Original Article

Kannappan S, Jayaraman T, Rajasekar P, Ravichandran MK, Anuradha CV
Correspondence: Prof C V Anuradha, cvaradha@hotmail.com

ABSTRACT
Introduction The present study was designed to investigate whether cinnamon bark extract (CBEt) mitigates the adverse effects of fructose loading on glucose metabolism and lipid profile in rats.
Methods Adult male albino rats of body weight 150-170 g were divided into five groups and fed with either control or high fructose diet (HFD). CBEt was administered to HFD-fed rats orally at two doses (a low and a high dose) while the control diet-fed rats were treated with a high dose of CBEt. The treatment protocol was carried out for 60 days after which the oral glucose tolerance test was carried out. Biochemical parameters related to glucose metabolism and lipid profile were assayed.
Results The levels of glucose, insulin and protein-bound sugars were higher and activities of enzymes of glucose metabolism were altered in HFD-fed rats, as compared to control animals. The levels were brought back to near-normal when administered with CBEt at high dose. CBEt also prevented the hyperlipidaemia observed in fructose-fed rats and improved glucose tolerance. CBEt did not show any significant effect in fructose-fed rats when administered at low dose.
Conclusion These findings indicate the improvement of glucose metabolism in-vivo by CBEt in fructose-fed rats.

Keywords: cinnamon bark, fructose diet, glucose metabolism, insulin resistance, lipids
Singapore Med J 2006; 47(10): 858-863

Muttarak M, Pojchamarnwiputh S, Chaiwun B
Correspondence: Prof Malai Muttarak, mmuttara@mail.med.cmu.ac.th

ABSTRACT
Introduction Mammography has proven to be an effective modality for the detection of early breast carcinoma. However, 4-34 percent of breast cancers may be missed at mammography. Delayed diagnosis of breast carcinoma results in an unfavourable prognosis. The objective of this study was to determine the causes and characteristics of breast carcinomas missed by mammography at our institution, with the aim of reducing the rate of missed carcinoma.
Methods We reviewed the reports of 13,191 mammograms performed over a five-year period. Breast Imaging Reporting and Data Systems (BI-RADS) were used for the mammographical assessment, and reports were cross-referenced with the histological diagnosis of breast carcinoma. Causes of missed carcinomas were classified.
Results Of 344 patients who had breast carcinoma and had mammograms done prior to surgery, 18 (5.2 percent) failed to be diagnosed by mammography. Of these, five were caused by dense breast parenchyma obscuring the lesions, 11 were due to perception and interpretation errors, and one each from unusual lesion characteristics and poor positioning.
Conclusion Several factors, including dense breast parenchyma obscuring a lesion, perception error, interpretation error, unusual lesion characteristics, and poor technique or positioning, are possible causes of missed breast cancers.

Keywords: breast cancer, mammography, missed diagnosis
Singapore Med J 2006; 47(10): 851-857

Bhalla V, Fong CW, Chew SK, Satku K
Correspondence: Dr Vineta Bhalla, vineta_bhalla@moh.gov.sg

ABSTRACT
Introduction The National Healthy Lifestyle Programme, a population-wide non-communicable disease intervention programme, was started in 1992. A National Health Survey is carried out every six years to evaluate the impact of this programme on the cardiovascular risk factor profile of the resident population of Singapore.
Methods The 2004 National Health Survey (NHS 04) was a population-based survey carried out over a period of four months from September to December 2004. A combination of disproportionate stratified sampling and systematic sampling was used to select a representative sample (n=7,078) for the survey. The reference population comprised 2.4 million multi-racial Singaporeans aged 18-69 years. Anthropometric and blood pressure measurements were carried out on all subjects and blood samples were taken for biochemical analysis. The results were compared with those of a similar survey conducted in 1998.
Results A total of 4,084 Singapore residents took part in the survey, giving a response rate of 57.7 percent. The age-standardised prevalence of hypertension (greater than or equal to 140/90 mmHg) in Singapore residents aged 30-69 years decreased from 28.0 percent in 1998 to 24.0 percent (p-value is less than 0.001) in 2004. The prevalence of high total cholesterol (greater than or equal to 6.2 mmol/L) among those aged 18-69 years fell from 26.0 percent in 1998 to 18.1 percent (p-value is less than 0.001) in 2004. The prevalence of diabetes mellitus in residents aged 18-69 years in 2004 was 7.8 percent, compared to the 1998 level of 9.5 percent (p-value is less than 0.01). The level of obesity (body mass index is greater than or equal to 30 kg/sqm) increased slightly from 6.2 percent in 1998 to 6.8 percent (p-value equals 0.1627). The prevalence of daily smoking decreased from 15.0 percent in 1998 to 12.5 percent in 2004 (p-value is less than 0.001), while that of regular exercise increased from 17.0 percent to 25.0 percent (p-value is less than 0.001). Ethnic differences in the prevalence of diabetes mellitus, hypertension, hypercholesterolaemia, and exercise were observed.
Conclusion The NHS 04 results suggest that the National Healthy Lifestyle Programme significantly decreased daily smoking, high blood cholesterol and hypertension, and increased regular exercise over 1998 levels. The results also suggest that the programme stabilised the prevalence of obesity and diabetes mellitus.

