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  1. Mukhtar AA, Ibrahim LS, Khairil AO
    Nepal Med Coll J, 2007 Dec;9(4):289-91.
    PMID: 18298025
    A 20 year old male presented to the emergency department with generalized tonic clonic convulsions and up rolling of eye balls. He had history of seizure disorder for three years and on regular medical treatment and is compliant to medication. A non-contrast CT scan of the head was only done on 14th day of admission which showed hypodense areas in the right and left cerebellar hemisphere. MR imaging was performed four days later revealed high signal intensity in the both cerebellar hemispheres, both external capsules, both occipital and right parietal regions on fluid-attenuated inversion recovery (FLAIR). The post contrast MR imaging revealed diffuse cerebral and cerebellar hypervascularity in the similar region. This change of diffuse hypervascularity of both cerebral and cerebellar associated with seizure activity on post-contrast magnetic resonance imaging (MRI) has not been reported in any literature.
  2. Rashid A, Manan AA, Yahya N, Ibrahim L
    PLoS One, 2014;9(10):e109429.
    PMID: 25338116 DOI: 10.1371/journal.pone.0109429
    This cross sectional survey was conducted to determine the support in making Penang UNESCO World Heritage Site (GTWHS) smoke free and to determine the influence of tolerance towards smoking on this support. This is the first phase in making Penang, Malaysia a smoke free state. A multistage sampling process was done to select a sample of respondents to represent the population of GTWHS. Attitude towards smoking was assessed using tolerance as a proxy. A total of 3,268 members of the community participated in the survey. A big majority (n = 2969; 90.9%) of the respondents supported the initiative. Support was lowest among the owners and residents/tenants, higher age groups, the Chinese, men, respondents who had poor knowledge of the places gazetted as smoke free, and respondents with poor knowledge of the health effects on smokers and on passive smokers. The odds (both adjusted and unadjusted) of not supporting the initiative was high among those tolerant to smoking in public areas. Tolerance towards smoking was associated with 80.3% risk of non-support in the respondents who were tolerant to smoking and a 57.2% risk in the population. Health promotion and education concerning the harm of tobacco smoke in Malaysia, which has mainly targeted smokers, must change. Health education concerning the risks of second hand smoke must also be given to non-smokers and efforts should be made to denormalize smoking.
  3. Rajion ZA, Townsend GC, Netherway DJ, Anderson PJ, Yusof A, Hughes T, et al.
    Cleft Palate Craniofac J, 2006 Sep;43(5):513-8.
    PMID: 16986980
    To investigate anatomical variations and abnormalities of cervical spine morphology in unoperated infants with cleft lip and palate.
  4. Rajion ZA, Townsend GC, Netherway DJ, Anderson PJ, Hughes T, Shuaib IL, et al.
    Cleft Palate Craniofac J, 2006 Sep;43(5):532-8.
    PMID: 16986987
    To compare morphological and positional variations of the hyoid bone in unoperated infants with cleft lip and palate (CL/P) with those in noncleft infants.
  5. Ratnasingam J, Ibrahim L, Paramasivam S, Lim LL, Boon AT, Vethakkan S
    Clin Cases Miner Bone Metab, 2016 05 11;13(1):61-3.
    PMID: 27252750 DOI: 10.11138/ccmbm/2016.13.1.061
    BACKGROUND: Poliomyelitis survivors suffer from post-myelitic complications including osteoporosis that are often overlooked.

    METHODS: We report a case of a 49-year-old lady with history of poliomyelitis with resultant flaccid paralysis of the involved limb.

    RESULTS: The bone mineral density revealed asymmetrical severe osteoporosis in the poliomyelitic limb. Given the risk of falls and fractures, she was commenced on oral bisphosphonate therapy.

    CONCLUSION: Poliomyelitis is an important acquired risk factor for regional osteoporosis. This condition should be detected and treated in this cohort of patients who are clearly at higher risk of fractures.

  6. Ratnasingam J, Karim N, Paramasivam SS, Ibrahim L, Lim LL, Tan AT, et al.
    Pituitary, 2015 Aug;18(4):448-55.
    PMID: 25134488 DOI: 10.1007/s11102-014-0593-6
    PURPOSE: Radiation fields for nasopharyngeal cancer (NPC) include the base of skull, which places the hypothalamus and pituitary at risk of damage. We aimed to establish the prevalence, pattern and severity of hypothalamic pituitary (HP) dysfunction amongst NPC survivors.

