Original Article

Boo NY, Cheah GS
Correspondence: Prof Nem-Yun Boo, nemyun_boo@yahoo.com

ABSTRACT
Introduction This study aimed to identify the risk factors associated with necrotising enterocolitis (NEC) in very low birth weight (VLBW; weight < 1,501 g) infants in Malaysian neonatal intensive care units (NICUs).
Methods This was a retrospective study based on data collected in a standardised format for all VLBW infants born in 2007 (n = 3,601) and admitted to 31 NICUs in Malaysian public hospitals. A diagnosis of NEC was made based on clinical, radiological and/or histopathological evidence of stage II or III, according to Bell’s criteria. Logistic regression analysis was performed to determine the significant risk factors associated with NEC.
Results 222 (6.2%) infants developed NEC (stage II, n = 197; stage III, n = 25). 69 (31.3%) infants died (stage II, n = 58; stage III, n = 11). The significant risk factors associated with NEC were: maternal age (adjusted odds ratio [OR] 1.024, 95% confidence interval [CI] 1.003–1.046; p = 0.027), intrapartum antibiotics (OR 0.639, 95% CI 0.421–0.971; p = 0.036), birth weight (OR 0.999, 95% CI 0.998–0.999; p < 0.001), surfactant therapy (OR 1.590, 95% CI 1.170–2.161; p = 0.003), congenital pneumonia (OR 2.00, 95% CI 1.405–2.848; p < 0.001) and indomethacin therapy for the closure of patent ductus arteriosus (PDA) (OR 1.821, 95% CI 1.349–2.431; p = 0.001).
Conclusion Increasing maternal age, decreasing birth weight, surfactant therapy, congenital pneumonia and indomethacin therapy for the closure of PDA were associated with an increased risk of NEC in Malaysian VLBW infants. Infants that received intrapartum antibiotics were associated with a reduced risk of developing NEC.

Keywords: necrotising enterocolitis, risk factors
Singapore Med J 2012; 53(12): 826–831

Li S, Huang S, Mo ZN, Gao Y, Yang XB, Chen XJ, Zhao JM, Qin X
Correspondence: Dr Xue Qin, qinxue919@yahoo.cn

ABSTRACT
Introduction Circulating insulin concentrations provide important information for the evaluation of insulin secretion and insulin resistance. Reference intervals are the most widely applied tool for the interpretation of clinical laboratory results. We carried out an analysis of the data available from the Fangchenggang Area Male Health and Examination Survey in order to derive a reference interval for fasting insulin specific to the Chinese population.
Methods A total of 1,434 fasting serum insulin results were obtained from healthy nondiabetic adult men aged 20–69 years, after taking into consideration the inclusion and exclusion criteria. Serum insulin was measured using electrochemiluminescence immunoassays. Nonparametric statistical methods were used to calculate and analyse the data.
Results The reference interval for fasting serum insulin for Chinese adults was in the range 1.57–16.32 μU/mL (median 5.79 μU/mL). Significant correlations were found between fasting serum insulin and glucose and diastolic blood pressure (p < 0.001). Statistically significant differences were observed in insulin concentration with respect to age and body mass index (BMI; p < 0.001). Younger people had a higher fasting serum insulin concentration. Increased fasting serum insulin was also found to be associated with BMI.
Conclusion We established a reference interval for fasting serum insulin in healthy nondiabetic adult Chinese men that is lower than what was previously suggested. BMI and age (but not smoking, alcohol consumption or physical activity) were found to be important factors associated with fasting serum insulin. Our results will help improve the diagnostic interpretation of investigations for metabolic and cardiovascular disorders in a Chinese population.

Keywords: elecsys assay, fasting insulin, male, metabolism, reference interval
Singapore Med J 2012; 53(12): 821–825

Chew WF, Rokiah P, Chan SP, Chee SS, Lee LF, Chan YM
Correspondence: Prof Dr Chan Siew Pheng, spchan88@hotmail.com

