Original Article

Lee WS, Chai PF, Boey CM, Looi LM
Correspondence: Dr Way Seah Lee, leews@um.edu.my

ABSTRACT
Introduction Little is known about the epidemiology, causes and outcomes of neonatal cholestasis in the Asian population beyond Japan and Taiwan.
Methods This was a prospective, observational study on patients with neonatal cholestasis who were referred to the University of Malaya Medical Centre, Malaysia, between November 1996 and May 2004.
Results Biliary atresia (BA) (29 percent) and idiopathic neonatal hepatitis (38 percent) were the two commonest causes of neonatal cholestasis (n is 146) that were referred. Out of the 39 patients (27 percent of the total) who died at the time of review, 35 succumbed to end-stage liver disease. Three of the four patients (three BA, one progress-ive familial intrahepatic cholestasis [PFIC]) who had a living-related liver transplant (LT) died after the surgery (two BA, one PFIC). Six (four percent) of the remaining 107 survivors had liver cirrhosis. The overall four-year survival rates for patients with native liver and LT as well as those with native liver alone for all cases of neonatal cholestasis were 72 percent and 73 percent, respectively, while the respective survival rates for BA were 38 percent and 36 percent.
Conclusion BA and idiopathic neonatal hepatitis are important causes of neonatal cholestasis in Malaysian infants. In Malaysia, the survival rate of patients with neonatal cholestasis, especially BA, is adversely affected by the lack of a timely LT.

Keywords: liver transplant, neonatal cholestasis, outcome
Singapore Med J 2010; 51(5): 434-439

Tyebally A, Ang SY
Correspondence: Dr Arif Tyebally, arif.tyebally@kkh.com.sg

ABSTRACT
Introduction The aim of this research was to study the epidemiology of paediatric near-drowning and drowning victims in Singapore so as to determine the risk factors that will guide drowning prevention strategies.
Methods A total of 38 children aged 0–16 years, who were managed in the Emergency Departments of the Singapore Health Services network or the Department of Forensic Medicine, Health Sciences Authority, for drowning and near-drowning between February 2002 and January 2004, were surveyed as part of the Childhood Injury Surveillance Project. Data on demographics, the location of injury, environmental factors and injury particulars was collected by means of questionnaire forms, review of the in-patient records and the coron-er’s reports.
Results A total of 38 drowning or near-drowning cases in Singapore were reported during the study period, with nine deaths. The median age of the victims was 6.3 years. 52.6 percent of the incidents occurred in swimming pools. 60 percent of the swimming pools had a lifeguard on duty, and all the deaths that occurred in swimming pools were in those without a lifeguard. In 39.5 percent of the cases, no safety features were present at the site of the incident. Most of the deaths by drowning occurred in the sea (55.5 percent).
Conclusion Deaths by drowning are preventable, and appropriate environmental redesign, legislation and public education are necessary to reduce the rate of paediatric drowning. The important factors that are lacking include the absence of pool fencing and lifeguards at swimming pools and recreational beaches.

Keywords: epidemiology, paediatric drowning, prevention, risk factors, water safety
Singapore Med J 2010; 51(5): 429-433

Sathyanarayana Rao KN, Subbalakshmi NK
Correspondence: Dr Sathyanarayana Rao KN, knsrao2008@rediffmail.com

ABSTRACT
Introduction The need for the rational development of newer and adjuvant drugs to treat epilepsy has prompted this study of the potential anticonvulsant effect of amlodipine.
Methods The acute effect was studied in mice in single doses of 1 mg/kg, 2 mg/kg and 4 mg/kg of amlodipine and the chronic effect was studied in doses of 1 mg/kg and 4 mg/kg (administered daily for 21 days) using the maximal electroshock seizure and pentylenetetrazole-induced seizure models of epilepsy. Sodium valproate and normal saline were used as the standard and control, respectively.
Results For the acute study, in the maximal electroshock seizure model, the administration of 1 mg/kg of amlodipine resulted in the complete abolition of seizures in 33 percent of the mice, and this was increased to 67 percent with the administration of 4 mg/kg. In the pentylenetetrazole-induced seizure model, the administration of 1 mg/kg and 2 mg/kg amlodipine protected 33 percent of the animals from mortality, and 67 percent were protected with the administration of 4 mg/kg. For the chronic study, in the maximal electroshock seizure model, the administration of 1 mg/kg amlodipine resulted in the complete abolition of seizures in 40 percent of the mice and in 60 percent, with the administration of 4 mg/kg. In the pentylenetetrazole-induced seizure model, 50 percent of the mice were protected from mortality with 1 mg/kg amlodipine and 60 percent, with 4 mg/kg amlodipine.
Conclusion These findings indicate that amlodipine may be a good candidate as an add-on therapy for epilepsy.