Keywords: cardiovascular risk factors, diabetes mellitus, hypertension, lipids, National Health Survey
Singapore Med J 2006; 47(10): 841-850

Hawkins RC, Leong L
Correspondence: Dr Robert C Hawkins, robert_hawkins@ttsh.com.sg

ABSTRACT
Introduction The Centers for Disease Control and Prevention (CDC) and the American Heart Association (AHA) have endorsed the optional use of high sensitive C-reactive protein (hsCRP) to identify patients without known coronary heart disease but who may be at higher absolute risk than estimated by major risk factors. This study assessed the potential value of hsCRP measurement in addition to routine lipid and risk factor assessment on patient management for individuals undergoing multiphasic health screening.
Methods hsCRP was measured on fasting lipid samples on patients attending the Health Enrichment Clinic at Tan Tock Seng Hospital between January and April 2004. These results were then compared with the outcome of individual patient risk assessment (using the 2001 Singapore Ministry of Heath Clinical Practice Guidelines on Lipids), the patient's lipid results and whether the patient was already on anti-lipid treatment.
Results 212 samples were analysed for hsCRP. Seven patients were already on anti-lipid drugs. Using the AHA/CDC guidelines, hsCRP measurement would be of value in deciding management in 12.7 percent of all patients. Of this group, 11 percent had hsCRP concentrations in the high risk category. Restricting hsCRP measurement to only those patients with two or more cardiac risk factors and not on anti-lipid drugs would increase the proportion of patients where hsCRP could be useful in deciding management, to 81.8 percent.
Conclusion For clinicians prepared to consider treatment in patients with elevated hsCRP levels, hsCRP measurement should be included as part of health screening packages to selected patients based on individual cardiac risk assessment.

Keywords: atherosclerosis, C-reactive protein, coronary heart disease, evidence-based medicine, health screening
Singapore Med J 2006; 47(10): 837-840

Tan EL, Looi LM, Sam CK
Correspondence: Dr Tan Eng Lai, englaitan@gmail.com

ABSTRACT
Introduction Nasopharyngeal carcinoma (NPC) is an important cancer in Malaysia and is one of the major causes of cancer mortality in this country. This study evaluates the diagnostic and prognostic values in the quantitative relationship between the cell-free Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) load and the tumour burden.
Methods Blood plasma from 18 untreated NPC patients, 20 NPC patients who had been treated with radiotherapy, and 12 healthy individuals were evaluated. EBV copy number was determined following DNA extraction using real-time quantitative polymerase chain reaction.
Results The cell-free EBV DNA load was shown to be proportionately related to the presence of malignant disease. While the EBV copy number in untreated NPC patients had a median of 2,043 copies/ml, viral load in plasma of healthy controls was significantly lower (median of 0 copy/ml). A significant decrease in EBV load was observed in patients who had undergone radiotherapy while a high viral load indicated in one patient correlated to tumour relapse and presence of distant metastasis upon clinical investigation.
Conclusion The blood plasma EBV DNA load was shown to be proportionately related to the presence of malignant disease. This preliminary study underscores the prognostic value of cell-free EBV DNA quantification.