ABSTRACT
Introduction Women with previous gestational diabetes mellitus (PGDM) are at increased risk of future glucose intolerance. This study aimed to determine the prevalence of prediabetes and type 2 diabetes mellitus (T2DM), and the associated antenatal and historical risk factors among women with PGDM.
Methods This was a cross-sectional study conducted at University Malaya Medical Centre, Kuala Lumpur, Malaysia. A 75-g 2-hour oral glucose tolerance test was performed in a cohort of multiethnic women with PGDM. Body mass index, waist and hip circumferences, fasting lipid profile and blood pressure were obtained. Data pertaining to the index gestational diabetes mellitus (GDM) were obtained from medical records and interviews.
Results 448 women were enrolled in the study. The prevalence of prediabetes and T2DM was 26.2% and 35.5%, respectively. On multinomial logistic regression analysis, fasting plasma glucose at diagnosis of index GDM and duration lapse after index GDM were shown to be significantly higher in women with isolated impaired fasting glucose (IFG), combined IFG/impaired glucose tolerance and T2DM, as compared to women with normal glucose tolerance (p < 0.05). 2-hour plasma glucose at diagnosis of index GDM was significantly higher only in women who progressed to T2DM when compared to those that remained normal glucose tolerant (p < 0.05).
Conclusion In this study, duration lapse after index GDM, fasting plasma glucose and 2-hour plasma glucose at diagnosis of index GDM were important risk factors for early identification of women at high risk for future glucose intolerance. These may be useful for developing potential preventive strategies.

Arrabal-Polo MA, Arrabal-Martin M, Arias-Santiago S, Garrido-Gomez J, De Haro-Muñoz T, Zuluaga-Gomez A
Correspondence: Dr Miguel Angel Arrabal-Polo, arrabalp@ono.com

ABSTRACT
Introduction This study assessed the presence of osteoporosis/osteopenia in patients with severe lithogenic activity and compared their metabolisms with those in patients without lithiasis or with mild lithogenic activity.
Methods From a sample of 182 patients, those with osteopenia/osteoporosis at the hip and lumbar spine were studied separately in a two-pronged study. 66 patients with bone mineral densities (BMDs) < −1 standard deviation (SD) on a T-score scale at the hip were divided into three groups: group A1 without lithiasis (n = 15); group A2 with lithiasis and mild lithogenic activity (n = 22); and group A3 with lithiasis and severe lithogenic activity (n = 29). Similarly, 86 patients with BMDs < −1 SD on a T-score scale at the lumbar spine were divided into three groups: group B1 without lithiasis (n = 15); group B2 with lithiasis and mild lithogenic activity (n = 29); and group B3 with lithiasis and severe lithogenic activity (n = 42).
Results Patients from group A3 exhibited significantly higher levels of bone remodelling markers as compared to groups A1 and A2. Urinalysis also revealed higher excretion of calcium in 24-hour assessments in this group. Patients from group B3 differed from groups B1 and B2 mainly in bone remodelling markers and 24-hour urinary calcium excretion, which were significantly elevated in patients from group B3.
Conclusion Patients with calcium lithiasis and severe lithogenic activity in addition to osteopenia/osteoporosis present with higher levels of hypercalciuria and negative osseous balance, which possibly perpetuate and favour lithiasic activity.

Keywords: bone density, calcium stones, mineral metabolism, osteopenia, osteoporosis
Singapore Med J 2012; 53(12): 808–813

Said MA, Sulaiman AH, Habil MH, Das S, Bakar AK, Yusoff RM, Loo TH, Bakar SA
Correspondence: Dr Ahmad Hatim Sulaiman, hatim@um.edu.my

ABSTRACT
Introduction This study aimed to determine the prevalence of metabolic syndrome and risk of coronary heart disease (CHD) in patients with schizophrenia receiving antipsychotics in Malaysia.
Methods This cross-sectional study, conducted at multiple centres, involved 270 patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV-TR diagnostic criteria for schizophrenia, were on antipsychotic medications for at least one year, and were screened for metabolic syndrome. Patients receiving mood stabilisers were excluded. Metabolic syndrome was defined according to the National Cholesterol Education Program ATP III criteria modified for Asian waist circumference. Risk for cardiovascular disease was assessed by using Framingham function (all ten-year CHD events).
Results The prevalence of metabolic syndrome was 46.7% (126/270). Among all the antipsychotics used, atypical antipsychotics (monotherapy) were most commonly used in both the metabolic and non-metabolic syndrome groups (50.8% vs. 58.3%). The ten-year risk for CHD was significantly higher in patients with metabolic syndrome. The proportion of patients with high/very high risk for CHD (Framingham ≥ 10%) was greater in patients with metabolic syndrome than in those with non-metabolic syndrome (31.5% vs. 11.0%, odds ratio 3.9, 95% confidence interval 2.0–7.6; p < 0.001). The mean body mass index was higher in patients with metabolic syndrome than in those without (29.4 ± 5.1 kg/m2 vs. 25.0 ± 5.6 kg/m2; p < 0.001).
Conclusion Patients with schizophrenia receiving antipsychotics in Malaysia have a very high incidence of metabolic syndrome and increased cardiovascular risk. Urgent interventions are needed to combat these problems in patients.