Keywords: abolition of seizure, add-on therapy, amlodipine, anticonvulsant, epilepsy, maximal electroshock, pentylenetetrazole
Singapore Med J 2010; 51(5): 424-428

Jaovisidha S, Suvikapakornkul Y, Woratanarat P, Subhadrabandhu T, Nartthanarung A, Siriwongpairat P
Correspondence: Dr Suphaneewan Jaovisidha, rasjv@yahoo.com

ABSTRACT
Introduction This study aimed to retrospectively review the magnetic resonance (MR) imaging features of the lipomatous tumour in order to differentiate between lipoma and liposarcoma.
Methods The MR images of 38 patients (24 female and 14 male with a mean age 48 years) in a consecutive five-year period, who had histologically verified lipoma (n is 29) and liposarcoma (n is 9), were retrospectively reviewed. The images were assessed for the number, site, size and margin of the lesions, as well as the signal intensity (homogenous, bright signal on T1-weighted [T1W] image, bright signal suppressed on T1W with fat-suppression image, bright signal on T2-weighted with fat-suppression image), the internal architecture (thin/thick septum, cystic change), the effect on the surrounding tissue (oedema, neurovascular involvement) and the enhancement pattern.
Results A partially ill-defined margin, neurovascular involvement, enhancing thick/nodular septum and a partially bright signal intensity on T1W images were statistically significant MR imaging features that favoured a diagnosis of liposarcoma (p-value is less than 0.0001). Male gender, an internal cystic change and surrounding soft tissue oedema increased the risk of liposarcoma approximately 2.8, 3.5 and 3.5 times, respectively, compared with the reference group (lipoma), but this was not a statistically significant finding. Thick/nodular septum was significantly associated with liposarcoma compared with lipoma (odds ratio 69.3, 95 percent confidence interval 5.2–3184.8, p-value is less than 0.0001).
Conclusion Statistically significant MR imaging features that favour a diagnosis of liposarcoma included a partially ill-defined margin, neurovascular involvement, enhancing thick/nodular septum, and a partially bright signal intensity on T1W images. The most statistically significant predictor of liposarcoma was thick/nodular septum.

Keywords: lipoma, liposarcoma, magnetic resonance imaging, soft tissue neoplasm
Singapore Med J 2010; 51(5): 418-423

Avadhani A, Rao PS, Rao SK
Correspondence: Dr Ashwin Avadhani, ashwinavadhani@yahoo.com

ABSTRACT
Introduction The aim of this research was to study the effect of the tibial tunnel position in anterior cruciate ligament (ACL) reconstruction using bone-patellar tendon-bone (BPTB) grafts in ensuring optimal knee functioning.
Methods A prospective study was conducted on 41 patients who underwent arthroscopically assisted ACL reconstruction using a BPTB graft and who were followed up for a minimum period of two years. The radiographic position of the tibial tunnel was compared with the clinical outcome using the International Knee Documentation Committee (IKDC) and modified Lysholm knee scores at two years after surgery.
Results Six out of eight patients with a fair outcome based on the modified Lysholm score and five out of eight patients with an abnormal outcome based on the IKDC score had their tibial tunnel within the 10 percent to 25 percent antero-posterior width of the tibial plateau. The tibial tunnel of patients with a fair Lysholm outcome (mean 22.2 percent) was significantly anterior compared to that of those with an excellent (mean 38.1 percent) and good (mean 34.1 percent) outcome (p is less than 0.01). The analysis using the IKDC score showed a similar trend.
Conclusion Placing the tibial tunnel in the anterior 25 percent of the tibial plateau is associated with a poor knee outcome. More predictable results can be achieved through 35 percent to 46 percent anteroposterior placement of the tibial tunnel.