    METHODS: We studied 50 patients (31 males) with mean age 57 ± 12.2 years who had treatment for NPC between 3 and 21 years (median 8 years) without pre-existing HP disorder from other causes. All patients had a baseline cortisol, fT4, TSH, LH, FSH, oestradiol/testosterone, prolactin and renal function. All patients underwent dynamic testing with insulin tolerance test to assess the somatotroph and corticotroph axes. Baseline blood measurements were used to assess thyrotroph, gonadotroph and lactotroph function.

    RESULTS: Hypopituitarism was present in 82% of patients, 30% single axis, 28% two axes, 18% three axes and 6% four axes deficiencies. Somatotroph deficiency was most common (78%) while corticotroph, gonadotroph and thyrotroph deficiencies were noted in 40% (4 complete/16 partial), 22 and 4% of the patients respectively. Hyperprolactinaemia was present in 30% of patients. The development of HP dysfunction was significantly associated with the time elapsed from irradiation, OR 2.5 (1.2, 5.3), p = 0.02, for every 2 years post treatment. The use of concurrent chemo-irradiation (CCRT) compared to those who had radiotherapy alone was also significantly associated with HP dysfunction, OR 14.5 (2.4, 87.7), p < 0.01.

    CONCLUSION: Despite low awareness and detection rates, HP dysfunction post-NPC irradiation is common. Use of CCRT may augment time related pituitary damage. As these endocrinopathies result in significant morbidity and mortality we recommend periodic assessment of pituitary function amongst NPC survivors.

  7. Ratnasingam J, Tan AT, Vethakkan SR, Paramasivam SS, Ibrahim L, Lim LL, et al.
    J Clin Endocrinol Metab, 2013 Mar;98(3):869-70.
    PMID: 23337722 DOI: 10.1210/jc.2012-3839
  8. Kasim NB, Huri HZ, Vethakkan SR, Ibrahim L, Abdullah BM
    Biomark Med, 2016 Apr;10(4):403-15.
    PMID: 26999420 DOI: 10.2217/bmm-2015-0037
    Generally, obese and overweight individuals display higher free fatty acid levels, which stimulate insulin resistance. The combination of overweight or obesity with insulin resistance can trigger Type 2 diabetes mellitus (T2DM) and are primary contributing factors to the development of uncontrolled T2DM. Genetic polymorphisms also play an important role as they can impact a population's susceptibility to becoming overweight or obese and developing related chronic complications, such as uncontrolled T2DM. This review specifically examines the genetic polymorphisms associated with overweight and obesity in patients with uncontrolled T2DM. Particularly, gene polymorphisms in ADIPOQ (rs1501299 and rs17300539), LepR (rs1137101 and rs1045895), IRS2 (rs1805092), GRB14 (rs10195252 and rs3923113) and PPARG (rs1801282) have been associated with overweight and obesity in uncontrolled T2DM.
  9. Lewis GE, Miller LH, Ibrahim L, Wong PW, McGinniss M, Ooi WL
    Trans R Soc Trop Med Hyg, 1988;82(3):509-10.
    PMID: 3068862
    Duffy phenotypes were determined for 314 Malaysian Orang Asli. The most common gene, Fya, was present in 313; there were no Duffy negative individuals. A previous study found evidence of Plasmodium vivax infection in 5 of 7 Orang Asli reported to be of the Duffy negative genotype. In this study, 5 of the 7 previously tested Orang Asli were retested in triplicate, and each of the 5 was found to be Duffy positive, having the Fya gene and a phenotype of Fy (a + b-).
  10. Ratnasingam J, Chooi KC, Samsuddin S, Paramasivam S, Ibrahim L, Lim LL, et al.
    Endocr Pract, 2017 Jun;23(6):752.
    PMID: 27967223 DOI: 10.4158/EP161568.VV
  11. Lim LL, Kitan N, Paramasivam SS, Ratnasingam J, Ibrahim L, Chan SP, et al.
    J Med Case Rep, 2015;9:277.
    PMID: 26619967 DOI: 10.1186/s13256-015-0757-7
    Determining the etiology of Cushing's syndrome is very challenging to endocrinologists, with most of the difficulty arising from subtype differentiation of adrenocorticotropic hormone-dependent Cushing's syndrome. We present the pitfalls of evaluating a rare cause of adrenocorticotropic hormone-independent Cushing's syndrome in the transition period between adolescence and adulthood.
  12. Abdullah NA, Wan Mahiyuddin WR, Muhammad NA, Ali ZM, Ibrahim L, Ibrahim Tamim NS, et al.
    Asian Pac J Cancer Prev, 2013;14(8):4591-4.
    PMID: 24083707
    Breast cancer is the most common cancer among Malaysian women. Other than hospital-based results, there are no documented population-based survival rates of Malaysian women for breast cancers. This population- based retrospective cohort study was therefore conducted. Data were obtained from Health Informatics Centre, Ministry of Health Malaysia, National Cancer Registry and National Registration Department for the period from 1st Jan 2000 to 31st December 2005. Cases were captured by ICD-10 and linked to death certificates to identify the status. Only complete data were analysed. Survival time was calculated from the estimated date of diagnosis to the date of death or date of loss to follow-up. Observed survival rates were estimated by Kaplan- Meier method using SPSS Statistical Software version 17. A total of 10,230 complete data sets were analysed. The mean age at diagnosis was 50.6 years old. The overall 5-year survival rate was 49% with median survival time of 68.1 months. Indian women had a higher survival rate of 54% compared to Chinese women (49%) and Malays (45%). The overall 5-year survival rate of breast cancer patient among Malaysian women was still low for the cohort of 2000 to 2005 as compared to survival rates in developed nations. Therefore, it is necessary to enhance the strategies for early detection and intervention.
  13. Lim LL, Brnabic AJ, Chan SP, Ibrahim L, Paramasivam SS, Ratnasingam J, et al.
    J Diabetes Investig, 2017 Jul;8(4):453-461.
    PMID: 27863088 DOI: 10.1111/jdi.12596
    AIMS/INTRODUCTION: Studies on the relative contributions of fasting and postprandial hyperglycemia (FH and PPH) to glycated hemoglobin (HbA1c ) in patients with type 2 diabetes have yielded inconsistent results. We aimed to assess the relationship by using continuous glucose monitoring in a multi-ethnic cohort.