Keywords: body mass index, cardiovascular risk, metabolic syndrome, prevalence, schizophrenia
Singapore Med J 2012; 53(12): 801–807

Lian WB, Ho S
Correspondence: Dr Lian Wee Bin, lian.wee.bin@sgh.com.sg

ABSTRACT
Introduction There has been a rising trend in childhood developmental and behavioural disorders (CDABD). This study reports the profile of children with autistic spectrum disorders (ASD) initially referred for evaluation of CDABD.
Methods The CDABD database prospectively collected data of all consenting children referred in 2003 to the then Child Development Unit at KK Women’s and Children’s Hospital. All received medical consultation, followed by further assessments and intervention. Patients were tracked for one year.
Results Among 542 referred children, 32% (n = 170) received a diagnosis of ASD one year after the first consultation. Most were male, with a male to female ratio of 4.5:1. The median age at the first consultation was 41 (19,109) months. The main presenting concern was a delay in the development of speech and language skills in 78% of the children. A significant number had behavioural (63%) and social interaction (34%) issues. Criteria for the diagnosis of ASD according to the Diagnostic Statistical Manual IV-Revised were fulfilled in almost 90%. With the remaining refusing or deferring evaluation, only 74% received a psychological assessment. ASD was assessed to be severe or moderate in 86% of the children. Three-quarters remained on follow-up one year after the first consultation. The majority were referred for either centre- or school-based intervention programmes, with 70% assessed to have improved at the one-year mark.
Conclusion This is the first presentation of local data that aids programme planning and resource allocation. Children with ASD have varied outcomes. It is important to identify and intervene early in order to optimise development and functionality.

Keywords: autistic spectrum disorder, childhood development, childhood developmental and behavioural disorders, speech and language delay, social interaction
Singapore Med J 2012; 53(12): 794–800

Chung WL, Ng SS, Koh M, Peh LH, Liu TT
Correspondence: Dr Wan Ling Chung, gnilnaw@gmail.com

ABSTRACT
Introduction Recognising and appropriately treating psychosomatic factors in dermatological conditions can have a significant positive impact on the outcomes of patients. Treatment of psychodermatological patients requires a multidisciplinary approach that involves dermatologists, psychiatrists and allied health professionals.
Methods This was a retrospective case series of patients seen in our psychodermatology liaison conferences from November 2009 to July 2011. We reviewed all the case notes and analysed data such as age, gender, dermatologic and psychiatric diagnoses, treatment and outcome.
Results The majority of patients in our cohort were diagnosed with either a psychophysiologic disorder or a primary psychiatric disorder. The most common diagnosis among patients with primary psychiatric disorder was delusions of parasitosis. Other common primary psychiatric disorders seen were trichotillomania and dermatitis artefacta. About a fifth of our patients had psychiatric disorders resulting from their underlying dermatological conditions. A third of our patients were lost to follow-up.
Conclusion Managing patients with psychocutaneous disorders can be challenging, with many patients defaulting treatments. Psychodermatology clinics will benefit both patients and their caregivers. A collaborative approach using a consultation-liaison relationship between two medical departments in a friendly environment would result in more effective, integrated and holistic treatment strategies for such patients. Further studies should be conducted to determine how beneficial such services are to patients. With more experience, we hope to improve this service.