Keywords: DNA, Epstein-Barr virus, human herpes virus, nasopharyngeal carcinoma
Singapore Med J 2006; 47(9): 803-807

Kasodekar VB, Yeo SJ, Othman S
Correspondence: Dr Yeo Seng Jin, gocysj@sgh.com.sg

ABSTRACT
Introduction Various factors that affect the longevity of unicompartmental knee arthroplasty (UKA) include patient activity level, habitus, competence of cruciate ligaments, postoperative alignment, implant positioning and ligament balancing. The purpose of this study was to evaluate the clinical outcome of the open standard UKA and establish the influence of radiological alignment on the survivorship of the prosthesis.
Methods We consecutively reviewed the results of 20 open standard UKAs performed in 17 patients between 1996 and 2000. A single implant type, the Press Fit Condylar Unicompartmental Knee System (DePuy, Leeds, UK), was used in all patients. All patients were evaluated clinically using the Knee Society Rating. Implant positioning and limb alignment were recorded in the standing long leg anteroposterior and lateral radiographs, and various angles were measured.
Results The alignment of the prosthesis was found to be good in 19 out of 20 operated knees. One knee with malalignment of prosthesis had to be revised at 23 months follow-up. There was a significant increase in Knee Society Rating of all patients, at a follow-up of 4-8 years. The Kaplan-Meier survival rate using revision to total knee arthroplasty as an endpoint was 91.7 percent.
Conclusion The long-term outcome of UKA is influenced by positioning and alignment of the prosthesis. With proper patient selection and surgical technique, the outcome of UKA can be definitely improved.

Keywords: arthroplasty, knee alignment, knee arthroplasty, prosthesis, unicompartmental knee arthroplastsy
Singapore Med J 2006; 47(9): 796-802

Koh KH
Correspondence: Dr Koh Keng Hee, kohkenghee@yahoo.com

ABSTRACT
Introduction Infusing the replacement solution before the filter (pre-dilution) and regular flushing have not been accounted for in conventional mathematical equations. Their effects on various continuous renal replacement therapy (CRRT) parameters, such as ultrafiltration fraction and urea clearance, have not been well studied. We incorporated these parameters into mathematical equations to help in understanding and prescribing CRRT.
Methods We built a mathematical model to evaluate the plasma flow rate, filter fluid inflow rate with pre- and post-dilution and ultrafiltration rate, plasma clearance of urea, and ultrafiltration fraction.
Results In pre-dilutional therapy, the volume of replacement needed to be increased in order to achieve the target plasma clearance rate. The extra volume needed increased exponentially with higher target plasma clearance rate. The higher the targeted plasma clearance in relation to blood flow rate (Qb), the greater the increase. Increasing blood flow rate reduced the ultrafiltration fraction for both pre- and post-dilution therapy. It had no effect on plasma clearance with post-dilution therapy but significantly improved the clearance in pre-dilution therapy. Higher haematocrit resulted in higher ultrafiltration fraction in both pre- and post-dilution therapy. Higher haematocrit had no effect on plasma clearance with post-dilution therapy but slightly reduced clearance in pre-dilution therapy. For a given total volume of ultrafiltration, flushing reduced plasma clearance with both pre- and post-dilution therapy. Flushing slightly reduced ultrafiltration fraction of post-dilution therapy but minimally increased the ultrafiltration fraction of pre-dilution therapy. This mathematical model could be utilised in prescribing Qb and replacement rate based on targeted plasma clearance, ultrafiltration fraction, fluid removal rate and haematocrit. There was close approximation of predicted and measured urea plasma clearance.
Conclusion Pre-dilution therapy reduced urea clearance significantly and this needed to be compensated for by increasing the volume of ultrafiltration or Qb. Flushing was of limited benefit and may reduce urea clearance. In prescribing haemofiltration, Qb and replacement rate could be determined with this model.

Keywords: continuous renal replacement therapy, flushing, haemofiltration, mathematical modelling, pre-dilution haemofiltration, ultrafiltration fraction
Singapore Med J 2006; 47(9): 785-795

Sittiwangkul R, Pongprot Y, Silvilairat S, Phornphutkul C
Correspondence: Dr Rekwan Sittiwangkul, rsittiwa@mail.med.cmu.ac.th

ABSTRACT
Introduction This study aimed to determine the prevalence and risk of intravenous gammaglobulin (IVIG)-resistant Kawasaki disease (KD) and report the outcome of treatment in patients with persistent or recurrent fever.
Methods 70 KD patients, who received IVIG treatment (2 g/kg) at a tertiary care hospital from January 1995 to June 2004, were retrospectively reviewed.
Results Nine (13 percent) of the 70 patients failed to respond to initial treatment with IVIG. The patients who did not respond to IVIG had higher erythrocyte sedimentation rate (ESR) (104 versus 74 mm/h; p-value is 0.003), longer total days of fever (14.4 +/- 3.8 versus 9.2 +/- 2.3 days; p-value is 0.003) and higher initial coronary artery lesions (CAL) (7 of 9 [77.7 percent] versus 10 of 61 [16.3 percent]; p-value is 0.001) than those who responded to initial treatment. Seven of the nine patients who were retreated with IVIG (2 g/kg) responded to the second dose. The remaining two patients (two of nine, 22 percent) had persistent fever, which subsided after two to three doses of pulse intravenous methylprednisolone. At two months follow-up, IVIG-resistant patients had higher CAL by echocardiogram than IVIG-responsive patients (33 percent versus 3.2 percent, p-value is less than 0.05). Two IVIG-resistant KD patients had delayed diagnosis and developed giant aneurysms.
Conclusion Patients with high ESR had increased risk of IVIG-resistant KD. IVIG-resistant Kawasaki patients had a higher prevalence of CAL at the acute phase and two months after onset.