    MATERIALS AND METHODS: A total of 100 adults with type 2 diabetes were assessed with 6-day continuous glucose monitoring and HbA1c . Area under the curve (AUC) ≥5.6 mmol/L was defined as AUCTOTAL . AUC equal to or greater than each preprandial glucose for 4-h duration was defined as AUCPPH . The total PPH (AUCTPPH ) was the sum of the various AUCPPH. The postprandial contribution to overall hyperglycemia was calculated as (AUCTPPH / AUCTOTAL ) × 100%.

    RESULTS: The present study comprised of Malay, Indian, and Chinese type 2 diabetes patients at 34, 34 and 28% respectively. Overall, the mean PPH significantly decreased as HbA1c advanced (mixed model repeated measures adjusted, beta-estimate = -3.0, P = 0.009). Age (P = 0.010) and hypoglycemia (P = 0.006) predicted the contribution difference. In oral antidiabetic drug-treated patients (n = 58), FH contribution increased from 54% (HbA1c 6-6.9%) to 67% (HbA1c ≥10%). FH predominance was significant in poorly-controlled groups (P = 0.028 at HbA1c 9-9.9%; P = 0.015 at HbA1c ≥10%). Among insulin users (n = 42), FH predominated when HbA1c was ≥10% before adjustment for hypoglycemia (P = 0.047), whereas PPH was numerically greater when HbA1c was <8%.

    CONCLUSIONS: FH and PPH contributions were equal in well-controlled Malaysian type 2 diabetes patients in real-world practice. FH predominated when HbA1c was ≥9 and ≥10% in oral antidiabetic drug- and insulin-treated patients, respectively. A unique observation was the greater PPH contribution when HbA1c was <8% despite the use of basal and mealtime insulin in this multi-ethnic cohort, which required further validation.

  14. Paramasivam SS, Chinna K, Singh AKK, Ratnasingam J, Ibrahim L, Lim LL, et al.
    Diabet Med, 2018 08;35(8):1118-1129.
    PMID: 29663517 DOI: 10.1111/dme.13649
    AIMS: To determine if therapeutic, retrospective continuous glucose monitoring (CGM) improves HbA1c with less hypoglycaemia in women with insulin-treated gestational diabetes mellitus (GDM).