Keywords: anterior cruciate ligament, bone-patellar tendon-bone graft, treatment outcome
Singapore Med J 2010; 51(5): 413-417

Som S, Pal M, Chakrabarty S, Bharati P
Correspondence: Dr Premananda Bharati, bharati@isical.ac.in

ABSTRACT
Introduction Knowledge of inter-district variations in immunisation coverage and the reasons for their existence is of utmost importance in a region in which variations in the socioeconomic factors are known to have a marked influence on immunisation coverage.
Methods This study was based on a sample of 1,279 children aged 12–35 months. Data was obtained from the District Level Household Survey under the Reproductive and Child Health project (DLHS-RCH-2) that was conducted from 2002 to 2004. Descriptive studies and logistic regression analyses were conducted to examine the variations in immunisation coverage.
Results Approximately 54 percent of children in West Bengal were covered for immunisation. The results for receiving full immunisation varied greatly between the various districts, ranging from 23.3 percent in Murshidabad to 72.2 percent in Hugli. Low rates of coverage were found among the vulnerable groups of poor minorities, especially in rural areas. No evidence of gender differences was found. The educational level of the parents was found to have a significant influence on child immunisation coverage.
Conclusion In order to improve upon the rates of child immunisation coverage in West Bengal, efforts should be concentrated on poor children from minority groups and those living in rural areas.

Keywords: child, districts of West Bengal, immunisation, India, socioeconomic factors
Singapore Med J 2010; 51(5): 406-412

Joshi VD, Lim JFY
Correspondence: Dr Veena Joshi, joshiveena0@gmail.com

ABSTRACT
Introduction Health insurance and the consequent risk pooling are believed to be essential components of a sustainable healthcare financing system. We sought to determine the profile of Singaporeans who had not procured health insurance over and above MediShield, the national government-spearheaded health insurance program and the factors associated with insurance procurement.
Methods A total of 1,783 respondents were interviewed via telephone and asked to rank their agreement with statements pertaining to healthcare cost, quality and financing on a five-point Likert scale.
Results Respondents were representative of the general population in terms of ethnicity and housing type, but lower income households were over-represented. Respondents also had a higher education level compared to the general population. Data on 1,510 respondents, with full information on household (HH) income,education and insurance status, was analysed. HH income below S$1,500 per month (odds ratio [OR] is 5.66, 95 percent confidence interval [CI] is 3.9–8.3, p is less than 0.0001) and a secondary education and below (OR is 2.05, 95 percent CI is 1.5–2.8, p is less than 0.0001) were associated with not procuring insurance over and above MediShield coverage. Respondents with insurance were less likely to agree that healthcare was affordable and that the “3M” framework was sufficient to meet healthcare needs.
Conclusion Singaporeans with a lower HH income and a lower education level were less likely to possess health insurance. This may be related to a stronger belief that healthcare is affordable even without insurance. Educational efforts to encourage the more widespread use of health insurance should be targeted toward lower income groups with less formal education and should be complemented by other interventions to address other aspects of insurance procurement considerations.

Keywords: affordability, health insurance, uninsured
Singapore Med J 2010; 51(5): 399-405

Pooranaperundevi M, Sumiyabanu MS, Viswanathan P, Sundarapandiyan R, Anuradha CV
Correspondence: Dr Carani Venkatraman Anuradha, cvaradha@hotmail.com

ABSTRACT
Introduction Insulin resistance (IR) is recognised as an aetiopathogenic factor for a variety of liver diseases. This study investigated the susceptibility of the liver to the toxic actions of thioacetamide (TA) in a rat model of IR, induced by feeding the rats a high-fructose diet (60 g/100 g) for 30 days.
Methods Hepatic function and damage were assessed at 0 hour and at 6, 12, 24 and 36 hours after a sublethal dose of TA (300 mg/kg intraperitoneally) was administered.
Results After 30 days of fructose feeding, the rats showed IR, a decline in their liver antioxidant status and a rise in lipid peroxidation. Liver dysfunction in fructose-fed rats was evident from a rise in transaminase and total bilirubin, a decrease in the albumin/globulin ratio in plasma, a decrease in nitrite and arginase, and an increase in protein carbonyl and nitrosothiol content in the liver. Increased staining for the 3-nitrotyrosine antibody was observed in the fructose-fed rat livers as compared to the controls. TA (300 mg/kg) caused 80 percent mortality in fructose-fed rats within 48 hours, while no death occurred among the controls.
Conclusion Fructose-fed rats suffered from liver dysfunction and damage. TA caused liver injury in both control and fructose-fed rats. Time-based studies showed that progressive liver injury occurred only in rats that were fructose-fed from 6, 12 and 24 hours after TA administration, with a peak at 36 hours. In control diet-fed rats, the extent of damage was maximal at 24 hours, and declined at 36 hours. Thus, the toxic effects of TA are potentiated due to compromised liver function in the setting of IR.