Keywords: coronary artery lesion, gammaglobulin refractory Kawasaki disease, gammaglobulin resistance, intravenous immunoglobulin therapy, Kawasaki disease, methylprednisolone pulse therapy
Singapore Med J 2006; 47(9): 780-784

Ng DK, Hui HN, Chan CH, Kwok KL, Chow PY, Cheung JM, Leung SY
Correspondence: Dr Daniel K Ng, dkkng@ha.org.hk

ABSTRACT
Introduction Children with Down syndrome (DS) are prone to develop obstructive sleep apnoea (OSA) for a combination of reasons, including small upper airway, midfacial hypoplasia, micrognathia and muscular hypotonia. The objective of this study was to compare the prevalence of OSA in DS children, with or without snoring, with snoring children matched for gender, age and weight for height.
Methods DS children were prospectively recruited from the Hong Kong Down Syndrome Association. All recruited DS children underwent a sleep polysomnography (PSG) in our sleep laboratory. The same number of patients without DS who underwent sleep PSG in the same period were enrolled as controls after they were matched for gender, age and weight for height. OSA was defined as apnoea-hypopnoea index (AHI) greater than 1.5.
Results 22 DS patients and 22 snoring controls completed the overnight PSG. The mean age of DS children and snoring controls was 10.82 +/- 5.93 and 10.27 +/- 5.68 years, respectively. The prevalence of OSA was 59 percent in DS children and 32 percent in snoring controls. Median and interquartile range (IQR) of AHI of DS children (median 1.80, IQR is 0.40 to 7.10) were significantly higher than those of controls (median 0.50, IQR is 0.00 to 2.03, p-value equals 0.041). Out of 13 DS children with OSA, eight of them (61.5 percent) had no habitual snoring.
Conclusion 59 percent of DS children in the current series were found to have OSA and they were more likely to develop OSA than controls. Nearly 40 percent of DS children with OSA did not have habitual snoring.

Keywords: apnoea-hypopnoea index, Down syndrome, obesity, obstructive sleep apnoea, polysomnography, snoring
Singapore Med J 2006; 47(9): 774-779

Kumar S, Ratho RK, Chawla YK, Chakraborti A
Correspondence: Professor R K Ratho, rathopgi@yahoo.com

ABSTRACT
Introduction Hepatitis E virus (HEV) infection is of major public health concern in the developing countries, including the Indian subcontinent, due to epidemics of large proportions, increased morbidity and high mortality, especially in pregnant women. This study shows the findings of two different epidemics that occurred due to HEV.
Methods Blood samples were collected from 116 suspected HEV patients. Sera were separated and tested for hepatitis A virus HAV immunoglobulin M (IgM), hepatitis B virus surface antigen, hepatitis C virus (HCV) antibody and HEV IgM by Micro ELISA. 15 acute samples were subjected to reverse transcriptase polymerase chain reaction (RT-PCR) for the detection of HEV ribonucleic acid (RNA).
Results Of the 116 blood samples collected, 68 (58.6 percent) were positive for HEV IgM antibodies. Mixed infections of HEV with HAV and HCV were detected in three (4.4 percent) and five (7.4 percent) cases, respectively. 15 HEV IgM-positive acute blood samples subjected to RT-PCR showed the presence of specific 343 bp amplified HEV ORF1 gene product in five cases. No untoward effects were observed in the five HEV-infected pregnant women during their follow-up.
Conclusion This study confirms the HEV aetiology and highlights a major disease outbreak that occurred due to mixing of drinking water with sewerage.

Keywords: enterically-transmitted non-A non-B hepatitis virus, hepatitis E virus, pregnancy complications, viral epidemic
Singapore Med J 2006; 47(9): 769-773