    METHODS: This prospective, randomized controlled, open-label trial evaluated 50 women with insulin-treated GDM randomized to either retrospective CGM (6-day sensor) at 28, 32 and 36 weeks' gestation (Group 1, CGM, n = 25) or usual antenatal care without CGM (Group 2, control, n = 25). All women performed seven-point capillary blood glucose (CBG) profiles at least 3 days per week and recorded hypoglycaemic events (symptomatic and asymptomatic CBG l; non-fasting l). HbA1c was measured at 28, 33 and 37 weeks. In Group 1, both CGM and CBG data were used to manage diabetes, whereas mothers in Group 2 were managed based on CBG data alone.

    RESULTS: Baseline characteristics (age, pre-pregnancy BMI, HbA1c , total insulin dose) were similar between groups. There was a lower increase in HbA1c from 28 to 37 weeks' gestation in the CGM group [∆HbA1c : CGM + 1 mmol/mol (0.09%), control + 3mmol/mol (0.30%); P = 0.024]. Mean HbA1c remained unchanged throughout the trial in the CGM group, but increased significantly in controls as pregnancy advanced. Mean HbA1c in the CGM group was lower at 37 weeks compared with controls [33 ± 4 mmol/mol (5.2 ± 0.4%) vs. 38 ± 7 mmol/mol (5.6 ± 0.6%), P 

  15. Venugopal Y, Hatta SFWM, Musa N, Rahman SA, Ratnasingam J, Paramasivam SS, et al.
    Asia Pac J Clin Nutr, 2017 May;26(3):412-420.
    PMID: 28429905 DOI: 10.6133/apjcn.042016.10
    BACKGROUND AND OBJECTIVES: Vitamin D3 (cholecalciferol) dose required to maintain sufficiency in non- Caucasian women with postmenopausal osteoporosis (PMO) inthe tropics has not been well studied. Some guidelines mandate 800-1000 IU vitamin D/day but the Endocrine Society (US) advocates 1500-2000 IU/day to maintain 25-hydroxyvitamin-D (25(OH)D) concentration at >75 nmol/L. We aimed to establish oral cholecalciferol dose required to maintain 25(OH)D concentration at >75 nmol/L in PMO Chinese Malaysian women, postulating lower dose requirements amongst light-skinned subjects in the tropics.

    METHODS AND STUDY DESIGN: 90 Chinese Malaysian PMO women in Kuala Lumpur, Malaysia (2°30'N) with baseline serum 25(OH)D levels >=50 nmol/L were recruited. Prior vitamin D supplements were discontinued and subjects randomized to oral cholecalciferol 25,000 IU/4-weekly (Group-A) or 50,000 IU/4-weekly (Group- B) for 16 weeks, administered under direct observation. Serum 25(OH)D, PTH, serum/urinary calcium were measured at baseline, 8 and 16 weeks.

    RESULTS: Baseline characteristics, including osteoporosis severity, sun exposure (~3 hours/week), and serum 25(OH)D did not differ between treatment arms. After 16 weeks, 91% of women sufficient at baseline, remained sufficient on 25,000 IU/4-weekly compared with 97% on 50,000 IU/4-weekly with mean serum 25(OH)D 108.1±20.4 and 114.7±18.4 SD nmol/L respectively (p=0.273). At trial's end, 39% and 80% of insufficient women at baseline attained sufficiency in Group A and Group B (p=0.057). Neither dose was associated with hyperparathyroidism or toxicity.

    CONCLUSIONS: Despite pretrial vitamin D supplementation and adequate sun exposure, 25.6% Chinese Malaysian PMO women were vitamin D insufficient indicating sunshine alone cannot ensure sufficiency in the tropics. Both ~900 IU/day and ~1800 IU/day cholecalciferol can safely maintain vitamin D sufficiency in >90% of Chinese Malaysian PMO women. Higher doses are required with baseline concentration <75 nmol/L.
  16. Samsuddin S, Arumugam PA, Md Amin MS, Yahya A, Musa N, Lim LL, et al.
    BJOG, 2020 03;127(4):490-499.
    PMID: 31778255 DOI: 10.1111/1471-0528.16031
    OBJECTIVE: To determine the association between maternal lipaemia and neonatal anthropometrics in Malaysian mother-offspring pairs.