Keywords: CYP2E1, fructose, insulin resistance, mortality, thioacetamide
Singapore Med J 2010; 51(5): 389-398

Kurian GA, Paddikkala J
Correspondence: Dr Gino A Kurian, ginokurian@hotmail.com

ABSTRACT
Introduction The clinical presentation of ischaemic reperfusion in postoperative patients correlates with oxidative stress. The limited clinical success of anti-ischaemic reperfusion agents has prompted a comparison of the efficacy of N-acetylcysteine (NAC) and magnesium (Mg) in South Indian patients undergoing coronary artery bypass grafting (CABG).
Methods In Clinical Trial I, 52 South Indian patients who had undergone CABG surgery (with intraoperative Mg supplementation) and 40 controls (without Mg supplementation) were selected and matched. The control patients underwent the same protocol without Mg. In Clinical Trial II, the study population consisted of 50 patients, where 25 patients received NAC just before the release of the aortic cross clamp. In the NAC untreated group, dextrose solution was administered at the same time as the placebo. Six blood samples were taken at different times during the cardiac surgery and the antioxidant enzymes, ATPase and cardiac markers from the coronary sinus blood samples were analysed.
Results Increased blood lipid peroxidation was observed in patients who were not treated with Mg/NAC. The administration of Mg/NAC just before the release of the aortic cross clamp reduced the lipid peroxidation significantly (p-value is less than 0.05). The above observations were supported by the antioxidant enzyme levels. Significant improvements to the erythrocyte ATPase and cardiac markers in patients treated with Mg/NAC correlated with a reduction in postoperative abnormalities. Based on the biochemical status of the patients, Mg was shown to mediate better recovery from postoperative changes.
Conclusion NAC and Mg decreased pump-induced oxidative stress during cardiopulmonary bypass (CPB), suggesting that it could be a novel therapy for assisting in the prevention of CPB-induced oxidative stress.

Keywords: coronary artery bypass graft, free radicals, N-acetylcysteine, reperfusion injury
Singapore Med J 2010; 51(5): 381-388

Baig S, Ho SSY, Ng BL, Chiu L, Koay ESC, Leow GH, Gole L, Kothandaraman N, Chan J, Sun X, Chan YH, Rauff M, Su LL, Biswas A, Choolani M
Correspondence: A/Prof Mahesh Choolani, obgmac@nus.edu.sg

ABSTRACT
Introduction We aimed to develop a rapid quantitative-fluorescence polymerase chain reaction (QF-PCR) to detect common foetal aneuploidies in the Singapore population within 48 hours of sample collection in order to alleviate parental anxiety.
Methods DNA from 1,000 foetal samples (978 amniotic fluids, 14 chorion villi and eight foetal blood samples) was analysed using a QF-PCR of 19 microsatellite markers located on chromosomes 13, 18, 21, X and Y. A total of 523 samples were archived before the QF-PCR analysis (archived), while QF-PCR was performed and the results obtained within 48 hours of sample collection in the remaining 477 samples (live). The results were confirmed with their respective karyotypes.
Results In total, 47 autosomal trisomies (T) were found: 30 among the archived (three T13, 12 T18, 15 T21) and 17 among the live (four T18, 13 T21) samples. The QF-PCR results were verified with their respective karyotypes. We achieved 100 percent sensitivity (lower 95 percent confidence interval [CI], 92.8 percent) and specificity (lower 95 percent CI, 99.5 percent), and the time taken from sample collection to the obtaining of results for the 477 live samples was less than 48 hours.
Conclusion Prenatal diagnostic results of common chromosomal abnormalities can be released within 48 hours of sample collection using QF-PCR. Parental anxiety is alleviated and clinical management is enhanced with this short waiting time.

Keywords: amniocentesis, Down syndrome, FISH, karyotype, short tandem repeat
Singapore Med J 2010; 51(4): 343-348