Keywords: cutaneous sensory disorders, primary psychiatric disorders, psychodermatology, psychophysiological disorders, secondary psychiatric disorders
Singapore Med J 2012; 53(12): 789–793

Mamatha H, D’Souza AS, Pallavi, Suhani S
Correspondence: Dr Mamatha H, mamatha2010@yahoo.com

ABSTRACT
Introduction Nourishment for the brain, a highly vascular organ, is derived from a unique structure called the ‘circle of Willis’, which is formed by the terminal branches of the internal carotid arteries (ICAs) and basilar arteries (BAs). The circle of Willis forms an anastomotic link between the carotid and vertebrobasilar systems in the arterial supply of the brain, while the BA forms an important component of the brain’s posterior circulation and supplies its many vital parts.
Methods A study was performed on 20 brain specimens used for routine dissections at the Anatomy Department, Kasturba Medical College, in order to examine the morphology of BAs in the brain.
Results In most specimens, the position of the termination of BA was normal, although variations were present in the mode of termination. In one specimen, the BA terminated by dividing into two superior cerebellar arteries. The posterior cerebral arteries (PCAs) arose from ICAs on both sides in this specimen, and a communicating branch was present between the terminal point of the BA and PCA on the left. In another specimen, unilateral variation was seen, with the PCA arising from the ICA on the right and a posterior communicating artery arising from the PCA, connecting it with the BA. The anatomy on the left side was normal.
Conclusion We highlight the morphological aspects of the BA, the knowledge of which would help neurosurgeons safely diagnose, as well as plan and execute vascular bypass and shunting procedures for the treatment of stenosis,aneurysms and arteriovenous malformations in the posterior cranial fossa.

Keywords: basilar artery, circle of Willis, internal carotid artery, posterior cerebral artery
Singapore Med J 2012; 53(11): 760–763

Lee WS, Chai PF, Ismail Z
Correspondence: Dr Lee Way-Seah, leews@um.edu.my

ABSTRACT
Introduction This study aimed to determine the emotional impact on parents of young children who require hospitalisation for acute diarrhoea (AD), and the disruption of daily activities experienced and costs incurred by them.
Methods A prospective study was conducted on children below two years of age with AD admitted to two urban hospitals in Malaysia. Parents were interviewed on the emotional impact and disruption of daily activities experienced by them, as well as the extra costs incurred as a result of the hospitalisation of their child.
Results The parents of 85 children (median age 13 months; boys n = 58, 68%; girls n = 27, 32%) were recruited for the study. The proportions of parents who reported that they were very worried about the symptoms of diarrhoea, vomiting and fever in their child were 82%, 83% and 78%, respectively. Parents also reported being upset, helpless, mentally and physically exhausted, and having experienced loss of sleep and disruption of daily routine during the hospitalisation of their child (median four days). The median extra cost (including out-of-pocket cost and loss of income) incurred by parents as a result of the hospitalisation was USD 252.86, which constituted 16% of the combined monthly family income.
Conclusion Although short, AD-related hospitalisation in young children has considerable emotional impact and creates significant distress, in addition to causing significant financial burden for parents.

Keywords: acute diarrhoea, hospitalisation, parental distress
Singapore Med J 2012; 53(11): 755–759

Maduri S, Atla VR
Correspondence: Sairam Maduri, sairammaduri@zoho.com

ABSTRACT
Introduction In spite of being the fastest acting drug available for the control of an acute gout attack, colchicine is generally considered a last alternative in gout therapy. This is mainly due to the severe adverse effects associated with its administration through the enteral and parenteral routes, as well as its high risk/benefit ratio. The preparation of dosage forms of colchicine that can be administered by alternative routes is therefore a beneficial exercise. Among the formulable substitute dosage forms of colchicine, its ointment seems to be the best option available due to its ability to deliver the drug transdermally as well as its ease of preparation and evaluation. In this study, we prepared and tested 0.2% and 0.5% colchicine ointments for their effectiveness in delivering colchicine transdermally.
Methods Colchicine ointment was prepared using a self-formulated water-in-oil type of emulsion ointment base, with the colchicine dissolved in the water portion of the ointment base. In vitro drug release studies were carried out using the Franz diffusion test apparatus and an ultraviolet (UV)-visible spectrophotometer was used to quantify the drug in the samples. Rabbits were used as test animals for in vivo studies and the blood samples were analysed using the UV-visible spectrophotometer.
Results Colchicine was found to be well-absorbed transdermally, although absorption was not 100%. No side effects were associated with its 0.2% formulation.
Conclusion Ointments containing colchicine in low concentrations may be a feasible and effective treatment option for the prevention and treatment of acute gout attacks.
 

Keywords: colchicine, Franz diffusion test apparatus, in vitro drug release studies, in vivo drug release studies
Singapore Med J 2012; 53(11): 750–754