    DESIGN: Prospective observational cohort study.

    SETTING: Single tertiary multidisciplinary antenatal clinic in Malaysia.

    POPULATION: A total of 507 mothers: 145 with gestational diabetes mellitus (GDM); 94 who were obese with normal glucose tolerance (NGT) (pre-gravid body mass index, BMI ≥ 27.5 kg/m2 ), and 268 who were not obese with NGT.

    METHODS: Maternal demographic, anthropometric, and clinical data were collected during an interview/examination using a structured questionnaire. Blood was drawn for insulin, C-peptide, triglyceride (Tg), and non-esterified fatty acid (NEFA) during the 75-g 2-hour oral glucose tolerance test (OGTT) screening, and again at 36 weeks of gestation. At birth, neonatal anthropometrics were assessed and data such as gestational weight gain (GWG) were extracted from the records.

    MAIN OUTCOME MEASURES: Macrosomia, large-for-gestational-age (LGA) status, cohort-specific birthweight (BW), neonatal fat mass (NFM), and sum of skinfold thickness (SSFT) > 90th centile.

    RESULTS: Fasting Tg > 95th centile (3.6 mmol/L) at screening for OGTT was independently associated with LGA (adjusted odds ratio, aOR 10.82, 95% CI 1.26-93.37) after adjustment for maternal glucose, pre-gravid BMI, and insulin sensitivity. Fasting glucose was independently associated with a birthweight ratio (BWR) of >90th centile (aOR 2.06, 95% CI 1.17-3.64), but not with LGA status, in this well-treated GDM cohort with pre-delivery HbA1c of 5.27%. In all, 45% of mothers had a pre-gravid BMI of <23 kg/m2 and 61% had a pre-gravid BMI of ≤ 25 kg/m2 , yet a GWG of >10 kg was associated with a 4.25-fold risk (95% CI 1.71-10.53) of BWR > 90th centile.

    CONCLUSION: Maternal lipaemia and GWG at a low threshold (>10 kg) adversely impact neonatal adiposity in Asian offspring, independent of glucose, insulin resistance and pre-gravid BMI. These may therefore be important modifiable metabolic targets in pregnancy.

    TWEETABLE ABSTRACT: Maternal lipids are associated with adiposity in Asian babies independently of pre-gravid BMI, GDM status, and insulin resistance.

  17. Zhang X, Yip TC, Wong GL, Leow WX, Liang LY, Lim LL, et al.
    Gut, 2023 Nov 24;72(12):2364-2371.
    PMID: 37549979 DOI: 10.1136/gutjnl-2023-330269
    OBJECTIVE: We aimed to test the hypothesis that automated fibrosis score calculation and electronic reminder messages could increase the detection of advanced liver disease in patients with type 2 diabetes.

    DESIGN: In this pragmatic randomised controlled trial at five general medical or diabetes clinics in Hong Kong and Malaysia, we randomly assigned patients in a 1:1 ratio to the intervention group with Fibrosis-4 index and aspartate aminotransferase-to-platelet ratio index automatically calculated based on routine blood tests, followed by electronic reminder messages to alert clinicians of abnormal results, or the control group with usual care. The primary outcome was the proportion of patients with increased fibrosis scores who received appropriate care (referred for hepatology care or specific fibrosis assessment) within 1 year.

    RESULTS: Between May 2020 and Oct 2021, 1379 patients were screened, of whom 533 and 528 were assigned to the intervention and control groups, respectively. A total of 55 out of 165 (33.3%) patients with increased fibrosis scores in the intervention group received appropriate care, compared with 4 of 131 (3.1%) patients in the control group (difference 30.2% (95% CI 22.4% to 38%); p<0.001). Overall, 11 out of 533 (2.1%) patients in the intervention group and 1 out of 528 (0.2%) patients in the control group were confirmed to have advanced liver disease (difference 1.9% (95% CI 0.61% to 3.5%); p=0.006).

    CONCLUSION: Automated fibrosis score calculation and electronic reminders can increase referral of patients with type 2 diabetes and abnormal fibrosis scores at non-hepatology settings.

    TRIAL REGISTRATION NUMBER: NCT04241575.

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