprevalence of acute dengue in Universiti Kebangsaan Malaysia (UKM) Medical Centre and its correlation with selected haematological and biochemical parameters.
METHODS: This cross-sectional study was conducted from January to June 2015. A patient was serologically diagnosed with acute dengue if the dengue virus IgG, IgM or NS-1 antigen was reactive.
RESULTS: Out of 1,774 patients suspected to have acute dengue, 1,153 were serologically diagnosed with the infection, resulting in a seroprevalence of 64.9%. Dengue-positive patients had a lower mean platelet count (89 × 10(9)/L) compared to the dengue-negative patients (171 × 10(9)/L) (p<0.0001). The mean total white cell count was also lower in the dengue-positive cases (4.7 × 10(9)/L vs. 7.2 × 10(9)/L; p<0.0001). The mean haematocrit was higher in patients with acute dengue (42.5% vs. 40.0%; p<0.0001). Likewise, the serum alanine transaminase level was also higher in patients with acute dengue (108 U/L vs. 54 U/L; p<0.0001).
CONCLUSIONS: Dengue is very prevalent in UKM Medical Centre as most patients suspected to have acute dengue had serological evidence of the infection. The platelet count was the single most likely parameter to be abnormal (i.e. low) in patients with acute dengue.
KEYWORDS: DENV; Dengue; IgG; IgM; NS1; Seroprevalence
Fulltext Predictor of cardiovascular risks in end stage renal failure patients on maintenance dialysis

Lim CT, Yap XH, Chung KJ, Khalid MA, Yayha N, Latiff LA, et al.

Pak J Med Sci, 2015 Nov-Dec;31(6):1300-5.
PMID: 26870086 DOI: 10.12669/pjms.316.8039

OBJECTIVE: Cardiovascular disease (CVD) is the main cause of morbidity and premature mortality in end stage renal failure patients (ESRD) receiving dialysis. The aim of our study was to evaluate the impact of various risk factors in this group of high CVD risk patients in local population.
METHODS: We carried out a cross-sectional retrospective study in a single hospital. A total of 136 ESRF patients, consisted of 43 haemodialysis (HD) and 93 continuous ambulatory peritoneal dialysis (CAPD) patients, were recruited and followed up for 36 months duration. Midweek clinical and laboratory data were collected. The occurrence of existing and new CVD events was recorded.
RESULTS: Multiple Logistic Regression showed pre-existing cardiovascular event (odds ratio, 4.124; 95% confidence interval [CI], 0.990 to 17.187), elevated total cholesterol level (odds ratio, 0.550; 95% CI, 0.315 to 0.963), elevated serum phosphate level (odds ratio, 5.862; 95% CI, 1.041 to 33.024) and elevated random blood glucose level (odds ratio, 1.193; 95% CI, 1.012 to 1.406) were significantly associated with occurrence of CVD events.
CONCLUSIONS: History of cardiovascular event before the initiation of dialysis, elevated level of serum phosphate and random blood glucose levels are the risk factors of CVD whereas paradoxically a high total cholesterol level has CVD protective effect towards the ESRF patients.
KEYWORDS: CVD risk; End Stage Renal Failure (ESRF); Haemodialysis; Peritoneal dialysis
Treatment decisions in severely ill newborns

Lim CT

Med J Malaysia, 2000 Aug;55 Suppl B:17-22.
PMID: 11125515
Group B streptococcus: maternal carriage rate and early neonatal septicaemia

Lim CT, Thong MK, Parasakthi N, Ngeow YF

Ann Acad Med Singap, 1997 Jul;26(4):421-5.
PMID: 9395802

Between January 1984 and December 1994, 30 cases of early neonatal group B streptococcus (GBS) septicaemia were managed in the Neonatal Unit, University Hospital, Kuala Lumpur. Two neonates were outborn and 28 were inborn, giving an average annual incidence of neonatal GBS septicaemia of 0.4/1000 livebirths among inborn babies. In a separate survey over a three-month period, GBS genital carriage rate among 196 parturients was found to be 9.7%. Of the infants with GBS septicaemia, the mean gestational age was 37.5 +/- 3.8 weeks and the mean birthweight was 2540 +/- 716 g. Twelve (40%) were preterm infants and 14 (47%) were low birthweight infants. Male and female infants were almost equally affected. Prolonged rupture of membranes and maternal pyrexia accounted for only 5 (17%) and 3 (10%) of the cases respectively. Twenty-four (80%) neonates had onset of symptoms within 6 hours of life and respiratory symptoms were observed in 24 (80%) of the cases, while meningitis was uncommon. Six (20%) neonates died. Preterm and low birthweight infants had higher mortality than their term counterparts: 42% versus 6% and 36% versus 6% respectively. Of those who died, 4 (67%) required respiratory support right from birth and the mean time of onset of symptoms was 4 hours (range 0 to 21 hours) and the duration of survival was only 28.8 hours (range 12 to 38 hours). As the incidence of neonatal GBS septicaemia was low, mass screening and chemoprophylaxis for GBS were not recommended. All the GBS isolates were sensitive to penicillin and ampicillin, thus one of these antibiotics should be included in the antimicrobial therapy of septic neonates.
Fulltext Early congenital syphilis--a continuing problem in Malaysia

Lim CT, Koh MT, Sivanesaratnam V

Med J Malaysia, 1995 Jun;50(2):131-5.
PMID: 7565181

Between February 1990 and May 1993, 13 cases of early congenital syphilis (ECS) were managed in the Paediatrics Unit, University Hospital, Kuala Lumpur. Twelve mothers were unbooked with 10 inborn babies. Only one mother had antenatal booking at this hospital but she defaulted antenatal follow-up. Several risk factors associated with ECS were identified: inadequate or no prenatal care (5/13), failure to repeat a serological test for syphilis in the third trimester when it was tested negative at first booking (5/13), sexual promiscuity, substance abuse and a past history of contracting sexually transmitted disease. All 10 mothers who had their serological test repeated at delivery were found to have a positive VDRL and TPHA. Adequate antenatal care early referral of infected, expectant mothers for treatment, and a repeat serological test for syphilis could have prevented these cases of ECS.

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